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Sample records for lewy bodies disease

  1. Lewy Body Disease

    MedlinePlus

    Lewy body disease is one of the most common causes of dementia in the elderly. Dementia is the loss of mental ... to affect normal activities and relationships. Lewy body disease happens when abnormal structures, called Lewy bodies, build ...

  2. Parkinson disease and incidental Lewy body disease

    PubMed Central

    Geraci-Erck, Maria; Rabin, Marcie L.; Adler, Charles H.; Serrano, Geidy; Beach, Thomas G.; Kurlan, Roger

    2015-01-01

    Objective: To quantify the loss of pigmented neurons in the substantia nigra (SN) of autopsy-confirmed Parkinson disease (PD) and incidental Lewy body disease (ILBD) vs age-matched controls (C). Methods: Unbiased stereology methods were used to rigorously count number and measure volumes of nigral pigmented neurons in PD, ILBD, and C brains. The obtained stereologic results were correlated with Lewy body (LB), amyloid plaque (AP), neurofibrillary tangle (NFT), and vascular pathology loads assessed in nigral and extranigral regions of each PD, ILBD, and C brain. The stereologic measurements were also correlated to predeath motor and cognitive scores as available for each participant. Results: A marked nigral neuronal loss (NNL) in PD (−82%) and ILBD (−40%) compared to C (p < 0.0001) was found. While there was significant correlation between NNL and LB in some cortical areas of PD (i.e., olfactory bulb), there were no correlations between NNL and LB, AP, or NFT loads or cerebral infarct volumes in any other examined regions for PD and ILBD brains. Conclusions: Using unbiased stereology methods, we show that there is a significant loss and absence of hypertrophic changes in nigral pigmented neurons of ILBD in comparison to C brains. Intriguingly, no significant correlations were found between NNL and LB loads in the SN of both PD and ILBD brains. These autopsy-verified stereologically based findings are novel and support ILBD as a pathologic condition. These results suggest possible new and alternative pathophysiologic hypotheses on the actual relationship between NNL and LB pathology. PMID:26468408

  3. False memories in Lewy-body disease.

    PubMed

    Algarabel, Salvador; Pitarque, Alfonso; Sales, Alicia; Meléndez, Juan Carlos; Escudero, Joaquín

    2015-12-01

    Recently, de Boysson, Belleville, Phillips et al. (2011) found that patients with Lewy-body disease (LBD) showed significantly lower rates of false memories than healthy controls, using the Deese-Roediger-McDermott (DRM) experimental procedure. Given that this result could be explained by the practically null rate of true recognition in the LBD group (0.09), we decided to replicate the study by de Boysson et al. (2011), but including a new condition that would maximize the true recognition rate (and analyze its effect on the rate of false memories). Specifically, in a DRM experiment, we manipulated (within subjects) two study and recognition conditions: in the "immediate" condition, both the LBD patients and the control group of healthy older people received a different recognition test after each study list (containing twelve words associated with a non-presented critical word), while in the "delayed" condition (similar to the one in de Boysson et al., 2011), the participants received the entire series of study lists and then took only one recognition test. The results showed that, in both samples, the "immediate" condition produced higher corrected rates of both true and false recognition than the "delayed" condition, although they were both lower in the LBD patients, which shows that these patients are capable of encoding and recognizing the general similitude underlying information (gist memory) in the right conditions.

  4. DatSCAN In Differential Diagnostics of Lewy Body Disease.

    PubMed

    Luzny, Jan; Ivanova, Katerina

    2016-06-01

    Differential diagnosis between Lewy body disease and Alzheimer´s disease might be difficult because of similarities of clinical symptoms in both neurodegenerative diseases. DatSCAN is a modern functional neuroimmaging method which differentiates between this similar diseases and helps in correct treatment strategy. We report our positive experience with DatSCAN in differentiating Lewy body disease from Alzheimer´s disease. This is a case report of a woman with Lewy body disease, initially diagnosed as Alzheimer´s disease. DatSCAN neuroimmaging method was used in differential diagnosis of dementia. Memory impairment, impaired activities of daily living, sleep and behavioral disturbances were present in our case. Donepezil was well tolerated, but haloperidol administration was followed by development of severe dystonia. DatSCAN showed deficient dopaminergic presynaptic transport in substantia nigra and striatum. This finding is typical for Lewy body disease not for Alzheimer´s disease. DatSCAN neuroimmaging is a suitable method for differentiating Lewy body disease from Alzheimer´s disease. Deficient dopaminergic presynaptic transport in substantia nigra and striatum is typical for Lewy body disease.

  5. Incidental Lewy Body Disease: Electrophysiological Findings Suggesting Pre-clinical Lewy Body Disorders

    PubMed Central

    Caviness, John N.; Adler, Charles H.; Hentz, Joseph G.; Shill, Holly A.; Evidente, Virgilio G.H.; Driver-Dunckley, Erika D.; Sabbagh, Marwan N.; Sue, Lucia; Beach, Thomas G.

    2011-01-01

    Objective Evaluate electrophysiologic findings in incidental Lewy Body disease (ILBD). Methods ILBD, Control, and Parkinson's disease (PD) subjects had electrophysiological evaluation within two years prior to autopsy. Data analyzed included surface electromyography (EMG) of upper extremity muscles during rest and muscle activation, and electroencephalography (EEG) recording at rest. For EMG, gross tracings and spectral peaks were analyzed. EEG measures analyzed were background frequency and power in delta, theta, alpha, and beta bands. Results Three of ten ILBD subjects (30%) showed unilateral rhythmic EMG discharges at rest without a visually apparent rest tremor. The ILBD resting EMG frequency was lower than in the Control group with no overlap (P=0.03) and close to that of the PD group. The ILBD group had significantly lower background rhythm frequency than the Control group (P=0.001) but was greater than the PD group (P=0.01). Conclusions The electrophysiologic changes in ILBD cases are between those of Control and PD, suggesting that these findings may reflect changes correlating with ILBD as a possible precursor to PD. Significance Electrophysiologic changes in ILBD may assist with the identification of a preclinical stage for Lewy body disorders and help the development of a therapeutic agent for modifying Lewy body disease progression. PMID:21616709

  6. Lewy bodies

    PubMed Central

    Shults, Clifford W.

    2006-01-01

    Lewy bodies (LB) in the substantia nigra are a cardinal pathological feature of Parkinson's disease, but they occur in a number of neurodegenerative diseases and can be widespread in the nervous system. The characteristics, locations, and composition of LB are reviewed, with particular attention to α-synuclein (α-SYN), which appears to be the major component of LB. The propensity for α-SYN, a presynaptic protein widely expressed in the brain, to aggregate is because of an amyloidogenic central region. The factors that favor the aggregation of α-SYN and mechanisms of toxicity are examined, and a mechanism through which aggregates of α-SYN could induce mitochondrial dysfunction and/or release of proapoptotic molecules is proposed. PMID:16449387

  7. False Recognition in Lewy-Body Disease and Frontotemporal Dementia

    ERIC Educational Resources Information Center

    de Boysson, C.; Belleville, S.; Phillips, N. A.; Johns, E. K.; Goupil, D.; Souchay, C.; Bouchard, R.; Chertkow, H.

    2011-01-01

    The primary goal of this study was to evaluate the false recognition phenomenon in persons with frontotemporal dementia (FTD) and those with Lewy-body disease (LBD). Patients with LBD (n=10) or FTD (n=15) and their corresponding controls (n=30) were subjected to the Deese-Roediger-McDermott (DRM) paradigm to induce false recognition. Patients were…

  8. Emerging pathways in genetic Parkinson's disease: Potential role of ceramide metabolism in Lewy body disease.

    PubMed

    Bras, Jose; Singleton, Andrew; Cookson, Mark R; Hardy, John

    2008-12-01

    Heterozygous loss-of-function mutations at the glucosecerebrosidase locus have recently been shown to be a potent risk factor for Lewy body disease. Based on this observation, we have re-evaluated the likelihood that the different PARK loci (defined using clinical criteria for disease) may be misleading attempts to find common pathways to pathogenesis. Rather, we suggest, grouping the different loci which lead to different Lewy body disease may be more revealing. Doing this, we suggest that several of the genes involved in disparate Lewy body diseases impinge on ceramide metabolism and we suggest that this may be a common theme for pathogenesis.

  9. Disease-modifying therapeutic directions for Lewy-Body dementias

    PubMed Central

    Zhang, Qiang; Kim, Young-Cho; Narayanan, Nandakumar S.

    2015-01-01

    Dementia with Lewy bodies (DLB) is the second leading cause of dementia following Alzheimer's disease (AD) and accounts for up to 25% of all dementia. DLB is distinct from AD in that it involves extensive neuropsychiatric symptoms as well as motor symptoms, leads to enormous societal costs in terms of direct medical care and is associated with high financial and caregiver costs. Although, there are no disease-modifying therapies for DLB, we review several new therapeutic directions in treating DLB. We discuss progress in strategies to decrease the level of alpha-synuclein, to prevent the cell to cell transmission of misfolded alpha-synuclein, and the potential of brain stimulation in DLB. PMID:26347604

  10. Biomarkers of Parkinson's disease and Dementia with Lewy bodies.

    PubMed

    Henchcliffe, Claire; Dodel, Richard; Beal, M Flint

    2011-12-01

    Parkinson's disease (PD) and Dementia with Lewy bodies (DLB) are progressive and disabling neurodegenerative disorders, in which signs and symptoms overlap with each other and with other neurodegenerative conditions. Currently, diagnosis, measurement of progression, and response to therapeutic intervention rely upon clinical observation. However, there remains a critical need for validated biomarkers in each of these areas. A definitive diagnostic test would improve clinical management and enrollment into clinical trials. An objective measure of progression is vitally important in identifying neuroprotective interventions. Biomarkers may also provide insight into pathogenesis, and might therefore suggest possible novel targets for therapeutic intervention. In addition, certain biomarkers might be of use in monitoring the biochemical and physiological effects of therapeutic interventions. Development of diagnostic biomarkers has focused until recently upon imaging techniques based upon measuring loss of dopamine neurons. Additionally, advances in understanding the genetic contribution to neurodegenerative disorders, in particular in PD, have identified multiple causative genes and risk factors that in some cases may help estimate PD risk. However, recent availability of increasingly sophisticated bioinformatics technology has rendered development of fluid biomarkers feasible, opening the possibility of generally accessible blood or cerebrospinal fluid (CSF) tests that could impact upon diagnosis, management, and research in PD, PDD, and DLB.

  11. Transcriptional network analysis in frontal cortex in Lewy body diseases with focus on dementia with Lewy bodies.

    PubMed

    Santpere, Gabriel; Garcia-Esparcia, Paula; Andres-Benito, Pol; Lorente-Galdos, Belen; Navarro, Arcadi; Ferrer, Isidro

    2017-03-21

    The present study investigates global transcriptional changes in frontal cortex area 8 in incidental Lewy Body disease (iLBD), Parkinson disease (PD) and Dementia with Lewy bodies (DLB). We identified different co-expressed gene sets associated with disease stages, and gene ontology categories enriched in gene modules and differentially expressed genes including modules or gene clusters correlated to iLBD comprising upregulated dynein genes and taste receptors, and down-regulated innate inflammation. Focusing on DLB, we found modules with genes significantly enriched in functions related to RNA and DNA production, mitochondria and energy metabolism, purine metabolism, chaperone and protein folding system, and synapses and neurotransmission (particularly the GABAergic system). The expression of more than fifty selected genes was assessed with RT-qPCR. Our findings provide, for the first time, evidence of molecular cortical alterations in iLBD and involvement of several key metabolic pathways and gene hubs in DLB which may underlie cognitive impairment and dementia. This article is protected by copyright. All rights reserved.

  12. Brain amyloid and cognition in Lewy body diseases.

    PubMed

    Gomperts, Stephen N; Locascio, Joseph J; Marquie, Marta; Santarlasci, Andrea L; Rentz, Dorene M; Maye, Jacqueline; Johnson, Keith A; Growdon, John H

    2012-07-01

    Many patients with PD develop PD with dementia (PDD), a syndrome that overlaps clinically and pathologically with dementia with Lewy bodies (DLB); PDD and DLB differ chiefly in the relative timing of dementia and parkinsonism. Brain amyloid deposition is an early feature of DLB and may account, in part, for its early dementia. We sought to confirm this hypothesis and also to determine whether amyloid accumulation contributes to cognitive impairment and dementia in the broad range of parkinsonian diseases. Twenty-nine cognitively healthy PD, 14 PD subjects with mild cognitive impairment (PD-MCI), 18 with DLB, 12 with PDD, and 85 healthy control subjects (HCS) underwent standardized neurologic and neuropsychological examinations and Pittsburgh compound B (PiB) imaging with PET. Apolipoprotein E (ApoE) genotypes were obtained in many patients. PiB retention was expressed as the distribution volume ratio using a cerebellar tissue reference. PiB retention was significantly higher in DLB than in any of the other diagnostic groups. PiB retention did not differ across PDD, PD-MCI, PD, and HCS. Amyloid burden increased with age and with the presence of the ApoE ε4 allele in all patient groups. Only in the DLB group was amyloid deposition associated with impaired cognition. DLB subjects have higher amyloid burden than subjects with PDD, PD-MCI, PD, or HCS; amyloid deposits are linked to cognitive impairment only in DLB. Early amyloid deposits in DLB relative to PDD may account for their difference in the timing of dementia and parkinsonism.

  13. Dementia with Lewy bodies

    PubMed Central

    Ferman, Tanis J.; Boeve, Bradley F.

    2009-01-01

    Synopsis The advent of new immunostains have improved our ability to detect limbic and cortical Lewy bodies, and it is now evident that Dementa with Lewy bodies (DLB) is the second most common neurodegenerative dementia, after Alzheimer’s disease (AD). Distinguishing DLB from AD has important implications for treatment, in terms of substances that may worsen symptoms (i.e., anticholinergic and certain neuroleptic medications) and those that may improve them (i.e., cholinesterase inhibitors, carbidopa-levodopa). Neurocognitive patterns, psychiatric features, extrapyramidal signs and sleep disturbance are helpful in differentiating DLB from AD early in the disease course. Differences in the severity of cholinergic depletion as well as type and distribution of neuropathology contribute to these clinical differences, though DLB patients with a high density of co-occuring AD pathology are less clinical distinguishable from AD. PMID:17659188

  14. Prospective study of relations between cortical Lewy bodies, poor eyesight, and hallucinations in Alzheimer's disease.

    PubMed

    McShane, R; Gedling, K; Reading, M; McDonald, B; Esiri, M M; Hope, T

    1995-08-01

    The presence of hallucinations is included in some, but not all, of the sets of clinical diagnostic criteria that have been proposed for dementia associated with cortical Lewy bodies. These criteria were developed from retrospective casenote analyses. This prospective, longitudinal study suggests that, in patients with Alzheimer's disease, cortical Lewy bodies are associated with more persistent and severe hallucinations, independently of any association with severity of cognitive decline. Poor eyesight contributes to the severity but not the persistence of the hallucinations.

  15. Neural correlates of attention‐executive dysfunction in lewy body dementia and Alzheimer's disease

    PubMed Central

    Kobeleva, Xenia; Cherry, George; Killen, Alison; Gallagher, Peter; Burn, David J.; Thomas, Alan J.; O'Brien, John T.; Taylor, John‐Paul

    2015-01-01

    Abstract Attentional and executive dysfunction contribute to cognitive impairment in both Lewy body dementia and Alzheimer's disease. Using functional MRI, we examined the neural correlates of three components of attention (alerting, orienting, and executive/conflict function) in 23 patients with Alzheimer's disease, 32 patients with Lewy body dementia (19 with dementia with Lewy bodies and 13 with Parkinson's disease with dementia), and 23 healthy controls using a modified Attention Network Test. Although the functional MRI demonstrated a similar fronto‐parieto‐occipital network activation in all groups, Alzheimer's disease and Lewy body dementia patients had greater activation of this network for incongruent and more difficult trials, which were also accompanied by slower reaction times. There was no recruitment of additional brain regions or, conversely, regional deficits in brain activation. The default mode network, however, displayed diverging activity patterns in the dementia groups. The Alzheimer's disease group had limited task related deactivations of the default mode network, whereas patients with Lewy body dementia showed heightened deactivation to all trials, which might be an attempt to allocate neural resources to impaired attentional networks. We posit that, despite a common endpoint of attention‐executive disturbances in both dementias, the pathophysiological basis of these is very different between these diseases. Hum Brain Mapp 37:1254–1270, 2016. © 2015 The Authors Human Brain Mapping Published by Wiley Periodicals, Inc. PMID:26705763

  16. Neural correlates of attention-executive dysfunction in lewy body dementia and Alzheimer's disease.

    PubMed

    Firbank, Michael; Kobeleva, Xenia; Cherry, George; Killen, Alison; Gallagher, Peter; Burn, David J; Thomas, Alan J; O'Brien, John T; Taylor, John-Paul

    2016-03-01

    Attentional and executive dysfunction contribute to cognitive impairment in both Lewy body dementia and Alzheimer's disease. Using functional MRI, we examined the neural correlates of three components of attention (alerting, orienting, and executive/conflict function) in 23 patients with Alzheimer's disease, 32 patients with Lewy body dementia (19 with dementia with Lewy bodies and 13 with Parkinson's disease with dementia), and 23 healthy controls using a modified Attention Network Test. Although the functional MRI demonstrated a similar fronto-parieto-occipital network activation in all groups, Alzheimer's disease and Lewy body dementia patients had greater activation of this network for incongruent and more difficult trials, which were also accompanied by slower reaction times. There was no recruitment of additional brain regions or, conversely, regional deficits in brain activation. The default mode network, however, displayed diverging activity patterns in the dementia groups. The Alzheimer's disease group had limited task related deactivations of the default mode network, whereas patients with Lewy body dementia showed heightened deactivation to all trials, which might be an attempt to allocate neural resources to impaired attentional networks. We posit that, despite a common endpoint of attention-executive disturbances in both dementias, the pathophysiological basis of these is very different between these diseases.

  17. Effectiveness of low-dose pregabalin in three patients with Lewy body disease and central neuropathic pain.

    PubMed

    Ukai, Katsuyuki; Fujishiro, Hiroshige; Ozaki, Norio

    2017-03-01

    Many patients with Lewy body disease complain of pain, and their pain may be associated with this disease. Recently, pain has become a focus of attention in Parkinson's disease, but there is little information regarding pain in patients who have dementia with Lewy bodies. We used pregabalin to treat three Lewy body disease patients with chronic pain that may have been related to degeneration of central neurons. All three patients responded well to pregabalin at 25-50 mg/day. To our knowledge, there have been no previous reports of pregabalin showing efficacy for central neuropathic pain in Parkinson's disease or Lewy body disease.

  18. Mitochondrial function, GSH and iron in neurodegeneration and Lewy body diseases.

    PubMed

    Gu, M; Owen, A D; Toffa, S E; Cooper, J M; Dexter, D T; Jenner, P; Marsden, C D; Schapira, A H

    1998-06-11

    The cause of neuronal loss in patients with idiopathic Parkinson's disease is unknown. Oxidative stress and complex I deficiency have both been identified in the substantia nigra in Parkinson's disease but their place in the sequence of events resulting in dopaminergic cell death is uncertain. We have analysed respiratory chain activity, iron and reduced glutathione concentrations in Parkinson's disease substantia innominata and in the cingulate cortex of patients with Parkinson's disease, Alzheimer's disease and dementia with Lewy bodies to investigate their association with neuronal death and Lewy body formation. No abnormalities of mitochondrial function, iron or reduced glutathione levels were identified in Parkinson's disease substantia innominata or cingulate cortex. Mitochondrial function also appeared to be unchanged in cingulate cortex from patients with Alzheimer's disease and from patients with dementia with Lewy bodies, however, iron concentrations were mildly increased in both, and reduced glutathione decreased only in Alzheimer's disease. These results confirm the anatomic specificity of the complex I deficiency and decreased levels of reduced glutathione within the Parkinson's disease brain and suggest that these parameters are not associated with cholinergic cell loss in Parkinson's disease nor with Lewy body formation in this or other diseases. We propose that our data support a 'two-hit' hypothesis for the cause of neuronal death in Parkinson's disease.

  19. Comparative analysis of cognitive impairments in lewy body dementia and Alzheimer's disease.

    PubMed

    Preobrazhenskaya, I S; Mkhitaryan, E A; Yakhno, N N

    2006-01-01

    Neuropsychological studies of 50 patients with Lewy body dementia (LBD) and 50 patients with Alzheimer's disease (AD) were performed to assess the characteristics of the cognitive impairments in these diseases. In patients with dementias of similar severities, patients with LBD showed greater impairment of executive and visuospatial functions and had more marked neurodynamic dysfunction. Patients with AD showed more profound memory disorders.

  20. Deubiquitinase Usp8 regulates α-synuclein clearance and modifies its toxicity in Lewy body disease.

    PubMed

    Alexopoulou, Zoi; Lang, Johannes; Perrett, Rebecca M; Elschami, Myriam; Hurry, Madeleine E D; Kim, Hyoung Tae; Mazaraki, Dimitra; Szabo, Aron; Kessler, Benedikt M; Goldberg, Alfred Lewis; Ansorge, Olaf; Fulga, Tudor A; Tofaris, George K

    2016-08-09

    In Parkinson's disease, misfolded α-synuclein accumulates, often in a ubiquitinated form, in neuronal inclusions termed Lewy bodies. An important outstanding question is whether ubiquitination in Lewy bodies is directly relevant to α-synuclein trafficking or turnover and Parkinson's pathogenesis. By comparative analysis in human postmortem brains, we found that ubiquitin immunoreactivity in Lewy bodies is largely due to K63-linked ubiquitin chains and markedly reduced in the substantia nigra compared with the neocortex. The ubiquitin staining in cells with Lewy bodies inversely correlated with the content and pathological localization of the deubiquitinase Usp8. Usp8 interacted and partly colocalized with α-synuclein in endosomal membranes and, both in cells and after purification, it deubiquitinated K63-linked chains on α-synuclein. Knockdown of Usp8 in the Drosophila eye reduced α-synuclein levels and α-synuclein-induced eye toxicity. Accordingly, in human cells, Usp8 knockdown increased the lysosomal degradation of α-synuclein. In the dopaminergic neurons of the Drosophila model, unlike knockdown of other deubiquitinases, Usp8 protected from α-synuclein-induced locomotor deficits and cell loss. These findings strongly suggest that removal of K63-linked ubiquitin chains on α-synuclein by Usp8 is a critical mechanism that reduces its lysosomal degradation in dopaminergic neurons and may contribute to α-synuclein accumulation in Lewy body disease.

  1. Deubiquitinase Usp8 regulates α-synuclein clearance and modifies its toxicity in Lewy body disease

    PubMed Central

    Alexopoulou, Zoi; Lang, Johannes; Perrett, Rebecca M.; Elschami, Myriam; Hurry, Madeleine E. D.; Kim, Hyoung Tae; Mazaraki, Dimitra; Szabo, Aron; Kessler, Benedikt M.; Goldberg, Alfred Lewis; Ansorge, Olaf; Fulga, Tudor A.; Tofaris, George K.

    2016-01-01

    In Parkinson’s disease, misfolded α-synuclein accumulates, often in a ubiquitinated form, in neuronal inclusions termed Lewy bodies. An important outstanding question is whether ubiquitination in Lewy bodies is directly relevant to α-synuclein trafficking or turnover and Parkinson’s pathogenesis. By comparative analysis in human postmortem brains, we found that ubiquitin immunoreactivity in Lewy bodies is largely due to K63-linked ubiquitin chains and markedly reduced in the substantia nigra compared with the neocortex. The ubiquitin staining in cells with Lewy bodies inversely correlated with the content and pathological localization of the deubiquitinase Usp8. Usp8 interacted and partly colocalized with α-synuclein in endosomal membranes and, both in cells and after purification, it deubiquitinated K63-linked chains on α-synuclein. Knockdown of Usp8 in the Drosophila eye reduced α-synuclein levels and α-synuclein–induced eye toxicity. Accordingly, in human cells, Usp8 knockdown increased the lysosomal degradation of α-synuclein. In the dopaminergic neurons of the Drosophila model, unlike knockdown of other deubiquitinases, Usp8 protected from α-synuclein–induced locomotor deficits and cell loss. These findings strongly suggest that removal of K63-linked ubiquitin chains on α-synuclein by Usp8 is a critical mechanism that reduces its lysosomal degradation in dopaminergic neurons and may contribute to α-synuclein accumulation in Lewy body disease. PMID:27444016

  2. Dementia with Lewy bodies.

    PubMed

    McKeith, Ian G; Burn, David J; Ballard, Clive G; Collerton, Daniel; Jaros, Evelyn; Morris, Chris M; McLaren, Andrew; Perry, Elaine K; Perry, Robert; Piggott, Margaret A; O'Brien, John T

    2003-01-01

    The objective was to summarize recent findings about the clinical features, diagnosis and investigation of dementia with Lewy (DLB) bodies, together with its neuropathology, neurochemistry and genetics. Dementia with Lewy bodies (DLB) is a primary, neurodegenerative dementia sharing clinical and pathological characteristics with both Parkinson's disease (PD) and Alzheimer's disease (AD). Antiubiquitin immunocytochemical staining, developed in the early 1990s, allowed the frequency and distribution of cortical LBs to be defined. More recently, alpha-synuclein antibodies have revealed extensive neuritic pathology in DLB demonstrating a neurobiological link with other "synucleinopathies" including PD and multiple system atrophy (MSA). The most significant correlates of cognitive failure in DLB appear to be with cortical LB and Lewy neurites (LNs) rather than Alzheimer type pathology. Clinical diagnostic criteria for DLB, published in 1996, have been subjected to several validation studies against autopsy findings. These conclude that although diagnostic specificity is high (range 79- 100%, mean 92%), sensitivity is lower (range 0- 83 %, mean, 49%). Improved methods of case detection are therefore required. Fluctuating impairments in attention, visual recognition and construction are more indicative of DLB than AD. Relative preservation of medial temporal lobe volume on structural MRI and the use of SPECT tracers for regional blood flow and the dopamine transporter are the most reliable current biomarkers for DLB. There are no genetic or CSF tests recommended for the diagnosis of DLB at present. Between 15 and 20% of all elderly demented cases reaching autopsy have DLB, making it the most common cause of degenerative dementia after AD. Exquisite, not infrequently fatal, sensitivity to neuroleptic drugs and encouraging reports of the effects of cholinesterase inhibitors on cognitive, psychiatric and neurological features, mean that an accurate diagnosis of DLB is more

  3. Evidence for Angiogenesis in Parkinson’s disease, Incidental Lewy Body disease, and Progressive Supranuclear Palsy

    PubMed Central

    Bradaric, Brinda Desai; Patel, Aditiben; Schneider, Julie A.; Carvey, Paul M.; Hendey, Bill

    2012-01-01

    Angiogenesis has not been extensively studied in Parkinson’s disease (PD) despite being associated with other neurodegenerative disorders. Post-mortem human brain tissues were obtained from subjects with pathologically confirmed Parkinson’s disease (PD) and progressive supranuclear palsy (PSP), a rapidly progressing Parkinsonian-like disorder. Tissues were also obtained from subjects with incidental Lewy body disease (iLBD) who had Lewy bodies in the substantia nigra pars compacta (SNpc) but had not been diagnosed with PD and age-matched controls without Lewy body pathology. The SNpc, putamen, locus ceruleus (LC) and midfrontal cortex were examined for integrin αvβ3, a marker for angiogenesis, along with vessel number and activated microglia. All parkinsonian syndromes had greater αvβ3 in the LC and the SNpc, while only PD and PSP subjects had elevated αvβ3 in the putamen compared to controls. PD and PSP subjects also had increases in microglia number and activation in the SNpc suggesting a link between inflammation and clinical disease. Microglia activation in iLBD subjects was limited to the LC, an area involved at an early stage of PD. Likewise, iLBD subjects did not differ from controls in αvβ3 staining in the putamen, a late area of involvement in PD. The presence of αvβ3 reactive vessels in PD and its syndromes is indicative of newly created vessels that have not likely developed the restrictive properties of the blood brain barrier. Such angiogenic vessels could contribute to neuroinflammation by failing to protect the parenchyma from peripheral immune cells and inflammatory or toxic factors in the peripheral circulation. PMID:21748523

  4. Imaging amyloid in Parkinson's disease dementia and dementia with Lewy bodies with positron emission tomography.

    PubMed

    Brooks, David J

    2009-01-01

    Although Parkinson's disease with later dementia (PDD) and dementia with Lewy bodies (DLB) are pathologically characterized by the presence of intraneuronal Lewy inclusion bodies, amyloid deposition is also associated to varying degrees with both these disorders. Fibrillar amyloid load can now be quantitated in vivo with positron emission tomography (PET) using imaging biomarkers. Here the reported findings of 11C-PIB PET studies concerning the amyloid load associated with PD and its influence on dementia are reviewed. It is concluded that the presence of amyloid acts to accelerate the dementia process in Lewy body disorders, though has little influence on its nature. Anti-amyloid strategies could be a relevant approach for slowing dementia in a number of DLB and PDD cases.

  5. Intra-neuronal vesicular uptake of catecholamines is decreased in patients with Lewy body diseases.

    PubMed

    Goldstein, David S; Holmes, Courtney; Kopin, Irwin J; Sharabi, Yehonatan

    2011-08-01

    Several neurodegenerative disorders, including Parkinson disease (PD), are characterized by the presence of Lewy bodies - cytoplasmic inclusions containing α-synuclein protein aggregates - in the affected neurons. A poorly understood feature of Lewy body diseases is loss of sympathetic nerves in the heart and other organs, manifesting as orthostatic hypotension (OH; also known as postural hypotension). We asked whether sympathetic denervation is associated with decreased uptake of catecholamines, such as dopamine and norepinephrine, into storage vesicles within sympathetic neurons. We used 6-[18F]-dopamine (18F-DA) to track myocardial uptake and retention of catecholamines. Concurrently, the fate of intra-neuronal 18F-DA was followed by assessment of arterial plasma levels of the 18F-DA metabolite 18F-dihydroxyphenylacetic acid (18F-DOPAC). The ratio of myocardial 18F-DA to arterial 18F-DOPAC provided an index of vesicular uptake. Tracer concentrations were measured in patients with PD with or without orthostatic hypotension (PD+OH, PD-No-OH); in patients with pure autonomic failure (PAF, a Lewy body disease without parkinsonism); in patients with multiple system atrophy (MSA, a non-Lewy body synucleinopathy); and in normal controls. Patients with PD+OH or PAF had decreased vesicular 18F-DA uptake and accelerated 18F-DA loss, compared with MSA and control subjects. PD-No-OH patients could be subtyped into one of these categories based on their initial 18F-DA uptake. We conclude that sympathetic denervation in Lewy body diseases is associated with decreased vesicular uptake of neuronal catecholamines, suggesting that vesicular monoamine transport is impaired. Vesicular uptake may constitute a novel target for diagnosis, treatment, and prevention.

  6. Extrapyramidal signs by dementia severity in Alzheimer disease and dementia with Lewy bodies.

    PubMed

    Kaur, Berneet; Harvey, Danielle J; Decarli, Charles S; Zhang, Lin; Sabbagh, Marwan N; Olichney, John M

    2013-01-01

    Alzheimer disease (AD) and dementia with Lewy bodies (DLB) are common etiologies of dementia with overlapping clinical features. Our objective was to determine which extrapyramidal signs (EPSs) are most helpful in identifying DLB. We analyzed data from the National Alzheimer's Coordinating Center, including demographics, Unified Parkinson's Disease Rating Scale (UPDRS) scores, Mini-Mental State Examination (MMSE) scores, and clinical diagnosis. The subjects were divided into 3 groups: AD, DLB, or Lewy body variant (LBV). The UPDRS motor scores were totaled and analyzed within and across the MMSE strata using regression techniques. Further, we divided UPDRS subscores into 9 EPSs, dichotomized as either present or absent. Logistic regression analysis was used to compare each of the EPS in the AD and Lewy body (DLB+LBV) groups. DLB subjects (n=130) were more likely to be male individuals, younger, and have higher MMSE scores (P<0.001) compared with that in AD (n=1826) or LBV (n=105) subjects. Differences were found for total UPDRS score and number of EPSs (P<0.001), after controlling for age, sex, and MMSE. Logistic regression models demonstrated that masked facies best differentiated AD from Lewy body (odds ratio=6.5, P<0.001, 95% confidence interval, 3.8-11.1). If these findings are neuropathologically validated, then the presence of specific EPS may help clinicians better differentiate AD and DLB.

  7. Nonselenium glutathione peroxidase in human brain : elevated levels in Parkinson's disease and dementia with lewy bodies.

    PubMed

    Power, John H T; Shannon, John M; Blumbergs, Peter C; Gai, Wei-Ping

    2002-09-01

    Nonselenium glutathione peroxidase (NSGP) is a new member of the antioxidant family. Using antibodies to recombinant NSGP we have examined the distribution of this enzyme in normal, Parkinson's disease (PD), and dementia with Lewy body disease (DLB) brains. We have also co-localized this enzyme with alpha-synuclein as a marker for Lewy bodies. In normal brains there was a very low level of NSGP staining in astrocytes. In PD and DLB there were increases in the number and staining intensity of NSGP-positive astrocytes in both gray and white matter. Cell counting of NSGP cells in PD and DLB frontal and cingulated cortices indicated there was 10 to 15 times more positive cells in gray matter and three times more positive cells in white matter than in control cortices. Some neurons were positive for both alpha-synuclein and NSGP in PD and DLB, and double staining indicated that NSGP neurons contained either diffuse cytoplasmic alpha-synuclein deposits or Lewy bodies. In concentric Lewy bodies, alpha-synuclein staining was peripheral whereas NSGP staining was confined to the central core. Immunoprecipitation indicated there was direct interaction between alpha-synuclein and NSGP. These results suggest oxidative stress conditions exist in PD and DLB and that certain cells have responded by up-regulating this novel antioxidant enzyme.

  8. Cardiac sympathetic denervation precedes neuronal loss in the sympathetic ganglia in Lewy body disease.

    PubMed

    Orimo, Satoshi; Amino, Takeshi; Itoh, Yoshinori; Takahashi, Atsushi; Kojo, Tohru; Uchihara, Toshiki; Tsuchiya, Kuniaki; Mori, Fumiaki; Wakabayashi, Koichi; Takahashi, Hitoshi

    2005-06-01

    Decreased cardiac uptake of meta-iodobenzylguanidine (MIBG) on [123I]MIBG myocardial scintigraphy has been reported in Parkinson's disease (PD) and dementia with Lewy bodies (DLB). We hypothesized that cardiac sympathetic denervation might account for the pathomechanism. To elucidate the extent, frequency and pattern of cardiac sympathetic nerve involvement in Lewy body disease and related neurodegenerative disorders, we immunohistochemically examined heart tissues from patients with PD (n=11), DLB (n=7), DLB with Alzheimer's disease (DLB/AD; n=4), multiple system atrophy (MSA; n=8), progressive supranuclear palsy (PSP; n=5), pure AD (n=10) and control subjects (n=5) together with sympathetic ganglia from patients with PD (n=5) and control subjects (n=4), using an antibody against tyrosine hydroxylase (TH). TH-immunoreactive nerve fibers in the hearts had almost entirely disappeared in nearly all the patients with PD, DLB and DLB/AD, whereas they were well preserved in all the patients with PSP and pure AD as well as in all except for one patient with MSA. In PD, neurons in the sympathetic ganglia were preserved in all except for one patient. Decreased cardiac uptake of MIBG in Lewy body disease reflects actual cardiac sympathetic denervation, which precedes the neuronal loss in the sympathetic ganglia.

  9. Lewy Body Dementia Diagnosis

    MedlinePlus

    ... as part of their protocols. Participating in research studies is a good way to benefit others with Lewy body dementia. Medications Medications are one of the most controversial subjects in dealing with LBD. A medication that doesn't work for one person may work for another person. ...

  10. The first autopsied case of diffuse Lewy body disease (DLBD): re-examination by recent immunostaining methods: The 50th Anniversary of Japanese Society of Neuropathology.

    PubMed

    Kosaka, Kenji; Manabe, Yuta

    2010-10-01

    Materials from our first autopsied case of diffuse Lewy body disease (DLBD), that was originally reported in 1976, were re-examined using recent immunohistochemical methods. Lewy pathology consisting of Lewy bodies and Lewy neurites appeared much more marked with alpha-synuclein immunostaining than had been detected with classical stainings. This case and our other similar cases prompted us to propose the terms "Lewy body disease" in 1980 and "diffuse Lewy body disease" in 1984. We also reported in 1990 that DLBD was classified into two forms: a pure form and a common form. Based on these studies the term "dementia with Lewy bodies (DLB)" was proposed in 1996. Since 1980, we have insisted that DLB, Parkinson disease (PD), and PD with dementia (PDD) should be understood within the spectrum of Lewy body disease. This insistence has been recently accepted by the International Workshop and the International Working Group on DLB and PDD in 2005 and in 2006, respectively.

  11. α-Synuclein pathology in the cranial and spinal nerves in Lewy body disease.

    PubMed

    Nakamura, Keiko; Mori, Fumiaki; Tanji, Kunikazu; Miki, Yasuo; Toyoshima, Yasuko; Kakita, Akiyoshi; Takahashi, Hitoshi; Yamada, Masahito; Wakabayashi, Koichi

    2016-06-01

    Accumulation of phosphorylated α-synuclein in neurons and glial cells is a histological hallmark of Lewy body disease (LBD) and multiple system atrophy (MSA). Recently, filamentous aggregations of phosphorylated α-synuclein have been reported in the cytoplasm of Schwann cells, but not in axons, in the peripheral nervous system in MSA, mainly in the cranial and spinal nerve roots. Here we conducted an immunohistochemical investigation of the cranial and spinal nerves and dorsal root ganglia of patients with LBD. Lewy axons were found in the oculomotor, trigeminal and glossopharyngeal-vagus nerves, but not in the hypoglossal nerve. The glossopharyngeal-vagus nerves were most frequently affected, with involvement in all of 20 subjects. In the spinal nerve roots, Lewy axons were found in all of the cases examined. Lewy axons in the anterior nerves were more frequent and numerous in the thoracic and sacral segments than in the cervical and lumbar segments. On the other hand, axonal lesions in the posterior spinal nerve roots appeared to increase along a cervical-to-sacral gradient. Although Schwann cell cytoplasmic inclusions were found in the spinal nerves, they were only minimal. In the dorsal root ganglia, axonal lesions were seldom evident. These findings indicate that α-synuclein pathology in the peripheral nerves is axonal-predominant in LBD, whereas it is restricted to glial cells in MSA.

  12. CSF alpha-synuclein levels in dementia with Lewy bodies and Alzheimer's disease.

    PubMed

    Noguchi-Shinohara, Moeko; Tokuda, Takahiko; Yoshita, Mitsuhiro; Kasai, Takashi; Ono, Kenjiro; Nakagawa, Masanori; El-Agnaf, Omar M A; Yamada, Masahito

    2009-01-28

    Dementia with Lewy bodies (DLB) is characterized by widespread depositions of alpha-synuclein, which are described as Lewy bodies. Recently, it was shown that neuronal cells in culture constitutively release alpha-synuclein into the culture medium and that alpha-synuclein is normally present in human cerebrospinal fluid (CSF). The aim of the present study was to evaluate the diagnostic value of CSF alpha-synuclein levels in discriminating DLB from Alzheimer's disease (AD). Alpha-synuclein was measured in CSF from 16 patients with DLB and 21 patients with AD. Iodine-123 metaiodobenzylguanidine cardiac scintigraphy was also performed to assess Lewy body pathology. CSF alpha-synuclein levels did not differ significantly between DLB and AD patients. However, the duration of illness was associated with lower alpha-synuclein levels (p<0.05) in DLB, while no such association was found in AD. The present data show CSF alpha-synuclein levels are not sensitive diagnostic markers to discriminate DLB from AD. However, the lower alpha-synuclein levels in DLB patients with longer duration suggest a reduction in CSF alpha-synuclein in association with increased severity of alpha-synucleinopathy in the brain.

  13. Cholinergic and other neurotransmitter mechanisms in Parkinson's disease, Parkinson's disease dementia, and dementia with Lewy bodies.

    PubMed

    Francis, Paul T; Perry, Elaine K

    2007-09-01

    It is now 30 years since the beginning of intensive efforts to understand the neurotransmitter biochemistry of dementia as exemplified by Alzheimer's disease and such studies have led to the development of rational treatment strategies, which are continuing to benefit patients. However, as studies became more sophisticated and clinicians rediscovered an interest in dementia, because of the potential for symptomatic treatment, it has become clear that there are several different neurodegenerative conditions that gives rise to dementia syndromes and that each has distinct neurochemical pathology. This has important treatment implications since what works for one may not work for another or at the extreme, may make matters worse. Therefore it is clear that a detailed understanding of the neurotransmitter function in each condition is not merely academic but can lead to rationale drug design and treatment strategies appropriate for that group of patients. Dementia with Lewy bodies (DLB) has clinico-pathological features, which overlap with either AD or Parkinson's disease (PD) as well as features that help to distinguish it, such as fluctuations in cognitive impairment and a higher prevalence of visual hallucinations. On this basis, it would be expected that the neurochemistry would have some similarities with both disorders.

  14. New brain-specific beta-synuclein isoforms show expression ratio changes in Lewy body diseases.

    PubMed

    Beyer, Katrin; Munoz-Marmol, Ana M; Sanz, Carolina; Marginet-Flinch, Ruth; Ferrer, Isidro; Ariza, Aurelio

    2012-02-01

    Lewy body diseases (LBDs) include dementia with Lewy bodies (DLB) and Parkinson disease (PD). Alpha-synuclein (AS) aggregation is a key event in the pathogenesis of LBDs and beta-synuclein (BS) inhibits AS aggregation in vitro and in vivo. Recently, BS has been shown to interact directly with AS regulating its functionality and preventing its oligomerization, and a molecular subgroup of pure DLB lacks BS in cortical regions. In this study, we characterized four new BS transcript variants and analyzed their expression in neuronal and non-neuronal tissue, and their differential expression in frozen samples of three areas from brains of patients with pure Lewy body pathology (LBP), common LBP, Alzheimer pathology, and of controls. Relative mRNA expression was determined by real-time PCR with neuron-specific enolase 2 and synaptophysin as housekeeping genes, and expression changes were evaluated by the ΔΔCt method. Two main findings are in concordance with earlier studies. First, all BS isoforms are drastically diminished in the cortex of patients with pure LBP that had presented clinically as DLB but not PD with dementia. Second, an important shift of the isoform expression ratio was observed in the temporal cortex of all LBD cases, and the minor isoforms, normally absent in the midbrain, were detected in the caudate nucleus of all DLB samples. Our results provide further evidence for the role of minor transcript variants in the development of complex diseases and provide new insights into the pathogenesis of LBDs that may be important for the understanding of molecular mechanisms involved in these complex diseases.

  15. Alzheimer disease with amygdala Lewy bodies: a distinct form of alpha-synucleinopathy.

    PubMed

    Uchikado, Hirotake; Lin, Wen-Lang; DeLucia, Michael W; Dickson, Dennis W

    2006-07-01

    Lewy bodies (LBs) are alpha-synuclein-immunoreactive neuronal inclusions with a predilection for specific cortical and subcortical regions, including the amygdala. In this study, the presence of LBs was assessed in 347 cases of Alzheimer disease (AD). In 87 cases, LB pathology was diagnostic of brainstem (n=3), transitional (n=32), or diffuse (n=52) Lewy body disease (LBD). The remaining 260 cases of AD were screened for amygdala LBs (AD/ALB) and 62 (24%) cases were found. If AD/LBD cases are included, LBs were detected in 149 (43%) cases of AD. The presence alpha-synuclein pathology was assessed in multiple brain regions of the 62 cases of AD/ALB and 57 randomly selected cases of AD, and only sparse alpha-synuclein pathology was detected in both. The burden of alpha-synuclein pathology in brainstem nuclei, amygdala, and neocortex was significant lower in AD/ALB than in AD/LBD. In comparison to AD/LBD, AD/ALB did not differ in age at death, disease duration, male-to-female ratio, brain weight, Braak neurofibrillary tangle stage, average senile plaque density, or apolipoprotein E epsilon4 allele frequency. The results suggest that AD/ALB is pathologically different from AD/LBD, suggesting that it is a neuropathologically distinct and isolated alpha-synucleinopathy.

  16. The brainstem pathologies of Parkinson’s disease and dementia with Lewy bodies

    PubMed Central

    Kay, Seidel; Josefine, Mahlke; Siswanto, Sonny; Reijko, Krüger; Helmut, Heinsen; Georg, Auburger; Mohamed, Bouzrou; Grinberg, LT; Helmut, Wicht; Horst-Werner, Korf; Wilfred, den Dunnen; Udo, Rüb

    2015-01-01

    Parkinson’s disease (PD) and dementia with Lewy bodies (DLB) are among the human synucleinopathies, which share the neuropathological features of alpha-synuclein immunoreactive neuronal and/or glial aggregations, as well as progressive neuronal loss in select brain regions (e.g. dopaminergic substantia nigra and ventral tegmental area, cholinergic pedunculopontine nucleus). Despite a number of studies about brainstem pathologies in PD and DLB, there is currently no detailed information available regarding the presence of alpha-synuclein immunoreactive inclusions (a) in the cranial nerve, precerebellar, vestibular and oculomotor brainstem nuclei and (b) in brainstem fiber tracts and oligodendroctyes. Therefore, we performed a detailed analysis of the alpha-synuclein immunoreactive inclusion pathologies in the brainstem nuclei (Lewy bodies, LB; Lewy neurites, LN; coiled bodies, CB) and fiber tracts (LN, CB) of clinically diagnosed and neuropathologically confirmed PD and DLB patients. As also reported in previous studies, LB and LN were most prevalent in the substantia nigra, ventral tegmental area, pedunculopontine and raphe nuclei, periaqueductal gray, locus coeruleus, parabrachial nuclei, reticular formation, prepositus hypoglossal, dorsal motor vagal, and solitary nuclei. However, we for the first time demonstrated LB and LN in all cranial nerve nuclei, premotor oculomotor, precerebellar and vestibular brainstem nuclei, as well as LN in all brainstem fiber tracts. CB were present in nearly all brainstem nuclei and brainstem fiber tracts containing LB and/or LN. These novel brainstem findings can account for or contribute to a large variety of less well-explained PD and DLB symptoms (e.g. gait and postural instability, impaired balance and postural reflexes, falls, ingestive and oculomotor dysfunctions), and point to the occurrence of disturbances of intra-axonal transport processes and a transneuronal spread of the underlying pathological processes of PD and

  17. Cortical PIB binding in Lewy body disease is associated with Alzheimer-like characteristics.

    PubMed

    Maetzler, Walter; Liepelt, Inga; Reimold, Matthias; Reischl, Gerald; Solbach, Christoph; Becker, Clemens; Schulte, Claudia; Leyhe, Thomas; Keller, Stefanie; Melms, Arthur; Gasser, Thomas; Berg, Daniela

    2009-04-01

    About one fourth of Lewy body disease (LBD) patients show cortical beta-amyloid load, basically a hallmark of Alzheimer disease (AD). Using [11C]PIB-PET, we tested whether LBD patients with beta-amyloid burden differ from those without with respect to demographic, clinical, biochemical and genetic parameters. Thirty-five LBD subjects (9 patients with Lewy body dementia, DLB; 12 demented Parkinson patients, PDD; 14 non-demented PD, PDND) underwent [11C]PIB-PET, and were classified as either PIB(+) or PIB(-) according to cortical PIB uptake. PIB+ and PIB(-) patients were then compared according to demographic, clinical, biochemical and genetic parameters. None of the PDND, but four PDD and four DLB subjects were PIB+. In PIB+ subjects, ApoE4 prevalence was higher, CSF Abeta42 levels were lower and, among demented patients, PIB-binding was associated with a lower MMSE score. Motor symptoms were not associated with PIB binding. Thus, LBD patients with cortical beta-amyloid show characteristics usually observed in AD.

  18. An order in Lewy body disorders: Retrograde degeneration in hyperbranching axons as a fundamental structural template accounting for focal/multifocal Lewy body disease.

    PubMed

    Uchihara, Toshiki

    2016-11-14

    Initial clinical recognition of "paralysis agitans" by James Parkinson was expanded by Jean-Martin Charcot, who recognized additional clinical findings of his own, such as slowness (distinct from paralysis), rigidity (distinct from spasticity) and characteristic countenance. Charcot assembled these findings under the umbrella of "Parkinson disease (PD)". This purely clinical concept was so prescient and penetrating that subsequent neuropathological and biochemical evidences were ordered along this axis to establish the nigra-central trinity of PD (dopamine depletion, nigral lesion with Lewy bodies: LBs). Although dramatic efficacy of levodopa boosted an enthusiasm for this nigra-centralism, extranigral lesions were identified, especially after identification of alpha-synuclein (αS) as a major constituent of LBs. Frequent αS lesions in the lower brainstem with their presumed upward spread were coupled with the self-propagating property of αS molecule, as a molecular template, to constitute the prion-Braak hypothesis. This hybrid concept might expectedly explain clinical, structural and biochemical features of PD/dementia with Lewy bodies (DLB) as if they were stereotypic. In spite of this ordered explanation, recent studies have demonstrated unexpectedly that αS lesions in the human brain, as well as their corresponding clinical manifestations, are much more disordered. Even with such a chaos of LB disorders, affected neuronal groups are uniformly characterized by hyperbranching axons, which may facilitate distal-dominant degeneration and retrograde progression of LB-related degeneration along axons as a fundamental structural order to template LB disorders. This "structural template" hypothesis may explain why: (i) some selective groups are prone to develop Lewy pathology; (ii) their clinical manifestations (especially non-motor components) are vague and generalized without somatotopic accentuation; (iii) distal axons and terminals are preferentially affected

  19. Genome-wide analysis of genetic correlation in dementia with Lewy bodies, Parkinson's and Alzheimer's diseases

    PubMed Central

    Guerreiro, Rita; Escott-Price, Valentina; Darwent, Lee; Parkkinen, Laura; Ansorge, Olaf; Hernandez, Dena G.; Nalls, Michael A.; Clark, Lorraine; Honig, Lawrence; Marder, Karen; van der Flier, Wiesje; Holstege, Henne; Louwersheimer, Eva; Lemstra, Afina; Scheltens, Philip; Rogaeva, Ekaterina; St George-Hyslop, Peter; Londos, Elisabet; Zetterberg, Henrik; Ortega-Cubero, Sara; Pastor, Pau; Ferman, Tanis J.; Graff-Radford, Neill R.; Ross, Owen A.; Barber, Imelda; Braae, Anne; Brown, Kristelle; Morgan, Kevin; Maetzler, Walter; Berg, Daniela; Troakes, Claire; Al-Sarraj, Safa; Lashley, Tammaryn; Compta, Yaroslau; Revesz, Tamas; Lees, Andrew; Cairns, Nigel J.; Halliday, Glenda M.; Mann, David; Pickering-Brown, Stuart; Powell, John; Lunnon, Katie; Lupton, Michelle K.; Dickson, Dennis; Hardy, John; Singleton, Andrew; Bras, Jose

    2016-01-01

    The similarities between dementia with Lewy bodies (DLB) and both Parkinson's disease (PD) and Alzheimer's disease (AD) are many and range from clinical presentation, to neuropathological characteristics, to more recently identified, genetic determinants of risk. Because of these overlapping features, diagnosing DLB is challenging and has clinical implications since some therapeutic agents that are applicable in other diseases have adverse effects in DLB. Having shown that DLB shares some genetic risk with PD and AD, we have now quantified the amount of sharing through the application of genetic correlation estimates, and show that, from a purely genetic perspective, and excluding the strong association at the APOE locus, DLB is equally correlated to AD and PD. PMID:26643944

  20. Genome-wide analysis of genetic correlation in dementia with Lewy bodies, Parkinson's and Alzheimer's diseases.

    PubMed

    Guerreiro, Rita; Escott-Price, Valentina; Darwent, Lee; Parkkinen, Laura; Ansorge, Olaf; Hernandez, Dena G; Nalls, Michael A; Clark, Lorraine; Honig, Lawrence; Marder, Karen; van der Flier, Wiesje; Holstege, Henne; Louwersheimer, Eva; Lemstra, Afina; Scheltens, Philip; Rogaeva, Ekaterina; St George-Hyslop, Peter; Londos, Elisabet; Zetterberg, Henrik; Ortega-Cubero, Sara; Pastor, Pau; Ferman, Tanis J; Graff-Radford, Neill R; Ross, Owen A; Barber, Imelda; Braae, Anne; Brown, Kristelle; Morgan, Kevin; Maetzler, Walter; Berg, Daniela; Troakes, Claire; Al-Sarraj, Safa; Lashley, Tammaryn; Compta, Yaroslau; Revesz, Tamas; Lees, Andrew; Cairns, Nigel J; Halliday, Glenda M; Mann, David; Pickering-Brown, Stuart; Powell, John; Lunnon, Katie; Lupton, Michelle K; Dickson, Dennis; Hardy, John; Singleton, Andrew; Bras, Jose

    2016-02-01

    The similarities between dementia with Lewy bodies (DLB) and both Parkinson's disease (PD) and Alzheimer's disease (AD) are many and range from clinical presentation, to neuropathological characteristics, to more recently identified, genetic determinants of risk. Because of these overlapping features, diagnosing DLB is challenging and has clinical implications since some therapeutic agents that are applicable in other diseases have adverse effects in DLB. Having shown that DLB shares some genetic risk with PD and AD, we have now quantified the amount of sharing through the application of genetic correlation estimates, and show that, from a purely genetic perspective, and excluding the strong association at the APOE locus, DLB is equally correlated to AD and PD.

  1. Alpha-Synuclein Oligomers—Neurotoxic Molecules in Parkinson's Disease and Other Lewy Body Disorders

    PubMed Central

    Ingelsson, Martin

    2016-01-01

    Adverse intra- and extracellular effects of toxic α-synuclein are believed to be central to the pathogenesis in Parkinson's disease and other disorders with Lewy body pathology in the nervous system. One of the physiological roles of α-synuclein relates to the regulation of neurotransmitter release at the presynapse, although it is still unclear whether this mechanism depends on the action of monomers or smaller oligomers. As for the pathogenicity, accumulating evidence suggest that prefibrillar species, rather than the deposits per se, are responsible for the toxicity in affected cells. In particular, larger oligomers or protofibrils of α-synuclein have been shown to impair protein degradation as well as the function of several organelles, such as the mitochondria and the endoplasmic reticulum. Accumulating evidence further suggest that oligomers/protofibrils may have a toxic effect on the synapse, which may lead to disrupted electrophysiological properties. In addition, recent data indicate that oligomeric α-synuclein species can spread between cells, either as free-floating proteins or via extracellular vesicles, and thereby act as seeds to propagate disease between interconnected brain regions. Taken together, several lines of evidence suggest that α-synuclein have neurotoxic properties and therefore should be an appropriate molecular target for therapeutic intervention in Parkinson's disease and other disorders with Lewy pathology. In this context, immunotherapy with monoclonal antibodies against α-synuclein oligomers/protofibrils should be a particularly attractive treatment option. PMID:27656123

  2. Cholinesterase inhibitors in Alzheimer's disease and Lewy body spectrum disorders: the emerging pharmacogenetic story

    PubMed Central

    2009-01-01

    This review provides an update on the current state of pharmacogenetic research in the treatment of Alzheimer's disease (AD) and Lewy body disease (LBD) as it pertains to the use of cholinesterase inhibitors (ChEI). AD and LBD are first reviewed from clinical and pathophysiological perspectives. This is followed by a discussion of ChEIs used in the symptomatic treatment of these conditions, focusing on their unique and overlapping pharmacokinetic and pharmacodynamic profiles, which can be used to identify candidate genes for pharmacogenetics studies. The literature published to date is then reviewed and limitations are discussed. This is followed by a discussion of potential endophenotypes which may help to refine future pharmacogenetic studies of response and adverse effects to ChEIs. PMID:20038497

  3. Prevalence and impact of vascular and Alzheimer pathologies in Lewy body disease.

    PubMed

    Jellinger, Kurt A; Attems, Johannes

    2008-04-01

    Whereas the prevalence and impact of vascular pathology in Alzheimer diease (AD) are well established, the role of vascular and Alzheimer pathologies in the progression of neurodegeneration and cognitive impairment in Parkinson disease (PD) is under discussion. A retrospective clinico-pathologic study of 100 patients with autopsy proven PD (including 44 cases with dementia/PDD) and 20 cases of dementia with Lewy bodies (DLB) confirmed essential clinical (duration of illness, Mini-Mental State Examination/MMSE, age at death) and morphologic differences between these groups; Lewy body Braak scores and Alzheimer pathologies (neuritic Braak stage, cortical Abeta plaque load, and generalized cerebral amyloid angiopathy or CAA) were significantly higher/more severe in DLB and PDD than in PD without dementia. Duration of illness showed no association to any of the examined pathologic parameters, while there was a moderate association between LB scores and neuritic Braak stages, the latter significantly increasing with age. Significant association between cerebrovascular lesions and neuritic Braak stage was seen in PDD but not in PD subjects without dementia. These data suggest an influence of Alzheimer-related lesions on the progression of the neurodegenerative process and, in particular, on cognitive decline in both PDD and DLB. On the other hand, both these factors in PD and DLB appear to be largely independent from coexistent vascular pathology, except in cases with severe cerebrovascular lesions or those related to neuritic AD pathology. Assessment of ApoE genotype in a small number of cases showed no significant differences in the severity of Abeta plaque load and CAA except for much lower intensities in non-demented epsilon3/3 patients. Despite increasing evidence suggesting synergistic reactions between alpha-synuclein (alphaSyn), tau and Abeta-peptides, the major protein markers of both AD and Lewy body diseases, and of both vascular pathology and AD, the

  4. Comparing Cognitive Profiles of Licensed Drivers with Mild Alzheimer's Disease and Mild Dementia with Lewy Bodies

    PubMed Central

    Gagnon, Sylvain

    2016-01-01

    Purpose. Alzheimer's disease (AD) and dementia with Lewy Bodies (DLB) constitute two of the most common forms of dementia in North America. Driving is a primary means of mobility among older adults and the risk of dementia increases with advanced age. The purpose of this paper is to describe the cognitive profile of licensed drivers with mild AD and mild DLB. Method. Licensed drivers with mild AD, mild DLB, and healthy controls completed neuropsychological tests measuring general cognition, attention, visuospatial/perception, language, and cognitive fluctuations. Results. The results showed differences between healthy controls and demented participants on almost all neuropsychological measures. Participants with early DLB were found to perform significantly worse on some measures of attention and visuospatial functioning in comparison with early AD. Discussion. Future research should examine the relationship between neuropsychological measures and driving outcomes among individuals with mild AD and mild DLB. PMID:27774333

  5. Genetic Alzheimer Disease and Sporadic Dementia With Lewy Bodies: A Comorbidity Presenting as Primary Progressive Aphasia.

    PubMed

    Picková, Tereza; Matěj, Radoslav; Bezdicek, Ondrej; Keller, Jiří; van der Zee, Julie; Van Broeckhoven, Christine; Cséfalvay, Zsolt; Rusina, Robert

    2017-03-01

    We report a 44-year-old woman, with a family history of early-onset dementia, presenting with primary progressive aphasia. This clinically variable syndrome has multiple underlying pathologies, and correlations between clinical manifestations and postmortem neuropathologic findings are controversial. Our patient suffered worsening language impairment with major word-finding difficulties but preserved comprehension. She also developed episodic memory impairment. Her condition progressed to dementia with behavioral changes. Magnetic resonance imaging showed early left perisylvian and bitemporal atrophy. The patient died shortly afterward from colon cancer. Neuropathologic examination revealed advanced early-onset Alzheimer and Lewy body disease, plus a clinically nonrelevant metastasis of her colon cancer in her left parietal lobe. Genetic examination revealed a p.Glu184Asp mutation in the presenilin1 gene. Our findings confirm the importance of a thorough appreciation for the clinical and neuropathologic correlations in patients with atypical neurodegenerative dementias.

  6. Dementia severity and Lewy bodies affect circadian rhythms in Alzheimer disease.

    PubMed

    Harper, David G; Stopa, Edward G; McKee, Ann C; Satlin, Andrew; Fish, David; Volicer, Ladislav

    2004-07-01

    Sleep disturbance is a symptom shared by all neurodegenerative, dementing illnesses, such as Alzheimer's disease (AD) and dementia with Lewy bodies (DLB), and its presence frequently precipitates decisions to seek institutional care for patients. Although the sleep disturbances of AD and DLB are qualitatively similar, they appear to be more prominent in patients with DLB. Disturbance of the circadian rhythm has been noted and is a potential factor underlying the nocturnal sleep fragmentation and daytime sleepiness observed in these patients. We studied the circadian variation of core-body temperature and motor activity in a total of 32 institutionalized patients with probable AD by NINCDS-ADRDA criteria, 9 of whom also met pathologic criteria for DLB. Eight, healthy, elderly male controls were studied on a clinical research unit designed to simulate the hospital environment where the dementia patients were studied. Circadian variables generally had greater deviations from normal associated with increasing AD pathology, as measured by postmortem-determined Braak stage, supporting the hypothesis that central changes mediate circadian disturbances in AD and DLB. Patients with a postmortem diagnosis of DLB manifested greater disturbances of locomotor activity circadian rhythms than patients with AD, possibly reflecting the greater sleep disturbances seen in this population, but the differences from normal in the circadian rhythms of the AD and DLB patients were qualitatively similar.

  7. GDF15/MIC1 and MMP9 Cerebrospinal Fluid Levels in Parkinson’s Disease and Lewy Body Dementia

    PubMed Central

    Bernard, Alice; Brockmann, Kathrin; Marquetand, Justus; Wurster, Isabel; Rattay, Tim W.; Roncoroni, Lorenzo; Schaeffer, Eva; Lerche, Stefanie; Apel, Anja; Deuschle, Christian; Berg, Daniela

    2016-01-01

    Based on animal and ex-vivo experiments, Growth/Differentiation Factor-15 (GDF15, also called Macrophage Inhibitory Cytokine-1, MIC1), a member of the transforming growth factor-beta family, and Matrix Metalloproteinase-9 (MMP9), a member of the matrix metalloprotease family may be potential markers for Lewy body disorders, i.e. Parkinson’s disease with (PDD) and without dementia (PDND) and Lewy body dementia (DLB). GDF15 has a prominent role in development, cell proliferation, differentiation, and repair, whereas MMP9 degrades, as a proteolytic enzyme, components of the extracellular matrix. In this study, cerebrospinal fluid GDF15 and MMP9 levels of 59 PDND, 17 PDD and 23 DLB patients, as well as of 95 controls were determined, and associated with demographic, clinical and biochemical parameters. Our analysis confirmed the already described association of GDF15 levels with age and gender. Corrected GDF15 levels were significantly higher in PDD than in PDND patients, and intermediate in DLB patients. Within Lewy body disorders, GDF15 levels correlated positively with age at onset of Parkinsonism and dementia, Hoehn & Yahr stage and cerebrospinal fluid t-Tau and p-Tau levels, and negatively with the Mini Mental State Examination. Remarkably, it does not relevantly correlate with disease duration. MMP9 was not relevantly associated with any of these parameters. Cerebrospinal GDF15, but not MMP9, may be a potential marker of and in Lewy body disorders. PMID:26938614

  8. GDF15/MIC1 and MMP9 Cerebrospinal Fluid Levels in Parkinson's Disease and Lewy Body Dementia.

    PubMed

    Maetzler, Walter; Deleersnijder, Willy; Hanssens, Valérie; Bernard, Alice; Brockmann, Kathrin; Marquetand, Justus; Wurster, Isabel; Rattay, Tim W; Roncoroni, Lorenzo; Schaeffer, Eva; Lerche, Stefanie; Apel, Anja; Deuschle, Christian; Berg, Daniela

    2016-01-01

    Based on animal and ex-vivo experiments, Growth/Differentiation Factor-15 (GDF15, also called Macrophage Inhibitory Cytokine-1, MIC1), a member of the transforming growth factor-beta family, and Matrix Metalloproteinase-9 (MMP9), a member of the matrix metalloprotease family may be potential markers for Lewy body disorders, i.e. Parkinson's disease with (PDD) and without dementia (PDND) and Lewy body dementia (DLB). GDF15 has a prominent role in development, cell proliferation, differentiation, and repair, whereas MMP9 degrades, as a proteolytic enzyme, components of the extracellular matrix. In this study, cerebrospinal fluid GDF15 and MMP9 levels of 59 PDND, 17 PDD and 23 DLB patients, as well as of 95 controls were determined, and associated with demographic, clinical and biochemical parameters. Our analysis confirmed the already described association of GDF15 levels with age and gender. Corrected GDF15 levels were significantly higher in PDD than in PDND patients, and intermediate in DLB patients. Within Lewy body disorders, GDF15 levels correlated positively with age at onset of Parkinsonism and dementia, Hoehn & Yahr stage and cerebrospinal fluid t-Tau and p-Tau levels, and negatively with the Mini Mental State Examination. Remarkably, it does not relevantly correlate with disease duration. MMP9 was not relevantly associated with any of these parameters. Cerebrospinal GDF15, but not MMP9, may be a potential marker of and in Lewy body disorders.

  9. Risk of decline in functional activities in dementia with Lewy bodies and Alzheimer disease.

    PubMed

    Gill, Dawn P; Koepsell, Thomas D; Hubbard, Rebecca A; Kukull, Walter A

    2011-01-01

    We examined the risk of 1-year decline in 4 everyday activities in patients with dementia with Lewy bodies (DLB), relative to patients with Alzheimer disease (AD). Data were from the National Alzheimer's Coordinating Center, gathered from 32 Alzheimer's Disease Centers. Participants (n=1880) were: aged 60+ years, demented with a primary clinical diagnosis of probable AD or DLB, and had a global Clinical Dementia Rating of 0.5 to 2. The activities were measured with the Functional Activities Questionnaire. In modified Poisson regression models adjusted for demographics, baseline activity, years from symptom onset, cognitive impairment, and comorbidities; DLB participants aged 67 to 81 years had 1.5 to 2 times increased risk of decline in performing basic kitchen tasks, engaging in games/hobbies, and paying attention/understanding, relative to AD participants of the same age (P<0.05). There was no significant difference between AD and DLB participants beyond this age range. For decline in ability to go shopping alone, there was also no significant difference between AD and DLB participants. In summary, the functional course of DLB, relative to AD, may depend on the age of the patient. These findings may provide anticipatory guidance to families and healthcare providers, which may be useful in the planning of care strategies.

  10. Nilotinib Effects in Parkinson’s disease and Dementia with Lewy bodies

    PubMed Central

    Pagan, Fernando; Hebron, Michaeline; Valadez, Ellen H.; Torres-Yaghi, Yasar; Huang, Xu; Mills, Reversa R.; Wilmarth, Barbara M.; Howard, Hellen; Dunn, Connell; Carlson, Alexis; Lawler, Abigail; Rogers, Sean L.; Falconer, Ramsey A.; Ahn, Jaeil; Li, Zhaoxia; Moussa, Charbel

    2016-01-01

    Background: We evaluated the effects of low doses of the tyrosine kinase Abelson (Abl) inhibitor Nilotinib, on safety and pharmacokinetics in Parkinson’s disease dementia or dementia with Lewy bodies. Objectives: The primary outcomes of this study were safety and tolerability; pharmacokinetics and target engagement were secondary, while clinical outcomes were exploratory. Methods: Twelve subjects were randomized into 150 mg (n = 5) or 300 mg (n = 7) groups and received Nilotinib orally every day for 24 weeks. Results: This study shows that 150 mg and 300 mg doses of Nilotinib appear to be safe and tolerated in subjects with advanced Parkinson’s disease. Nilotinib is detectable in the cerebrospinal fluid (CSF) and seems to engage the target Abl. Motor and cognitive outcomes suggest a possible beneficial effect on clinical outcomes. The CSF levels of homovanillic acid are significantly increased between baseline and 24 weeks of treatment. Exploratory CSF biomarkers were measured. Conclusions: This small proof-of-concept study lacks a placebo group and participants were not homogenous, resulting in baseline differences between and within groups. This limits the interpretations of the biomarker and clinical data, and any conclusions should be drawn cautiously. Nonetheless, the collective observations suggest that it is warranted to evaluate the safety and efficacy of Nilotinib in larger randomized, double-blind, placebo-controlled trials. PMID:27434297

  11. PET radioligands reveal the basis of dementia in Parkinson disease and dementia with Lewy bodies

    PubMed Central

    Gomperts, Stephen N.; Marquie, Marta; Locascio, Joseph J.; Bayer, Stephen; Johnson, Keith A.; Growdon, John H.

    2015-01-01

    Background Effective therapies for dementia with Lewy bodies (DLB) and Parkinson disease dementia (PDD) will require accurate diagnosis and an understanding of the contribution of distinct molecular pathologies to these diseases. We seek to use imaging biomarkers to improve diagnostic accuracy and to clarify the contribution of molecular species to cognitive impairment in DLB and PD. Summary We have performed cross-sectional and prospective cohort studies in subjects with DLB, PD with normal cognition (PD-nl), PD with mild cognitive impairment (PD-MCI), and PD with dementia (PDD), contrasted with Alzheimer's disease (AD) and healthy control subjects (HCS). Subjects underwent formal neurologic examination, detailed neuropsychological assessments, MRI, and PET scans with radioligands altropane (DAT: dopamine transporter) and PiB (Aβ amyloid). Putamen DAT concentrations were similar in DLB and PD and differentiated them from HCS and AD. Decreased caudate DAT concentration related to functional impairment in DLB but not PD. PiB uptake was greatest in DLB. However, cortical PiB retention was common in PD and predicted cognitive decline. PET imaging of tau aggregates holds promise both to clarify the contribution of tau to cognitive decline in these diseases and to differentiate DLB and PD from the parkinsonian tauopathies. Key messages Together, DAT and amyloid PET imaging discriminate DLB from PD and from other disease groups and identify pathologic processes that contribute to their course. Multimodal PET imaging has potential to increase diagnostic accuracy of DLB and PD in the clinic, improve cohort uniformity for clinical trials, and serve as biomarkers for targeted molecular therapies. PMID:26655867

  12. Clinical Correlations With Lewy Body Pathology in LRRK2-Related Parkinson Disease

    PubMed Central

    Kalia, Lorraine V.; Lang, Anthony E.; Hazrati, Lili-Naz; Fujioka, Shinsuke; Wszolek, Zbigniew K.; Dickson, Dennis W.; Ross, Owen A.; Van Deerlin, Vivianna M.; Trojanowski, John Q.; Hurtig, Howard I.; Alcalay, Roy N.; Marder, Karen S.; Clark, Lorraine N.; Gaig, Carles; Tolosa, Eduardo; Ruiz-Martínez, Javier; Marti-Masso, Jose F.; Ferrer, Isidre; de Munain, Adolfo López; Goldman, Samuel M.; Schüle, Birgitt; Langston, J. William; Aasly, Jan O.; Giordana, Maria T.; Bonifati, Vincenzo; Puschmann, Andreas; Canesi, Margherita; Pezzoli, Gianni; De Paula, Andre Maues; Hasegawa, Kazuko; Duyckaerts, Charles; Brice, Alexis; Stoessl, A. Jon; Marras, Connie

    2015-01-01

    IMPORTANCE Mutations in leucine-rich repeat kinase 2 (LRRK2) are the most common cause of genetic Parkinson disease (PD) known to date. The clinical features of manifesting LRRK2 mutation carriers are generally indistinguishable from those of patients with sporadic PD. However, some PD cases associated with LRRK2 mutations lack Lewy bodies (LBs), a neuropathological hallmark of PD. We investigated whether the presence or absence of LBs correlates with different clinical features in LRRK2-related PD. OBSERVATIONS We describe genetic, clinical, and neuropathological findings of 37 cases of LRRK2-related PD including 33 published and 4 unpublished cases through October 2013. Among the different mutations, the LRRK2 p.G2019S mutation was most frequently associated with LB pathology. Nonmotor features of cognitive impairment/dementia, anxiety, and orthostatic hypotension were correlated with the presence of LBs. In contrast, a primarily motor phenotype was associated with a lack of LBs. CONCLUSIONS AND RELEVANCE To our knowledge, this is the first report of clinicopathological correlations in a series of LRRK2-related PD cases. Findings from this selected group of patients with PD demonstrated that parkinsonian motor features can occur in the absence of LBs. However, LB pathology in LRRK2-related PD may be a marker for a broader parkinsonian symptom complex including cognitive impairment. PMID:25401511

  13. A systematic review of cognitive decline in dementia with Lewy bodies versus Alzheimer’s disease

    PubMed Central

    2014-01-01

    Introduction The aim of this review was to investigate whether there is a faster cognitive decline in dementia with Lewy bodies (DLB) than in Alzheimer’s disease (AD) over time. Methods PsycINFO and Medline were searched from 1946 to February 2013. A quality rating from 1 to 15 (best) was applied to the included studies. A quantitative meta-analysis was done on studies with mini mental state examination (MMSE) as the outcome measure. Results A total of 18 studies were included. Of these, six (36%) reported significant differences in the rate of cognitive decline. Three studies reported a faster cognitive decline on MMSE in patients with mixed DLB and AD compared to pure forms, whereas two studies reported a faster decline on delayed recall and recognition in AD and one in DLB on verbal fluency. Mean quality scores for studies that did or did not differ were not significantly different. Six studies reported MMSE scores and were included in the meta-analysis, which showed no significant difference in annual decline on MMSE between DLB (mean 3.4) and AD (mean 3.3). Conclusions Our findings do not support the hypothesis of a faster rate of cognitive decline in DLB compared to AD. Future studies should apply recent diagnostic criteria, as well as extensive diagnostic evaluation and ideally autopsy diagnosis. Studies with large enough samples, detailed cognitive tests, at least two years follow up and multivariate statistical analysis are also needed. PMID:25478024

  14. Changes to the lateral geniculate nucleus in Alzheimer's disease but not dementia with Lewy bodies

    PubMed Central

    Erskine, Daniel; Taylor, John Paul; Firbank, Michael J.; Patterson, Lina; Onofrj, Marco; O'Brien, John T.; McKeith, Ian G.; Attems, Johannes; Thomas, Alan J.; Morris, Chris M.

    2015-01-01

    Aims Complex visual hallucinations occur in 70% of dementia with Lewy bodies (DLB) cases and significantly affect patient well‐being. Visuo‐cortical and retinal abnormalities have been recorded in DLB and may play a role in visual hallucinations. The present study aimed to investigate the lateral geniculate nucleus (LGN), a visual relay centre between the retina and visual cortex, to see if changes to this structure underlie visual hallucinations in DLB. Methods Fifty‐one [17 probable DLB, 19 control and 15 probable Alzheimer's disease (AD)] cases were recruited for a functional magnetic resonance imaging study, in which patients' response to a flashing checkerboard stimulus was detected and measured in the LGN, before comparison across experimental groups. Additionally, post mortem  LGN tissue was acquired for a cross‐sectional study using 20 (six DLB, seven control and seven AD) cases and analysed using stereology. α‐Synuclein, phosphorylated tau and amyloid‐β pathology was also assessed in all cases. Results DLB cases did not significantly differ from controls on neuroimaging, morphometry or pathology. However, a significant increase in amyloid‐β pathology, a reduction in number of parvocellular neurones and magnocellular gliosis was found in AD cases compared with control and DLB cases. Conclusions These findings suggest that the early visual system is relatively spared in DLB, which implies that upstream visual structures may be largely responsible for the generation of hallucinatory percepts. The significance of the degeneration of the LGN in AD cases is uncertain. PMID:25967384

  15. Atrophy of hippocampal subfields and adjacent extrahippocampal structures in dementia with Lewy bodies and Alzheimer's disease.

    PubMed

    Delli Pizzi, Stefano; Franciotti, Raffaella; Bubbico, Giovanna; Thomas, Astrid; Onofrj, Marco; Bonanni, Laura

    2016-04-01

    The hippocampus and adjacent extrahippocampal structures are organized in distinct and specialized regions which process heterogeneous functions, including memory, and visuospatial functions. Specific alterations of the different hippocampal subfields and adjacent extrahippocampal structures could differently contribute to the pathophysiology of Alzheimer's disease (AD) and dementia with Lewy bodies (DLB). Based on visual symptoms which characterize DLB patients, the hippocampal subfields and the adjacent extrahippocampal structures which are mainly involved in the visual functions could be impaired in DLB and preserved in AD. To test this hypothesis, we performed structural magnetic resonance imaging on 19 DLB, 15 AD, and 19 age-matched healthy controls. FreeSurfer's pipelines were used to perform parcellation of hippocampus and adjacent extrahippocampal structures and to assess the structural changes within each region. The cornu ammonis and subiculum were bilaterally damaged in AD and preserved in DLB. The perirhinal cortex and parahippocampus were damaged in DLB but not in AD. Our findings demonstrate that the hippocampal subfields and adjacent extrahippocampal structures were differently altered in AD and DLB. Particularly, DLB patients showed a more focused alteration of the extrahippocampal structures linked to visual functions.

  16. No differences of butyrylcholinesterase protein activity and allele frequency in Lewy body diseases.

    PubMed

    Maetzler, Walter; Keller, Stefanie; Michelis, Joan; Koehler, Niklas; Stransky, Elke; Becker, Clemens; Schulte, Claudia; Melms, Arthur; Gasser, Thomas; Berg, Daniela

    2009-08-01

    Butyrylcholinesterase (BChE) genotypes and protein (BuChE) activity, especially in combination with Apolipoprotein E4 (ApoE4), have been investigated as risk factors for developing Alzheimer disease (AD) and may be associated with the rate of progression of cognitive decline. Despite similar pathologic (e.g. amyloid deposition) and neurochemical (e.g. cholinergic deficits) aspects between AD and Lewy body diseases (LBD), scarce data is obtainable about BChE genotypes and BuChE activity in LBD. We measured BuChE activity levels in serum and cerebrospinal fluid (CSF) of 114 LBD subjects (59 of them were demented) and 31 elderly controls. We found higher CSF BuChE activity in males compared to females, and a negative correlation of serum BuChE activity with age and cognitive function. Demented LBD patients, non-demented LBD patients and controls did not differ significantly with regard to serum and CSF BuChE activity. Furthermore, BChE K variant and ApoE4 allele frequencies were determined. The BChE K variant was significantly associated with lower serum activity; the same trend was observable in CSF. The subgroups did not differ significantly with regard to BChE K/ApoE4 occurrence. These data confirm and extend previous results on the relationship between BChE gene and BuChE activity, and argue rather against a major impact of BuChE on LBD-associated pathologies.

  17. Multimodal EEG-MRI in the differential diagnosis of Alzheimer's disease and dementia with Lewy bodies

    PubMed Central

    Colloby, Sean J.; Cromarty, Ruth A.; Peraza, Luis R.; Johnsen, Kristinn; Jóhannesson, Gísli; Bonanni, Laura; Onofrj, Marco; Barber, Robert; O'Brien, John T.; Taylor, John-Paul

    2016-01-01

    Differential diagnosis of Alzheimer's disease (AD) and dementia with Lewy bodies (DLB) remains challenging; currently the best discriminator is striatal dopaminergic imaging. However this modality fails to identify 15–20% of DLB cases and thus other biomarkers may be useful. It is recognised electroencephalography (EEG) slowing and relative medial temporal lobe preservation are supportive features of DLB, although individually they lack diagnostic accuracy. Therefore, we investigated whether combined EEG and MRI indices could assist in the differential diagnosis of AD and DLB. Seventy two participants (21 Controls, 30 AD, 21 DLB) underwent resting EEG and 3 T MR imaging. Six EEG classifiers previously generated using support vector machine algorithms were applied to the present dataset. MRI index was derived from medial temporal atrophy (MTA) ratings. Logistic regression analysis identified EEG predictors of AD and DLB. A combined EEG-MRI model was then generated to examine whether there was an improvement in classification compared to individual modalities. For EEG, two classifiers predicted AD and DLB (model: χ2 = 22.1, df = 2, p < 0.001, Nagelkerke R2 = 0.47, classification = 77% (AD 87%, DLB 62%)). For MRI, MTA also predicted AD and DLB (model: χ2 = 6.5, df = 1, p = 0.01, Nagelkerke R2 = 0.16, classification = 67% (77% AD, 52% DLB). However, a combined EEG-MRI model showed greater prediction in AD and DLB (model: χ2 = 31.1, df = 3, p < 0.001, Nagelkerke R2 = 0.62, classification = 90% (93% AD, 86% DLB)). While suggestive and requiring validation, diagnostic performance could be improved by combining EEG and MRI, and may represent an alternative to dopaminergic imaging. PMID:27060340

  18. CSF amyloid-β peptides in neuropathologically diagnosed dementia with Lewy bodies and Alzheimer's disease.

    PubMed

    Mollenhauer, Brit; Esselmann, Herrmann; Trenkwalder, Claudia; Schulz-Schaeffer, Walter; Kretzschmar, Hans; Otto, Markus; Wiltfang, Jens; Bibl, Mirko

    2011-01-01

    Appropriate treatment of dementia requires biomarkers that provide an exact and differential diagnosis. We recently presented differentially expressed amyloid-β (Aβ) peptide patterns in cerebrospinal fluid (CSF) as biomarker candidates for neurochemical diagnosis of Alzheimer's disease (AD) and dementia with Lewy bodies (DLB). The objective of the present study was to investigate CSF Aβ peptide patterns in both neuropathologically and clinically defined diagnostic groups of AD and DLB. Using the quantitative Aβ-SDS-PAGE/immunoblot, we analyzed CSF samples of neuropathologically defined patients with AD (definite AD, dAD; n = 11) and DLB (definite, dDLB; n = 12). We compared absolute and relative quantities of CSF Aβ-peptides with a larger cohort of clinically diagnosed patients with probable AD (pAD; n = 71), probable DLB (pDLB; n = 32), and non-demented controls (NDC; n = 71). Each neuropathologically and clinically defined diagnostic group showed a similar relative distribution of CSF Aβ-peptides (Aβ(1-X%)). Aβ(1-42%) was lowered in dAD compared to NDC (p = 1.6 × 10⁻⁷, but did not differ between dAD and pAD. Aβ(1-40ox%) was elevated in dDLB as compared to NDC (p = 1.8 × 10⁻⁵, but did not differ between dDLB and pDLB. Thus, we were able to confirm previous results on Aβ peptide patterns in neuropathologically characterized patients with AD and DLB. Our results underline the usefulness of the CSF Aβ(1-42%) and Aβ(1-40ox%) as diagnostic biomarkers for AD and DLB, respectively.

  19. Recognition memory span in autopsy-confirmed Dementia with Lewy Bodies and Alzheimer's Disease.

    PubMed

    Salmon, David P; Heindel, William C; Hamilton, Joanne M; Vincent Filoteo, J; Cidambi, Varun; Hansen, Lawrence A; Masliah, Eliezer; Galasko, Douglas

    2015-08-01

    Evidence from patients with amnesia suggests that recognition memory span tasks engage both long-term memory (i.e., secondary memory) processes mediated by the diencephalic-medial temporal lobe memory system and working memory processes mediated by fronto-striatal systems. Thus, the recognition memory span task may be particularly effective for detecting memory deficits in disorders that disrupt both memory systems. The presence of unique pathology in fronto-striatal circuits in Dementia with Lewy Bodies (DLB) compared to AD suggests that performance on the recognition memory span task might be differentially affected in the two disorders even though they have quantitatively similar deficits in secondary memory. In the present study, patients with autopsy-confirmed DLB or AD, and Normal Control (NC) participants, were tested on separate recognition memory span tasks that required them to retain increasing amounts of verbal, spatial, or visual object (i.e., faces) information across trials. Results showed that recognition memory spans for verbal and spatial stimuli, but not face stimuli, were lower in patients with DLB than in those with AD, and more impaired relative to NC performance. This was despite similar deficits in the two patient groups on independent measures of secondary memory such as the total number of words recalled from long-term storage on the Buschke Selective Reminding Test. The disproportionate vulnerability of recognition memory span task performance in DLB compared to AD may be due to greater fronto-striatal involvement in DLB and a corresponding decrement in cooperative interaction between working memory and secondary memory processes. Assessment of recognition memory span may contribute to the ability to distinguish between DLB and AD relatively early in the course of disease.

  20. Magnetic resonance imaging reveals Creutzfeldt-Jakob disease in a patient with apparent dementia with Lewy bodies.

    PubMed

    Tsivgoulis, Georgios; Bonakis, Anastasios; Papathanasiou, Matilda A; Chondrogianni, Maria; Papageorgiou, Sokratis G; Voumvourakis, Konstantinos; Stefanis, Leonidas

    2014-05-15

    The differential diagnosis of dementia with Lewy bodies (DLB) and sporadic Creutzfeldt-Jakob disease (CJD) may be challenging. Patients with the original diagnosis of possible CJD may occasionally prove to have a pathological diagnosis of DLB, while other cases may fulfill the diagnostic clinical criteria for DLB but subsequent clinical course, cerebrospinal fluid (CSF) and neuropathology findings necessitate diagnostic revision to CJD. We describe a 79-year old patient recently diagnosed with dementia with Lewy bodies (DLB) on the basis of subacute cognitive decline, visual hallucinations and Parkinsonian features, who presented with increasing agitation. Brain neuroimaging with MRI raised the diagnostic suspicion of CJD and subsequent diagnostic work-up with electroencephalography (EEG) and CSF analysis led to the establishment of CJD diagnosis. The present case highlights the clinical utility of novel diagnostic CJD criteria that also incorporate neuroimaging findings in the diagnostic CJD panel.

  1. The involvement of dityrosine crosslinking in α-synuclein assembly and deposition in Lewy Bodies in Parkinson’s disease

    PubMed Central

    Al-Hilaly, Youssra K.; Biasetti, Luca; Blakeman, Ben J. F.; Pollack, Saskia J.; Zibaee, Shahin; Abdul-Sada, Alaa; Thorpe, Julian R.; Xue, Wei-Feng; Serpell, Louise C.

    2016-01-01

    Parkinson’s disease (PD) is characterized by intracellular, insoluble Lewy bodies composed of highly stable α-synuclein (α-syn) amyloid fibrils. α-synuclein is an intrinsically disordered protein that has the capacity to assemble to form β-sheet rich fibrils. Oxidiative stress and metal rich environments have been implicated in triggering assembly. Here, we have explored the composition of Lewy bodies in post-mortem tissue using electron microscopy and immunogold labeling and revealed dityrosine crosslinks in Lewy bodies in brain tissue from PD patients. In vitro, we show that dityrosine cross-links in α-syn are formed by covalent ortho-ortho coupling of two tyrosine residues under conditions of oxidative stress by fluorescence and confirmed using mass-spectrometry. A covalently cross-linked dimer isolated by SDS-PAGE and mass analysis showed that dityrosine dimer was formed via the coupling of Y39-Y39 to give a homo dimer peptide that may play a key role in formation of oligomeric and seeds for fibril formation. Atomic force microscopy analysis reveals that the covalent dityrosine contributes to the stabilization of α-syn assemblies. Thus, the presence of oxidative stress induced dityrosine could play an important role in assembly and toxicity of α-syn in PD. PMID:27982082

  2. The Organization of Narrative Discourse in Lewy Body Spectrum Disorder

    ERIC Educational Resources Information Center

    Ash, Sharon; McMillan, Corey; Gross, Rachel G.; Cook, Philip; Morgan, Brianna; Boller, Ashley; Dreyfuss, Michael; Siderowf, Andrew; Grossman, Murray

    2011-01-01

    Narrative discourse is an essential component of day-to-day communication, but little is known about narrative in Lewy body spectrum disorder (LBSD), including Parkinson's disease (PD), Parkinson's disease with dementia (PDD), and dementia with Lewy bodies (DLB). We performed a detailed analysis of a semi-structured speech sample in 32 non-aphasic…

  3. Lack of Neuronal IFN-β-IFNAR Causes Lewy Body- and Parkinson’s Disease-like Dementia

    PubMed Central

    Ejlerskov, Patrick; Hultberg, Jeanette Göransdotter; Wang, JunYang; Carlsson, Robert; Ambjørn, Malene; Kuss, Martin; Liu, Yawei; Porcu, Giovanna; Kolkova, Kateryna; Friis Rundsten, Carsten; Ruscher, Karsten; Pakkenberg, Bente; Goldmann, Tobias; Loreth, Desiree; Prinz, Marco; Rubinsztein, David C.; Issazadeh-Navikas, Shohreh

    2015-01-01

    Summary Neurodegenerative diseases have been linked to inflammation, but whether altered immunomodulation plays a causative role in neurodegeneration is not clear. We show that lack of cytokine interferon-β (IFN-β) signaling causes spontaneous neurodegeneration in the absence of neurodegenerative disease-causing mutant proteins. Mice lacking Ifnb function exhibited motor and cognitive learning impairments with accompanying α-synuclein-containing Lewy bodies in the brain, as well as a reduction in dopaminergic neurons and defective dopamine signaling in the nigrostriatal region. Lack of IFN-β signaling caused defects in neuronal autophagy prior to α-synucleinopathy, which was associated with accumulation of senescent mitochondria. Recombinant IFN-β promoted neurite growth and branching, autophagy flux, and α-synuclein degradation in neurons. In addition, lentiviral IFN-β overexpression prevented dopaminergic neuron loss in a familial Parkinson’s disease model. These results indicate a protective role for IFN-β in neuronal homeostasis and validate Ifnb mutant mice as a model for sporadic Lewy body and Parkinson’s disease dementia. PMID:26451483

  4. Impairments of Speech Fluency in Lewy Body Spectrum Disorder

    ERIC Educational Resources Information Center

    Ash, Sharon; McMillan, Corey; Gross, Rachel G.; Cook, Philip; Gunawardena, Delani; Morgan, Brianna; Boller, Ashley; Siderowf, Andrew; Grossman, Murray

    2012-01-01

    Few studies have examined connected speech in demented and non-demented patients with Parkinson's disease (PD). We assessed the speech production of 35 patients with Lewy body spectrum disorder (LBSD), including non-demented PD patients, patients with PD dementia (PDD), and patients with dementia with Lewy bodies (DLB), in a semi-structured…

  5. Difficulty Processing Temporary Syntactic Ambiguities in Lewy Body Spectrum Disorder

    ERIC Educational Resources Information Center

    Grossman, Murray; Gross, Rachel G.; Moore, Peachie; Dreyfuss, Michael; McMillan, Corey T.; Cook, Philip A.; Ash, Sherry; Siderowf, Andrew

    2012-01-01

    While grammatical aspects of language are preserved, executive deficits are prominent in Lewy body spectrum disorder (LBSD), including Parkinson's disease (PD), Parkinson's dementia (PDD) and dementia with Lewy bodies (DLB). We examined executive control during sentence processing in LBSD by assessing temporary structural ambiguities. Using an…

  6. Goal Setting for Cognitive Rehabilitation in Mild to Moderate Parkinson's Disease Dementia and Dementia with Lewy Bodies.

    PubMed

    Watermeyer, Tamlyn J; Hindle, John V; Roberts, Julie; Lawrence, Catherine L; Martyr, Anthony; Lloyd-Williams, Huw; Brand, Andrew; Gutting, Petra; Hoare, Zoe; Edwards, Rhiannon Tudor; Clare, Linda

    2016-01-01

    Alongside the physical symptoms associated with Parkinson's disease dementia and dementia with Lewy bodies, health services must also address the cognitive impairments that accompany these conditions. There is growing interest in the use of nonpharmacological approaches to managing the consequences of cognitive disorder. Cognitive rehabilitation is a goal-orientated behavioural intervention which aims to enhance functional independence through the use of strategies specific to the individual's needs and abilities. Fundamental to this therapy is a person's capacity to set goals for rehabilitation. To date, no studies have assessed goal setting in early-stage Parkinson's disease dementia or dementia with Lewy bodies. Semistructured interviews were carried out with 29 participants from an ongoing trial of cognitive rehabilitation for people with these conditions. Here, we examined the goal statements provided by these participants using qualitative content analysis, exploring the types and nature of the goals set. Participants' goals reflected their motivations to learn new skills or improve performance in areas such as technology-use, self-management and orientation, medication management, and social and leisure activities. These results suggest that goal setting is achievable for these participants, provide insight into the everyday cognitive difficulties that they experience, and highlight possible domains as targets for intervention. The trial is registered with ISRCTN16584442 (DOI 10.1186/ISRCTN16584442 13/04/2015).

  7. Mini Review: Anticholinergic Activity as a Behavioral Pathology of Lewy Body Disease and Proposal of the Concept of "Anticholinergic Spectrum Disorders".

    PubMed

    Hori, Koji; Konishi, Kimiko; Hosoi, Misa; Tomioka, Hiroi; Tani, Masayuki; Kitajima, Yuka; Hachisu, Mitsugu

    2016-01-01

    Given the relationship between anticholinergic activity (AA) and Alzheimer's disease (AD), we rereview our hypothesis of the endogenous appearance of AA in AD. Briefly, because acetylcholine (ACh) regulates not only cognitive function but also the inflammatory system, when ACh downregulation reaches a critical level, inflammation increases, triggering the appearance of cytokines with AA. Moreover, based on a case report of a patient with mild AD and slightly deteriorated ACh, we also speculate that AA can appear endogenously in Lewy body disease due to the dual action of the downregulation of ACh and hyperactivity of the hypothalamic-pituitary-adrenal axis. Based on these hypotheses, we consider AA to be a behavioral pathology of Lewy body disease. We also propose the concept of "anticholinergic spectrum disorders," which encompass a variety of conditions, including AD, Lewy body disease, and delirium. Finally, we suggest the prescription of cholinesterase inhibitors to patients in this spectrum of disorders to abolish AA by upregulating ACh.

  8. 123I-Metaiodobenzylguanidine Myocardial Scintigraphy in Lewy Body-Related Disorders: A Literature Review

    PubMed Central

    Chung, Eun Joo; Kim, Sang Jin

    2015-01-01

    Lewy body-related disorders are characterized by the presence of Lewy bodies and Lewy neurites, which have abnormal aggregations of α-synuclein in the nigral and extranigral areas, including in the heart. 123I-metaiodobenzylguanidine (MIBG) scintigraphy is a well-known tool to evaluate cardiac sympathetic denervation in the Lewy body-related disorders. MIBG scintigraphy showed low uptake of MIBG in the Lewy body-related disorders, including Parkinson’s disease, dementia with Lewy bodies, pure autonomic failure and rapid eye movement sleep behavior disorder. This review summarizes previous results on the diagnostic applications of MIBG scintigraphy in Lewy body-related disorders. PMID:26090077

  9. Creutzfeldt-jakob, Parkinson, lewy body dementia and Alzheimer diseases: from diagnosis to therapy.

    PubMed

    Dupiereux, Ingrid; Zorzi, Willy; Quadrio, Isabelle; Perret-Liaudet, Armand; Kovacs, Gabor G; Heinen, Ernst; Elmoualij, Benaïssa

    2009-03-01

    Depositions of proteins in form of amyloid and non-amyloid plaques are common pathogenic signs of more than 20 degenerative diseases affecting the central nervous system or a variety of peripheral tissues. Among the neuropathological conditions, Alzheimer's, Parkinson's and the prion diseases, such as Creutzfeldt-Jakob disease (CJD), present ambiguities as regarding their differential diagnosis. At present, their diagnosis must be confirmed by post-mortem examination of the brain. Currently the ante-mortem diagnosis is still based on the integration of multiple data (clinical, paraclinical and biological analyses) because no unique marker exists for such diseases. The detection of specific biomarkers would be useful to develop a differential diagnostic, distinguishing not only different neurodegenerative diseases but also the disease from the non-pathological effects of aging. Several neurodegenerative biomarkers are present at very low levels during the early stages of the disease development and their ultra-low detection is needed for early diagnosis, which should permit more effective therapeutic interventions, before the disease concerned can progress to a stage where considerable damage to the brain has already occurred. In the case of prion diseases, there are concerns regarding not only patient care, but the wider community too, with regard to the risk of transmission of prions, especially during blood transfusion, for which, four cases of variant CJD infection associated with transfusion of non-leukocyte-depleted blood components have been confirmed. Therefore the development of techniques with high sensitivity and specificity represent the major challenge in the field of the protein misfolding diseases. In this paper we review the current analytical and/or biochemical diagnostic technologies used mainly in prion, but also in Alzheimer and Parkinson diseases and emphasizing work on the protein detection as a surrogates and specific biomarker in the body

  10. Synchrotron FTIR micro-spectroscopy for structural analysis of Lewy bodies in the brain of Parkinson's disease patients.

    PubMed

    Araki, Katsuya; Yagi, Naoto; Ikemoto, Yuka; Yagi, Hisashi; Choong, Chi-Jing; Hayakawa, Hideki; Beck, Goichi; Sumi, Hisae; Fujimura, Harutoshi; Moriwaki, Taro; Nagai, Yoshitaka; Goto, Yuji; Mochizuki, Hideki

    2015-12-01

    Lewy bodies (LBs), which mainly consist of α-synuclein (α-syn), are neuropathological hallmarks of patients with Parkinson's disease (PD). The fine structure of LBs is unknown, and LBs cannot be made artificially. Nevertheless, many studies have described fibrillisation using recombinant α-syn purified from E. coli. An extremely fundamental problem is whether the structure of LBs is the same as that of recombinant amyloid fibrils. Thus, we used synchrotron Fourier transform infrared micro-spectroscopy (FTIRM) to analyse the fine structure of LBs in the brain of PD patients. Our results showed a shift in the infrared spectrum that indicates abundance of a β-sheet-rich structure in LBs. Also, 2D infrared mapping of LBs revealed that the content of the β-sheet structure is higher in the halo than in the core, and the core contains a large amount of proteins and lipids.

  11. Synchrotron FTIR micro-spectroscopy for structural analysis of Lewy bodies in the brain of Parkinson’s disease patients

    NASA Astrophysics Data System (ADS)

    Araki, Katsuya; Yagi, Naoto; Ikemoto, Yuka; Yagi, Hisashi; Choong, Chi-Jing; Hayakawa, Hideki; Beck, Goichi; Sumi, Hisae; Fujimura, Harutoshi; Moriwaki, Taro; Nagai, Yoshitaka; Goto, Yuji; Mochizuki, Hideki

    2015-12-01

    Lewy bodies (LBs), which mainly consist of α-synuclein (α-syn), are neuropathological hallmarks of patients with Parkinson’s disease (PD). The fine structure of LBs is unknown, and LBs cannot be made artificially. Nevertheless, many studies have described fibrillisation using recombinant α-syn purified from E. coli. An extremely fundamental problem is whether the structure of LBs is the same as that of recombinant amyloid fibrils. Thus, we used synchrotron Fourier transform infrared micro-spectroscopy (FTIRM) to analyse the fine structure of LBs in the brain of PD patients. Our results showed a shift in the infrared spectrum that indicates abundance of a β-sheet-rich structure in LBs. Also, 2D infrared mapping of LBs revealed that the content of the β-sheet structure is higher in the halo than in the core, and the core contains a large amount of proteins and lipids.

  12. Glial fibrillar acidic protein in the cerebrospinal fluid of Alzheimer's disease, dementia with Lewy bodies, and frontotemporal lobar degeneration.

    PubMed

    Ishiki, Aiko; Kamada, Maki; Kawamura, Yuki; Terao, Chiaki; Shimoda, Fumiko; Tomita, Naoki; Arai, Hiroyuki; Furukawa, Katsutoshi

    2016-01-01

    Biomarkers in the cerebrospinal fluid (CSF) are currently regarded as indispensable indicators for accurate differential diagnosis of neurodegenerative disorders. Although high levels of astrocyte-secreted glial fibrillar acidic protein (GFAP) in the CSF of patients with Alzheimer's disease (AD) have been reported, the levels of GFAP in the CSF have not been fully investigated in other neurological disorders that cause dementia, such as dementia with Lewy bodies (DLB) and frontotemporal lobar degeneration (FTLD). In this study, we determined the levels of GFAP in the CSF of healthy control subjects and AD, DLB, and FTLD patients to address two questions: (i) Do the levels of GFAP differ among these disorders? and (ii) Can GFAP be used as a biomarker for the differential diagnosis of these neurodegenerative disorders? The levels of GFAP in AD, DLB, and FTLD patients were significantly higher than those in the healthy control subjects. Although the levels of GFAP were not significantly different between AD and DLB patients, a higher level of GFAP was observed in FTLD patients than in AD and DLB patients. It is concluded that representative neurological disorders causing dementia were associated with higher levels of GFAP in the CSF. We propose the following mechanism concerning the amount of glial fibrillar acidic protein (GFAP) in the cerebrospinal fluid (CSF) in Alzheimer's disease (AD), dementia with Lewy bodies (DLB), and frontotemporal lobar degeneration (FTLD). The increase in the release of GFAP into CSF is considered to reflect the sum of degeneration of astrocytes and astrocytosis. The sum of degeneration and astrocytosis or the GFAP release could be in the order of FTLD > DLB > AD > normal condition.

  13. Regulation of dopamine D3 receptor in the striatal regions and substantia nigra in diffuse Lewy body disease (DLBD)

    PubMed Central

    Sun, Jianjun; Cairns, Nigel J.; Perlmutter, Joel S.; Mach, Robert H.; Xu, Jinbin

    2013-01-01

    The regulation of D3 receptor has not been well documented in diffuse Lewy body disease (DLBD). In this study, a novel D3 preferring radioligand [3H]WC-10 and a D2-preferring radioligand [3H]raclopride were used and the absolute densities of the dopamine D3 and D2 receptors were determined in the striatal regions and substantia nigra (SN) from postmortem brains from 5 cases DLBD, which included dementia with Lewy bodies (DLB, n=4) and Parkinson disease dementia (PDD, n=1). The densities of the dopamine D1 receptor, vesicular monoamine transporter 2(VMAT2), and dopamine transporter (DAT) were also measured by quantitative autoradiography using [3H]SCH23390, [3H]dihydrotetrabenazine, and [3H]WIN35428, respectively. The densities of these dopaminergic markers were also measured in the same brain regions in 10 age-matched control cases. Dopamine D3 receptor density was significantly increased in the striatal regions including caudate, putamen and nucleus accumbens (NAc). There were no significant changes in the dopamine D1 and D2 receptor densities in any brain regions measured. VMAT2 and DAT densities were reduced in all the brain regions measured in DLB/PDD, however the significant reduction was found in putamen for DAT and in the NAc and SN for VMAT2. The decrease of dopamine pre-synaptic markers implies neuronal loss in the substantia nigra pars compacta (SNpc) in these DLB/PDD cases, while the increase of D3 receptors in striatal regions could be attributed to dopaminergic medication history and psychiatric state such as hallucinations. Whether it also reflects compensatory regulation upon dopaminergic denervation warrants further confirmations on larger populations. PMID:23732230

  14. Different Clinical and Neuroimaging Characteristics in Early Stage Parkinson’s Disease with Dementia and Dementia with Lewy Bodies

    PubMed Central

    Takemoto, Mami; Sato, Kota; Hatanaka, Noriko; Yamashita, Toru; Ohta, Yasuyuki; Hishikawa, Nozomi; Abe, Koji

    2016-01-01

    Parkinson’s disease with dementia (PDD) and dementia with Lewy bodies (DLB) both commonly exhibit brain Lewy body pathology and similar end-stage symptoms, but early symptoms differ. To clarify these differences, we compared the demographic characteristics, symptoms, cognitive and affective functioning, activities of daily life, and neuroimaging results between PDD (n = 52) and DLB (n = 46) patients. In measures of cognitive functioning, PDD patients had worse Hasegawa dementia scale-revised (HDS-R) scores (11.2±4.8) and better frontal assessment battery (FAB) scores (11.3±4.1) compared with DLB (17.0±6.4, p = 0.013 and 8.6±4.7, p = 0.039, respectively). DLB patients performed worse than PDD patients in “orientation to place” tasks. In affective functions, DLB patients had worse GDS (7.6±3.4) and ABS (9.9±5.3) scores than PDD patients (5.1±4.1 and 4.8±3.0, respectively). 99mTc-ECD images showed greater CBF in the whole cingulate gyrus and a lower CBF in the precuneus area in DLB than in PDD. These results suggest that PDD patients’ lower average scores for “repetition” (MMSE), “recent memory” (HDS-R), and “lexical fluency” (FAB) were related to lower CBF in the cingulate gyrus than in DLB. Furthermore, DLB patients’ poorer average subscale scores of “orientation to place” (MMSE) and “similarities”, “conflicting instructions”, and “go-no go” (FAB) tasks may be related to the lower CBF in the precuneus area in DLB than PDD. PMID:27060948

  15. Induction of α-synuclein aggregate formation by CSF exosomes from patients with Parkinson’s disease and dementia with Lewy bodies

    PubMed Central

    Stuendl, Anne; Kunadt, Marcel; Kruse, Niels; Bartels, Claudia; Moebius, Wiebke; Danzer, Karin M.; Mollenhauer, Brit

    2016-01-01

    Extracellular α-synuclein has been proposed as a crucial mechanism for induction of pathological aggregate formation in previously healthy cells. In vitro, extracellular α-synuclein is partially associated with exosomal vesicles. Recently, we have provided evidence that exosomal α-synuclein is present in the central nervous system in vivo. We hypothesized that exosomal α-synuclein species from patients with α-synuclein related neurodegeneration serve as carriers for interneuronal disease transmission. We isolated exosomes from cerebrospinal fluid from patients with Parkinson’s disease, dementia with Lewy bodies, progressive supranuclear palsy as a non-α-synuclein related disorder that clinically overlaps with Parkinson’s disease, and neurological controls. Cerebrospinal fluid exosome numbers, α-synuclein protein content of cerebrospinal fluid exosomes and their potential to induce oligomerization of α-synuclein were analysed. The quantification of cerebrospinal fluid exosomal α-synuclein showed distinct differences between patients with Parkinson’s disease and dementia with Lewy bodies. In addition, exosomal α-synuclein levels correlated with the severity of cognitive impairment in cross-sectional samples from patients with dementia with Lewy bodies. Importantly, cerebrospinal fluid exosomes derived from Parkinson’s disease and dementia with Lewy bodies induce oligomerization of α-synuclein in a reporter cell line in a dose-dependent manner. Our data suggest that cerebrospinal fluid exosomes from patients with Parkinson’s disease and dementia with Lewy bodies contain a pathogenic species of α-synuclein, which could initiate oligomerization of soluble α-synuclein in target cells and confer disease pathology. PMID:26647156

  16. α-Synuclein interferes with the ESCRT-III complex contributing to the pathogenesis of Lewy body disease.

    PubMed

    Spencer, Brian; Kim, Changyoun; Gonzalez, Tania; Bisquertt, Alejandro; Patrick, Christina; Rockenstein, Edward; Adame, Anthony; Lee, Seung-Jae; Desplats, Paula; Masliah, Eliezer

    2016-03-15

    α-Synuclein (α-syn) has been implicated in neurological disorders with parkinsonism, including Parkinson's disease and Dementia with Lewy body. Recent studies have shown α-syn oligomers released from neurons can propagate from cell-to-cell in a prion-like fashion exacerbating neurodegeneration. In this study, we examined the role of the endosomal sorting complex required for transport (ESCRT) pathway on the propagation of α-syn. α-syn, which is transported via the ESCRT pathway through multivesicular bodies for degradation, can also target the degradation of the ESCRT protein-charged multivesicular body protein (CHMP2B), thus generating a roadblock of endocytosed α-syn. Disruption of the ESCRT transport system also resulted in increased exocytosis of α-syn thus potentially increasing cell-to-cell propagation of synuclein. Conversely, delivery of a lentiviral vector overexpressing CHMP2B rescued the neurodegeneration in α-syn transgenic mice. Better understanding of the mechanisms of intracellular trafficking of α-syn might be important for understanding the pathogenesis and developing new treatments for synucleinopathies.

  17. Genetic Association between Presenilin 2 Polymorphisms and Alzheimer's Disease and Dementia of Lewy Body Type in a Japanese Population

    PubMed Central

    Suzuki, Ayako; Shibata, Nobuto; Kasanuki, Koji; Nagata, Tomoyuki; Shinagawa, Shunichiro; Kobayashi, Nobuyuki; Ohnuma, Tohru; Takeshita, Yoshihide; Kawai, Eri; Takayama, Toshiki; Nishioka, Kenya; Motoi, Yumiko; Hattori, Nobutaka; Nakayama, Kazuhiko; Yamada, Hisashi; Arai, Heii

    2016-01-01

    Background/Aims Mutations in the presenilin 2 (PSEN2) gene cause familial Alzheimer's disease (AD). Common polymorphisms affect gene activity and increase the risk of AD. Nonsynonymous polymorphisms in the PSEN2 gene showed Lewy body dementia (LBD) phenotypes clinically. Therefore, we aimed to investigate whether PSEN2 gene polymorphisms were associated with AD or LBD. Methods Seven single nucleotide polymorphisms (SNPs) of the gene were analyzed using a case-control study design comprising 288 AD patients, 76 LBD patients, and 105 age-matched controls. Results Linkage disequilibrium (LD) examination showed strong LD from rs1295645 to rs8383 on the gene in our cases from Japan. There were no associations between the SNPs studied here and AD onset, and haplotypic analyses did not detect genetic associations between AD and the PSEN2 gene. Although the number of the cases was small, the SNPs studied did not modify the risk of developing LBD in a Japanese population. Conclusion The common SNPs of the PSEN2 gene did not affect the risk of AD or LBD in a Japanese population. Because genetic variability of the PSEN2 gene is associated with behavioral and psychological symptoms of dementia (BPSD) in AD and LBD, further detailed analyses considering BPSD of both diseases would be required. PMID:27065294

  18. Dementia with Lewy bodies: early diagnostic challenges.

    PubMed

    Fujishiro, Hiroshige; Iseki, Eizo; Nakamura, Shinichiro; Kasanuki, Koji; Chiba, Yuhei; Ota, Kazumi; Murayama, Norio; Sato, Kiyoshi

    2013-06-01

    Dementia with Lewy bodies (DLB) is defined pathologically as neurodegeneration associated with Lewy bodies (LB). LB-related symptoms, including olfactory dysfunction, dysautonomia, and mood and sleep disorders, are increasingly recognized as clinical signs that enable the early detection of DLB, because these symptoms often antedate dementia by years or even decades. It remains unknown if the clinical history of LB-related symptoms is sufficient for the prodromal state of DLB to be suspected in memory clinics. We retrospectively investigated the clinical courses, including olfactory dysfunction, dysautonomia, depression, and rapid eye movement sleep behaviour disorder, of 90 patients with probable DLB. The timing of LB-related symptoms that preceded or followed relative to the onset of memory loss was calculated. LB-related symptoms were present in 79 of 90 patients (87.8%) with probable DLB before or at the time of memory loss onset. These symptoms preceded the onset of memory loss between 1.2 and 9.3 years. We also report on four non-demented patients with a clinical history of LB-related symptoms in our memory clinic. All four patients showed reduced cardiac [(123) I]-metaiodobenzylguanidine levels. Moreover, [(18) F]fluoro-D-glucose positron emission tomography scans revealed glucose hypometabolism in the occipital cortex in two patients. One patient converted to probable DLB with the development of parkinsonism 2 years after major depression was diagnosed. Based on a clinical history of LB-related symptoms, we propose a conceptual framework to identify these symptomatic but non-demented individuals that led us to suspect the underlying pathophysiology of Lewy body disease. Further prospective study is warranted to determine the clinical significance of LB-related symptoms in non-demented patients.

  19. Proteinase K-resistant alpha-synuclein is deposited in presynapses in human Lewy body disease and A53T alpha-synuclein transgenic mice.

    PubMed

    Tanji, Kunikazu; Mori, Fumiaki; Mimura, Junsei; Itoh, Ken; Kakita, Akiyoshi; Takahashi, Hitoshi; Wakabayashi, Koichi

    2010-08-01

    Abnormally modified alpha-synuclein is a pathological hallmark of Parkinson's disease and the other alpha-synucleinopathies. Since proteinase K (PK) treatment is known to enhance the immunoreactivity of abnormal alpha-synuclein, we immunohistochemically examined the brain of transgenic (Tg) mice expressing human mutant A53T alpha-synuclein using this retrieval method. PK treatment abolished the immunoreactivity of alpha-synuclein in abnormal inclusions as well as of endogenous alpha-synuclein in Tg mice, whereas PK-resistant alpha-synuclein was found in the presynaptic nerve terminals, especially in the hippocampus and temporal cortex. In human Lewy body disease, PK-resistant alpha-synuclein was deposited in Lewy bodies and Lewy neurites, as well as in the presynapses in distinct brain regions, including the hippocampus, temporal cortex and substantia nigra. Biochemical analysis revealed that PK-resistant alpha-synuclein was detected in the presynaptic fraction in Tg mice and human Lewy body disease. Although PK-resistant alpha-synuclein was found in the presynapse in Tg mice even at 1 week of age, it was not phosphorylated until at least 8 months of age. Moreover, PK-resistant alpha-synuclein in the presynapse was not phosphorylated in human Lewy body disease. These findings suggest that phosphorylation is not necessary to cause the conversion of soluble form to PK-resistant alpha-synuclein. Considering that native alpha-synuclein is a soluble protein localized to the presynaptic terminals, our findings suggest that PK-resistant alpha-synuclein may disturb the neurotransmission in alpha-synucleinopathies.

  20. Dementia with Lewy bodies: current concepts.

    PubMed

    Buracchio, Teresa; Arvanitakis, Zoe; Gorbien, Martin

    2005-01-01

    As life expectancy continues to increase over time, dementia is becoming an increasingly more common problem and a major cause of disability in older persons. It is now more important than ever to identify and manage common causes of dementia given variations in disease course, treatments and the possibility for modification of risk factors. Dementia with Lewy bodies (DLB) is a dementia syndrome characterized by progressive cognitive decline, with fluctuating cognition, recurrent detailed and well-formed hallucinations, and parkinsonism. This article aims to provide an overview of current concepts of DLB, including a description of the key clinical features and neuropathology, neurochemistry, and genetics of DLB, then a discussion of the relationship of DLB with Alzheimer's disease and Parkinson's disease, and, finally, a summary of current management strategies available for this disorder.

  1. Putamen-midbrain functional connectivity is related to striatal dopamine transporter availability in patients with Lewy body diseases.

    PubMed

    Rieckmann, A; Gomperts, S N; Johnson, K A; Growdon, J H; Van Dijk, K R A

    2015-01-01

    Prior work has shown that functional connectivity between the midbrain and putamen is altered in patients with impairments in the dopamine system. This study examines whether individual differences in midbrain-striatal connectivity are proportional to the integrity of the dopamine system in patients with nigrostriatal dopamine loss (Parkinson's disease and dementia with Lewy bodies). We assessed functional connectivity of the putamen during resting state fMRI and dopamine transporter (DAT) availability in the striatum using 11C-Altropane PET in twenty patients. In line with the hypothesis that functional connectivity between the midbrain and the putamen reflects the integrity of the dopaminergic neurotransmitter system, putamen-midbrain functional connectivity was significantly correlated with striatal DAT availability even after stringent control for effects of head motion. DAT availability did not relate to functional connectivity between the caudate and thalamus/prefrontal areas. As such, resting state functional connectivity in the midbrain-striatal pathway may provide a useful indicator of underlying pathology in patients with nigrostriatal dopamine loss.

  2. Neurophysiological biomarkers for Lewy body dementias

    PubMed Central

    Cromarty, Ruth A.; Elder, Greg J.; Graziadio, Sara; Baker, Mark; Bonanni, Laura; Onofrj, Marco; O’Brien, John T.; Taylor, John-Paul

    2016-01-01

    Objective Lewy body dementias (LBD) include both dementia with Lewy bodies (DLB) and Parkinson’s disease with dementia (PDD), and the differentiation of LBD from other neurodegenerative dementias can be difficult. Currently, there are few biomarkers which might assist early diagnosis, map onto LBD symptom severity, and provide metrics of treatment response. Traditionally, biomarkers in LBD have focussed on neuroimaging modalities; however, as biomarkers need to be simple, inexpensive and non-invasive, neurophysiological approaches might also be useful as LBD biomarkers. Methods In this review, we searched PubMED and PsycINFO databases in a semi-systematic manner in order to identify potential neurophysiological biomarkers in the LBDs. Results We identified 1491 studies; of these, 37 studies specifically examined neurophysiological biomarkers in LBD patients. We found that there was substantial heterogeneity with respect to methodologies and patient cohorts. Conclusion Generally, many of the findings have yet to be replicated, although preliminary findings reinforce the potential utility of approaches such as quantitative electroencephalography and motor cortical stimulation paradigms. Significance Various neurophysiological techniques have the potential to be useful biomarkers in the LBDs. We recommend that future studies focus on maximising the diagnostic specificity and sensitivity of the most promising neurophysiological biomarkers. PMID:26183755

  3. Mini Review: Anticholinergic Activity as a Behavioral Pathology of Lewy Body Disease and Proposal of the Concept of “Anticholinergic Spectrum Disorders”

    PubMed Central

    Tomioka, Hiroi; Hachisu, Mitsugu

    2016-01-01

    Given the relationship between anticholinergic activity (AA) and Alzheimer's disease (AD), we rereview our hypothesis of the endogenous appearance of AA in AD. Briefly, because acetylcholine (ACh) regulates not only cognitive function but also the inflammatory system, when ACh downregulation reaches a critical level, inflammation increases, triggering the appearance of cytokines with AA. Moreover, based on a case report of a patient with mild AD and slightly deteriorated ACh, we also speculate that AA can appear endogenously in Lewy body disease due to the dual action of the downregulation of ACh and hyperactivity of the hypothalamic-pituitary-adrenal axis. Based on these hypotheses, we consider AA to be a behavioral pathology of Lewy body disease. We also propose the concept of “anticholinergic spectrum disorders,” which encompass a variety of conditions, including AD, Lewy body disease, and delirium. Finally, we suggest the prescription of cholinesterase inhibitors to patients in this spectrum of disorders to abolish AA by upregulating ACh. PMID:27738546

  4. Whole-brain patterns of 1H-magnetic resonance spectroscopy imaging in Alzheimer's disease and dementia with Lewy bodies

    PubMed Central

    Su, L; Blamire, A M; Watson, R; He, J; Hayes, L; O'Brien, J T

    2016-01-01

    Magnetic resonance spectroscopy has demonstrated metabolite changes in neurodegenerative disorders such as Alzheimer's disease (AD) and dementia with Lewy bodies (DLB); however, their pattern and relationship to clinical symptoms is unclear. To determine whether the spatial patterns of brain-metabolite changes in AD and DLB are regional or diffused, and to examine whether the key metabolite levels are associated with cognitive and non-cognitive symptoms, we acquired whole-brain spatially resolved 3T magnetic resonance spectroscopic imaging (MRSI) data from subjects with AD (N=36), DLB (N=35) and similarly aged controls (N=35). Voxel-wise measurement of N-acetylaspartate to creatine (NAA/Cr), choline to Cr (Cho/Cr), myo-inositol to Cr (mI/Cr) as well as glutamate and glutamine to Cr (Glx/Cr) ratios were determined using MRSI. Compared with controls, AD and DLB groups showed a significant decrease in most brain metabolites, with NAA/Cr, Cho/Cr and mI/Cr levels being reduced in posterior cingulate, thalamus, frontotemporal areas and basal ganglia. The Glx/Cr level was more widely decreased in DLB (posterior cingulate, hippocampus, temporal regions and caudate) than in AD (only in posterior cingulate). DLB was also associated with increased levels of Cho/Cr, NAA/Cr and mI/Cr in occipital regions. Changes in metabolism in the brain were correlated with cognitive and non-cognitive symptoms in the DLB but not in the AD group. The different patterns between AD and DLB may have implications for improving diagnosis, better understanding disease-specific neurobiology and targeting therapeutics. In addition, the study raised important questions about the role of occipital neuroinflammation and glial activation as well as the glutamatergic treatment in DLB. PMID:27576166

  5. Pareidolias: complex visual illusions in dementia with Lewy bodies.

    PubMed

    Uchiyama, Makoto; Nishio, Yoshiyuki; Yokoi, Kayoko; Hirayama, Kazumi; Imamura, Toru; Shimomura, Tatsuo; Mori, Etsuro

    2012-08-01

    Patients rarely experience visual hallucinations while being observed by clinicians. Therefore, instruments to detect visual hallucinations directly from patients are needed. Pareidolias, which are complex visual illusions involving ambiguous forms that are perceived as meaningful objects, are analogous to visual hallucinations and have the potential to be a surrogate indicator of visual hallucinations. In this study, we explored the clinical utility of a newly developed instrument for evoking pareidolic illusions, the Pareidolia test, in patients with dementia with Lewy bodies-one of the most common causes of visual hallucinations in the elderly. Thirty-four patients with dementia with Lewy bodies, 34 patients with Alzheimer's disease and 26 healthy controls were given the Pareidolia test. Patients with dementia with Lewy bodies produced a much greater number of pareidolic illusions compared with those with Alzheimer's disease or controls. A receiver operating characteristic analysis demonstrated that the number of pareidolias differentiated dementia with Lewy bodies from Alzheimer's disease with a sensitivity of 100% and a specificity of 88%. Full-length figures and faces of people and animals accounted for >80% of the contents of pareidolias. Pareidolias were observed in patients with dementia with Lewy bodies who had visual hallucinations as well as those who did not have visual hallucinations, suggesting that pareidolias do not reflect visual hallucinations themselves but may reflect susceptibility to visual hallucinations. A sub-analysis of patients with dementia with Lewy bodies who were or were not treated with donepzil demonstrated that the numbers of pareidolias were correlated with visuoperceptual abilities in the former and with indices of hallucinations and delusional misidentifications in the latter. Arousal and attentional deficits mediated by abnormal cholinergic mechanisms and visuoperceptual dysfunctions are likely to contribute to the development

  6. Cortical Thickness in Dementia with Lewy Bodies and Alzheimer's Disease: A Comparison of Prodromal and Dementia Stages

    PubMed Central

    Blanc, Frederic; Colloby, Sean J.; Philippi, Nathalie; de Pétigny, Xavier; Jung, Barbara; Demuynck, Catherine; Phillipps, Clélie; Anthony, Pierre; Thomas, Alan; Bing, Fabrice; Lamy, Julien; Martin-Hunyadi, Catherine; O'Brien, John T.; Cretin, Benjamin; McKeith, Ian; Armspach, Jean-Paul; Taylor, John-Paul

    2015-01-01

    Objectives To assess and compare cortical thickness (CTh) of patients with prodromal Dementia with Lewy bodies (pro-DLB), prodromal Alzheimer's disease (pro-AD), DLB dementia (DLB-d), AD dementia (AD-d) and normal ageing. Methods Study participants(28 pro-DLB, 27 pro-AD, 31 DLB-d, 54 AD-d and 33 elderly controls) underwent 3Tesla T1 3D MRI and detailed clinical and cognitive assessments. We used FreeSurfer analysis package to measure CTh and investigate patterns of cortical thinning across groups. Results Comparison of CTh between pro-DLB and pro-AD (p<0.05, FDR corrected) showed more right anterior insula thinning in pro-DLB, and more bilateral parietal lobe and left parahippocampal gyri thinning in pro-AD. Comparison of prodromal patients to healthy elderly controls showed the involvement of the same regions. In DLB-d (p<0.05, FDR corrected) cortical thinning was found predominantly in the right temporo-parietal junction, and insula, cingulate, orbitofrontal and lateral occipital cortices. In AD-d(p<0.05, FDR corrected),the most significant areas affected included the entorhinal cortices, parahippocampal gyri and parietal lobes. The comparison of AD-d and DLB-d demonstrated more CTh in AD-d in the left entorhinal cortex (p<0.05, FDR corrected). Conclusion Cortical thickness is a sensitive measure for characterising patterns of grey matter atrophy in early stages of DLB distinct from AD. Right anterior insula involvement may be a key region at the prodromal stage of DLB and needs further investigation. PMID:26061655

  7. Quantification of myelin loss in frontal lobe white matter in vascular dementia, Alzheimer's disease, and dementia with Lewy bodies.

    PubMed

    Ihara, Masafumi; Polvikoski, Tuomo M; Hall, Ros; Slade, Janet Y; Perry, Robert H; Oakley, Arthur E; Englund, Elisabet; O'Brien, John T; Ince, Paul G; Kalaria, Raj N

    2010-05-01

    The aim of this study was to characterize myelin loss as one of the features of white matter abnormalities across three common dementing disorders. We evaluated post-mortem brain tissue from frontal and temporal lobes from 20 vascular dementia (VaD), 19 Alzheimer's disease (AD) and 31 dementia with Lewy bodies (DLB) cases and 12 comparable age controls. Images of sections stained with conventional luxol fast blue were analysed to estimate myelin attenuation by optical density. Serial adjacent sections were then immunostained for degraded myelin basic protein (dMBP) and the mean percentage area containing dMBP (%dMBP) was determined as an indicator of myelin degeneration. We further assessed the relationship between dMBP and glutathione S-transferase (a marker of mature oligodendrocytes) immunoreactivities. Pathological diagnosis significantly affected the frontal but not temporal lobe myelin attenuation: myelin density was most reduced in VaD compared to AD and DLB, which still significantly exhibited lower myelin density compared to ageing controls. Consistent with this, the degree of myelin loss was correlated with greater %dMBP, with the highest %dMBP in VaD compared to the other groups. The %dMBP was inversely correlated with the mean size of oligodendrocytes in VaD, whereas it was positively correlated with their density in AD. A two-tier regression model analysis confirmed that the type of disorder (VaD or AD) determines the relationship between %dMBP and the size or density of oligodendrocytes across the cases. Our findings, attested by the use of three markers, suggest that myelin loss may evolve in parallel with shrunken oligodendrocytes in VaD but their increased density in AD, highlighting partially different mechanisms are associated with myelin degeneration, which could originate from hypoxic-ischaemic damage to oligodendrocytes in VaD whereas secondary to axonal degeneration in AD.

  8. Cognitive fluctuations in connection to dysgraphia: a comparison of Alzheimer’s disease with dementia Lewy bodies

    PubMed Central

    Onofri, Emanuela; Mercuri, Marco; Donato, Giuseppe; Ricci, Serafino

    2015-01-01

    Background The purpose of the present study was to examine the relationship between cognitive impairment and the performance of handwritten scripts presented as “letter-writing” to a close relative by patients with dementia Lewy bodies (DLB), as fluctuations of the symptoms phase, and in a matched group of patients with Alzheimer’s disease (AD). The degree of writing disability and personal, spatial, and temporal orientation was compared in these two groups. Design and methods Fourteen simple questions, designed in a form that could be utilized by any general practitioner in order to document the level of cognitive functioning of each patient, were presented to 30 AD patients and 26 DLB patients. The initial cognition test was designated PQ1. The patients were examined on tests of letter-writing ability. Directly after the letter-writing, the list of 14 questions presented in PQ1 was presented again in a repeated procedure that was designated PQ2. The difference between these two measures (PQ1 – PQ2) was designated DΔ. This test of letter-writing ability and cognitive performance was administered over 19 days. Results Several markedly strong relationships between dysgraphia and several measures of cognitive performance in AD patients and DLB patients were observed, but the deterioration of performance from PQ1 to PQ2 over all test days were markedly significant in AD patients and not significant in DLB patients. It is possible that in graphic expression even by patients diagnosed with moderate to relatively severe AD and DLB there remains some residual capacity for understanding and intention that may be expressed. Furthermore, the deterioration in performance and the differences noted in AD and DLB patients may be due to the different speed at which the process of the protein degradation occurs for functional modification of synapses. Conclusion Our method can be used as part of neuropsychological tests to differentiate the diagnosis between AD and DLB

  9. Lewy Body Disease Treatment

    MedlinePlus

    ... order to avoid potential medication side-effects. Visual Hallucinations If hallucinations are disruptive or upsetting, your physician may recommend ... also been shown to be effective in treating hallucinations and other psychiatric symptoms of LBD. For more ...

  10. Anomalies occurring in lipid profiles and protein distribution in frontal cortex lipid rafts in dementia with Lewy bodies disclose neurochemical traits partially shared by Alzheimer's and Parkinson's diseases.

    PubMed

    Marin, Raquel; Fabelo, Noemí; Martín, Virginia; Garcia-Esparcia, Paula; Ferrer, Isidre; Quinto-Alemany, David; Díaz, Mario

    2017-01-01

    Lipid rafts are highly dynamic membrane microdomains intimately associated with cell signaling. Compelling evidence has demonstrated that alterations in lipid rafts are associated with neurodegenerative diseases such Alzheimer's disease, but at present, whether alterations in lipid raft microdomains occur in other types of dementia such dementia with Lewy bodies (DLB) remains unknown. Our analyses reveal that lipid rafts from DLB exhibit aberrant lipid profiles including low levels of n-3 long-chain polyunsaturated fatty acids (mainly docosahexaenoic acid), plasmalogens and cholesterol, and reduced unsaturation and peroxidability indexes. As a consequence, lipid raft resident proteins holding principal factors of the β-amyloidogenic pathway, including β-amyloid precursor protein, presenilin 1, β-secretase, and PrP, are redistributed between lipid rafts and nonraft domains in DLB frontal cortex. Meta-analysis discloses certain similarities in the altered composition of lipid rafts between DLB and Parkinson's disease which are in line with the spectrum of Lewy body diseases. In addition, redistribution of proteins linked to the β-amyloidogenic pathway in DLB can facilitate generation of β-amyloid, thus providing mechanistic clues to the intriguing convergence of Alzheimer's disease pathology, particularly β-amyloid deposition, in DLB.

  11. Homovanillic acid and 5-hydroxyindole acetic acid as biomarkers for dementia with Lewy bodies and coincident Alzheimer’s disease: An autopsy-confirmed study

    PubMed Central

    Takao, Masaki; Hatsuta, Hiroyuki; Nishina, Yasushi; Komiya, Tadashi; Sengoku, Renpei; Nakano, Yuta; Uchino, Akiko; Sumikura, Hiroyuki; Saito, Yuko; Kanemaru, Kazutomi; Murayama, Shigeo

    2017-01-01

    Dementia with Lewy bodies (DLB) and Alzheimer’s disease (AD) are the two most common causes of dementia. Both pathologies often coexist, and AD patients with concomitant neocortical LB pathology (referred to as the Lewy body variant of AD) generally show faster cognitive decline and accelerated mortality relative to patients with pure AD. Thus, discriminating among patients with DLB, AD, and coincident DLB and AD is important in clinical practice. We examined levels of homovanillic acid (HVA), 5-hydroxyindole acetic acid (5-HIAA), tau, phosphorylated tau (p-tau), and beta-amyloid (Aβ) 1–42 in cerebrospinal fluid (CSF) to evaluate their viability as biomarkers to discriminate among different forms of dementia. We obtained a total of 3498 CSF samples from patients admitted to our hospital during the period from 1996 to 2015. Of these patients, we were able to carry out a brain autopsy in 94 cases. Finally, 78 neuropathologically diagnosed cases (10 AD, six DLB, five DLB with AD, five controls without neurological diseases, and 52 cases with other neurological diseases) were studied. CSF levels of HVA and 5-HIAA were consistently decreased in pathologically advanced Lewy body disorder (LBD; Braak LB stages >3) compared with pathologically incipient LBD (Braak LB stages <2). These results suggest that if an individual has LB pathology in the central nervous system, CSF levels of HVA and 5-HIAA may decrease after the onset of clinical symptoms. In addition, CSF levels of HVA and 5-HIAA decreased with LB pathology, and were especially low in cases of DLB and DLB with AD. Furthermore, the combination of HVA, 5-HIAA, and brain specific proteins t-tau, p-tau, and Aβ 1–42 in CSF were useful for discriminating among DLB, DLB with AD, and AD with high diagnostic accuracy. PMID:28166276

  12. Cholinesterase Inhibitors for Lewy Body Disorders: A Meta-Analysis

    PubMed Central

    Yasue, Ichiro; Iwata, Nakao

    2016-01-01

    Background: We performed a meta-analysis of cholinesterase inhibitors for patients with Lewy body disorders, such as Parkinson’s disease, Parkinson’s disease dementia, and dementia with Lewy bodies. Methods: The meta-analysis included only randomized controlled trials of cholinesterase inhibitors for Lewy body disorders. Results: Seventeen studies (n = 1798) were assessed. Cholinesterase inhibitors significantly improved cognitive function (standardized mean difference [SMD] = −0.53], behavioral disturbances (SMD = −0.28), activities of daily living (SMD = −0.28), and global function (SMD = −0.52) compared with control treatments. Changes in motor function were not significantly different from control treatments. Furthermore, the cholinesterase inhibitor group had a higher all-cause discontinuation (risk ratio [RR] = 1.48, number needed to harm [NNH] = 14), discontinuation due to adverse events (RR = 1.59, NNH = 20), at least one adverse event (RR = 1.13, NNH = 11), nausea (RR = 2.50, NNH = 13), and tremor (RR = 2.30, NNH = 20). Conclusions: Cholinesterase inhibitors appear beneficial for the treatment of Lewy body disorders without detrimental effects on motor function. However, a careful monitoring of treatment compliance and side effects is required. PMID:26221005

  13. Neuroimaging characteristics of dementia with Lewy bodies.

    PubMed

    Mak, Elijah; Su, Li; Williams, Guy B; O'Brien, John T

    2014-01-01

    This review summarises the findings and applications from neuroimaging studies in dementia with Lewy bodies (DLB), highlighting key differences between DLB and other subtypes of dementia. We also discuss the increasingly important role of imaging biomarkers in differential diagnosis and outline promising areas for future research in DLB. DLB shares common clinical, neuropsychological and pathological features with Parkinson's disease dementia and other dementia subtypes, such as Alzheimer's disease. Despite the development of consensus diagnostic criteria, the sensitivity for differential diagnosis of DLB in clinical practice remains low and many DLB patients will be misdiagnosed. The importance of developing accurate imaging markers in dementia is highlighted by the potential for treatments targeting specific molecular abnormalities as well as the responsiveness to cholinesterase inhibitors and marked neuroleptic sensitivity of DLB. We review various brain imaging techniques that have been applied to investigate DLB, including the characteristic nigrostriatal degeneration in DLB using positron emission tomography (PET) and single-photon emission computed tomography (SPECT) tracers. Dopamine transporter loss has proven to reliably differentiate DLB from other dementias and has been incorporated into the revised clinical diagnostic criteria for DLB. To date, this remains the 'gold standard' for diagnostic imaging of DLB. Regional cerebral blood flow, 18 F-fluorodeoxygluclose-PET and SPECT have also identified marked deficits in the occipital regions with relative sparing of the medial temporal lobe when compared to Alzheimer's disease. In addition, structural, diffusion, and functional magnetic resonance imaging techniques have shown alterations in structure, white matter integrity, and functional activity in DLB. We argue that the multimodal identification of DLB-specific biomarkers has the potential to improve ante-mortem diagnosis and contribute to our

  14. Impairment of script comprehension in Lewy body spectrum disorders.

    PubMed

    Gross, Rachel G; Camp, Emily; McMillan, Corey T; Dreyfuss, Michael; Gunawardena, Delani; Cook, Philip A; Morgan, Brianna; Siderowf, Andrew; Hurtig, Howard I; Stern, Matthew B; Grossman, Murray

    2013-06-01

    A disabling impairment of higher-order language function can be seen in patients with Lewy body spectrum disorders such as Parkinson's disease (PD), Parkinson's disease dementia (PDD), and dementia with Lewy bodies (DLB). We focus on script comprehension in patients with Lewy body spectrum disorders. While scripts unfold sequentially, constituent events are thought to contain an internal organization. Executive dysfunction in patients with Lewy body spectrum disorders may interfere with comprehension of this internal structure. We examined 42 patients (30 non-demented PD and 12 mildly demented PDD/DLB patients) and 12 healthy seniors. We presented 22 scripts (e.g., "going fishing"), each consisting of six events. Pilot data from young controls provided the basis for organizing associated events into clusters and arranging them hierarchically into scripts. We measured accuracy and latency to judge the order of adjacent events in the same cluster versus adjacent events in different clusters. PDD/DLB patients were less accurate in their ordering judgments than PD patients and controls. Healthy seniors and PD patients were significantly faster to judge correctly the order of highly associated within-cluster event pairs relative to less closely associated different-cluster event pairs, while PDD/DLB patients did not consistently distinguish between these event-pair types. This relative insensitivity to the clustered-hierarchical organization of events was related to executive impairment and to frontal atrophy as measured by volumetric MRI. These findings extend prior work on script processing to patients with Lewy body spectrum disorders and highlight the potential impact of frontal/executive dysfunction on the daily lives of affected patients.

  15. The First Confirmed Case of Down Syndrome with Dementia with Lewy Bodies

    ERIC Educational Resources Information Center

    Prasher, V. P.; Airuehia, E.; Carey, M.

    2010-01-01

    Dementia with Lewy bodies (DLB) is the second commonest cause of dementia in the general population. Several researches have established an association between Down syndrome (DS) and Alzheimer's disease. Very few studies have however showed such an association between dementia with Lewy bodies and Down syndrome. The occurrence of DLB in persons…

  16. Coexistence of mixed phenotype Creutzfeldt-Jakob disease, Lewy body disease and argyrophilic grain disease plus histological features of possible Alzheimer's disease: a multi-protein disorder in an autopsy case.

    PubMed

    Fernández-Vega, Iván; Ruiz-Ojeda, Javier; Juste, Ramon A; Geijo, Maria; Zarranz, Juan Jose; Sánchez Menoyo, Jose Luis; Vicente-Etxenausia, Ikerne; Mediavilla-García, Jennifer; Guerra-Merino, Isabel

    2015-02-01

    We report hereby an autopsy case of sporadic mixed phenotype CJD without hereditary burden and a long-term clinical course. An 80-year old man was diagnosed with mild cognitive impairment 27 months before death, caused by bronchopneumonia and severe respiratory impairment. During this time, the patient developed gradual mental deterioration, some sleeping problems and myoclonus. Other clinical manifestations were progressive gait problems, language deterioration, presence of primitive reflexes and irritability. In keeping with those symptoms, a rapidly evolving dementia was clinically suspected. Cerebrospinal fluid test for 14-3-3 protein was negative. However, an abnormal EEG and MRI at end-stage of disease were finally consistent with CJD. Post-mortem examination revealed a massive cortical neuronal loss with associated reactive astrocytosis, also evident in the white matter. Diffuse spongiform changes involving some basal ganglia, especially medial thalamus, some troncoencephalic nuclei, mainly inferior olivary nucleus and the molecular layer of the cerebellum were seen. Immunorreactive deposits for anti-prion protein antibody were present at different areas of the CNS. Additionally, Lewy bodies were observed at the brainstem and amygdala. Furthermore, argirophilic grains together with oligodendroglial coiled bodies and pre-tangle inclusions in the neurons from the limbic system containing hyperphosphorylated 4R tau were noted. To the best of our knowledge, this is the first case of CJD combined with Lewy body disease and argirophilic grain disease. Furthermore, we believe this case is an extremely rare combination of MM2-cortical-type and MM2-thalamic-type sporadic CJD (sCJD), which explains the broad spectrum of MM2-type sCJD findings and symptoms. Moreover, histological features of possible Alzheimer's disease were also reported.

  17. Altered Expression Patterns of Inflammation-Associated and Trophic Molecules in Substantia Nigra and Striatum Brain Samples from Parkinson's Disease, Incidental Lewy Body Disease and Normal Control Cases

    PubMed Central

    Walker, Douglas G.; Lue, Lih-Fen; Serrano, Geidy; Adler, Charles H.; Caviness, John N.; Sue, Lucia I.; Beach, Thomas G.

    2016-01-01

    Evidence of inflammation has been consistently associated with pathology in Parkinson's disease (PD)-affected brains, and has been suggested as a causative factor. Dopaminergic neurons in the substantia nigra (SN) pars compacta, whose loss results in the clinical symptoms associated with PD, are particularly susceptible to inflammatory damage and oxidative stress. Inflammation in the striatum, where SN dopaminergic neurons project, is also a feature of PD brains. It is not known whether inflammatory changes occur first in striatum or SN. Many animal models of PD have implicated certain inflammatory molecules with dopaminergic cell neuronal loss; however, there have been few studies to validate these findings by measuring the levels of these and other inflammatory factors in human PD brain samples. This study also included samples from incidental Lewy body disease (ILBD) cases, since ILBD is considered a non-symptomatic precursor to PD, with subjects having significant loss of tyrosine hydroxylase-producing neurons. We hypothesized that there may be a progressive change in key inflammatory factors in ILBD samples intermediate between neurologically normal and PD. To address this, we used a quantitative antibody-array platform (Raybiotech-Quantibody arrays) to measure the levels of 160 different inflammation-associated cytokines, chemokines, growth factors, and related molecules in extracts of SN and striatum from clinically and neuropathologically characterized PD, ILBD, and normal control cases. Patterns of changes in inflammation and related molecules were distinctly different between SN and striatum. Our results showed significantly different levels of interleukin (IL)-5, IL-15, monokine induced by gamma interferon, and IL-6 soluble receptor in SN between disease groups. A different panel of 13 proteins with significant changes in striatum, with IL-15 as the common feature, was identified. Although the ability to detect some proteins was limited by sensitivity

  18. Associations between APOE polymorphisms and seven diseases with cognitive impairment including Alzheimer’s disease, frontotemporal dementia, and dementia with Lewy bodies in southeast China

    PubMed Central

    Chen, Ke-Liang; Sun, Yi-Min; Zhou, Yan; Zhao, Qian-Hua; Ding, Ding

    2016-01-01

    Objective To explore the effect of APOE polymorphisms on patients with cognitive impairments in The Chinese Han population. Materials and methods A total of 1027 cases with Alzheimer’s disease (AD), 40 cases with vascular dementia (VaD), 28 cases with behavioral variant frontotemporal dementia (bvFTD), 54 cases with semantic dementia (SD), 44 cases with dementia with Lewy bodies (DLB), 583 cases with mild cognitive impairment (MCI), and 32 cases with vascular cognitive impairment no dementia (VCIND) were recruited consecutively from memory disorders clinics in Huashan Hospital between January 2010 and December 2014. The 1149 cognitively normal controls were recruited from the community epidemiologic investigations. The APOE genotypes were determined using the TaqMan assay. Results The distribution of genotype and allele frequencies of APOE differed significantly between control and AD or MCI, with ε4 increasing the risk of AD and MCI in a dose-dependent pattern and ε2 decreasing the risk of AD, but not the risk of MCI. As for VaD, significant differences in the APOE genotype distribution were found compared with the controls. E4/4 increased the risk of VaD and ε4 increased the risk of VCIND in women. The allele distribution differed between bvFTD and controls, but genotype and allele frequencies of APOE did not affect the risk of bvFTD, SD, and DLB. Conclusion In The Chinese Han population, APOE ε4 increased the risk of AD and MCI in a dose-dependent manner and ε2 decreased the risk of AD as reported previously. APOE ε4 might increase risk in VaD and female patients with VCIND, but no effects of APOE on bvFTD, DLB, and SD were found. PMID:26981880

  19. The Qualitative Scoring MMSE Pentagon Test (QSPT): A New Method for Differentiating Dementia with Lewy Body from Alzheimer’s Disease

    PubMed Central

    Caffarra, Paolo; Gardini, Simona; Dieci, Francesca; Copelli, Sandra; Maset, Laura; Concari, Letizia; Farina, Elisabetta; Grossi, Enzo

    2013-01-01

    The differential diagnosis across different variants of degenerative diseases is sometimes controversial. This study aimed to validate a qualitative scoring method for the pentagons copy test (QSPT) of Mini-Mental State Examination (MMSE) based on the assessment of different parameters of the pentagons drawing, such as number of angles, distance/intersection, closure/opening, rotation, closing-in, and to verify its efficacy to differentiate dementia with Lewy Body (DLB) from Alzheimer's disease (AD). We established the reliability of the qualitative scoring method through the inter-raters and intra-subjects analysis. QSPT was then applied to forty-six AD and forty-six DLB patients, using two phases statistical approach, standard and artificial neural network respectively. DLB patients had significant lower total score in the copy of pentagons and number of angles, distance/intersection, closure/opening, rotation compared to AD. However the logistic regression did not allow to establish any suitable modeling, whereas using Auto-Contractive Map (Auto-CM) the DLB was more strongly associated with low scores in some qualitative parameters of pentagon copying, i.e. number of angles and opening/closure and, for the remaining subitems of the MMSE, in naming, repetition and written comprehension, and for demographic variables of gender (male) and education (6–13 years). Twist system modeling showed that the QSPT had a good sensitivity (70.29%) and specificity (78.67%) (ROC-AUC 0.74). The proposed qualitative method of assessment of pentagons copying used in combination with non-linear analysis, showed to be consistent and effective in the differential diagnosis between Lewy Body and Alzheimer’s dementia. PMID:23396218

  20. Optimized statistical parametric mapping for partial-volume-corrected amyloid positron emission tomography in patients with Alzheimer's disease and Lewy body dementia

    NASA Astrophysics Data System (ADS)

    Oh, Jungsu S.; Kim, Jae Seung; Chae, Sun Young; Oh, Minyoung; Oh, Seung Jun; Cha, Seung Nam; Chang, Ho-Jong; Lee, Chong Sik; Lee, Jae Hong

    2017-03-01

    We present an optimized voxelwise statistical parametric mapping (SPM) of partial-volume (PV)-corrected positron emission tomography (PET) of 11C Pittsburgh Compound B (PiB), incorporating the anatomical precision of magnetic resonance image (MRI) and amyloid β (A β) burden-specificity of PiB PET. First, we applied region-based partial-volume correction (PVC), termed the geometric transfer matrix (GTM) method, to PiB PET, creating MRI-based lobar parcels filled with mean PiB uptakes. Then, we conducted a voxelwise PVC by multiplying the original PET by the ratio of a GTM-based PV-corrected PET to a 6-mm-smoothed PV-corrected PET. Finally, we conducted spatial normalizations of the PV-corrected PETs onto the study-specific template. As such, we increased the accuracy of the SPM normalization and the tissue specificity of SPM results. Moreover, lobar smoothing (instead of whole-brain smoothing) was applied to increase the signal-to-noise ratio in the image without degrading the tissue specificity. Thereby, we could optimize a voxelwise group comparison between subjects with high and normal A β burdens (from 10 patients with Alzheimer's disease, 30 patients with Lewy body dementia, and 9 normal controls). Our SPM framework outperformed than the conventional one in terms of the accuracy of the spatial normalization (85% of maximum likelihood tissue classification volume) and the tissue specificity (larger gray matter, and smaller cerebrospinal fluid volume fraction from the SPM results). Our SPM framework optimized the SPM of a PV-corrected A β PET in terms of anatomical precision, normalization accuracy, and tissue specificity, resulting in better detection and localization of A β burdens in patients with Alzheimer's disease and Lewy body dementia.

  1. Lewy Bodies, Vascular Risk Factors, and Subcortical Arteriosclerotic Leukoencephalopathy, but not Alzheimer Pathology, are Associated with Development of Psychosis in Alzheimer’s Disease

    PubMed Central

    Fischer, Corinne E.; Qian, Winnie; Schweizer, Tom A.; Millikin, Colleen P.; Ismail, Zahinoor; Smith, Eric E.; Lix, Lisa M.; Shelton, Paul; Munoz, David G.

    2016-01-01

    Background The neuropathological correlates of psychosis in Alzheimer’s disease (AD) is unclear, with some studies reporting a correlation between psychosis and increased AD pathology while others have found no association. Objective To determine the demographic, clinical, and neuropathological features associated with psychotic symptoms in clinically attributed and neuropathologically proven AD. Method We separately reviewed two overlapping groups of clinically diagnosed (cAD) AD patients with neuropathology data and neuropathologically definite (npAD) cases (regardless of clinical diagnosis) from the NACC database, and explored the relationships between psychosis and clinical variables, neuropathologic correlates, and vascular risk factors. Delusions and hallucinations, defined according to the NPI-Q, were analyzed separately. Results 1,073 subjects in the database fulfilled our criteria (890 cAD and 728 npAD patients). 34% of cAD and 37% of npAD had psychotic symptoms during their illness. Hallucinations were associated with greater cognitive and functional impairments on the MMSE and CDR, while delusional patients showed less impairment on CDR, consistent across cAD and npAD groups. Burden of AD pathology appears to relate to presence of psychotic symptoms in the clinical AD group, but this result is not confirmed in the neuropathologically confirmed group suggesting the findings in the clinical group were due to misdiagnosis of AD. Lewy body pathology, subcortical arteriosclerotic leukoencephalopathy, and vascular risk factors, including a history of hypertension and diabetes, were associated with the development of psychosis. Conclusions Vascular and Lewy body pathologies and vascular risk factors are important modifiers of the risk of psychosis in AD. PMID:26682680

  2. Sentence Processing in Lewy Body Spectrum Disorder: The Role of Working Memory

    ERIC Educational Resources Information Center

    Gross, Rachel G.; McMillan, Corey T.; Chandrasekaran, Keerthi; Dreyfuss, Michael; Ash, Sharon; Avants, Brian; Cook, Philip; Moore, Peachie; Libon, David J.; Siderowf, Andrew; Grossman, Murray

    2012-01-01

    Prior work has related sentence processing to executive deficits in non-demented patients with Parkinson's disease (PD). We extended this investigation to patients with dementia with Lewy bodies (DLB) and PD dementia (PDD) by examining grammatical and working memory components of sentence processing in the full range of patients with Lewy body…

  3. LEWY BODY DEMENTIA: THE CAREGIVER EXPERIENCE OF CLINICAL CARE

    PubMed Central

    Galvin, James E.; Duda, John E.; Kaufer, Daniel I.; Lippa, Carol F.; Taylor, Angela; Zarit, Steven H.

    2010-01-01

    BACKGROUND Lewy body dementia (LBD) is the second most common cause of dementia, however, little is known about how the clinical diagnosis of LBD is obtained in the community or the caregiver experience while seeking the diagnosis. METHODS The Lewy Body Dementia Association (www.LBDA.org) conducted a web-based survey of 962 caregivers over a 6-month period. RESULTS The mean age of respondents was 55.9y; 88% were female and 64% had daily contact with patients. The mean age of LBD patients was 75.4y; 62% were male and 46% lived with a caregiver. The most common presentation of symptoms as reported by LBD caregivers was cognitive (48%), motor (39%) or both (13%). The first diagnoses given to the patients were Parkinson disease or other movement disorder (39%), Alzheimer disease or other cognitive disorder (36%), or mental illness (24%). Fifty percent of patients saw >3 doctors for more than 10 visits over the course of 1 year before an LBD diagnosis was established. Neurologists diagnosed most cases (62%), while primary care-providers diagnosed only 6% of cases. No differences were found between the presentation of disease and the number of physicians, number of office visits, length of time to establish diagnosis, or type of doctor who finally made an LBD diagnosis. Caregivers viewed physicians as knowledgeable about disease manifestations and treatment options, but not about disease course/prognosis and available community resources and referrals. CONCLUSIONS These data highlight a need for increasing physician awareness and knowledge of LBD, which will facilitate accurate diagnosis and treatment. Community resources such as the Lewy Body Dementia Association may serve this end, while also providing practical information and support for caregivers. PMID:20434939

  4. Lewy Bodies Contain Altered α-Synuclein in Brains of Many Familial Alzheimer’s Disease Patients with Mutations in Presenilin and Amyloid Precursor Protein Genes

    PubMed Central

    Lippa, Carol F.; Fujiwara, Hideo; Mann, David M.A.; Giasson, Benoit; Baba, Minami; Schmidt, Marie L.; Nee, Linda E.; O’Connell, Brendan; Pollen, Dan A.; St. George-Hyslop, Peter; Ghetti, Bernardino; Nochlin, David; Bird, Thomas D.; Cairns, Nigel J.; Lee, Virginia M.-Y.; Iwatsubo, Takeshi; Trojanowski, John Q.

    1998-01-01

    Missense mutations in the α-synuclein gene cause familial Parkinson’s disease (PD), and α-synuclein is a major component of Lewy bodies (LBs) in sporadic PD, dementia with LBs (DLB), and the LB variant of Alzheimer’s disease (AD). To determine whether α-synuclein is a component of LBs in familial AD (FAD) patients with known mutations in presenilin (n = 65) or amyloid precursor protein (n = 9) genes, studies were conducted with antibodies to α-, β-, and γ-synuclein. LBs were detected with α- but not β- or γ-synuclein antibodies in 22% of FAD brains, and α-synuclein-positive LBs were most numerous in amygdala where some LBs co-localized with tau-positive neurofibrillary tangles. As 12 (63%) of 19 FAD amygdala samples contained α-synuclein-positive LBs, these inclusions may be more common in FAD brains than previously reported. Furthermore, α-synuclein antibodies decorated LB filaments by immunoelectron microscopy, and Western blots revealed that the solubility of α-synuclein was reduced compared with control brains. The presence of α-synuclein-positive LBs was not associated with any specific FAD mutation. These studies suggest that insoluble α-synuclein aggregates into filaments that form LBs in many FAD patients, and we speculate that these inclusions may compromise the function and/or viability of affected neurons in the FAD brain. PMID:9811326

  5. Leucine-rich repeat kinase 2 is associated with the endoplasmic reticulum in dopaminergic neurons and accumulates in the core of Lewy bodies in Parkinson disease.

    PubMed

    Vitte, Jérémie; Traver, Sabine; Maués De Paula, André; Lesage, Suzanne; Rovelli, Giorgio; Corti, Olga; Duyckaerts, Charles; Brice, Alexis

    2010-09-01

    Mutation of the leucine-rich repeat kinase 2 (LRRK2) gene is the most frequent genetic cause of Parkinson disease (PD). To understand the role of LRRK2 in the neuropathology of PD, we investigated the protein expression in a healthy brain and brains from patients with PD and its subcellular localization in dopaminergic neurons. LRRK2 was found to be widely expressed in healthy adult brain, including areas involved in PD. By double fluorescent staining, we found that endogenous LRRK2 is colocalized with the endoplasmic reticulum (ER) markers Neurotrace and KDEL in human dopaminergic neurons. Labeling of brain sections with anti-LRRK2 and anti-α-synuclein antibodies revealed localization of LRRK2 in the core of 24% of Lewy bodies (LBs) in the substantia nigra and 11% of LBs in the locus coeruleus in idiopathic PD patients. The percentage was increased to 50% in both areas in a patient with the G2019S LRRK2 mutation. The finding of ER localization suggests the possibility that LRRK2 is involved in the ER stress response and could account for the susceptibility to neuronal degeneration of LRRK2 mutation carriers. The localization of LRRK2 protein in the core of a subset of LBs demonstrates the contribution of LRRK2 to LB formation and disease pathogenesis.

  6. TRAF6 promotes atypical ubiquitination of mutant DJ-1 and alpha-synuclein and is localized to Lewy bodies in sporadic Parkinson's disease brains.

    PubMed

    Zucchelli, Silvia; Codrich, Marta; Marcuzzi, Federica; Pinto, Milena; Vilotti, Sandra; Biagioli, Marta; Ferrer, Isidro; Gustincich, Stefano

    2010-10-01

    Parkinson's disease (PD) is a neurodegenerative disorder characterized by loss of dopaminergic neurons in the Substantia Nigra and the formation of ubiquitin- and alpha-synuclein (aSYN)-positive cytoplasmic inclusions called Lewy bodies (LBs). Although most PD cases are sporadic, families with genetic mutations have been found. Mutations in PARK7/DJ-1 have been associated with autosomal recessive early-onset PD, while missense mutations or duplications of aSYN (PARK1, PARK4) have been linked to dominant forms of the disease. In this study, we identify the E3 ubiquitin ligase tumor necrosis factor-receptor associated factor 6 (TRAF6) as a common player in genetic and sporadic cases. TRAF6 binds misfolded mutant DJ-1 and aSYN. Both proteins are substrates of TRAF6 ligase activity in vivo. Interestingly, rather than conventional K63 assembly, TRAF6 promotes atypical ubiquitin linkage formation to both PD targets that share K6-, K27- and K29- mediated ubiquitination. Importantly, TRAF6 stimulates the accumulation of insoluble and polyubiquitinated mutant DJ-1 into cytoplasmic aggregates. In human post-mortem brains of PD patients, TRAF6 protein colocalizes with aSYN in LBs. These results reveal a novel role for TRAF6 and for atypical ubiquitination in PD pathogenesis.

  7. Dementia with Lewy bodies: a comprehensive review for nurses.

    PubMed

    Ajon Gealogo, Gretchel

    2013-12-01

    Much of the current nursing literature on dementia focuses on Alzheimer disease (AD), the dementia subtype most commonly diagnosed in the older adults. There is a paucity of nursing literature on dementia with Lewy bodies (DLB), the second most common subtype of dementia, which is closely associated with Parkinson disease with dementia (PDD), considered the third most common dementia subtype. Both are aging-related disorders attributed to Lewy bodies, abnormal protein aggregates or "clumps" found to cause cumulative neurodegeneration over time. DLB is defined as dementia onset that is preceded by Parkinsonian symptoms for 1 year or less, whereas in PDD, 2 or more years of Parkinsonian symptoms precede dementia onset. Although basic science knowledge of DLB has increased exponentially, the lack of nursing research on DLB indicates that this knowledge excludes the nursing perspective and its implications for nursing practice. The purpose of this article is to provide nurses with a comprehensive overview of DLB as it compares with PDD and Alzheimer disease and to propose key nursing interventions for clinical practice.

  8. A comparison of gray and white matter density in patients with Parkinson's disease dementia and dementia with Lewy bodies using voxel-based morphometry.

    PubMed

    Lee, Ji E; Park, Bosuk; Song, Sook K; Sohn, Young H; Park, Hae-Jeong; Lee, Phil Hyu

    2010-01-15

    Despite clinical and neuropsychological similarities between Parkinson's disease dementia (PDD) and dementia with Lewy bodies (DLB), recent studies have demonstrated that structural and pathological changes are more severe in DLB than in PDD. We used voxel-based morphometry using a 3-T MRI scanner to compare gray and white matter densities in 20 patients with probable PDD and 18 patients with probable DLB, who had similar overall severity of dementia and similar demographic characteristics. The gray matter density was significantly decreased in the left occipital, parietal, and striatal areas in patients with DLB compared with patients with PDD. The white matter density was significantly decreased in bilateral occipital and left occipito-parietal areas in patients with DLB compared with those with PDD. The degree of white and gray matter atrophy was similar in patients with DLB; in contrast, there was markedly less atrophy in the white matter than in the gray matter in patients with PDD. On analyzing the change of WM density relative to that of GM density in patients with DLB compared to those with PDD, the area of WM atrophy in the occipital areas was more extensive than that of GM atrophy. Our data demonstrate that atrophy of both gray and white matter was more severe in patients with DLB and that white matter atrophy relative to gray matter atrophy was less severe in patients with PDD. These data may reflect a difference in the underlying nature of PDD and DLB.

  9. Malnutrition in Alzheimer’s Disease, Dementia with Lewy Bodies, and Frontotemporal Lobar Degeneration: Comparison Using Serum Albumin, Total Protein, and Hemoglobin Level

    PubMed Central

    Hashimoto, Mamoru; Tanaka, Hibiki; Fujise, Noboru; Matsushita, Masateru; Miyagawa, Yusuke; Hatada, Yutaka; Fukuhara, Ryuji; Hasegawa, Noriko; Todani, Shuji; Matsukuma, Kengo; Kawano, Michiyo; Ikeda, Manabu

    2016-01-01

    Malnutrition among dementia patients is an important issue. However, the biochemical markers of malnutrition have not been well studied in this population. The purpose of this study was to compare biochemical blood markers among patients with Alzheimer’s disease (AD), dementia with Lewy bodies (DLB), and frontotemporal lobar degeneration (FTLD). A total of 339 dementia outpatients and their family caregivers participated in this study. Low serum albumin was 7.2 times more prevalent among patients with DLB and 10.1 times more prevalent among those with FTLD than among those with AD, with adjustment for age. Low hemoglobin was 9.1 times more common in female DLB patients than in female AD patients, with adjustment for age. The levels of biochemical markers were not significantly correlated with cognitive function. Family caregivers of patients with low total protein, low albumin, or low hemoglobin were asked if the patients had loss of weight or appetite; 96.4% reported no loss of weight or appetite. In conclusion, nutritional status was worse in patients with DLB and FTLD than in those with AD. A multidimensional approach, including blood testing, is needed to assess malnutrition in patients with dementia. PMID:27336725

  10. Capgras syndrome in Dementia with Lewy Bodies

    PubMed Central

    Thaipisutikul, Papan; Lobach, Iryna; Zweig, Yael; Gurnani, Ashita; Galvin, James E.

    2014-01-01

    Background Capgras syndrome is characterized by the recurrent, transient belief that a person has been replaced by an identical imposter. We reviewed clinical characteristics of Dementia with Lewy Bodies (DLB) patients with Capgras syndrome compared to those without Capgras. Methods We identified 55 consecutive DLB patients (11 cases with Capgras syndrome (DLB-C) and 44 cases without evidence of Capgras (DLB). Semi-structured interviews with the patient and an informant, neurological exams, and neuropsychological testing were performed. Caregivers were assessed for caregiver burden and depression. Primary comparisons were made between DLB-C and DLB. Exploratory analyses using stepwise logistic regression and bootstrap analyses were performed to determine clinical features associated with Capgras. Results DLB-C patients experienced more visual hallucinations and self-reported anxiety, had higher scores on the Neuropsychiatric Inventory, and were less likely to be treated with cholinesterase inhibitors at time of initial evaluation. Extrapyramidal symptoms and depression were not associated with Capgras. Caregivers of DLB-C patients had higher caregiver burden. DLB-C was associated with self-reported anxiety (OR 10.9; 95% CI 2.6-47.6). In a bootstrap analysis, clinical findings that were predictors of Capgras included visual hallucinations (log(OR) 18.3; 95% CI 17.9-19.3) and anxiety (log(OR) 2.9; 95% CI (0.31-20.2). Conclusions Our study suggests that Capgras syndrome is common in DLB and usually occurs in the presence of anxiety and visual hallucinations, suggesting related etiopathogenesis. Early appreciation of Capgras syndrome may afford the opportunity to alleviate caregiver burden and improve patient and caregiver outcomes. PMID:23211760

  11. The Inflammatory Marker YKL-40 Is Elevated in Cerebrospinal Fluid from Patients with Alzheimer’s but Not Parkinson’s Disease or Dementia with Lewy Bodies

    PubMed Central

    Wennström, Malin; Surova, Yulia; Hall, Sara; Nilsson, Christer; Minthon, Lennart; Hansson, Oskar; Nielsen, Henrietta M.

    2015-01-01

    A major difference in the revised diagnostic criteria for Alzheimer’s disease (AD) is the incorporation of biomarkers to support a clinical diagnosis and allow the identification of preclinical AD due to AD neuropathological processes. However, AD-specific fluid biomarkers which specifically distinguish clinical AD dementia from other dementia disorders are still missing. Here we aimed to evaluate the disease-specificity of increased YKL-40 levels in cerebrospinal fluid (CSF) from AD patients with mild to moderate dementia (n = 49) versus Parkinson’s disease (PD) (n = 61) and dementia with Lewy bodies (DLB) patients (n = 36), and non-demented controls (n = 44). Second we aimed to investigate whether altered YKL-40 levels are associated with CSF levels of other inflammation-associated molecules. When correcting for age, AD patients exhibited 21.3%, 27.7% and 38.8% higher YKL-40 levels compared to non-demented controls (p = 0.0283), DLB (p = 0.0027) and PD patients (p<0.0001). The AD-associated increase in YKL-40 was not associated with CSF P-tau, T-tau or Aβ42. No relationship between increased YKL-40 and levels of the astrocytic marker glial-fibrillary acidic protein (GFAP), interleukin-8 (IL-8), monocyte chemoattractant protein-1 (MCP-1) and interferon gamma-induced protein 10 (IP-10) could be identified. Our results confirm previous reports of an age-associated increased in CSF YKL-40 levels and further demonstrate increased CSF YKL-40 in AD patients versus non-demented controls and patients with DLB or PD. The increase in YKL-40 levels in the AD patients was unrelated to the established CSF AD biomarkers and the inflammatory markers GFAP, MCP-1, IP-10 and IL-8, proposing YKL-40 as a marker of yet to be identified AD-related pathological processes. PMID:26270969

  12. Brain Insulin-Like Growth Factor and Neurotrophin Resistance in Parkinson's Disease and Dementia with Lewy Bodies: Potential Role of Manganese Neurotoxicity

    PubMed Central

    Tong, Ming; Dong, Matthew; de la Monte, Suzanne M.

    2010-01-01

    Parkinson's disease (PD) and dementia with Lewy bodies (DLB) frequently overlap with Alzheimer's disease, which is linked to brain impairments in insulin, insulin-like growth factor (IGF), and neurotrophin signaling. We explored whether similar abnormalities occur in PD or DLB, and examined the role of manganese toxicity in PD/DLB pathogenesis. Quantitative RT-PCR demonstrated reduced expression of insulin, IGF-II, and insulin, IGF-I, and IGF-II receptors (R) in PD and/or DLB frontal white matter and amygdala, and reduced IGF-IR and IGF-IIR mRNA in DLB frontal cortex. IGF-I and IGF-II resistance was present in DLB but not PD frontal cortex, and associated with reduced expression of Hu, nerve growth factor, and Trk neurotrophin receptors, and increased levels of glial fibrillary acidic protein, α-synuclein, dopamine-β-hydroxylase, 4-hydroxy-2-nonenal (HNE), and ubiquitin immunoreactivity. MnCl2 treatment reduced survival, ATP, and insulin, IGF-I and IGF-II receptor expression, and increased α-synuclein, HNE, and ubiquitin immunoreactivity in cultured neurons. The results suggest that: 1) IGF-I, IGF-II, and neurotrophin signaling are more impaired in DLB than PD, corresponding with DLB's more pronounced neurodegeneration, oxidative stress, and α-synuclein accumulation; 2) MnCl2 exposure causes PD/DLB associated abnormalities in central nervous system neurons, and therefore may contribute to their molecular pathogenesis; and 3) molecular abnormalities in PD/DLB overlap with but are distinguishable from Alzheimer's disease. PMID:19276553

  13. Quantitative measurement of [Na+] and [K+] in postmortem human brain tissue indicates disturbances in subjects with Alzheimer's disease and dementia with Lewy bodies.

    PubMed

    Graham, Stewart F; Nasarauddin, Muhammad Bin; Carey, Manus; McGuinness, Bernadette; Holscher, Christian; Kehoe, Patrick G; Love, Seth; Passmore, Anthony P; Elliott, Christopher T; Meharg, Andrew; Green, Brian D

    2015-01-01

    Alzheimer's disease (AD) is associated with significant disturbances in the homeostasis of Na+ and K+ ions as well as reduced levels of Na+/K+ ATPase in the brain. This study used ICP-MS to accurately quantify Na+ and K+ concentrations in human postmortem brain tissue. We analyzed parietal cortex (Brodmann area 7) from 28 cognitively normal age-matched controls, 15 cases of moderate AD, 30 severe AD, and 15 dementia with Lewy bodies (DLB). Associations were investigated between [Na+] and [K+] and a number of variables including diagnosis, age, gender, Braak tangle stage, amyloid-β (Aβ) plaque load, tau load, frontal tissue pH, and APOE genotype. Brains from patients with severe AD had significantly higher (26%; p < 0.001) [Na+] (mean 65.43 ± standard error 2.91 mmol/kg) than controls, but the concentration was not significantly altered in moderate AD or DLB. [Na+] correlated positively with Braak stage (r = 0.45; p < 0.0001), indicating association with disease severity. [K+] in tissue was 10% lower (p < 0.05) in moderate AD than controls. However, [K+] in severe AD and DLB (40.97 ± 1.31 mmol/kg) was not significantly different from controls. There was a significant positive correlation between [K+] and Aβ plaque load (r = 0.46; p = 0.035), and frontal tissue pH (r = 0.35; p = 0.008). [Na+] was not associated with [K+] across the groups, and neither ion was associated with tau load or APOE genotype. We have demonstrated disturbances of both [Na+] and [K+] in relation to the severity of AD and markers of AD pathology, although it is possible that these relate to late-stage secondary manifestations of the disease pathology.

  14. Immunotherapy targeting α-synuclein, with relevance for future treatment of Parkinson's disease and other Lewy body disorders.

    PubMed

    Lindström, Veronica; Ihse, Elisabet; Fagerqvist, Therese; Bergström, Joakim; Nordström, Eva; Möller, Christer; Lannfelt, Lars; Ingelsson, Martin

    2014-01-01

    Immunotherapy targeting α-synuclein has evolved as a potential therapeutic strategy for neurodegenerative diseases, such as Parkinson's disease, and initial studies on cellular and animal models have shown promising results. α-synuclein vaccination of transgenic mice reduced the number of brain inclusions, whereas passive immunization studies demonstrated that antibodies against the C-terminus of α-synuclein can pass the blood-brain barrier and affect the pathology. In addition, preliminary evidence suggests that transgenic mice treated with an antibody directed against α-synuclein oligomers/protofibrils resulted in reduced levels of such species in the CNS. The underlying mechanisms of immunotherapy are not yet fully understood, but may include antibody-mediated clearance of pre-existing aggregates, prevention of protein propagation between cells and microglia-dependent protein clearance. Thus, immunotherapy targeting α-synuclein holds promise, but needs to be further developed as a future disease-modifying treatment in Parkinson's disease and other α-synucleinopathies.

  15. Is brain copper deficiency in Alzheimer's, Lewy body, and Creutzfeldt Jakob diseases the common key for a free radical mechanism and oxidative stress-induced damage?

    PubMed

    Deloncle, Roger; Guillard, Olivier

    2015-01-01

    In Alzheimer's (AD), Lewy body (LBD), and Creutzfeldt Jakob (CJD) diseases, similar pathological hallmarks have been described, one of which is brain deposition of abnormal protease-resistant proteins. For these pathologies, copper bound to proteins is able to protect against free radicals by reduction from cupric Cu++ to cupreous Cu+. We have previously demonstrated in bovine brain homogenate that free radicals produce proteinase K-resistant prion after manganese is substituted for copper. Since low brain copper levels have been described in transmissible spongiform encephalopathies, in substantia nigra in Parkinson's disease, and in various brain regions in AD, LBD, and CJD, a mechanism has been proposed that may underlie the neurodegenerative processes that occur when copper protection against free radicals is impaired. In peptide sequences, the alpha acid proton near the peptide bond is highly mobile and can be pulled out by free radicals. It will produce a trivalent α-carbon radical and induce a free radical chain process that will generate a D-amino acid configuration in the peptide sequence. Since only L-amino acids are physiologically present in mammalian (human) proteins, it may be supposed that only physiological L-peptides can be recycled by physiological enzymes such as proteases. If a D-amino acid is found in the peptide sequence subsequent to deficient copper protection against free radicals, it will not be recognized and might alter the proteasome L-amino acid recycling from brain peptides. In the brain, there will result an accumulation of abnormal protease-resistant proteins such as those observed in AD, LBD, and CJD.

  16. Assessment of ZnT3 and PSD95 protein levels in Lewy body dementias and Alzheimer's disease: association with cognitive impairment.

    PubMed

    Whitfield, David R; Vallortigara, Julie; Alghamdi, Amani; Howlett, David; Hortobágyi, Tibor; Johnson, Mary; Attems, Johannes; Newhouse, Stephen; Ballard, Clive; Thomas, Alan J; O'Brien, John T; Aarsland, Dag; Francis, Paul T

    2014-12-01

    The loss of zinc transporter 3 (ZnT3) has been implicated in age-related cognitive decline in mice, and the protein has been associated with plaques. We investigated the levels of ZnT3 and postsynaptic density protein 95 (PSD95), a marker of the postsynaptic terminal, in people with Parkinson's disease dementia (PDD, n = 31), dementia with Lewy bodies (DLB, n = 44), Alzheimer's disease (AD, n = 16), and controls (n = 24), using semiquantitative western blotting and immunohistochemistry in 3 cortical regions. Standardized cognitive assessments during life and semiquantitative scoring of amyloid β (Aβ), tau, and α-synuclein at postmortem were used to investigate the relationship between ZnT3 and PSD95, cognition and pathology. Associations were observed between ZnT3 and PSD95 levels in prefrontal cortex and cognitive impairment (p = 0.001 and p = 0.002, respectively) and between ZnT3 levels in the parietal cortex and cognitive impairment (p = 0.036). Associations were also seen between ZnT3 levels in cingulate cortex and severity of Aβ (p = 0.003) and tau (p = 0.011) pathologies. DLB and PDD were characterized by significant reductions of PSD95 (p < 0.05) and ZnT3 (p < 0.001) in prefrontal cortex compared with controls and AD. PSD95 levels in the parietal cortex were found to be decreased in AD cases compared with controls (p = 0.02) and PDD (p = 0.005). This study has identified Zn(2+) modulation as a possible novel target for the treatment of cognitive impairment in DLB and PDD and the potential for synaptic proteins to be used as a biomarker for the differentiation of DLB and PDD from AD.

  17. Monoclonal antibodies selective for α-synuclein oligomers/protofibrils recognize brain pathology in Lewy body disorders and α-synuclein transgenic mice with the disease-causing A30P mutation.

    PubMed

    Fagerqvist, Therese; Lindström, Veronica; Nordström, Eva; Lord, Anna; Tucker, Stina M E; Su, Xingjian; Sahlin, Charlotte; Kasrayan, Alex; Andersson, Jessica; Welander, Hedvig; Näsström, Thomas; Holmquist, Mats; Schell, Heinrich; Kahle, Philipp J; Kalimo, Hannu; Möller, Christer; Gellerfors, Pär; Lannfelt, Lars; Bergström, Joakim; Ingelsson, Martin

    2013-07-01

    Inclusions of intraneuronal alpha-synuclein (α-synuclein) can be detected in brains of patients with Parkinson's disease and dementia with Lewy bodies. The aggregation of α-synuclein is a central feature of the disease pathogenesis. Among the different α-synuclein species, large oligomers/protofibrils have particular neurotoxic properties and should therefore be suitable as both therapeutic and diagnostic targets. Two monoclonal antibodies, mAb38F and mAb38E2, with high affinity and strong selectivity for large α-synuclein oligomers were generated. These antibodies, which do not bind amyloid-beta or tau, recognize Lewy body pathology in brains from patients with Parkinson's disease and dementia with Lewy bodies and detect pathology earlier in α-synuclein transgenic mice than linear epitope antibodies. An oligomer-selective sandwich ELISA, based on mAb38F, was set up to analyze brain extracts of the transgenic mice. The overall levels of α-synuclein oligomers/protofibrils were found to increase with age in these mice, although the levels displayed a large interindividual variation. Upon subcellular fractionation, higher levels of α-synuclein oligomers/protofibrils could be detected in the endoplasmic reticulum around the age when behavioral disturbances develop. In summary, our novel oligomer-selective α-synuclein antibodies recognize relevant pathology and should be important tools to further explore the pathogenic mechanisms in Lewy body disorders. Moreover, they could be potential candidates both for immunotherapy and as reagents in an assay to assess a potential disease biomarker.

  18. Delayed blink reflex in dementia with Lewy bodies

    PubMed Central

    Bonanni, Laura; Anzellotti, Francesca; Varanese, Sara; Thomas, Astrid; Manzoli, Lamberto; Onofrj, Marco

    2007-01-01

    Blink reflexes (BR) to electric stimuli of the supraorbital nerve were recorded in 26 patients with dementia with Lewy bodies (DLB), 26 patients with multiple system atrophy, 26 patients with Parkinson's disease, with or without REM sleep behaviour disorder (RBD), and in 20 patients with Alzheimer's disease and 20 with progressive supranuclear palsy without RBD, and compared with recordings in 30 healthy controls. BR were significantly delayed (p<0.001) only in DLB patients in comparison with controls and with the other groups of patients; 14 (53.8%) patients had BR latency above 2 SD of the control mean, ranging from 36.1 to 46.3 ms. BR latency was not related to the presence of RBD, while a Spearman correlation rho of 0.68 was found for scores assessing the presence of cognitive fluctuations. R2 delay was prominently (71.5%) bilateral. PMID:17878193

  19. Lewy body dementia: the impact on patients and caregivers.

    PubMed

    Zweig, Yael R; Galvin, James E

    2014-01-01

    Lewy body dementia (LBD) is the second most common neurodegenerative dementia in older adults, yet there remains a delay in diagnosis that limits healthcare providers' ability to maximize therapeutic outcomes and enhance patient and caregiver quality of life. The impact of LBD on patients includes limiting the potential exposure to medications that may cause adverse outcomes, and addressing how the disease manifestations, such as autonomic features and behavior, affect quality of life. LBD impact on caregivers has been discussed to a greater degree in the literature, and there is clear evidence of caregiver burden and grief associated with disease manifestations. Other common caregiving concerns, such as access to care, prevention of hospitalization, managing behavior, and reviewing prognosis and nursing home placement, are important to comprehensively address the needs of patients with LBD and their caregivers.

  20. A comparison of (99m)Tc-HMPAO SPET changes in dementia with Lewy bodies and Alzheimer's disease using statistical parametric mapping.

    PubMed

    Colloby, Sean J; Fenwick, John D; Williams, E David; Paling, Sean M; Lobotesis, Kyriakos; Ballard, Clive; McKeith, Ian; O'Brien, John T

    2002-05-01

    Differences in regional cerebral blood flow (rCBF) between subjects with Alzheimer's disease (AD), dementia with Lewy bodies (DLB) and healthy volunteers were investigated using statistical parametric mapping (SPM99). Forty-eight AD, 23 DLB and 20 age-matched control subjects participated. Technetium-99m hexamethylpropylene amine oxime (HMPAO) brain single-photon emission tomography (SPET) scans were acquired for each subject using a single-headed rotating gamma camera (IGE CamStar XR/T). The SPET images were spatially normalised and group comparison was performed by SPM99. In addition, covariate analysis was undertaken on the standardised images taking the Mini Mental State Examination (MMSE) scores as a variable. Applying a height threshold of P < or = 0.001 uncorrected, significant perfusion deficits in the parietal and frontal regions of the brain were observed in both AD and DLB groups compared with the control subjects. In addition, significant temporoparietal perfusion deficits were identified in the AD subjects, whereas the DLB patients had deficits in the occipital region. Comparison of dementia groups (height threshold of P < or = 0.01 uncorrected) yielded hypoperfusion in both the parietal [Brodmann area (BA) 7] and occipital (BA 17, 18) regions of the brain in DLB compared with AD. Abnormalities in these areas, which included visual cortex and several areas involved in higher visual processing and visuospatial function, may be important in understanding the visual hallucinations and visuospatial deficits which are characteristic of DLB. Covariate analysis indicated group differences between AD and DLB in terms of a positive correlation between cognitive test score and temporoparietal blood flow. In conclusion, we found evidence of frontal and parietal hypoperfusion in both AD and DLB, while temporal perfusion deficits were observed exclusively in AD and parieto-occipital deficits in DLB.

  1. Exercise for Individuals with Lewy Body Dementia: A Systematic Review

    PubMed Central

    Inskip, Michael; Mavros, Yorgi; Sachdev, Perminder S.; Fiatarone Singh, Maria A.

    2016-01-01

    Background Individuals with Lewy body Dementia (LBD), which encompasses both Parkinson disease dementia (PDD) and Dementia with Lewy Bodies (DLB) experience functional decline through Parkinsonism and sedentariness exacerbated by motor, psychiatric and cognitive symptoms. Exercise may improve functional outcomes in Parkinson’s disease (PD), and Alzheimer’s disease (AD). However, the multi-domain nature of the LBD cluster of symptoms (physical, cognitive, psychiatric, autonomic) results in vulnerable individuals often being excluded from exercise studies evaluating physical function in PD or cognitive function in dementia to avoid confounding results. This review evaluated existing literature reporting the effects of exercise interventions or physical activity (PA) exposure on cluster symptoms in LBD. Methods A high-sensitivity search was executed across 19 databases. Full-length articles of any language and quality, published or unpublished, that analysed effects of isolated exercise/physical activity on indicative Dementia with Lewy Bodies or PD-dementia cohorts were evaluated for outcomes inclusive of physical, cognitive, psychiatric, physiological and quality of life measures. The protocol for this review (Reg. #: CRD42015019002) is accessible at http://www.crd.york.ac.uk/PROSPERO/. Results 111,485 articles were initially retrieved; 288 full articles were reviewed and 89.6% subsequently deemed ineligible due to exclusion of participants with co-existence of dementia and Parkinsonism. Five studies (1 uncontrolled trial, 1 randomized controlled trial and 3 case reports) evaluating 16 participants were included. Interventions were diverse and outcome homogeneity was low. Habitual gait speed outcomes were measured in 13 participants and increased (0.18m/s, 95% CI -0.02, 0.38m/s), exceeding moderate important change (0.14m/s) for PD cohorts. Other outcomes appeared to improve modestly in most participants. Discussion Scarce research investigating exercise in LBD

  2. Association of Glucocerebrosidase Mutations With Dementia With Lewy Bodies

    PubMed Central

    Clark, Lorraine N.; Kartsaklis, Lykourgos A.; Wolf Gilbert, Rebecca; Dorado, Beatriz; Ross, Barbara M.; Kisselev, Sergey; Verbitsky, Miguel; Mejia-Santana, Helen; Cote, Lucien J.; Andrews, Howard; Vonsattel, Jean-Paul; Fahn, Stanley; Mayeux, Richard; Honig, Lawrence S.; Marder, Karen

    2009-01-01

    Background Mutations in the glucocerebrosidase (GBA) gene are associated with Lewy body (LB) disorders. Objective To determine the relationship of GBA mutations and APOE4 genotype to LB and Alzheimer disease (AD) pathological findings. Design Case-control study. Setting Academic research. Participants The 187 subjects included patients with primary neuropathological diagnoses of LB disorders with or without AD changes (95 cases), randomly selected patients with AD (without significant LB pathological findings; 60 cases), and controls with neither LB nor AD pathological findings (32 cases). Main Outcome Measures GBA mutation status, APOE4 genotype, LB pathological findings (assessed according to the third report of the Dementia With Lewy Body Consortium), and Alzheimer plaque and tangle pathological findings (rated by criteria of Braak and Braak, the Consortium to Establish a Registry for Alzheimer Disease, and the National Institute on Aging–Reagan Institute). Results GBA mutations were found in 18% (34 of 187) of all subjects, including 28% (27 of 95) of those with primary LB pathological findings compared with 10% (6 of 60) of those with AD pathological findings and 3% (1 of 32) of those without AD or LB pathological findings (P=.001). GBA mutation status was significantly associated with the presence of cortical LBs (odds ratio, 6.48; 95% confidence interval, 2.45–17.16; P<.001), after adjusting for sex, age at death, and presence of APOE4. GBA mutation carriers were significantly less likely to meet AD pathological diagnostic (National Institute on Aging–Reagan Institute intermediate or high likelihood) criteria (odds ratio, 0.35; 95% confidence interval, 0.15–0.79; P=.01) after adjustment for sex, age at death, and APOE4. Conclusion GBA mutations may be associated with pathologically “purer” LB disorders, characterized by more extensive (cortical) LB, and less severe AD pathological findings and may be a useful marker for LB disorders. PMID

  3. Dementia With Lewy Bodies: Diagnosis and Management for Primary Care Providers

    PubMed Central

    Mahajan, Aman; Handa, Kamna

    2011-01-01

    Objective: The purpose of this review is to aid primary care providers in distinguishing dementia with Lewy bodies (DLB) from Alzheimer's disease and from Parkinson's disease with dementia. Differentiating these entities has important treatment implications. Data Sources: A PubMed search was undertaken using the keywords Lewy body dementia, dementia with Lewy bodies, and Lewy body disease. There were no date restrictions. Only articles in the English language were reviewed. References of selected articles were reviewed for additional sources. Data Selection and Extraction: Initially, 2,967 articles were retrieved. All 3 authors participated in data selection and extraction. Articles were further selected for content specific to epidemiology, clinical presentation, diagnostic studies, treatment, and prognosis. For articles with repetitive information, the most current article was used. This resulted in a total of 62 articles included in the review. Data Synthesis: Dementia with Lewy bodies is the second leading cause of dementia after Alzheimer's disease. The core symptoms of DLB, including cognitive fluctuations, visual hallucinations, and parkinsonism, may not always be present as a triad, and clinicians may be unaware of associated symptoms. Thus, this diagnosis is frequently missed by primary care providers. Often, DLB is misdiagnosed as Alzheimer's disease, Parkinson's disease, or a primary psychiatric illness. Treatments for DLB include cholinesterase inhibitors and N-methyl-D-aspartate antagonists. Antipsychotics should be avoided or used with caution. Conclusions: Dementia with Lewy bodies is an often missed diagnosis. Symptoms are often attributed to other disorders. A high clinical suspicion is helpful in accurate diagnosis, and presence of any of the core symptoms should initiate clinical suspicion of DLB. Distinguishing DLB from other disorders has important treatment implications. PMID:22295275

  4. Metabolic connectomics targeting brain pathology in dementia with Lewy bodies.

    PubMed

    Caminiti, Silvia P; Tettamanti, Marco; Sala, Arianna; Presotto, Luca; Iannaccone, Sandro; Cappa, Stefano F; Magnani, Giuseppe; Perani, Daniela

    2017-04-01

    Dementia with Lewy bodies is characterized by α-synuclein accumulation and degeneration of dopaminergic and cholinergic pathways. To gain an overview of brain systems affected by neurodegeneration, we characterized the [18F]FDG-PET metabolic connectivity in 42 dementia with Lewy bodies patients, as compared to 42 healthy controls, using sparse inverse covariance estimation method and graph theory. We performed whole-brain and anatomically driven analyses, targeting cholinergic and dopaminergic pathways, and the α-synuclein spreading. The first revealed substantial alterations in connectivity indexes, brain modularity, and hubs configuration. Namely, decreases in local metabolic connectivity within occipital cortex, thalamus, and cerebellum, and increases within frontal, temporal, parietal, and basal ganglia regions. There were also long-range disconnections among these brain regions, all supporting a disruption of the functional hierarchy characterizing the normal brain. The anatomically driven analysis revealed alterations within brain structures early affected by α-synuclein pathology, supporting Braak's early pathological staging in dementia with Lewy bodies. The dopaminergic striato-cortical pathway was severely affected, as well as the cholinergic networks, with an extensive decrease in connectivity in Ch1-Ch2, Ch5-Ch6 networks, and the lateral Ch4 capsular network significantly towards the occipital cortex. These altered patterns of metabolic connectivity unveil a new in vivo scenario for dementia with Lewy bodies underlying pathology in terms of changes in whole-brain metabolic connectivity, spreading of α-synuclein, and neurotransmission impairment.

  5. Amyloid-β deposition and regional grey matter atrophy rates in dementia with Lewy bodies.

    PubMed

    Sarro, Lidia; Senjem, Matthew L; Lundt, Emily S; Przybelski, Scott A; Lesnick, Timothy G; Graff-Radford, Jonathan; Boeve, Bradley F; Lowe, Val J; Ferman, Tanis J; Knopman, David S; Comi, Giancarlo; Filippi, Massimo; Petersen, Ronald C; Jack, Clifford R; Kantarci, Kejal

    2016-10-01

    Alzheimer's disease pathology frequently coexists with Lewy body disease at autopsy in patients with probable dementia with Lewy bodies. More than half of patients with probable dementia with Lewy bodies have high amyloid-β deposition as measured with (11)C-Pittsburgh compound B binding on positron emission tomography. Biomarkers of amyloid-β deposition precede neurodegeneration on magnetic resonance imaging during the progression of Alzheimer's disease, but little is known about how amyloid-β deposition relates to longitudinal progression of atrophy in patients with probable dementia with Lewy bodies. We investigated the associations between baseline (11)C-Pittsburgh compound B binding on positron emission tomography and the longitudinal rates of grey matter atrophy in a cohort of clinically diagnosed patients with dementia with Lewy bodies (n = 20), who were consecutively recruited to the Mayo Clinic Alzheimer's Disease Research Centre. All patients underwent (11)C-Pittsburgh compound B positron emission tomography and magnetic resonance imaging examinations at baseline. Follow-up magnetic resonance imaging was performed after a mean (standard deviation) interval of 2.5 (1.1) years. Regional grey matter loss was determined on three-dimensional T1-weighted magnetic resonance imaging with the tensor-based morphometry-symmetric normalization technique. Linear regression was performed between baseline (11)C-Pittsburgh compound B standard unit value ratio and longitudinal change in regional grey matter volumes from an in-house modified atlas. We identified significant associations between greater baseline (11)C-Pittsburgh compound B standard unit value ratio and greater grey matter loss over time in the posterior cingulate gyrus, lateral and medial temporal lobe, and occipital lobe as well as caudate and putamen nuclei, after adjusting for age (P < 0.05). Greater baseline (11)C-Pittsburgh compound B standard unit value ratio was also associated with greater

  6. LEWY BODY DEMENTIA: CAREGIVER BURDEN AND UNMET NEEDS

    PubMed Central

    Galvin, James E.; Duda, John E.; Kaufer, Daniel I.; Lippa, Carol F.; Taylor, Angela; Zarit, Steven H.

    2010-01-01

    Lewy body dementia (LBD) is a common cause of dementia but to date, little is known about caregiver burden. The Lewy Body Dementia Association (www.LBDA.org) conducted a web-based survey of 962 caregivers (mean age 56y; 88% women). The most common initial symptoms were cognitive (48%), motor (39%), or both (13%). Caregivers expressed concerns about fear of future (77%), feeling stressed (54%), loss of social life (52%) and uncertainty about what to do next (50%). Caregivers reported moderate to severe burden; 80% felt the people around them did not understand their burden and 54% reported feelings of isolation with spousal caregivers reporting more burden than non-spousal caregivers. Only 29% hired in-home assistance while less than 40% used respite or adult day care, geriatric case managers or attended a support group meeting. Lack of service utilization occurred despite two-thirds of caregivers reporting medical crises requiring emergency services, psychiatric care or law enforcement. Caregivers reported preferences for web-based information, directories of LBD expert providers, information on LBD research and location of local support groups. These findings highlight significant unmet needs for LBD caregivers and provide targets for intervention to reduce caregiver burden. Community resources such as the Lewy Body Dementia Association may serve this end, while also providing practical information and support for caregivers. PMID:20505434

  7. Endothelin-converting enzymes degrade α-synuclein and are reduced in dementia with Lewy bodies.

    PubMed

    Miners, J Scott; Love, Seth

    2017-02-07

    We have examined the roles of the endothelin-converting enzyme-1 and -2 (ECE-1 and ECE-2) in the homeostasis of α-synuclein (α-syn) and pathogenesis of Lewy body disease. The ECEs are named for their ability to convert inactive big endothelin to the vasoactive peptide endothelin-1 (EDN1). We have found that ECE-1 and ECE-2 cleave and degrade α-syn in vitro and siRNA-mediated knockdown of ECE-1 and ECE-2 in SH-SY5Y neuroblastoma cells significantly increased α-syn both intracellularly (within the cell lysate) (P < 0.05 for both ECE-1 and -2) and extracellularly (in the surrounding medium) (P < 0.05 for ECE-1 and P = 0.07 for ECE-2). Double immunofluorescent labelling showed co-localisation of ECE-1 and ECE-2 with α-syn within the endolysosomal system (confirmed by a proximity ligation assay). To assess the possible relevance of these findings to human Lewy body disease, we measured ECE-1 and ECE-2 levels by sandwich ELISA in post-mortem samples of cingulate cortex (a region with a predilection for Lewy body pathology) in dementia with Lewy bodies (DLB) and age-matched controls. ECE-1 (P < 0.001) and ECE-2 (P < 0.01) levels were significantly reduced in DLB and both enzymes correlated inversely with the severity of Lewy body pathology as indicated by the level of α-syn phosphorylated at Ser129 (r = -0.54, P < 0.01 for ECE-1 and r = -0.49, P < 0.05 for ECE-2). Our novel findings suggest a role for ECEs in the metabolism of α-syn that could contribute to the development and progression of DLB. This article is protected by copyright. All rights reserved.

  8. Hippocampal α-Synuclein in Dementia with Lewy Bodies Contributes to Memory Impairment and Is Consistent with Spread of Pathology.

    PubMed

    Adamowicz, David H; Roy, Subhojit; Salmon, David P; Galasko, Douglas R; Hansen, Lawrence A; Masliah, Eliezer; Gage, Fred H

    2017-02-15

    Despite considerable research to uncover them, the anatomic and neuropathologic correlates of memory impairment in dementia with Lewy bodies (DLB) remain unclear. While some studies have implicated Lewy bodies in the neocortex, others have pointed to α-synuclein pathology in the hippocampus. We systematically examined hippocampal Lewy pathology and its distribution in hippocampal subfields in 95 clinically and neuropathologically characterized human cases of DLB, finding that α-synuclein pathology was highest in two hippocampal-related subregions: the CA2 subfield and the entorhinal cortex (EC). While the EC had numerous classic somatic Lewy bodies, CA2 contained mainly Lewy neurites in presumed axon terminals, suggesting the involvement of the EC → CA2 circuitry in the pathogenesis of DLB symptoms. Clinicopathological correlations with measures of verbal and visual memory supported a role for EC Lewy pathology, but not CA2, in causing these memory deficits. Lewy pathology in CA1-the main output region for CA2-correlated best with results from memory testing despite a milder pathology. This result indicates that CA1 may be more functionally relevant than CA2 in the context of memory impairment in DLB. These correlations remained significant after controlling for several factors, including concurrent Alzheimer's pathology (neuritic plaques and neurofibrillary tangles) and the interval between time of testing and time of death. Our data suggest that although hippocampal Lewy pathology in DLB is predominant in CA2 and EC, memory performance correlates most strongly with CA1 burden.SIGNIFICANCE STATEMENT This study provides a detailed neuropathologic analysis of hippocampal Lewy pathology in human patients with autopsy-confirmed dementia with Lewy bodies. The approach-informed by regional molecular markers, concurrent Alzheimer's pathology analysis, and relevant clinical data-helps tease out the relative contribution of Lewy pathology to memory dysfunction in the

  9. Reduced ubiquitin C-terminal hydrolase-1 expression levels in dementia with Lewy bodies.

    PubMed

    Barrachina, Marta; Castaño, Esther; Dalfó, Esther; Maes, Tamara; Buesa, Carlos; Ferrer, Isidro

    2006-05-01

    Parkinson disease (PD) and dementia with Lewy bodies (DLB) are characterized by the accumulation of abnormal alpha-synuclein and ubiquitin in protein aggregates conforming Lewy bodies and Lewy neurites. Ubiquitin C-terminal hydrolase-1 (UCHL-1) disassembles polyubiquitin chains to increase the availability of free monomeric ubiquitin to the ubiquitin proteasome system (UPS) thus favoring protein degradation. Since mutations in the UCHL-1 gene, reducing UPS activity by 50%, have been reported in autosomal dominant PD, and UCHL-1 inhibition results in the formation of alpha-synuclein aggregates in mesencephalic cultured neurons, the present study was initiated to test UCHL-1 mRNA and protein levels in post-mortem frontal cortex (area 8) of PD and DLB cases, compared with age-matched controls. TaqMan PCR assays, and Western blots demonstrated down-regulation of UCHL-1 mRNA and UCHL-1 protein in the cerebral cortex in DLB (either in pure forms, not associated with Alzheimer disease: AD, and in common forms, with accompanying AD changes), but not in PD, when compared with age-matched controls. Interestingly, UCHL-1 mRNA and protein expressions were reduced in the medulla oblongata in the same PD cases. Moreover, UCHL-1 protein was decreased in the substantia nigra in cases with Lewy body pathology. UCHL-1 down-regulation was not associated with reduced protein levels of several proteasomal subunits, including 20SX, 20SY, 19S and 11Salpha. Yet UCHL-3 expression was reduced in the cerebral cortex of PD and DLB patients. Together, these observations show reduced UCHL-1 expression as a contributory factor in the abnormal protein aggregation in DLB, and points UCHL-1 as a putative therapeutic target in the treatment of DLB.

  10. A Multicenter Study of Glucocerebrosidase Mutations in Dementia With Lewy Bodies

    PubMed Central

    Nalls, Michael A.; Duran, Raquel; Lopez, Grisel; Kurzawa-Akanbi, Marzena; McKeith, Ian G.; Chinnery, Patrick F.; Morris, Christopher M.; Theuns, Jessie; Crosiers, David; Cras, Patrick; Engelborghs, Sebastiaan; De Deyn, Peter Paul; Van Broeckhoven, Christine; Mann, David M. A.; Snowden, Julie; Pickering-Brown, Stuart; Halliwell, Nicola; Davidson, Yvonne; Gibbons, Linda; Harris, Jenny; Sheerin, Una-Marie; Bras, Jose; Hardy, John; Clark, Lorraine; Marder, Karen; Honig, Lawrence S.; Berg, Daniela; Maetzler, Walter; Brockmann, Kathrin; Gasser, Thomas; Novellino, Fabiana; Quattrone, Aldo; Annesi, Grazia; De Marco, Elvira Valeria; Rogaeva, Ekaterina; Masellis, Mario; Black, Sandra E.; Bilbao, Juan M.; Foroud, Tatiana; Ghetti, Bernardino; Nichols, William C.; Pankratz, Nathan; Halliday, Glenda; Lesage, Suzanne; Klebe, Stephan; Durr, Alexandra; Duyckaerts, Charles; Brice, Alexis; Giasson, Benoit I.; Trojanowski, John Q.; Hurtig, Howard I.; Tayebi, Nahid; Landazabal, Claudia; Knight, Melanie A.; Keller, Margaux; Singleton, Andrew B.; Wolfsberg, Tyra G.; Sidransky, Ellen

    2013-01-01

    Importance While mutations in glucocerebrosidase (GBA1) are associated with an increased risk for Parkinson disease (PD), it is important to establish whether such mutations are also a common risk factor for other Lewy body disorders. Objective To establish whether GBA1 mutations are a risk factor for dementia with Lewy bodies (DLB). Design We compared genotype data on patients and controls from 11 centers. Data concerning demographics, age at onset, disease duration, and clinical and pathological features were collected when available. We conducted pooled analyses using logistic regression to investigate GBA1 mutation carrier status as predicting DLB or PD with dementia status, using common control subjects as a reference group. Random-effects meta-analyses were conducted to account for additional heterogeneity. Setting Eleven centers from sites around the world performing genotyping. Participants Seven hundred twenty-one cases met diagnostic criteria for DLB and 151 had PD with dementia. We compared these cases with 1962 controls from the same centers matched for age, sex, and ethnicity. Main Outcome Measures Frequency of GBA1 mutations in cases and controls. Results We found a significant association between GBA1 mutation carrier status and DLB, with an odds ratio of 8.28 (95% CI, 4.78–14.88). The odds ratio for PD with dementia was 6.48 (95% CI, 2.53–15.37). The mean age at diagnosis of DLB was earlier in GBA1 mutation carriers than in noncarriers (63.5 vs 68.9 years; P<.001), with higher disease severity scores. Conclusions and Relevance Mutations in GBA1 are a significant risk factor for DLB. GBA1 mutations likely play an even larger role in the genetic etiology of DLB than in PD, providing insight into the role of glucocerebrosidase in Lewy body disease. PMID:23588557

  11. Exogenous α-Synuclein Fibrils Induce Lewy Body Pathology Leading to Synaptic Dysfunction and Neuron Death

    PubMed Central

    Volpicelli-Daley, Laura A.; Luk, Kelvin C.; Patel, Tapan P.; Tanik, Selcuk A.; Riddle, Dawn M.; Stieber, Anna; Meany, David F.; Trojanowski, John Q.; Lee, Virginia M.-Y.

    2011-01-01

    Summary Inclusions comprised of α-synuclein (α-syn), i.e. Lewy bodies (LBs) and Lewy neurites (LNs), define synucleinopathies including Parkinson’s Disease (PD) and dementia with Lewy Bodies (DLB). Here, we demonstrate that pre-formed fibrils generated from full length and truncated recombinant α-syn enter primary neurons, likely by adsorptive-mediated endocytosis and promote recruitment of soluble endogenous α-syn into insoluble PD-like LBs and LNs. Remarkably, endogenous α-syn was sufficient for formation of these aggregates, and overexpression of wild type or mutant α-syn was not required. LN-like pathology first developed in axons and propagated to form LB-like inclusions in perikarya. Accumulation of pathologic α-syn led to selective decreases in synaptic proteins, progressive impairments in neuronal excitability and connectivity, and eventually, neuron death. Thus, our data contribute important insights into the etiology and pathogenesis of PD-like α-syn inclusions, their impact on neuronal functions, and provide a model for discovering therapeutics targeting pathologic α-syn- mediated neurodegeneration. PMID:21982369

  12. Alcohol consumption, Lewis phenotypes, and risk of ischemic heart disease

    SciTech Connect

    Hein, H.O.; Suadicani, P.; Gyntelberg, F. . Epidemiological Research Unit); Sorenson, H. . Dept. of Chemical Immunology); Hein, H.O. . Dept. of Internal Medicine)

    1993-02-13

    The authors have previously found an increased risk of ischemic heart disease (IHD) in men with the Lewis phenotype Le(a[minus]b[minus]) and suggested that the Lewis blood group has a close genetic relation with insulin resistance. The authors have investigated whether any conventional risk factors explain the increased risk in Le(a[minus]b[minus]) men. 3,383 men aged 53-75 years were examined in 1985-86, and morbidity and mortality during the next 4 years were recorded. At baseline, the authors excluded 343 men with a history of myocardial infarction, angina pectoris, intermittent claudication, or stroke. The potential risk factors examined were alcohol consumption, physical activity, tobacco smoking, serum cotinine, serum lipids, body-mass index, blood pressure, prevalence of hypertension and non-insulin-dependent diabetes mellitus, and social class. In 280 (9.6%) men with Le(a[minus]b[minus]), alcohol was the only risk factor significantly associated with risk of IHD. There was a significant inverse dose-effect relation between alcohol consumption and risk; trend tests, with adjustment for age, were significant for fatal IHD (p=0.02), all IHD (p=0.03), and all causes of death (p=0.02). In 2649 (90.4%) men with other phenotypes, there was a limited negative association with alcohol consumption. In Le(a[minus]b[minus]) men, a group genetically at high risk of IHD, alcohol consumption seems to be especially protective. The authors suggest that alcohol consumption may modify insulin resistance in Le(a[minus]b[minus]) men.

  13. Predictors of survival in dementia with lewy bodies and Parkinson dementia.

    PubMed

    Jellinger, Kurt A; Wenning, Gregor K; Seppi, Klaus

    2007-01-01

    Retrospective analysis of 243 autopsy-confirmed cases of dementia with Lewy bodies (DLB) and Parkinson disease with dementia (PDD) showed an average age at symptom onset of 67 years and a median survival of 5 years from symptom onset. Older age at onset, fluctuating cognition, and hallucinations at onset predicted shorter survival; initial parkinsonism with delayed dementia significantly improved survival. Associated Alzheimer pathology also shortened survival. When adjusted for age, gender, and Alzheimer pathology, fluctuating dementia at symptom onset was identified as best predictor of poor outcome.

  14. Clinical and neuroimaging characteristics of Chinese dementia with Lewy bodies

    PubMed Central

    Wang, Ying; Shi, Zhihong; Cai, Li; Liu, Shuling; Han, Tong; Zhou, Yuying; Wang, Xinping; Gao, Shuo; Ji, Yong

    2017-01-01

    Dementia with Lewy bodies (DLB) is the second most common subtype of degenerative dementia. To our knowledge, available information about the clinical features of DLB in China remains limited. Our study therefore aimed to address this issue. Thirty-seven Chinese patients with probable DLB were recruited for this study. All subjects underwent neuropsychological assessment by trained neurologists, as well as undergoing MRI, 11C-PIB PET scans for Aβ deposition and 18F-FDG PET scans for regional cerebral glucose metabolism. Our results showed that the gender ratio of patients was 16:21 (F:M). The mean age of onset was 69.5 ± 9.0 years and the mean age at diagnosis was 71.8 ± 9.1 years. At diagnosis, the prevalence of three core clinical features of DLB was: 64.9% for fluctuating cognition, 73.0% for visual hallucinations and 62.2% for parkinsonism. The result from 11C-PiB PET and 18F-FDG PET scans confirmed Aβ deposition in the cortex and demonstrated hypometabolism in the bilateral temporoparietooccipital region, the frontal lobe, the insular lobe, and the posterior cingulate, precuneus and caudate nuclei. Our study elucidated the clinical features of Chinese DLB patients, and will improve the understanding and the early diagnosis of DLB in Chinese patients. PMID:28253276

  15. Dynamin1 concentration in the prefrontal cortex is associated with cognitive impairment in Lewy body dementia.

    PubMed

    Vallortigara, Julie; Rangarajan, Sindhoo; Whitfield, David; Alghamdi, Amani; Howlett, David; Hortobágyi, Tibor; Johnson, Mary; Attems, Johannes; Ballard, Clive; Thomas, Alan; O'Brien, John; Aarsland, Dag; Francis, Paul

    2014-01-01

    Dementia with Lewy Bodies (DLB) and Parkinson's Disease Dementia (PDD) together, represent the second most common cause of dementia, after Alzheimer's disease (AD). The synaptic dysfunctions underlying the cognitive decline and psychiatric symptoms observed throughout the development of PDD and DLB are still under investigation. In this study we examined the expression level of Dynamin1 and phospho-CaMKII, key proteins of endocytosis and synaptic plasticity respectively, as potential markers of molecular processes specifically deregulated with DLB and/or PDD. In order to measure the levels of these proteins, we isolated grey matter from post-mortem prefrontal cortex area (BA9), anterior cingulated gyrus (BA24) and parietal cortex (BA40) from DLB and PDD patients in comparison to age-matched controls and a group of AD cases. Clinical and pathological data available included the MMSE score, neuropsychiatric history, and semi-quantitative scores for AD pathology (plaques - tangles) and for α-synuclein (Lewy bodies). Changes in the expression of the synaptic markers, and correlates with neuropathological features and cognitive decline were predominantly found in the prefrontal cortex. On one hand, levels of Dynamin1 were significantly reduced, and correlated with a higher rate of cognitive decline observed in cases from three dementia groups. On the other hand, the fraction of phospho-CaMKII was decreased, and correlated with a high score of plaques and tangles in BA9. Interestingly, the correlation between the rate of cognitive decline and the level of Dynamin1 remained when the analysis was restricted to the PDD and DLB cases, highlighting an association of Dynamin1 with cognitive decline in people with Lewy Body dementia.

  16. Is It Lewy Body Dementia or Something Else?

    MedlinePlus

    ... Options Join the fight against LBD! Donate Is It LBD or Something Else? Early and accurate diagnosis ... dementia with Lewy bodies’ (DLB). Symptoms that differentiate it from Alzheimer’s include unpredictable levels of cognitive ability, ...

  17. Validation of the Korean Version of the Lewy Body Composite Risk Score (K-LBCRS).

    PubMed

    Ryu, Hui Jin; Kim, Minyoung; Moon, Yeonsil; Choi, Yeji; Han, Jee-Young; Galvin, James E; Han, Seol-Heui

    2017-01-01

    The Lewy body composite risk score (LBCRS) is a useful clinical screening tool to help determine whether the dementia is related to Lewy body pathology. The purpose of this study is to verify reliability, validity, and diagnostic usefulness of Korean version of LBCRS (K-LBCRS). CDR-sum of boxes, Mini-Mental State Examination, and standardized scales related to cognition, mood, behavior, and motor function were administered to a total of 107 subjects, including 30 dementia with Lewy bodies (DLB), 54 Alzheimer's disease (AD), and 23 cognitively normal elderly people and their collateral informants. Internal consistency of the K-LBCRS was good with Cronbach's alpha of 0.85, and concurrent validity was also satisfactory, with K-LBCRS correlating highly with CDR-SB and other scales. The test-retest reliability was very high with a Pearson correlation coefficient of 0.97. The mean scores of K-LBCRS were significantly different among three groups, with DLB (6.2±2.4), AD (1.4±1.3), and controls (0.3±0.6). We identified a cut-off score of 3 as best to differentiate between DLB and AD, having AUC of 0.97 (95% CI 0.94-1.00), sensitivity 97%, specificity 83%, positive predictive value 76%, negative predictive value 98%, which is the same score suggested in the original study. This study shows K-LBCRS as a new useful screening tool for Korean DLB patients in clinical settings.

  18. Visual Hallucinations in PD and Lewy Body Dementias: Old and New Hypotheses

    PubMed Central

    Onofrj, M.; Taylor, J. P.; Monaco, D.; Franciotti, R.; Anzellotti, F.; Bonanni, L.; Onofrj, V.; Thomas, A.

    2013-01-01

    Visual Hallucinations (VH) are a common non-motor symptom of Parkinson’s Disease (PD) and the Lewy body dementias (LBD) of Parkinson's disease with dementia (PDD) and Dementia with Lewy Bodies (DLB). The origin of VH in PD and LBD is debated: earlier studies considered a number of different possible mechanisms underlying VH including visual disorders, Rapid Eye Movement (REM) Sleep Intrusions, dysfunctions of top down or bottom up visual pathways, and neurotransmitter imbalance. More recently newer hypotheses introduce, among the possible mechanisms of VH, the role of attention networks (ventral and dorsal) and of the Default Mode Network (DMN) a network that is inhibited during attentional tasks and becomes active during rest and self referential imagery. Persistent DMN activity during active tasks with dysfunctional imbalance of dorsal and ventral attentional networks represents a new hypothesis on the mechanism of VH. We review the different methods used to classify VH and discuss reports supporting or challenging the different hypothetical mechanisms of VH. PMID:23242366

  19. Narrative Organization Deficit in Lewy Body Disorders Is Related to Alzheimer Pathology

    PubMed Central

    Grossman, Murray; Irwin, David J.; Jester, Charles; Halpin, Amy; Ash, Sharon; Rascovsky, Katya; Weintraub, Daniel; McMillan, Corey T.

    2017-01-01

    Background: Day-to-day interactions depend on conversational narrative, and we examine here the neurobiological basis for difficulty organizing narrative discourse in patients with Lewy body disorders (LBD). Method: Narrative organization was examined in 56 non-aphasic LBD patients, including a non-demented cohort (n = 30) with Parkinson's disease (PD) or PD-Mild Cognitive Impairment PD-MCI,) and a cohort with mild dementia (n = 26) including PD-dementia (PDD) and dementia with Lewy bodies (DLB), with similar age and education but differing in MMSE (p < 0.001). We used a previously reported procedure that probes patients' judgments of the organization of brief, familiar narratives (e.g., going fishing, wrapping a present). A subgroup of 24 patients had MRI assessment of regional gray matter (GM) atrophy and cerebrospinal fluid (CSF) levels of biomarkers for Alzheimer's disease (AD) pathology, including beta amyloid (Aβ), total-tau (t-tau), and phosphorylated-tau (p-tau). Results: Mildly demented LBD patients had a significant deficit judging narratives compared to non-demented patients, but this deficit was not correlated with MMSE. Regression analyses instead related narrative organization to regions of frontal GM atrophy, and CSF levels of Aβ and t-tau associated with presumed AD pathology in these frontal regions. Conclusion: These findings are consistent with the hypothesis that CSF markers of AD pathology associated with frontal regions play a role in difficulty organizing narratives in LBD. PMID:28228714

  20. Function of α-synuclein and PINK1 in Lewy body dementia (Review).

    PubMed

    Minami, Akari; Nakanishi, Atsuko; Matsuda, Satoru; Kitagishi, Yasuko; Ogura, Yasunori

    2015-01-01

    α-Synuclein (α-syn) is the major protein component of Lewy bodies, a key pathological characteristic of the degenerating brain. The misfolding and aggregation of α-syn is associated with both the idiopathic and familial forms of Parkinson's disease (PD) and Lewy body dementia (LBD). However, the function of α-syn is poorly understood, as it shows both neurotoxic and neuroprotective activities. Mutations in phosphatase and tensin homologue-induced putative kinase 1 (PINK1) also cause recessively inherited PD. Studies support the notion of neuroprotective roles for PINK1, as it protects cells from damage-induced mitochondrial dysfunction, oxidative stress and cell apoptosis. PINK1 plays an essential role in mitochondrial quality control and its homeostasis is maintained through mitochondrial stabilization. The α-syn aggregation is linked to various aspects of mitochondrial dysfunction and PINK1-related mitophagy. Determination of the molecular pathways that lead to α-syn oligomerization and further aggregation may be the basis for the successful design and development of treatments for these neurodegenerative diseases. The present review summarizes the function of PINK1 underlying α-syn aggregation and the mechanisms through which mitochondrial dysfunction plays a role in this process.

  1. Description of microcolumnar ensembles in association cortex and their disruption in Alzheimer and Lewy body dementias

    PubMed Central

    Buldyrev, S. V.; Cruz, L.; Gomez-Isla, T.; Gomez-Tortosa, E.; Havlin, S.; Le, R.; Stanley, H. E.; Urbanc, B.; Hyman, B. T.

    2000-01-01

    The cortex of the brain is organized into clear horizontal layers, laminae, which subserve much of the connectional anatomy of the brain. We hypothesize that there is also a vertical anatomical organization that might subserve local interactions of neuronal functional units, in accord with longstanding electrophysiological observations. We develop and apply a general quantitative method, inspired by analogous methods in condensed matter physics, to examine the anatomical organization of the cortex in human brain. We find, in addition to obvious laminae, anatomical evidence for tightly packed microcolumnar ensembles containing approximately 11 neurons, with a periodicity of about 80 μm. We examine the structural integrity of this new architectural feature in two common dementing illnesses, Alzheimer disease and dementia with Lewy bodies. In Alzheimer disease, there is a dramatic, nearly complete loss of microcolumnar ensemble organization. The relative degree of loss of microcolumnar ensembles is directly proportional to the number of neurofibrillary tangles, but not related to the amount of amyloid-β deposition. In dementia with Lewy bodies, a similar disruption of microcolumnar ensemble architecture occurs despite minimal neuronal loss. These observations show that quantitative analysis of complex cortical architecture can be applied to analyze the anatomical basis of brain disorders. PMID:10805766

  2. Visuospatial deficits predict rate of cognitive decline in autopsy-verified dementia with Lewy bodies.

    PubMed

    Hamilton, Joanne M; Salmon, David P; Galasko, Douglas; Raman, Rema; Emond, Jenn; Hansen, Lawrence A; Masliah, Eliezer; Thal, Leon J

    2008-11-01

    Dementia with Lewy bodies (DLB) is often characterized by pronounced impairment in visuospatial skills, attention, and executive functions. However, the strength of the phenotypic expression of DLB varies and may be weaker in patients with extensive concomitant Alzheimer's disease (AD). To determine whether strength of the DLB clinical phenotype impacts cognitive decline, visuospatial and language tests were retrospectively used to predict 2-year rate of global cognitive decline in 22 autopsy-confirmed DLB patients (21 with concomitant AD) and 44 autopsy-confirmed "pure" AD patients. Generalized estimating equations (GEE) revealed a significant interaction such that poor baseline performances on tests of visuospatial skills were strongly associated with a rapid rate of cognitive decline in DLB but not AD (p < .001). No effect of confrontation naming was found. DLB patients with poor visuospatial skills had fewer neurofibrillary tangles and were more likely to experience visual hallucinations than those with better visuospatial skills. These results suggest that the severity of visuospatial deficits in DLB may identify those facing a particularly malignant disease course and may designate individuals whose clinical syndrome is impacted more by Lewy body formation than AD pathology.

  3. Rapid eye movement sleep behavior disorder and subtypes in autopsy-confirmed dementia with Lewy bodies.

    PubMed

    Dugger, Brittany N; Boeve, Bradley F; Murray, Melissa E; Parisi, Joseph E; Fujishiro, Hiroshige; Dickson, Dennis W; Ferman, Tanis J

    2012-01-01

    The purpose of this study was to determine whether dementia with Lewy bodies with and without probable rapid eye movement sleep behavior disorder differ clinically or pathologically. Patients with dementia with Lewy bodies (DLB) with probable rapid eye movement sleep behavior sleep disorder (n = 71) were compared with those without it (n = 19) on demographics, clinical variables (core features of dementia with Lewy bodies, dementia duration, rate of cognitive/motor changes), and pathologic indices (Lewy body distribution, neuritic plaque score, Braak neurofibrillary tangle stage). Individuals with probable rapid eye movement sleep behavior disorder were predominantly male (82% vs 47%) and had a shorter duration of dementia (mean, 8 vs 10 years), earlier onset of parkinsonism (mean, 2 vs 5 years), and earlier onset of visual hallucinations (mean, 3 vs 6 years). These patients also had a lower Braak neurofibrillary tangle stage (stage IV vs stage VI) and lower neuritic plaque scores (18% vs 85% frequency), but no difference in Lewy body distribution. When probable rapid eye movement sleep behavior disorder developed early (at or before dementia onset), the onset of parkinsonism and hallucinations was earlier and Braak neurofibrillary tangle stage was lower compared with those who developed the sleep disorder after dementia onset. Women with autopsy-confirmed DLB without a history of dream enactment behavior during sleep had a later onset of hallucinations and parkinsonism and a higher Braak NFT stage. Probable rapid eye movement sleep behavior disorder is associated with distinct clinical and pathologic characteristics of dementia with Lewy bodies.

  4. The Organization and Anatomy of Narrative Comprehension and Expression in Lewy Body Spectrum Disorders

    PubMed Central

    Ash, Sharon; Xie, Sharon; Gross, Rachel Goldmann; Dreyfuss, Michael; Boller, Ashley; Camp, Emily; Morgan, Brianna; O’Shea, Jessica; Grossman, Murray

    2012-01-01

    Objective Patients with Lewy body spectrum disorders (LBSD) such as Parkinson’s disease (PD), Parkinson’s disease with dementia (PDD), and dementia with Lewy bodies (DLB) exhibit deficits in both narrative comprehension and narrative expression. The present research examines the hypothesis that these impairments are due to a material-neutral deficit in organizational executive resources rather than to impairments of language per se. We predicted that comprehension and expression of narrative would be similarly affected and that deficits in both expression and comprehension of narrative would be related to the same anatomic distribution of prefrontal disease. Method We examined 29 LBSD patients and 26 healthy seniors on their comprehension and expression of narrative discourse. For comprehension, we measured accuracy and latency in judging events with high and low associativity from familiar scripts such as “going fishing.” The expression task involved maintaining the connectedness of events while narrating a story from a wordless picture book. Results LBSD patients were impaired on measures of narrative organization during both comprehension and expression relative to healthy seniors. Measures of organization during narrative expression and comprehension were significantly correlated with each other. These measures both correlated with executive measures but not with neuropsychological measures of lexical semantics or grammar. Voxel-based morphometry revealed overlapping regressions relating frontal atrophy to narrative comprehension, narrative expression, and measures of executive control. Conclusions Difficulty with narrative discourse in LBSD stems in part from a deficit of organization common to comprehension and expression. This deficit is related to prefrontal cortical atrophy in LBSD. PMID:22309984

  5. Pathological α-synuclein Distribution in Subjects with Coincident Alzheimer’s and Lewy Body Pathology

    PubMed Central

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

    2016-01-01

    We investigated the distribution patterns of Lewy body related pathology (LRP) and the effect of coincident Alzheimer disease (AD) pathology using a data-driven clustering approach that identified groups with different LRP pathology distributions without any diagnostic or researcher’s input in two cohorts including: Parkinson disease patients without (PD, n=141) and with AD (PD-AD, n=80), dementia with Lewy bodies subjects without AD (DLB, n=13) and demented subjects with AD and LRP pathology (Dem-AD-LB, n=308). This latter group presented two LRP patterns, olfactory-amygdala and limbic LRP with negligible brainstem pathology, that were absent in the PD groups, are not currently included in the DLB staging system and lacked extracranial LRP as opposed to the PD group. The Dem-AD-LB individuals showed relative preservation of substantia nigra cells and dopamine active transporter in putamen. PD cases with AD pathology showed increased LRP. The cluster with occipital LRP was associated with non-AD type dementia clinical diagnosis in the Dem-AD-LB group and a faster progression to dementia in the PD groups. We found that 1) LRP pathology in Dem-AD-LB shows a distribution that differs from PD, without significant brainstem or extracranial LRP in initial phases, 2) coincident AD pathology is associated with increased LRP in PD indicating an interaction, 3) LRP and coincident AD pathology independently predict progression to dementia in PD, and 4) evaluation of LRP needs to acknowledge different LRP spreading patterns and evaluate substantia nigra integrity in the neuropathological assessment and consider the implications of neuropathological heterogeneity for clinical and biomarker characterization. PMID:26721587

  6. Stress and Burden among Caregivers of Patients with Lewy Body Dementia

    ERIC Educational Resources Information Center

    Leggett, Amanda N.; Zarit, Steven; Taylor, Angela; Galvin, James E.

    2011-01-01

    Purpose: Patients with Lewy body dementia (LBD) may present a unique set of symptoms and challenges to family caregivers compared with other types of dementia. Prominent difficulties include motor impairment, activities of daily living (ADLs) disability, recurrent behavioral and emotional problems (BEPs), and diagnostic difficulties. These…

  7. "PINK1"-Linked Parkinsonism Is Associated with Lewy Body Pathology

    ERIC Educational Resources Information Center

    Samaranch, Lluis; Lorenzo-Betancor, Oswaldo; Arbelo, Jose M.; Ferrer, Isidre; Lorenzo, Elena; Irigoyen, Jaione; Pastor, Maria A.; Marrero, Carmen; Isla, Concepcion; Herrera-Henriquez, Joanna; Pastor, Pau

    2010-01-01

    Phosphatase and tensin homolog-induced putative kinase 1 gene mutations have been associated with autosomal recessive early-onset Parkinson's disease. To date, no neuropathological reports have been published from patients with Parkinson's disease with both phosphatase and tensin homolog-induced putative kinase 1 gene copies mutated. We analysed…

  8. Brain tissue damage in dementia with Lewy bodies: an in vivo diffusion tensor MRI study.

    PubMed

    Bozzali, M; Falini, A; Cercignani, M; Baglio, F; Farina, E; Alberoni, M; Vezzulli, P; Olivotto, F; Mantovani, F; Shallice, T; Scotti, G; Canal, N; Nemni, R

    2005-07-01

    The aim of the present study was to apply diffusion tensor MRI (DT-MRI), a quantitative MRI measure which reflects tissue organization, to dementia with Lewy bodies (DLB). DT-MRI scans were obtained from 15 patients with probable DLB and 10 sex- and age-matched healthy controls. Abnormalities were found in the corpus callosum, pericallosal areas and the frontal, parietal, occipital and, less prominently, temporal white matter of patients compared with controls. Abnormalities were also found in the caudate nucleus and the putamen. The average grey matter volume was lower in patients than in controls. These findings of concomitant grey matter atrophy and white matter abnormalities (as detected by DT-MRI) in regions with a high prevalence of long connecting fibre tracts might suggest the presence of neurodegeneration involving associative cortices. The modest involvement of the temporal lobe fits with the relative preservation of global neuropsychological measures and memory tasks in the early stage of DLB. The selective involvement of parietal, frontal and occipital lobes might explain some of the clinical and neuropsychological features of DLB, providing a possible distinctive marker for this disease. The abnormalities found in the subcortical grey matter may indicate that DLB and Parkinson's disease share a similar nigrostriatal involvement caused by common pathophysiological mechanisms.

  9. Analysis of C9orf72 repeat expansions in a large international cohort of dementia with Lewy bodies.

    PubMed

    Kun-Rodrigues, Celia; Ross, Owen A; Orme, Tatiana; Shepherd, Claire; Parkkinen, Laura; Darwent, Lee; Hernandez, Dena; Ansorge, Olaf; Clark, Lorraine N; Honig, Lawrence S; Marder, Karen; Lemstra, Afina; Scheltens, Philippe; van der Flier, Wiesje; Louwersheimer, Eva; Holstege, Henne; Rogaeva, Ekaterina; St George-Hyslop, Peter; Londos, Elisabet; Zetterberg, Henrik; Barber, Imelda; Braae, Anne; Brown, Kristelle; Morgan, Kevin; Maetzler, Walter; Berg, Daniela; Troakes, Claire; Al-Sarraj, Safa; Lashley, Tammaryn; Holton, Janice; Compta, Yaroslau; Van Deerlin, Vivianna; Trojanowski, John Q; Serrano, Geidy E; Beach, Thomas G; Clarimon, Jordi; Lleó, Alberto; Morenas-Rodríguez, Estrella; Lesage, Suzanne; Galasko, Douglas; Masliah, Eliezer; Santana, Isabel; Diez, Monica; Pastor, Pau; Tienari, Pentti J; Myllykangas, Liisa; Oinas, Minna; Revesz, Tamas; Lees, Andrew; Boeve, Brad F; Petersen, Ronald C; Ferman, Tanis J; Escott-Price, Valentina; Graff-Radford, Neill; Cairns, Nigel J; Morris, John C; Stone, David J; Pickering-Brown, Stuart; Mann, David; Dickson, Dennis W; Halliday, Glenda M; Singleton, Andrew; Guerreiro, Rita; Bras, Jose

    2017-01-01

    C9orf72 repeat expansions are a common cause of amyotrophic lateral sclerosis and frontotemporal dementia. To date, no large-scale study of dementia with Lewy bodies (DLB) has been undertaken to assess the role of C9orf72 repeat expansions in the disease. Here, we investigated the prevalence of C9orf72 repeat expansions in a large cohort of DLB cases and identified no pathogenic repeat expansions in neuropathologically or clinically defined cases, showing that C9orf72 repeat expansions are not causally associated with DLB.

  10. Hallucinators find meaning in noises: pareidolic illusions in dementia with Lewy bodies.

    PubMed

    Yokoi, Kayoko; Nishio, Yoshiyuki; Uchiyama, Makoto; Shimomura, Tatsuo; Iizuka, Osamu; Mori, Etsuro

    2014-04-01

    By definition, visual illusions and hallucinations differ in whether the perceived objects exist in reality. A recent study challenged this dichotomy, in which pareidolias, a type of complex visual illusion involving ambiguous forms being perceived as meaningful objects, are very common and phenomenologically similar to visual hallucinations in dementia with Lewy bodies (DLB). We hypothesise that a common psychological mechanism exists between pareidolias and visual hallucinations in DLB that confers meaning upon meaningless visual information. Furthermore, we believe that these two types of visual misperceptions have a common underlying neural mechanism, namely, cholinergic insufficiency. The current study investigated pareidolic illusions using meaningless visual noise stimuli (the noise pareidolia test) in 34 patients with DLB, 34 patients with Alzheimer׳s disease and 28 healthy controls. Fifteen patients with DLB were administered the noise pareidolia test twice, before and after donepezil treatment. Three major findings were discovered: (1) DLB patients saw meaningful illusory images (pareidolias) in meaningless visual stimuli, (2) the number of pareidolic responses correlated with the severity of visual hallucinations, and (3) cholinergic enhancement reduced both the number of pareidolias and the severity of visual hallucinations in patients with DLB. These findings suggest that a common underlying psychological and neural mechanism exists between pareidolias and visual hallucinations in DLB.

  11. Cerebrospinal fluid total tau is associated with shorter survival in dementia with Lewy bodies.

    PubMed

    Boström, Fredrik; Hansson, Oskar; Blennow, Kaj; Gerhardsson, Lars; Lundh, Thomas; Minthon, Lennart; Zetterberg, Henrik; Londos, Elisabet

    2009-01-01

    A pathology typical of dementia with Lewy bodies (DLB) has been demonstrated to increase mortality to a greater extent than the pathology of Alzheimer's disease (AD). However, mortality in DLB has also been shown to increase with concomitant AD pathology. Furthermore, in a recent publication, we showed that there is a robust and specific increase in CSF calcium and magnesium in DLB patients compared to both AD patients and controls. Thus, in order to explore the influence of CSF AD markers and trace element concentrations on mortality in DLB, we undertook a longitudinal prospective study of 47 clinically diagnosed DLB patients and 157 AD patients as well as 49 healthy volunteers. Both AD and DLB patients showed an increased mortality compared to the healthy controls (relative risk: 10 and 8, respectively; p < 0.001). Increased levels of CSF total tau were associated with increased mortality among the DLB patients (p < 0.05), but not among the AD patients or controls. Gender, age, MMSE score, Abeta42 concentration and phosphorylated tau, and CSF trace element concentrations did not influence survival in the obtained models.

  12. Ligand autoradiographical quantification of histamine H3 receptor in human dementia with Lewy bodies.

    PubMed

    Lethbridge, Natasha L; Chazot, Paul L

    2016-11-01

    Dementia with Lewy bodies (DLB) is a serious age-dependent human neurodegenerative disease, with multiple debilitating symptoms, including dementia, psychosis and significant motor deficits, but with little or no effective treatments. This comparative ligand autoradiographical study has quantified histamine H3 receptors (H3R) in a series of major cortical and basal ganglia structures in human DLB and Alzheimer's (AD) post-mortem cases using the highly selective radioligand, [(3)H] GSK189254. In the main, the levels of H3 receptor were largely preserved in DLB cases when compared with aged-matched controls. However, we provide new evidence showing variable levels in the globus pallidus, and, moreover, raised levels of Pallidum H3 correlated with positive psychotic symptoms, in particular delusions and visual hallucinations, but not symptoms associated with depression. Furthermore, no correlation was detected for H3 receptor levels to MMSE or IUPRS symptom severity. This study suggests that H3R antagonists have scope for treating the psychotic symptomologies in DLB and other human brain disorders.

  13. Decision-Making Deficits Associated with Amyloidosis in Lewy Body Disorders

    PubMed Central

    Spotorno, Nicola; McMillan, Corey T.; Irwin, David J.; Clark, Robin; Lee, Edward B.; Trojanowski, John Q.; Weintraub, Daniel; Grossman, Murray

    2017-01-01

    Background: Lewy body disorders (LBD) are clinical syndromes characterized by pathological inclusions containing α-synuclein. Cognitive deficits are common or diagnostic in LBD, and may be associated with the presence of beta-amyloid (Aβ), which is a hallmark histopathologic abnormality characteristic of Alzheimer's disease (AD) that can also co-occur with LBD. Objective: In the present study we evaluated whether social decision-making difficulties in LBD are associated with Aβ burden. Methods: Decision-making abilities were measured with a simple, untimed, behavioral task previously validated in patients with behavioral variant frontotemporal dementia, and performance was related to gray matter atrophy on MRI. Aβ burden was assessed by examination of cerebrospinal fluid (CSF) level of Aβ1−42 and by autopsy confirmation in a subgroup of patients. Results: The results revealed that LBD patients with evidence of Aβ have reduced social decision-making abilities compared to patients with no evidence of Aβ. The imaging analysis related greater decision-making difficulty in Aβ-positive patients in respect to Aβ-negative patients to gray matter atrophy in medial orbitofrontal. This region is a critical node of a decision-making network as well as a region previously associated with comorbid α-synuclein and Aβ in LBD. Conclusions: These preliminary findings suggest that cognitive difficulties in LBD extend to include deficits in social decision-making and that this may be related to the presence of Aβ. PMID:28123364

  14. Bowel movement frequency in late-life and incidental Lewy bodies.

    PubMed

    Abbott, Robert D; Ross, G Webster; Petrovitch, Helen; Tanner, Caroline M; Davis, Daron G; Masaki, Kamal H; Launer, Lenore J; Curb, J David; White, Lon R

    2007-08-15

    It is not known if constipation is associated with the preclinical phase of Parkinson's disease (PD), often characterized by the presence of incidental Lewy bodies (ILB). Such an association could provide evidence that constipation is an early symptom of PD. The purpose of this report is to examine the association between late-life bowel movement frequency and ILB. Bowel movement frequency was assessed from 1991 to 1993 in 245 men aged 71 to 93 years in the Honolulu-Asia Aging Study who later received postmortem examinations. All were without clinical PD and dementia. Brains were examined for ILB in the substantia nigra and locus ceruleus. Among the decedents, 30 men had ILB (12.2%). After age-adjustment, the percent of brains with ILB declined with increasing bowel movement frequency (P=0.013). For men with <1, 1, and >1 bowel movement/day, corresponding percents were 24.1, 13.5, and 6.5%. Findings persisted after additional adjustment for time to death, mid-life pack-years of smoking and coffee intake, physical activity, and cognitive function. Infrequent bowel movements are associated with ILB. Findings provide evidence that constipation can predate the extrapyramidal signs of PD. Constipation could be one of the earliest markers of the beginning of PD processes.

  15. Preclinical Polymodal Hallucinations for 13 Years before Dementia with Lewy Bodies

    PubMed Central

    Abbate, Carlo; Trimarchi, Pietro Davide; Inglese, Silvia; Viti, Niccolò; Cantatore, Alessandra; De Agostini, Lisa; Pirri, Federico; Marino, Lorenza; Bagarolo, Renzo

    2014-01-01

    Objective. We describe a case of dementia with Lewy bodies (DLB) that presented long-lasting preclinical complex polymodal hallucinations. Background. Few studies have deeply investigated the characteristics of hallucinations in DLB, especially in the preclinical phase. Moreover, the clinical phenotype of mild cognitive impairment-(MCI-) DLB is poorly understood. Methods. The patient was followed for 4 years and a selective phenomenological and cognitive study was performed at the predementia stage. Results. The phenomenological study showed the presence of hypnagogic and hypnopompic hallucinations that allowed us to make a differential diagnosis between DLB and Charles Bonnet syndrome (CBS). The neuropsychological evaluation showed a multiple domain without amnesia MCI subtype with prefrontal dysexecutive, visuoperceptual, and visuospatial impairments and simultanagnosia, which has not previously been reported in MCI-DLB. Conclusions. This study extends the prognostic value of hallucinations for DLB to the preclinical phases. It supports and refines the MCI-DLB concept and identifies simultanagnosia as a possible early cognitive marker. Finally, it confirms an association between hallucinations and visuoperceptual impairments at an intermediate stage of the disease course and strongly supports the hypothesis that hallucinations in the earliest stages of DLB may reflect a narcolepsy-like REM-sleep disorder. PMID:24868122

  16. Dreaming and hallucinations - continuity or discontinuity? Perspectives from dementia with Lewy bodies.

    PubMed

    Collerton, Daniel; Perry, Elaine

    2011-12-01

    Comparing the phenomenology, neurochemical pathology, and psychopharmacology of hallucinations and dreaming is limited by the available data. Evidence to date reveals no simple correspondence between the two states. Differences in the phenomenology of visual hallucinations and the visual component of dreams may reflect variations in visual context acting on the same underlying mechanism - the minimal visual input during dreaming contrasts with the more substantial perceived context in hallucinations. Variations in cholinergic, dopaminergic and serotonergic neurotransmitter function during sleep and during hallucinations in Lewy body dementias, together with relevant drug effects suggest that, on the whole, different, potentially opposite, changes characterise the two states. A similar analysis of other psychotic features in Lewy body dementia and other disorders suggests that, in contrast to hallucinations, there may be more convincing parallels between dreaming and delusional states.

  17. Did Immanuel Kant have dementia with Lewy bodies and REM behavior disorder?

    PubMed

    Miranda, Marcelo; Slachevsky, Andrea; Garcia-Borreguero, Diego

    2010-06-01

    Immanuel Kant, one of the most brilliant minds of the XVIII century and of western philosophy, suffered from dementia in his late years. Based on the analysis of testimonies of his close friends, in this report we describe his neurological disorder which, after 8years of evolution, led to his death. His cognitive decline was strongly associated with a parasomnia compatible with a severe rapid eye movement (REM) behavior disorder (RBD) and dementia with Lewy bodies.

  18. Topiramate improves psychiatric symptoms in a patient with Lewy body dementia.

    PubMed

    Ochoa, Juan G

    2014-12-01

    Many patients with Lewy body dementia develop visual hallucinations and other psychiatric symptoms. These patients are hypersensitive to antipsychotic drugs. Although patients tolerate atypical better than typical antipsychotics, both types can cause major extrapyramidal side effects. The anticonvulsant mood stabilizer topiramate, which does not cause parkinsonism, has been used as adjuvant therapy for both the positive and negative symptoms of schizophrenia; these symptoms can resemble those of Lewy body dementia. This report documents a 65-year-old woman with a 3-year history of progressive dementia that over the past 2 years had become complicated by severe extrapyramidal symptoms and agitated hallucinations. Her hallucinations became daily and were disrupting to her family. She was given a clinical diagnosis of Lewy body dementia after imaging and laboratory studies ruled out other etiologies. Treatment with olanzapine relieved her psychotic symptoms but caused severe dystonias, daily myoclonic jerks, and tremors. Stopping the olanzapine and starting topiramate 25 mg daily eliminated the hallucinations and agitation without worsening her extrapyramidal side effects. However, the topiramate was stopped because the patient reportedly developed anorexia and significant weight loss. Her hallucinations returned. When topiramate was reinstated at 12.5 mg a day, her agitation resolved, although her hallucinations continued. After 6 months on this dose, her agitation was still fairly well controlled without serious side effects or worsening of her parkinsonian symptoms.

  19. Lower urinary tract function in dementia of Lewy body type

    PubMed Central

    Sakakibara, R; Ito, T; Uchiyama, T; Asahina, M; Liu, Z; Yamamoto, T; Yamanaka, Y; Hattori, T

    2005-01-01

    Methods: We examined 11 patients (eight men, three women; age range 65–81; disease duration 2–14 years) with probable DLB. Urodynamic studies consisted of: measurement of postvoid residual in all patients, uroflowmetry in five, and electromyography (EMG) cystometry in seven. Results: All patients had symptoms of LUT: urinary incontinence (urgency type/functional type due to dementia and immobility/both urgency and stress type in 7/2/1 patients, respectively); night-time frequency; urgency; and daytime frequency and voiding difficulty. Seven had postvoid residuals, and three had residual urine volume >100 ml. Decreased urinary flow was seen in all five and detrusor overactivity in 5/7 patients who underwent flowmetry and EMG cystometry, respectively. Low compliance detrusor (storage phase, n = 2; with bethanechol supersensitivity), an underactive detrusor (n = 4), an acontractile detrusor (n = 1), and detrusor–sphincter dyssynergia (voiding phase) (n = 1) were also seen; 2/3 patients who underwent motor unit potential analysis had neurogenic changes. Conclusion: LUT dysfunction is a common feature in DLB, not only due to dementia and immobility, but also to central and peripheral types of somato-autonomic dysfunction. PMID:15834036

  20. Adjunct treatment with levodopa in a patient with dementia with Lewy bodies, delusions and severe neuroleptic hypersensitivity syndrome.

    PubMed

    Majic, Tomislav; Mell, Thomas; Heinz, Andreas; Rapp, Michael A

    2010-06-01

    We report on the treatment of a patient suffering from dementia with Lewy bodies who initially presented with severe neurological and psychopathological symptoms. After treating the patient with levodopa and clozapine, these symptoms remitted.

  1. Altered Expression of Human Mitochondrial Branched Chain Aminotransferase in Dementia with Lewy Bodies and Vascular Dementia.

    PubMed

    Ashby, Emma L; Kierzkowska, Marta; Hull, Jonathon; Kehoe, Patrick G; Hutson, Susan M; Conway, Myra E

    2017-01-01

    Cytosolic and mitochondrial human branched chain aminotransferase (hBCATc and hBCATm, respectively) play an integral role in brain glutamate metabolism. Regional increased levels of hBCATc in the CA1 and CA4 region of Alzheimer's disease (AD) brain together with increased levels of hBCATm in frontal and temporal cortex of AD brains, suggest a role for these proteins in glutamate excitotoxicity. Glutamate toxicity is a key pathogenic feature of several neurological disorders including epilepsy associated dementia, AD, vascular dementia (VaD) and dementia with Lewy bodies (DLB). To further understand if these increases are specific to AD, the expression profiles of hBCATc and hBCATm were examined in other forms of dementia including DLB and VaD. Similar to AD, levels of hBCATm were significantly increased in the frontal and temporal cortex of VaD cases and in frontal cortex of DLB cases compared to controls, however there were no observed differences in hBCATc between groups in these areas. Moreover, multiple forms of hBCATm were observed that were particular to the disease state relative to matched controls. Real-time PCR revealed similar expression of hBCATm mRNA in frontal and temporal cortex for all cohort comparisons, whereas hBCATc mRNA expression was significantly increased in VaD cases compared to controls. Collectively our results suggest that hBCATm protein expression is significantly increased in the brains of DLB and VaD cases, similar to those reported in AD brain. These findings indicate a more global response to altered glutamate metabolism and suggest common metabolic responses that might reflect shared neurodegenerative mechanisms across several forms of dementia.

  2. Hippocampal volumes predict risk of dementia with Lewy bodies in mild cognitive impairment

    PubMed Central

    Lesnick, Timothy; Ferman, Tanis J.; Przybelski, Scott A.; Boeve, Bradley F.; Smith, Glenn E.; Kremers, Walter K.; Knopman, David S.; Jack, Clifford R.; Petersen, Ronald C.

    2016-01-01

    Objective: To predict the risk of probable dementia with Lewy bodies (DLB) competing with Alzheimer disease (AD) dementia by hippocampal volume (HV) in patients with mild cognitive impairment (MCI) with impairments in amnestic or nonamnestic cognitive domains. Methods: Patients with MCI (n = 160) from the Mayo Clinic Alzheimer's Disease Research Center, who participated in an MRI study at baseline from 2005 to 2014, were followed with approximately annual clinical evaluations. HVs were analyzed from 3T MRIs using FreeSurfer (5.3). Hippocampal atrophy was determined from the most normal 10th percentile of the measurement distributions in a separate cohort of clinically diagnosed patients with AD dementia. The subdistribution hazard ratios for progression to probable DLB and AD dementia were estimated by taking into account the competing risks. Results: During a median (range) follow-up of 2.0 (0.7–8.1) years, 20 (13%) patients with MCI progressed to probable DLB, and 61 (38%) progressed to AD dementia. The estimated subdistribution hazard ratio (95% confidence interval) for normal HV relative to hippocampal atrophy for progression to AD dementia was 0.56 (0.34–0.91; p = 0.02) after taking into account the competing risks. The estimated hazard ratio for normal HV relative to hippocampal atrophy for progression to probable DLB was 4.22 (1.42–12.6; p = 0.01) after adjusting for age and after including the MCI subtype in the model. Conclusions: Preserved hippocampal volumes are associated with increased risk of probable DLB competing with AD dementia in patients with MCI. Preservation of HV may support prodromal DLB over AD, particularly in patients with MCI with nonamnestic features. PMID:27807186

  3. Analysis of video-polysomnographic sleep findings in dementia with Lewy bodies.

    PubMed

    Terzaghi, Michele; Arnaldi, Dario; Rizzetti, Maria Cristina; Minafra, Brigida; Cremascoli, Riccardo; Rustioni, Valter; Zangaglia, Roberta; Pasotti, Chiara; Sinforiani, Elena; Pacchetti, Claudio; Manni, Raffaele

    2013-09-01

    Knowledge of sleep architecture and disorders of nocturnal sleep in dementia with Lewy bodies (DLB) is limited by a lack of systematic video-polysomnographic (video-PSG) investigations. We describe video-PSG findings in 29 consecutive subjects diagnosed with DLB. All the patients underwent a clinical interview and overnight video-PSG monitoring. Twenty-nine nondemented patients with Parkinson's disease (PD) matched for age and sex with the DLB cases were selected for comparison. The DLB subjects showed less 1NREM sleep (P = .000) and more 2NREM sleep (P = .000) than the PD subjects. Sleep apnea (30.7% vs. 34.8%) and periodic limb movements (60.9% versus 50.0%) were frequent in both groups. Disruptive motor behavioral manifestations were more frequent in subjects with DLB (69.6% vs. 26.9%, P = .008) and consisted of not only REM sleep behavior disorder (RBD) but also confusional events (30.3% vs. 3.8%, P = .020) and arousal-related episodes mimicking RBD. Subjects with DLB in whom a sleep disturbance had been the presenting symptom performed better than those with other onset symptoms on both the Mini-Mental State Examination (22.2 ± 4.1 vs. 18.1 ± 4.6, P = .019) and the Frontal Assessment Battery (15.8 vs. 10.3, P = .010). Polysomnographic findings in DLB show a complex mix of overlapping sleep alterations: impaired sleep structure, sleep comorbidities, and various motor-behavioral events (not restricted to RBD). Clinicians should be aware of the possibility of misleading symptoms and of the risk of overlooking sleep comorbidities, and consider performing polysomnographic sleep investigations in selected cases. We found evidence that a sleep disturbance as the presenting symptom might indicate a different phenotype of the disease, characterized by milder cognitive impairment.

  4. α-Synuclein as CSF and Blood Biomarker of Dementia with Lewy Bodies

    PubMed Central

    Kasuga, Kensaku; Nishizawa, Masatoyo; Ikeuchi, Takeshi

    2012-01-01

    Dementia with Lewy bodies (DLB) is a common subtype of dementia in the elderly. DLB is neuropathologically characterized by the presence of Lewy bodies and Lewy neurites, both of which are composed of α-synuclein. Although α-synuclein was initially considered to be an exclusively intracellular protein, it has been found to be secreted into biological fluids. α-Synuclein in biological fluids such as cerebrospinal fluid (CSF) and blood has been discussed as a potential biomarker of DLB and α-synuclein-related disorders, because α-synuclein is characteristically accumulated in the brain of patients with these disorders. The α-synuclein level in CSF has been examined by several investigators, and the majority of studies have shown a reduction in CSF α-synuclein level in DLB and α-synuclein-related disorders. Discrepant findings of studies of plasma α-synuclein level in patients with DLB have been reported. Because the level of α-synuclein stored in red blood cells is considerably high, blood contamination and haemolysis during sample collection and processing should be considered as a confounding factor for quantification of α-synuclein. Here, the recent progress in the studies of α-synuclein as a biomarker of DLB and their potential clinical applications are reviewed. PMID:23056991

  5. α-Synuclein binds and sequesters PIKE-L into Lewy bodies, triggering dopaminergic cell death via AMPK hyperactivation.

    PubMed

    Kang, Seong Su; Zhang, Zhentao; Liu, Xia; Manfredsson, Fredric P; He, Li; Iuvone, P Michael; Cao, Xuebing; Sun, Yi E; Jin, Lingjing; Ye, Keqiang

    2017-01-31

    The abnormal aggregation of fibrillar α-synuclein in Lewy bodies plays a critical role in the pathogenesis of Parkinson's disease. However, the molecular mechanisms regulating α-synuclein pathological effects are incompletely understood. Here we show that α-synuclein binds phosphoinositide-3 kinase enhancer L (PIKE-L) in a phosphorylation-dependent manner and sequesters it in Lewy bodies, leading to dopaminergic cell death via AMP-activated protein kinase (AMPK) hyperactivation. α-Synuclein interacts with PIKE-L, an AMPK inhibitory binding partner, and this action is increased by S129 phosphorylation through AMPK and is decreased by Y125 phosphorylation via Src family kinase Fyn. A pleckstrin homology (PH) domain in PIKE-L directly binds α-synuclein and antagonizes its aggregation. Accordingly, PIKE-L overexpression decreases dopaminergic cell death elicited by 1-methyl-4-phenylpyridinium (MPP(+)), whereas PIKE-L knockdown elevates α-synuclein oligomerization and cell death. The overexpression of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) or α-synuclein induces greater dopaminergic cell loss and more severe motor defects in PIKE-KO and Fyn-KO mice than in wild-type mice, and these effects are attenuated by the expression of dominant-negative AMPK. Hence, our findings demonstrate that α-synuclein neutralizes PIKE-L's neuroprotective actions in synucleinopathies, triggering dopaminergic neuronal death by hyperactivating AMPK.

  6. Cohort study of prevalence and phenomenology of tremor in dementia with Lewy bodies.

    PubMed

    Onofrj, Marco; Varanese, Sara; Bonanni, Laura; Taylor, John-Paul; Antonini, Angelo; Valente, Enza Maria; Petrucci, Simona; Stocchi, Fabrizio; Thomas, Astrid; Perfetti, Bernardo

    2013-07-01

    To study prevalence, specific patterns and response to treatment of tremor in dementia with Lewy bodies (DLB), in comparison with other tremulous disorders prevalence, qualitative and quantitative features of tremor were studied in an incident cohort of 67 dopaminergic treatment naive DLB, 111 Parkinson's Disease (PD) and 34 Essential Tremor (ET) patients. Tremulous DLB patients (tDLB) were compared with tremulous PD (tPD) and ET patients and followed for 2 years. Double blind placebo-controlled acute drug challenge with L-Dopa and alcohol was performed in all ET, 24 tDLB and 27 tPD. Effects of dopaminergic chronic treatment in all tDLB and tPD patients and primidone in 8 tDLB were also assessed. Tremor occurred in 44.76 % of DLB patients. The tDLB patients presented a complex pattern of mixed tremors, characterized by rest and postural/action tremor, including walking tremor and standing overflow in 50 % tDLB. Standing tremor with overflow was characteristic of tDLB (p < 0.001). Head tremor was more frequent in tDLB than tPD and ET (p = 0.001). The tDLB tremors were reduced by acute and chronic dopaminergic treatments (p < 0.01) but not by alcohol or primidone. Tremor occurs commonly in DLB patients with a complex mixed tremor pattern which shows a significant response to acute and chronic dopaminergic treatments. Recognizing that there is a clinical category of tremulous DLB may help the differential diagnosis of tremors.

  7. Partial loss of parvalbumin-containing hippocampal interneurons in dementia with Lewy bodies.

    PubMed

    Bernstein, Hans-Gert; Johnson, Mary; Perry, Robert H; LeBeau, Fiona E N; Dobrowolny, Henrik; Bogerts, Bernhard; Perry, Elaine K

    2011-02-01

    Dementia with Lewy bodies (DLB) is the second most common neurodegenerative dementia. Among many other neuropathological changes in DLB, brain region-specific cellular deficits have been reported. They include decreases in motor neuron and pyramidal cell densities, while neocortical parvalbumin (parv)-containing neurons are thought to be free of Lewy bodies and spared in DLB. However, elevated parv levels are found in the cerebrospinal fluid of patients suffering from dementia with Lewy bodies. We performed an immunohistochemical analysis of hippocampal parv-immunoreactive neurons in well-characterised DLB cases and from controls using a specific antibody against the calcium binding protein. In addition, an analysis of the regional and cellular distribution of alpha-synuclein was carried out. Subfield and laminar distribution of parv-immunoreactive (ir) neurons on the hippocampus in subjects with DLB and controls were present exclusively as non-granule cells of the dentate gyrus (DG)/hilus and non-pyramidal cells of CA1, CA2, CA3 and CA4 areas of the hippocampus. The distribution patterns did not differ qualitatively between DLB and controls. Quantitative estimation of parv-ir neuron density revealed significant decreases in the dentate (DG)/hilus region as well as in the CA1 subfield. Double immunolabelling experiments showed that only 2% of parv expressing interneurons were laden with alpha-synuclein immunoreactive material. No significant changes were found for the total neuron densities in DLB cases. Our results show a partial loss of parv-expressing hippocampal interneurons in DLB, which might be the result of long-lasting calcium overload in combination with a proposed impaired mitochondrial function. It remains to be elucidated if the numerical decrease of this particular subset of hippocampal interneurons has consequences for the gamma (20-80 Hz) frequency activity in DLB patients.

  8. Recurrent escitalopram-induced hyponatremia in an elderly woman with dementia with Lewy bodies.

    PubMed

    Tsai, Po-Hsin; Chen, Hsi-Chung; Liao, Shih-Cheng; Tseng, Mei-Chih Meg; Lee, Ming-Been

    2012-01-01

    We report the development of hyponatremia following initiation of escitalopram therapy in a 73-year-old woman. The patient, with a history of dementia with Lewy bodies, had presented with multiple neuropsychiatric symptoms. Within 2 months of escitalopram, she became delirious with a serum sodium level of 122 mmol/L. After discontinuation of escitalopram, her consciousness improved with resolving hyponatremia. Delirium and hyponatremia (122 mmol/L), however, recurred after escitalopram was rechallenged. Apart from eight other cases to date, this is the only one with recurrent hyponatremia. Rechallenge of the same antidepressant is discouraged especially in patients at risk of developing hyponatremia.

  9. Postprandial and Orthostatic Hypotension Treated by Sitagliptin in a Patient with Dementia with Lewy Bodies

    PubMed Central

    Saito, Yoshihiro; Ishikawa, Joji; Harada, Kazumasa

    2016-01-01

    Patient: Female, 78 Final Diagnosis: Dementia with Lewy body Symptoms: Dizziness • sycope Medication: — Clinical Procedure: — Specialty: Geriatrics Objective: Unusual setting of medical care Background: Postprandial hypotension, induced by an absorption of glucose from intestine, could be treated by acarbose; however, it was unclear whether dipeptidyl peptidase-4 inhibitor reduced postprandial hypotension. Case Report: A 78-year-old woman who had experienced episodes of dizziness and hypotension after eating was admitted to our hospital. During 24-hour ambulatory blood pressure monitoring, there were repeated episodes of marked postprandial hypotension; i.e., a significant systolic blood pressure reduction within two hours after eating (from ‒58 to ‒64 mm Hg after meals). The patient was diagnosed with dementia with Lewy bodies. The patient exhibited postprandial hyperglycemia and hypotension after a 75 g oral glucose tolerance test. After the administration of 25 mg sitagliptin, the patient’s postprandial and orthostatic hypotension was reduced remarkably. Moreover, her Mini-Mental State Examination score subsequently increased (from 22 to 25 points). Conclusions: The dipeptidyl peptidase-4 inhibitor sitagliptin can delay postprandial increases in glucose levels and hypotensive episodes, as well as sympathetic nervous system abnormalities and orthostatic hypotension. PMID:27885251

  10. Silver stainings distinguish Lewy bodies and glial cytoplasmic inclusions: comparison between Gallyas-Braak and Campbell-Switzer methods.

    PubMed

    Uchihara, Toshiki; Nakamura, Ayako; Mochizuki, Yoko; Hayashi, Masaharu; Orimo, Satoshi; Isozaki, Eiji; Mizutani, Toshio

    2005-09-01

    Lewy bodies (LBs) of idiopathic Parkinson's disease and glial cytoplasmic inclusions (GCIs) of multiple system atrophy are pathological deposits both composed of phosphorylated alpha-synuclein woven into different filaments. Although both LBs and GCIs are considered to be hallmarks for each independent synucleinopathy, until now they could not be clearly distinguished on the basis of their biochemical or immunohistochemical features. We have examined possible differences in their argyrophilic features and their relation to synuclein-like or ubiquitin-like immunoreactivity (IR). Pairs of mirror sections from different brain areas were triple-fluorolabeled with an anti-alpha-synuclein antibody, an anti-ubiquitin antibody and thiazin red (TR), a fluorochrome that labels fibrillary structures such as Lewy bodies or neurofibrillary tangles. One of the paired sections was subsequently stained using the Campbell-Switzer method (CS), and the other by the Gallyas-Braak method (GB). By comparing of the same microscopic field on the paired fluorolabeled sections, subsequently silver-stained with either CS or GB, five different profiles of each structure could be determined: alpha-synuclein-like IR, ubiquitin-like IR, affinity to TR, argyrophilia with CS or GB. GCIs exhibited argyrophilia with both CS and GB but lacked affinity to TR. In contrast, LBs exhibited argyrophilia with CS but not with GB and some affinity to TR. These disease-specific profiles of argyrophilia were consistent, and were not influenced by areas or cases examined. Although immunohistochemical features of LBs and GCIs were similar in exhibiting IR for alpha-synuclein and ubiquitin, the contrast in their argyrophilic profiles may indicate possible differences in the molecular composition or conformation of alpha-synuclein. Even though these empirical differences still remain to be explained, awareness of this clear distinction is potentially of diagnostic and pathological relevance.

  11. Spinocerebellar ataxia type 2 is associated with Parkinsonism and Lewy body pathology.

    PubMed

    Takao, Masaki; Aoyama, Masahiro; Ishikawa, Kinya; Sakiyama, Yoshio; Yomono, Harumi; Saito, Yuko; Kurisaki, Hiroshi; Mihara, Ban; Murayama, Shigeo

    2011-04-01

    Clinical phenotype of individuals with spinocerebellar ataxia 2 (SCA2) is characterised by cerebellar ataxia and cognitive impairment. Although L-dopa-responsive Parkinsonism is considered as a rare clinical presentation in SCA2, it has been brought to the attention of many neurologists in several studies. The authors report an autopsy case of SCA2 with Parkinsonism from a Japanese family using archival materials of our Brain Bank to describe unique neuropathologic findings. The individual clinically showed Parkinsonism as a predominant phenotype instead of cerebellar ataxia. Besides the classic SCA2 neuropathologic alterations, Lewy bodies and Lewy neurites were present in the brainstem nuclei. Genetic analysis revealed shorter abnormal expansion of CAG repeats (less than 39). In contrast, the authors could not find α-synuclein pathology in two SCA2 cases without Parkinsonism. The present case will provide a neuropathologic evidence of correlation between α-synucleinopathy and Parkinsonism of SCA2 as well as shed light on understanding the pathomechanism of Parkinsonism in SCA2.

  12. Dropped head syndrome preceding the onset of dementia with Lewy bodies.

    PubMed

    Tanaka, Kanta; Wada, Ikko; Okunomiya, Taro; Shima, Atsushi; Kambe, Daisuke; Shinde, Akiyo; Kageyama, Takashi; Suenaga, Toshihiko

    2014-01-01

    A 67-year-old woman developed dropped head. Her neck was severely flexed, with prominent cervical paraspinal muscles, although no parkinsonism was observed. Brain MRI showed no significant findings. We considered dystonia as the cause of the dropped head and administered trihexyphenidyl, an anticholinergic. After 10 years of follow-up, remarkable psychotic symptoms, including hallucinations regarding insects, appeared. Following the discontinuation of trihexyphenidyl, the psychotic symptoms decreased but still remained. (123)I-N-isopropyl-p-iodoamphetamine single-photon emission computed tomography ((123)I-IMP SPECT) revealed hypoperfusion in the bilateral occipital lobes. We diagnosed the patient with dementia with Lewy bodies (DLB). This case suggests that dropped head syndrome may precede the onset of DLB.

  13. Genetic analysis implicates APOE, SNCA and suggests lysosomal dysfunction in the etiology of dementia with Lewy bodies.

    PubMed

    Bras, Jose; Guerreiro, Rita; Darwent, Lee; Parkkinen, Laura; Ansorge, Olaf; Escott-Price, Valentina; Hernandez, Dena G; Nalls, Michael A; Clark, Lorraine N; Honig, Lawrence S; Marder, Karen; Van Der Flier, Wiesje M; Lemstra, Afina; Scheltens, Philip; Rogaeva, Ekaterina; St George-Hyslop, Peter; Londos, Elisabet; Zetterberg, Henrik; Ortega-Cubero, Sara; Pastor, Pau; Ferman, Tanis J; Graff-Radford, Neill R; Ross, Owen A; Barber, Imelda; Braae, Anne; Brown, Kristelle; Morgan, Kevin; Maetzler, Walter; Berg, Daniela; Troakes, Claire; Al-Sarraj, Safa; Lashley, Tammaryn; Compta, Yaroslau; Revesz, Tamas; Lees, Andrew; Cairns, Nigel; Halliday, Glenda M; Mann, David; Pickering-Brown, Stuart; Dickson, Dennis W; Singleton, Andrew; Hardy, John

    2014-12-01

    Clinical and neuropathological similarities between dementia with Lewy bodies (DLB), Parkinson's and Alzheimer's diseases (PD and AD, respectively) suggest that these disorders may share etiology. To test this hypothesis, we have performed an association study of 54 genomic regions, previously implicated in PD or AD, in a large cohort of DLB cases and controls. The cohort comprised 788 DLB cases and 2624 controls. To minimize the issue of potential misdiagnosis, we have also performed the analysis including only neuropathologically proven DLB cases (667 cases). The results show that the APOE is a strong genetic risk factor for DLB, confirming previous findings, and that the SNCA and SCARB2 loci are also associated after a study-wise Bonferroni correction, although these have a different association profile than the associations reported for the same loci in PD. We have previously shown that the p.N370S variant in GBA is associated with DLB, which, together with the findings at the SCARB2 locus, suggests a role for lysosomal dysfunction in this disease. These results indicate that DLB has a unique genetic risk profile when compared with the two most common neurodegenerative diseases and that the lysosome may play an important role in the etiology of this disorder. We make all these data available.

  14. Levodopa treatment and mood fluctuation in dementia with Lewy bodies: a case report.

    PubMed

    Fujishiro, Hiroshige; Kasanuki, Koji; Nakamura, Shinichiro

    2013-12-01

    L-3,4-dihydroxyphenylalanine (L-dopa) has been the gold standard for pharmacotherapy for parkinsonism in patients with dementia with Lewy bodies (DLB). While L-dopa treatment is related to visual hallucinations, its relationship to mood fluctuation in DLB is poorly understood. Herein, we report the improvement of behavioural and psychological symptoms of dementia through the adjustment of L-dopa treatment in a 78-year-old woman with probable DLB. Her marked mood swings were improved by changing L-dopa administration from three to five times per day while maintaining the same total daily dosage. This observation suggests that there may be an association between plasmatic L-dopa levels and mood fluctuation in patients with DLB. This pharmacological approach may be useful in the management of behavioural and psychological symptoms of dementia without the use of antipsychotic agents to avoid severe neuroleptic sensitivity, which is one of the suggestive clinical features in the Third Consortium on DLB clinical criteria.

  15. Prognostic Factors Related to Dementia with Lewy Bodies Complicated with Pneumonia: An Autopsy Study

    PubMed Central

    Manabe, Toshie; Mizukami, Katsuyoshi; Akatsu, Hiroyasu; Hashizume, Yoshio; Teramoto, Shinji; Nakamura, Seiji; Kudo, Koichiro; Hizawa, Nobuyuki

    2016-01-01

    Objective In patients demonstrating dementia with Lewy bodies (DLB), pneumonia is a common complication. However, the prognostic factors for the survival time in DLB with pneumonia have not been investigated by autopsy in patients with neuropathologically confirmed DLB. Methods We conducted a retrospective study of the medical and autopsy reports of 42 patients admitted to a Japanese hospital between 2005 and 2014. The patients were neuropathologically diagnosed as having DLB by post-mortem examinations. We analyzed the effects of various factors on the time from DLB onset to death. Results Thirty-nine of the 42 patients with DLB (92.9%) developed pneumonia during hospitalization. The median age at DLB onset was 78 years and the median time from DLB onset to death was 8 years. The Cox proportional hazard model demonstrated cerebral infarction [Hazard Ratio (HR), 2.36 (95% CI 1.12-4.96), p=0.023], muscle weakness [HR, 2.04 (0.95-4.39), p=0.067], male sex [HR, 2.84 (1.24-6.50), p=0.014], and age at onset (≥78 years.) [HR, 4.71 (1.82-12.18), p=0.001] to be prognostic factors for a shorter time from DLB onset to death. Conclusion Careful treatment of cerebral infarction and muscle weakness of the lower extremities is crucial for DLB patients with pneumonia, especially for those over 78 years of age, in order to maximize the patients' life expectancies. PMID:27725535

  16. Identifying Dynamic Functional Connectivity Changes in Dementia with Lewy Bodies Based on Product Hidden Markov Models

    PubMed Central

    Sourty, Marion; Thoraval, Laurent; Roquet, Daniel; Armspach, Jean-Paul; Foucher, Jack; Blanc, Frédéric

    2016-01-01

    Exploring time-varying connectivity networks in neurodegenerative disorders is a recent field of research in functional MRI. Dementia with Lewy bodies (DLB) represents 20% of the neurodegenerative forms of dementia. Fluctuations of cognition and vigilance are the key symptoms of DLB. To date, no dynamic functional connectivity (DFC) investigations of this disorder have been performed. In this paper, we refer to the concept of connectivity state as a piecewise stationary configuration of functional connectivity between brain networks. From this concept, we propose a new method for group-level as well as for subject-level studies to compare and characterize connectivity state changes between a set of resting-state networks (RSNs). Dynamic Bayesian networks, statistical and graph theory-based models, enable one to learn dependencies between interacting state-based processes. Product hidden Markov models (PHMM), an instance of dynamic Bayesian networks, are introduced here to capture both statistical and temporal aspects of DFC of a set of RSNs. This analysis was based on sliding-window cross-correlations between seven RSNs extracted from a group independent component analysis performed on 20 healthy elderly subjects and 16 patients with DLB. Statistical models of DFC differed in patients compared to healthy subjects for the occipito-parieto-frontal network, the medial occipital network and the right fronto-parietal network. In addition, pairwise comparisons of DFC of RSNs revealed a decrease of dependency between these two visual networks (occipito-parieto-frontal and medial occipital networks) and the right fronto-parietal control network. The analysis of DFC state changes thus pointed out networks related to the cognitive functions that are known to be impaired in DLB: visual processing as well as attentional and executive functions. Besides this context, product HMM applied to RSNs cross-correlations offers a promising new approach to investigate structural and

  17. Identifying Dynamic Functional Connectivity Changes in Dementia with Lewy Bodies Based on Product Hidden Markov Models.

    PubMed

    Sourty, Marion; Thoraval, Laurent; Roquet, Daniel; Armspach, Jean-Paul; Foucher, Jack; Blanc, Frédéric

    2016-01-01

    Exploring time-varying connectivity networks in neurodegenerative disorders is a recent field of research in functional MRI. Dementia with Lewy bodies (DLB) represents 20% of the neurodegenerative forms of dementia. Fluctuations of cognition and vigilance are the key symptoms of DLB. To date, no dynamic functional connectivity (DFC) investigations of this disorder have been performed. In this paper, we refer to the concept of connectivity state as a piecewise stationary configuration of functional connectivity between brain networks. From this concept, we propose a new method for group-level as well as for subject-level studies to compare and characterize connectivity state changes between a set of resting-state networks (RSNs). Dynamic Bayesian networks, statistical and graph theory-based models, enable one to learn dependencies between interacting state-based processes. Product hidden Markov models (PHMM), an instance of dynamic Bayesian networks, are introduced here to capture both statistical and temporal aspects of DFC of a set of RSNs. This analysis was based on sliding-window cross-correlations between seven RSNs extracted from a group independent component analysis performed on 20 healthy elderly subjects and 16 patients with DLB. Statistical models of DFC differed in patients compared to healthy subjects for the occipito-parieto-frontal network, the medial occipital network and the right fronto-parietal network. In addition, pairwise comparisons of DFC of RSNs revealed a decrease of dependency between these two visual networks (occipito-parieto-frontal and medial occipital networks) and the right fronto-parietal control network. The analysis of DFC state changes thus pointed out networks related to the cognitive functions that are known to be impaired in DLB: visual processing as well as attentional and executive functions. Besides this context, product HMM applied to RSNs cross-correlations offers a promising new approach to investigate structural and

  18. Nature and extent of person recognition impairments associated with Capgras syndrome in Lewy body dementia

    PubMed Central

    Fiacconi, Chris M.; Barkley, Victoria; Finger, Elizabeth C.; Carson, Nicole; Duke, Devin; Rosenbaum, R. Shayna; Gilboa, Asaf; Köhler, Stefan

    2014-01-01

    Patients with Capgras syndrome (CS) adopt the delusional belief that persons well-known to them have been replaced by an imposter. Several current theoretical models of CS attribute such misidentification problems to deficits in covert recognition processes related to the generation of appropriate affective autonomic signals. These models assume intact overt recognition processes for the imposter and, more broadly, for other individuals. As such, it has been suggested that CS could reflect the “mirror-image” of prosopagnosia. The purpose of the current study was to determine whether overt person recognition abilities are indeed always spared in CS. Furthermore, we examined whether CS might be associated with any impairments in overt affective judgments of facial expressions. We pursued these goals by studying a patient with Dementia with Lewy bodies (DLB) who showed clear signs of CS, and by comparing him to another patient with DLB who did not experience CS, as well as to a group of healthy control participants. Clinical magnetic resonance imaging scans revealed medial prefrontal cortex (mPFC) atrophy that appeared to be uniquely associated with the presence CS. We assessed overt person recognition with three fame recognition tasks, using faces, voices, and names as cues. We also included measures of confidence and probed pertinent semantic knowledge. In addition, participants rated the intensity of fearful facial expressions. We found that CS was associated with overt person recognition deficits when probed with faces and voices, but not with names. Critically, these deficits were not present in the DLB patient without CS. In addition, CS was associated with impairments in overt judgments of affect intensity. Taken together, our findings cast doubt on the traditional view that CS is the mirror-image of prosopagnosia and that it spares overt recognition abilities. These findings can still be accommodated by models of CS that emphasize deficits in autonomic

  19. AV‐1451 tau and β‐amyloid positron emission tomography imaging in dementia with Lewy bodies

    PubMed Central

    Lowe, Val J.; Boeve, Bradley F.; Senjem, Matthew L.; Tosakulwong, Nikki; Lesnick, Timothy G.; Spychalla, Anthony J.; Gunter, Jeffrey L.; Fields, Julie A.; Graff‐Radford, Jonathan; Ferman, Tanis J.; Jones, David T.; Murray, Melissa E.; Knopman, David S.; Jack, Clifford R.; Petersen, Ronald C.

    2016-01-01

    Objective Patients with probable dementia with Lewy bodies (DLB) often have Alzheimer's disease (AD)‐related pathology. Our objective was to determine the pattern of positron emission tomography (PET) tau tracer AV‐1451 uptake in patients with probable DLB, compared to AD, and its relationship to β‐amyloid deposition on PET. Methods Consecutive patients with clinically probable DLB (n = 19) from the Mayo Clinic Alzheimer's Disease Research Center underwent magnetic resonance imaging, AV‐1451, and Pittsburgh compound‐B (PiB) PET examinations. Age‐ and sex‐matched groups of AD dementia (n = 19) patients and clinically normal controls (n = 95) from an epidemiological cohort served as a comparison groups. Atlas‐ and voxel‐based analyses were performed. Results The AD dementia group had significantly higher AV‐1451 uptake than the probable DLB group, and medial temporal uptake completely distinguished AD dementia from probable DLB. Patients with probable DLB had greater AV‐1451 uptake in the posterior temporoparietal and occipital cortex compared to clinically normal controls, and in probable DLB, the uptake in these regions correlated with global cortical PiB uptake (Spearman rho = 0.63; p = 0.006). Interpretation Medial temporal lobe AV‐1451 uptake distinguishes AD dementia from probable DLB, which may be useful for differential diagnosis. Elevated posterior temporoparietal and occipital AV‐1451 uptake in probable DLB and its association with global cortical PiB uptake suggest an atypical pattern of tau deposition in DLB. ANN NEUROL 2017;81:58–67 PMID:27863444

  20. Human Neural Progenitor Transplantation Rescues Behavior and Reduces α-Synuclein in a Transgenic Model of Dementia with Lewy Bodies.

    PubMed

    Goldberg, Natalie R S; Marsh, Samuel E; Ochaba, Joseph; Shelley, Brandon C; Davtyan, Hayk; Thompson, Leslie M; Steffan, Joan S; Svendsen, Clive N; Blurton-Jones, Mathew

    2017-02-22

    Synucleinopathies are a group of neurodegenerative disorders sharing the common feature of misfolding and accumulation of the presynaptic protein α-synuclein (α-syn) into insoluble aggregates. Within this diverse group, Dementia with Lewy Bodies (DLB) is characterized by the aberrant accumulation of α-syn in cortical, hippocampal, and brainstem neurons, resulting in multiple cellular stressors that particularly impair dopamine and glutamate neurotransmission and related motor and cognitive function. Recent studies show that murine neural stem cell (NSC) transplantation can improve cognitive or motor function in transgenic models of Alzheimer's and Huntington's disease, and DLB. However, examination of clinically relevant human NSCs in these models is hindered by the challenges of xenotransplantation and the confounding effects of immunosuppressant drugs on pathology and behavior. To address this challenge, we developed an immune-deficient transgenic model of DLB that lacks T-, B-, and NK-cells, yet exhibits progressive accumulation of human α-syn (h-α-syn)-laden inclusions and cognitive and motor impairments. We demonstrate that clinically relevant human neural progenitor cells (line CNS10-hNPCs) survive, migrate extensively and begin to differentiate preferentially into astrocytes following striatal transplantation into this DLB model. Critically, grafted CNS10-hNPCs rescue both cognitive and motor deficits after 1 and 3 months and, furthermore, restore striatal dopamine and glutamate systems. These behavioral and neurochemical benefits are likely achieved by reducing α-syn oligomers. Collectively, these results using a new model of DLB demonstrate that hNPC transplantation can impact a broad array of disease mechanisms and phenotypes and suggest a cellular therapeutic strategy that should be pursued. © Stem Cells Translational Medicine 2017.

  1. Valosin-containing protein immunoreactivity in tauopathies, synucleinopathies, polyglutamine diseases and intranuclear inclusion body disease.

    PubMed

    Mori, Fumiaki; Tanji, Kunikazu; Toyoshima, Yasuko; Sasaki, Hidenao; Yoshida, Mari; Kakita, Akiyoshi; Takahashi, Hitoshi; Wakabayashi, Koichi

    2013-12-01

    Valosin-containing protein (VCP) is associated with multiple cellular functions, including ubiquitin-dependent protein degradation. Mutations in VCP are known to cause inclusion body myopathy with Paget's disease and frontotemporal dementia and familial amyotrophic lateral sclerosis (fALS; ALS14), both of which are characterized by trans-activation response DNA protein 43 (TDP-43)-positive neuronal cytoplasmic and nuclear inclusions. Recently, immunoreactivity for fALS-associated proteins (TDP-43, fused in sarcoma (FUS), optineurin and ubiquilin-2) were reported to be present in cytoplasmic and nuclear inclusions in various neurodegenerative diseases. However, the extent and frequency of VCP-immunoreactive structures in these neurodegenerative diseases are uncertain. We immunohistochemically examined the brains of 72 cases with neurodegenerative diseases and five control cases. VCP immunoreactivity was present in Lewy bodies in Parkinson's disease and dementia with Lewy bodies, and neuronal nuclear inclusions in five polyglutamine diseases and intranuclear inclusion body disease, as well as in Marinesco bodies in aged control subjects. However, other neuronal and glial cytoplasmic inclusions in tauopathies and TDP-43 proteinopathies were unstained. These findings suggest that VCP may have common mechanisms in the formation or degradation of cytoplasmic and nuclear inclusions of neurons, but not of glial cells, in several neurodegenerative conditions.

  2. Accumulation of α-synuclein in dementia with Lewy bodies is associated with decline in the α-synuclein-degrading enzymes kallikrein-6 and calpain-1.

    PubMed

    Miners, J Scott; Renfrew, Ruth; Swirski, Marta; Love, Seth

    2014-12-05

    Kallikrein-6 and calpain-1 are amongst a small group of proteases that degrade α-synuclein. We have explored the possibility that reduction in the level or activity of these enzymes contributes to the accumulation of α-synuclein in Lewy body diseases. We measured calpain-1 activity by fluorogenic activity assay, kallikrein-6 level by sandwich ELISA, and levels of α-synuclein and α-synuclein phosphorylated at serine 129 (α-synuclein-P129), in post-mortem brain tissue in pure dementia with Lewy bodies (DLB, n=12), Alzheimer's disease (AD, n=20) and age-matched controls (n=19). Calpain-1 activity was significantly reduced in DLB within the cingulate and parahippocampal cortex, regions with highest α-synuclein and α-synuclein-P129 load, and correlated inversely with the levels of α-synuclein and α-synuclein-P129. Calpain-1 was unaltered in the thalamus and frontal cortex, regions with less α-synuclein pathology. Kallikrein-6 level was reduced in the cingulate cortex in the DLB cohort, and correlated inversely with α-synuclein and α-synuclein-P129. Kallikrein-6 was also reduced in DLB in the thalamus but not in relation to α-synuclein or α-synuclein-P129 load and was unaltered in the frontal and parahippocampal cortex. In SH-SY5Y cells overexpressing wild-type α-synuclein there was partial co-localisation of kallikrein-6 and calpain-1 with α-synuclein, and siRNA-mediated knock-down of kallikrein-6 and calpain-1 increased the amount of α-synuclein in cell lysates. Our results indicate that reductions in kallikrein-6 and calpain-1 may contribute to the accumulation of α-synuclein in DLB.

  3. Increased phosphorylation of collapsin response mediator protein-2 at Thr514 correlates with β-amyloid burden and synaptic deficits in Lewy body dementias.

    PubMed

    Xing, Huayang; Lim, Yun-An; Chong, Joyce R; Lee, Jasinda H; Aarsland, Dag; Ballard, Clive G; Francis, Paul T; Chen, Christopher P; Lai, Mitchell K P

    2016-09-08

    Collapsin response mediator protein-2 (CRMP2) regulates axonal growth cone extension, and increased CRMP2 phosphorylation may lead to axonal degeneration. Axonal and synaptic pathology is an important feature of Lewy body dementias (LBD), but the state of CRMP2 phosphorylation (pCRMP2) as well as its correlations with markers of neurodegeneration have not been studied in these dementias. Hence, we measured CRMP2 phosphorylation at Thr509, Thr514 and Ser522, as well as markers of β-amyloid (Aβ), tau-phosphorylation, α-synuclein and synaptic function in the postmortem neocortex of a longitudinally assessed cohort of LBD patients characterized by low (Parkinson's disease dementia, PDD) and high (dementia with Lewy bodies, DLB) burden of Alzheimer type pathology. We found specific increases of pCRMP2 at Thr514 in DLB, but not PDD. The increased CRMP2 phosphorylation correlated with fibrillogenic Aβ as well as with losses of markers for axon regeneration (β-III-tubulin) and synaptic integrity (synaptophysin) in LBD. In contrast, pCRMP2 alterations did not correlate with tau-phosphorylation or α-synuclein, and also appear unrelated to immunoreactivities of putative upstream kinases glycogen synthase kinase 3β and cyclin-dependent kinase 5, as well as to protein phosphatase 2A. In conclusion, increased pCRMP2 may underlie the axonal pathology of DLB, and may be a novel therapeutic target. However, antecedent signaling events as well as the nature of pCRMP2 association with Aβ and other neuropathologic markers require further study.

  4. Autophagic adapter protein NBR1 is localized in Lewy bodies and glial cytoplasmic inclusions and is involved in aggregate formation in α-synucleinopathy.

    PubMed

    Odagiri, Saori; Tanji, Kunikazu; Mori, Fumiaki; Kakita, Akiyoshi; Takahashi, Hitoshi; Wakabayashi, Koichi

    2012-08-01

    Macroautophagy is a dynamic process whereby cytoplasmic components are initially sequestered within autophagosomes. Recent studies have shown that the autophagosome membrane can selectively recognize ubiquitinated proteins and organelles through interaction with adapter proteins such as p62 and NBR1. Both proteins are structurally similar at the amino acid level, and bind with ubiquitin and ubiquitinated proteins. Although p62 is incorporated into a wide spectrum of pathological inclusions in various neurodegenerative diseases, abnormalities of NBR1 have not been reported in these diseases. Our immunohistochemical examination revealed that the vast majority of Lewy bodies (LBs) in Parkinson's disease and dementia with LBs (DLB) as well as of glial cytoplasmic inclusions in multiple system atrophy (MSA) were positive for NBR1. Neuronal and glial inclusions in tauopathies and TAR DNA-binding protein of 43 kDa proteinopathies were rarely immunolabeled, or were unstained. Using cultured cells bearing LB-like inclusions, formation of α-synuclein aggregates was repressed in cells with NBR1 knockdown. Immunoblot analysis showed that the level of NBR1 was significantly increased by 2.5-fold in MSA, but not in DLB. These findings suggest that NBR1 is involved in the formation of cytoplasmic inclusions in α-synucleinopathy.

  5. Analysis of primary visual cortex in dementia with Lewy bodies indicates GABAergic involvement associated with recurrent complex visual hallucinations.

    PubMed

    Khundakar, Ahmad A; Hanson, Peter S; Erskine, Daniel; Lax, Nichola Z; Roscamp, Joseph; Karyka, Evangelia; Tsefou, Eliona; Singh, Preeti; Cockell, Simon J; Gribben, Andrew; Ramsay, Lynne; Blain, Peter G; Mosimann, Urs P; Lett, Deborah J; Elstner, Matthias; Turnbull, Douglass M; Xiang, Charles C; Brownstein, Michael J; O'Brien, John T; Taylor, John-Paul; Attems, Johannes; Thomas, Alan J; McKeith, Ian G; Morris, Christopher M

    2016-06-30

    Dementia with Lewy bodies (DLB) patients frequently experience well formed recurrent complex visual hallucinations (RCVH). This is associated with reduced blood flow or hypometabolism on imaging of the primary visual cortex. To understand these associations in DLB we used pathological and biochemical analysis of the primary visual cortex to identify changes that could underpin RCVH. Alpha-synuclein or neurofibrillary tangle pathology in primary visual cortex was essentially absent. Neurone density or volume within the primary visual cortex in DLB was also unchanged using unbiased stereology. Microarray analysis, however, demonstrated changes in neuropeptide gene expression and other markers, indicating altered GABAergic neuronal function. Calcium binding protein and GAD65/67 immunohistochemistry showed preserved interneurone populations indicating possible interneurone dysfunction. This was demonstrated by loss of post synaptic GABA receptor markers including gephyrin, GABARAP, and Kif5A, indicating reduced GABAergic synaptic activity. Glutamatergic neuronal signalling was also altered with vesicular glutamate transporter protein and PSD-95 expression being reduced. Changes to the primary visual cortex in DLB indicate that reduced GABAergic transmission may contribute to RCVH in DLB and treatment using targeted GABAergic modulation or similar approaches using glutamatergic modification may be beneficial.

  6. Spread Deficits in Initiation, Speed and Accuracy of Horizontal and Vertical Automatic Saccades in Dementia with Lewy Bodies

    PubMed Central

    Kapoula, Zoi; Yang, Qing; Vernet, Marine; Dieudonné, Benedicte; Greffard, Sandrine; Verny, Marc

    2010-01-01

    Background: Mosimann et al. (2005) reported prolongation of saccade latency of prosaccades in dementia with Lewy body (DLB). The goal of this study is to go further examining all parameters, such as rates of express latency, but also accuracy and velocity of saccades, and their variability. Methods: We examined horizontal and vertical saccades in 10 healthy elderly subjects and 10 patients with DLB. Two tasks were used: the gap (fixation target extinguishes prior to target onset) and the overlap (fixation stays on after target onset). Eye movements were recorded with the Eyelink II eye tracker. Results: The main findings were: (1) as for healthy, latencies were shorter in the gap than in the overlap task (a gap effect); (2) for both tasks latency of saccades was longer for DLB patients and for all directions; (3) express latency in the gap task was absent for large majority of DLB patients while such saccades occurred frequency for controls; (4) accuracy and peak velocity were lower in DLB patients; (5) variability of all parameters was abnormally high in DLB patients. Conclusions: Abnormalities of all parameters, latency, accuracy and peak velocity reflect spread deficits in cortical-subcortical circuits involved in the triggering and execution of saccades. PMID:21212841

  7. The role of 123I-ioflupane SPECT dopamine transporter imaging in the diagnosis and treatment of patients with dementia with Lewy bodies

    PubMed Central

    Antonini, Angelo

    2007-01-01

    The diagnosis of dementia with Lewy bodies (DLB) is difficult if one relies solely on clinical features. Current International Consensus Criteria for DLB have high specificity but a significant percentage of patients might be misdiagnosed. Reasons for clinical uncertainty regard the presence of concomitant motor signs in patients with Alzheimer’s disease as well as the observation that cognitive abnormalities in DLB might develop with memory impairment without significant parkinsonism. This has clinical relevance as DLB patients may be particularly sensitive to antipsychotics and even the effectiveness of atypical neuroleptics such as quetiapine for the treatment of agitation and hallucinations has been questioned by double-blind, placebo-controlled, randomized studies. By contrast, acetyl-cholinesterase inhibitors such as rivastigmine have shown benefit not only on cognitive but also on psychiatric symptoms. Recent evidence shows that striatal dopamine transporter binding of 123I-ioflupane SPECT is reduced in DLB and this is consistent with a significant loss of nigral dopamine neurons in this disorder. Several studies have demonstrated the diagnostic accuracy of 123I-ioflupane in the differential diagnosis of parkinsonism. Given the availability of SPECT, this investigation represents a useful marker to support clinical diagnosis and can help establishing appropriate treatment for this disorder. PMID:19300562

  8. Changes in pupil diameter are correlated with the occurrence of pareidolias in patients with dementia with Lewy bodies

    PubMed Central

    Suzuki, Yumi; Hirayama, Kazumi; Shimomura, Tatsuo; Uchiyama, Makoto; Fujii, Hiromi; Mori, Etsuro; Nishio, Yoshiyuki; Iizuka, Osamu; Inoue, Ryusuke; Otsuki, Mika

    2017-01-01

    Pareidolias are visual illusions of meaningful objects, such as faces and animals, that arise from ambiguous forms embedded in visual scenes. Pareidolias and visual hallucinations have been suggested to have a common underlying neural mechanism in patients with dementia with Lewy bodies (DLB). The aim of the present study was to find an externally observable physiological indicator of pareidolias. Using a pareidolia test developed by Uchiyama and colleagues, we evoked pareidolias in patients with DLB and recorded the resultant changes in the diameters of their pupil. The time frequencies of changes in pupil diameters preceding pareidolic utterances and correct utterances by the patients, as well as correct utterances by healthy control participants, were analyzed by a fast Fourier transform program. The power at time frequencies of 0–0.46 Hz was found to be greatest preceding pareidolic utterances in patients with DLB, followed by that preceding correct utterances in control participants, followed by that preceding correct utterances in patients with DLB. When the changes in power preceding the utterance were greater than the median value of correct utterances by the control group, the frequency of pareidolic utterances was significantly greater than that of correct utterances and when the changes were the same as or lower than the median value, the frequency of correct utterances was significantly greater than that of pareidolic utterances. Greater changes in power preceding the utterance at time frequencies of 0–0.46 Hz may thus be an externally observable physiological indicator of the occurrence of pareidolias. PMID:28134631

  9. The Italian dementia with Lewy bodies study group (DLB-SINdem): toward a standardization of clinical procedures and multicenter cohort studies design.

    PubMed

    Bonanni, L; Cagnin, A; Agosta, F; Babiloni, C; Borroni, B; Bozzali, M; Bruni, A C; Filippi, M; Galimberti, D; Monastero, R; Muscio, C; Parnetti, L; Perani, D; Serra, L; Silani, V; Tiraboschi, P; Padovani, A

    2017-01-01

    Dementia with Lewy bodies (DLB) causes elevated outlays for the National Health Systems due to high institutionalization rate and patients' reduced quality of life and high mortality. Furthermore, DLB is often misdiagnosed as Alzheimer's disease. These data motivate harmonized multicenter longitudinal cohort studies to improve clinical management and therapy monitoring. The Italian DLB study group of the Italian Neurological Society for dementia (SINdem) developed and emailed a semi-structured questionnaire to 572 national dementia centers (from primary to tertiary) to prepare an Italian large longitudinal cohort. The questionnaire surveyed: (1) prevalence and incidence of DLB; (2) clinical assessment; (3) relevance and availability of diagnostic tools; (4) pharmacological management of cognitive, motor, and behavioural disturbances; (5) causes of hospitalization, with specific focus on delirium and its treatment. Overall, 135 centers (23.6 %) contributed to the survey. Overall, 5624 patients with DLB are currently followed by the 135 centers in a year (2042 of them are new patients). The percentage of DLB patients was lower (27 ± 8 %) than that of Alzheimer's disease and frontotemporal dementia (56 ± 27 %) patients. The majority of the centers (91 %) considered the clinical and neuropsychological assessments as the most relevant procedure for a DLB diagnosis. Nonetheless, most of the centers has availability of magnetic resonance imaging (MRI; 95 %), electroencephalography (EEG; 93 %), and FP-CIT single photon emission-computerized tomography (SPECT; 75 %) scan for clinical applications. It will be, therefore, possible to recruit a large harmonized Italian cohort of DLB patients for future cross-sectional and longitudinal multicenter studies.

  10. Lewy Body Dementia

    MedlinePlus

    ... Policy Notice of Privacy Practices Notice of Nondiscrimination Advertising Mayo Clinic is a not-for-profit organization and proceeds from Web advertising help support our mission. Mayo Clinic does not ...

  11. Lewy Body Dementia Research

    MedlinePlus

    ... According to a new RAND Corporation study, the monetary cost of dementia in the United States ranges ... Caregivers Professionals Volunteer Shop Search Sitemap Terms and Policies Disclaimer Careers State Fundraising Notices latest tweets Tweets ...

  12. Lewy Body Dementia Association

    MedlinePlus

    ... milestones Contact Us staff contacts social media State Fundraising Notices Careers at LBDA ways to give events ... Black Dress Host a LBD5K fundraise First Giving Fundraising Everyday Hero raise awareness awareness month photos raise ...

  13. Dementia with Lewy Bodies

    MedlinePlus

    ... cognitive decline, “fluctuations” in alertness and attention, visual hallucinations, and parkinsonian motor symptoms, such as slowness of ... cognitive decline, “fluctuations” in alertness and attention, visual hallucinations, and parkinsonian motor symptoms, such as slowness of ...

  14. Lewy Body Dementia Glossary

    MedlinePlus

    ... due to dysfunction of the muscles involved in speaking, but with the neurological coordination of these muscles. ... dysphonias, where an individual has an impairment in speaking such as hoarseness or weakness of the voice. ...

  15. [Disease, body and corporeity: an anthropological perspective].

    PubMed

    Moreno-Altamirano, Laura

    2010-01-01

    The aim of this article is to present a reflection on the perception of disease, taking the body and its relation to the world as a crucial point of departure. We develop some key notions of body and corporeity that throughout history involve different symbolic conceptions of the diseased body from an anthropological perspective. We highlight the polysemic nature of bodily performance that involves nature and culture as well as the mind-body dual condition. Thus, the notion of embodiment involves our body consciousness, not just the experience of what we feel through it, but the set of meanings from it that we give the world.

  16. Friedrich Heinrich Lewy (1885-1950) and his work.

    PubMed

    Holdorff, Bernd

    2002-03-01

    In 1912, Friedrich Heinrich Lewy first described the inclusion bodies named after him and seen in paralysis agitans (p.a.). Tretiakoff had found (1919) that the nucleus niger is most likely to be affected but in a subsequent large-scale series of post-mortem examinations (1923). Lewy was able to confirm this for a minority of cases only, with the exception of those that displayed postencephalitic Parkinsonism (and an unknown number of atypical Parkinson syndrome cases not identified until the 1960s). In a speculative paper (1932), he saw similarities between inclusion bodies in p.a. and viral diseases like lyssa and postulated a viral genesis of p.a. In a historical review of basal ganglia diseases (1942), he did not mention the putative significance of the inclusion bodies for the post-mortem diagnosis. It seems that their importance was seen only after Lewy's death, long after Tretiakoff's initial naming of the 'corps de Lewy'. Lewy, however, had already described their diffuse and cortical distribution (1923). An identification of diffuse Lewy body disease or dementia followed much later. Lewy's career in many diverse branches of neurology and internal medicine was strongly affected by World War I and the difficult situation faced by Jews in Germany. Shortly after the Neurological Institute was founded in Berlin in 1932 (as a clinic and research institute), he was forced, in 1933, to emigrate. His exile in England and the United States mirrors the fate of many German Jews and academics in the first half of the 20th century.

  17. Identification of Splice Variants as Molecular Markers in Parkinson’s Disease

    DTIC Science & Technology

    2006-09-01

    immunoreactivity in neu- rons of the substantia nigra (78). Patients with multiple sys- tem atrophy (MSA) and dementia with Lewy bodies (DLB) also...disease, the intracellular inclu- sions are called Lewy bodies and contain -synuclein. This protein, which also accumulates with huntingtin in Hunting...in the form of small aggregates called protofibrils (72). Nevertheless, their accumulation in Lewy bodies may not be toxic. Since mature Lewy bodies

  18. Ketone body metabolism and cardiovascular disease

    PubMed Central

    Cotter, David G.; Schugar, Rebecca C.

    2013-01-01

    Ketone bodies are metabolized through evolutionarily conserved pathways that support bioenergetic homeostasis, particularly in brain, heart, and skeletal muscle when carbohydrates are in short supply. The metabolism of ketone bodies interfaces with the tricarboxylic acid cycle, β-oxidation of fatty acids, de novo lipogenesis, sterol biosynthesis, glucose metabolism, the mitochondrial electron transport chain, hormonal signaling, intracellular signal transduction pathways, and the microbiome. Here we review the mechanisms through which ketone bodies are metabolized and how their signals are transmitted. We focus on the roles this metabolic pathway may play in cardiovascular disease states, the bioenergetic benefits of myocardial ketone body oxidation, and prospective interactions among ketone body metabolism, obesity, metabolic syndrome, and atherosclerosis. Ketone body metabolism is noninvasively quantifiable in humans and is responsive to nutritional interventions. Therefore, further investigation of this pathway in disease models and in humans may ultimately yield tailored diagnostic strategies and therapies for specific pathological states. PMID:23396451

  19. Early-onset Lafora body disease

    PubMed Central

    Turnbull, Julie; Girard, Jean-Marie; Lohi, Hannes; Chan, Elayne M.; Wang, Peixiang; Tiberia, Erica; Omer, Salah; Ahmed, Mushtaq; Bennett, Christopher; Chakrabarty, Aruna; Tyagi, Atul; Liu, Yan; Pencea, Nela; Zhao, XiaoChu; Scherer, Stephen W.; Ackerley, Cameron A.

    2012-01-01

    The most common progressive myoclonus epilepsies are the late infantile and late infantile-variant neuronal ceroid lipofuscinoses (onset before the age of 6 years), Unverricht–Lundborg disease (onset after the age of 6 years) and Lafora disease. Lafora disease is a distinct disorder with uniform course: onset in teenage years, followed by progressively worsening myoclonus, seizures, visual hallucinations and cognitive decline, leading to a vegetative state in status myoclonicus and death within 10 years. Biopsy reveals Lafora bodies, which are pathognomonic and not seen with any other progressive myoclonus epilepsies. Lafora bodies are aggregates of polyglucosans, poorly constructed glycogen molecules with inordinately long strands that render them insoluble. Lafora disease is caused by mutations in the EPM2A or EPM2B genes, encoding the laforin phosphatase and the malin ubiquitin ligase, respectively, two cytoplasmically active enzymes that regulate glycogen construction, ensuring symmetric expansion into a spherical shape, essential to its solubility. In this work, we report a new progressive myoclonus epilepsy associated with Lafora bodies, early-onset Lafora body disease, map its locus to chromosome 4q21.21, identify its gene and mutation and characterize the relationship of its gene product with laforin and malin. Early-onset Lafora body disease presents early, at 5 years, with dysarthria, myoclonus and ataxia. The combination of early-onset and early dysarthria strongly suggests late infantile-variant neuronal ceroid lipofuscinosis, not Lafora disease. Pathology reveals no ceroid lipofuscinosis, but Lafora bodies. The subsequent course is a typical progressive myoclonus epilepsy, though much more protracted than any infantile neuronal ceroid lipofuscinosis, or Lafora disease, patients living into the fourth decade. The mutation, c.781T>C (Phe261Leu), is in a gene of unknown function, PRDM8. We show that the PRDM8 protein interacts with laforin and malin and

  20. Modeling corticosteroid effects in a rat model of rheumatoid arthritis I: mechanistic disease progression model for the time course of collagen-induced arthritis in Lewis rats.

    PubMed

    Earp, Justin C; Dubois, Debra C; Molano, Diana S; Pyszczynski, Nancy A; Keller, Craig E; Almon, Richard R; Jusko, William J

    2008-08-01

    A mechanism-based model was developed to describe the time course of arthritis progression in the rat. Arthritis was induced in male Lewis rats with type II porcine collagen into the base of the tail. Disease progression was monitored by paw swelling, bone mineral density (BMD), body weights, plasma corticosterone (CST) concentrations, and tumor necrosis factor (TNF)-alpha, interleukin (IL)-1beta, IL-6, and glucocorticoid receptor (GR) mRNA expression in paw tissue. Bone mineral density was determined by PIXImus II dual energy X-ray densitometry. Plasma CST was assayed by high-performance liquid chromatography. Cytokine and GR mRNA were determined by quantitative real-time polymerase chain reaction. Disease progression models were constructed from transduction and indirect response models and applied using S-ADAPT software. A delay in the onset of increased paw TNF-alpha and IL-6 mRNA concentrations was successfully characterized by simple transduction. This rise was closely followed by an up-regulation of GR mRNA and CST concentrations. Paw swelling and body weight responses peaked approximately 21 days after induction, whereas bone mineral density changes were greatest at 23 days after induction. After peak response, the time course in IL-1beta, IL-6 mRNA, and paw edema slowly declined toward a disease steady state. Model parameters indicate TNF-alpha and IL-1beta mRNA most significantly induce paw edema, whereas IL-6 mRNA exerted the most influence on BMD. The model for bone mineral density captures rates of turnover of cancellous and cortical bone and the fraction of each in the different regions analyzed. This small systems model integrates and quantitates multiple factors contributing to arthritis in rats.

  1. Definition of an extended MHC class II-peptide binding motif for the autoimmune disease-associated Lewis rat RT1.BL molecule.

    PubMed

    Wauben, M H; van der Kraan, M; Grosfeld-Stulemeyer, M C; Joosten, I

    1997-02-01

    The Lewis rat, an inbred rat strain susceptible to several well-characterized experimental autoimmune diseases, provides a good model to study peptide-mediated immunotherapy. Peptide immunotherapy focussing on the modulation of T cell responses by interfering with TCR-peptide-MHC complex formation requires the elucidation of the molecular basis of TCR-peptide-MHC interactions for an efficient design of modulatory peptides. In the Lewis rat most autoimmune-associated CD4+ T cell responses are MHC class II RT1.BL restricted. In this study, the characteristics of RT1.BL-peptide interactions were explored. A series of substitution analogs of two Lewis rat T cell epitopes was examined in a direct peptide-MHC binding assay on isolated RT1.BL molecules. Furthermore, other autoimmune-related as well as non-disease-related T cell epitopes were tested in the binding assay. This has led to the definition of an extended RT1.BL-peptide binding motif. The RT1.BL-peptide binding motif established in this study is the first described rat MHC-peptide binding motif based on direct MHC-peptide binding experiments. To predict good or intermediate RT1.BL binding peptides, T cell epitope search profiles were deduced from this motif. The motif and search profiles will greatly facilitate the prediction of modulatory peptides based on autoimmune-associated T cell epitopes and the identification of target structures in experimental autoimmune diseases in Lewis rats.

  2. The effects of different schedules of total-body irradiation in heterotopic vascularized bone transplantation. An experimental study in the Lewis rat

    SciTech Connect

    Gonzalez del Pino, J.; Benito, M.; Randolph, M.A.; Weiland, A.J. )

    1990-12-01

    To evaluate the effects of irradiation on heterotopically placed vascularized knee isografts, a single dose of 10 Gy of total-body irradiation was given to Lewis donor rats. Irradiation was delivered either 2 or 6 days prior to harvesting or subsequent transplantation, and evaluated at 1, 2, and 4 weeks after grafting. Irradiation caused endothelial depopulation of the graft artery, although vascular pedicle patency was maintained throughout the study. Bone graft viability and mineralization were normal. Dramatic changes in the bone marrow were seen that included an increase of its fat content (P less than 0.001), and a concomitant decrease in bone marrow-derived immunocompetent cells. These changes were more prominent in recipients of grafts from day -6 irradiated donor rats. Total-body irradiation did not prejudice the use of vascularized bone grafts, and exhibited an associated immunosuppresant effect over the vascular endothelium and bone marrow. This may be a further rational conditioning procedure to avoid recipient manipulation in vascularized bone allotransplantation.

  3. Stanley Fahn Lecture 2005: The staging procedure for the inclusion body pathology associated with sporadic Parkinson's disease reconsidered.

    PubMed

    Braak, Heiko; Bohl, Jürgen R; Müller, Christian M; Rüb, Udo; de Vos, Rob A I; Del Tredici, Kelly

    2006-12-01

    The synucleinopathy known as sporadic Parkinson's disease (PD) is a multisystem disorder that severely damages predisposed nerve cell types in circumscribed regions of the human nervous system. A recent staging procedure for the inclusion body pathology associated with PD proposes that, in the brain, the pathological process (formation of proteinaceous intraneuronal Lewy bodies and Lewy neurites) begins at two sites and continues in a topographically predictable sequence in six stages, during which components of the olfactory, autonomic, limbic, and somatomotor systems become progressively involved. In stages 1 to 2, the Lewy body pathology is confined to the medulla oblongata/pontine tegmentum and anterior olfactory structures. In stages 3 to 4, the substantia nigra and other nuclei of the basal mid- and forebrain become the focus of initially subtle and, then, severe changes. During this phase, the illness probably becomes clinically manifest. In the final stages 5 to 6, the lesions appear in the neocortex. This cross-sectional study originally was performed on 168 autopsy cases using material from 69 incidental cases and 41 clinically diagnosed PD patients as well as 58 age- and gender-matched controls. Here, the staging hypothesis is critically reconsidered and discussed.

  4. Multisensory body representation in autoimmune diseases.

    PubMed

    Finotti, Gianluca; Costantini, Marcello

    2016-02-12

    Body representation has been linked to the processing and integration of multisensory signals. An outstanding example of the pivotal role played by multisensory mechanisms in body representation is the Rubber Hand Illusion (RHI). In this paradigm, multisensory stimulation induces a sense of ownership over a fake limb. Previous work has shown high interindividual differences in the susceptibility to the RHI. The origin of this variability remains largely unknown. Given the tight and bidirectional communication between the brain and the immune system, we predicted that the origin of this variability could be traced, in part, to the immune system's functioning, which is altered by several clinical conditions, including Coeliac Disease (CD). Consistent with this prediction, we found that the Rubber Hand Illusion is stronger in CD patients as compared to healthy controls. We propose a biochemical mechanism accounting for the dependency of multisensory body representation upon the Immune system. Our finding has direct implications for a range of neurological, psychiatric and immunological conditions where alterations of multisensory integration, body representation and dysfunction of the immune system co-exist.

  5. Multisensory body representation in autoimmune diseases

    PubMed Central

    Finotti, Gianluca; Costantini, Marcello

    2016-01-01

    Body representation has been linked to the processing and integration of multisensory signals. An outstanding example of the pivotal role played by multisensory mechanisms in body representation is the Rubber Hand Illusion (RHI). In this paradigm, multisensory stimulation induces a sense of ownership over a fake limb. Previous work has shown high interindividual differences in the susceptibility to the RHI. The origin of this variability remains largely unknown. Given the tight and bidirectional communication between the brain and the immune system, we predicted that the origin of this variability could be traced, in part, to the immune system’s functioning, which is altered by several clinical conditions, including Coeliac Disease (CD). Consistent with this prediction, we found that the Rubber Hand Illusion is stronger in CD patients as compared to healthy controls. We propose a biochemical mechanism accounting for the dependency of multisensory body representation upon the Immune system. Our finding has direct implications for a range of neurological, psychiatric and immunological conditions where alterations of multisensory integration, body representation and dysfunction of the immune system co-exist. PMID:26867786

  6. Integrated analysis of genetic, behavioral, and biochemical data implicates neural stem cell-induced changes in immunity, neurotransmission and mitochondrial function in Dementia with Lewy Body mice.

    PubMed

    Lakatos, Anita; Goldberg, Natalie R S; Blurton-Jones, Mathew

    2017-03-10

    We previously demonstrated that transplantation of murine neural stem cells (NSCs) can improve motor and cognitive function in a transgenic model of Dementia with Lewy Bodies (DLB). These benefits occurred without changes in human α-synuclein pathology and were mediated in part by stem cell-induced elevation of brain-derived neurotrophic factor (BDNF). However, instrastriatal NSC transplantation likely alters the brain microenvironment via multiple mechanisms that may synergize to promote cognitive and motor recovery. The underlying neurobiology that mediates such restoration no doubt involves numerous genes acting in concert to modulate signaling within and between host brain cells and transplanted NSCs. In order to identify functionally connected gene networks and additional mechanisms that may contribute to stem cell-induced benefits, we performed weighted gene co-expression network analysis (WGCNA) on striatal tissue isolated from NSC- and vehicle-injected wild-type and DLB mice. Combining continuous behavioral and biochemical data with genome wide expression via network analysis proved to be a powerful approach; revealing significant alterations in immune response, neurotransmission, and mitochondria function. Taken together, these data shed further light on the gene network and biological processes that underlie the therapeutic effects of NSC transplantation on α-synuclein induced cognitive and motor impairments, thereby highlighting additional therapeutic targets for synucleinopathies.

  7. Impact of 15-deoxyspergualin on effector cells in experimental autoimmune diseases of the nervous system in the Lewis rat.

    PubMed Central

    Jung, S; Toyka, K V; Hartung, H P

    1994-01-01

    The influence of the immunosuppressive antibiotic agent 15-deoxyspergualin (DSG) on macrophages and autoreactive T helper lymphocytes from Lewis rats was analysed in vitro and in vivo. DSG did not inhibit antigen- or mitogen-induced proliferation of encephalitogenic or neuritogenic T helper cell lines in vitro. However, the presence of DSG during in vitro activation of the T cells strongly suppressed or completely abrogated their capacity to induce encephalitis (EAE) or neuritis (EAN) after adoptive transfer to naive rats, although expression of activation markers or adhesion molecules on the T line blasts was not down-regulated by DSG. Like activation-induced T cell proliferation, IL-2-dependent growth of CD4+ T line cells was not affected by DSG. Preincubation of CD4+ T line cells in DSG during IL-2-driven proliferation for 48 h, however, inhibited the subsequent antigen- but not mitogen-induced activation of these T cells, although neither density of T cell receptors nor other surface molecules involved in antigen recognition were lowered on the cells exposed to DSG. Similar to its effect in vitro, in vivo administration of DSG for 10 days even at a concentration with cumulative toxicity did not suppress in vitro proliferation of spleen cells induced by mitogen or a mitogenic combination of anti-CD2 antibodies. Furthermore, spleen cell and peripheral blood lymphocyte (PBL) surface antigens, particularly MHC molecules, were not altered by long-term treatment with DSG for 30 days. While there was a slight reduction in the number of polymorphonuclear cells in both populations, the proportion of the different leucocyte subpopulations remained unchanged. In contrast to the strong functional impact of DSG on autoreactive T helper cells, the drug did not inhibit the oxidative burst of macrophages or their MHC antigen expression. This study demonstrates a clear inhibitory effect of DSG on CD4+ T lymphocytes, but not macrophages. It provides an explanation for recent

  8. The Protein Complex of Neurodegeneration-related Phosphoinositide Phosphatase Sac3 and ArPIKfyve Binds the Lewy Body-associated Synphilin-1, Preventing Its Aggregation*

    PubMed Central

    Ikonomov, Ognian C.; Sbrissa, Diego; Compton, Lauren M.; Kumar, Rita; Tisdale, Ellen J.; Chen, Xuequn; Shisheva, Assia

    2015-01-01

    The 5-phosphoinositide phosphatase Sac3, in which loss-of-function mutations are linked to neurodegenerative disorders, forms a stable cytosolic complex with the scaffolding protein ArPIKfyve. The ArPIKfyve-Sac3 heterodimer interacts with the phosphoinositide 5-kinase PIKfyve in a ubiquitous ternary complex that couples PtdIns(3,5)P2 synthesis with turnover at endosomal membranes, thereby regulating the housekeeping endocytic transport in eukaryotes. Neuron-specific associations of the ArPIKfyve-Sac3 heterodimer, which may shed light on the neuropathological mechanisms triggered by Sac3 dysfunction, are unknown. Here we conducted mass spectrometry analysis for brain-derived interactors of ArPIKfyve-Sac3 and unraveled the α-synuclein-interacting protein Synphilin-1 (Sph1) as a new component of the ArPIKfyve-Sac3 complex. Sph1, a predominantly neuronal protein that facilitates aggregation of α-synuclein, is a major component of Lewy body inclusions in neurodegenerative α-synucleinopathies. Modulations in ArPIKfyve/Sac3 protein levels by RNA silencing or overexpression in several mammalian cell lines, including human neuronal SH-SY5Y or primary mouse cortical neurons, revealed that the ArPIKfyve-Sac3 complex specifically altered the aggregation properties of Sph1-GFP. This effect required an active Sac3 phosphatase and proceeded through mechanisms that involved increased Sph1-GFP partitioning into the cytosol and removal of Sph1-GFP aggregates by basal autophagy but not by the proteasomal system. If uncoupled from ArPIKfyve elevation, overexpressed Sac3 readily aggregated, markedly enhancing the aggregation potential of Sph1-GFP. These data identify a novel role of the ArPIKfyve-Sac3 complex in the mechanisms controlling aggregate formation of Sph1 and suggest that Sac3 protein deficiency or overproduction may facilitate aggregation of aggregation-prone proteins, thereby precipitating the onset of multiple neuronal disorders. PMID:26405034

  9. Symptoms of Lewy Body Dementia

    MedlinePlus

    ... usually memory problems, changes in their way of speaking, such as forgetting words, and personality problems. Cognitive symptoms of dementia include poor problem solving, difficulty with learning new skills and impaired decision making. Other causes of dementia ...

  10. Fractal dynamics of body motion in patients with Parkinson's disease.

    PubMed

    Sekine, Masaki; Akay, Metin; Tamura, Toshiyo; Higashi, Yuji; Fujimoto, Toshiro

    2004-03-01

    In this paper, we assess the complexity (fractal measure) of body motion during walking in patients with Parkinson's disease. The body motion of 11 patients with Parkinson's disease and 10 healthy elderly subjects was recorded using a triaxial accelerometry technique. A triaxial accelerometer was attached to the lumbar region. An assessment of the complexity of body motion was made using a maximum-likelihood-estimator-based fractal analysis method. Our data suggest that the fractal measures of the body motion of patients with Parkinson's disease are higher than those of healthy elderly subjects. These results were statistically different in the X (anteroposterior), Y (lateral) and Z (vertical) directions of body motion between patients with Parkinson's disease and the healthy elderly subjects (p < 0.01 in X and Z directions and p < 0.05 in Y direction). The complexity (fractal measure) of body motion can be useful to assess and monitor the output from the motor system during walking in clinical practice.

  11. The Role of Nuclear Bodies in Gene Expression and Disease

    PubMed Central

    Morimoto, Marie; Boerkoel, Cornelius F.

    2013-01-01

    This review summarizes the current understanding of the role of nuclear bodies in regulating gene expression. The compartmentalization of cellular processes, such as ribosome biogenesis, RNA processing, cellular response to stress, transcription, modification and assembly of spliceosomal snRNPs, histone gene synthesis and nuclear RNA retention, has significant implications for gene regulation. These functional nuclear domains include the nucleolus, nuclear speckle, nuclear stress body, transcription factory, Cajal body, Gemini of Cajal body, histone locus body and paraspeckle. We herein review the roles of nuclear bodies in regulating gene expression and their relation to human health and disease. PMID:24040563

  12. Bernard Lewis: An Appreciation.

    ERIC Educational Resources Information Center

    Humphreys, R. Stephen

    1990-01-01

    Discusses the career and publications of Bernard Lewis, a noted scholar in the field of Middle-Eastern studies and Islamic history. Traces the history of Western-based Islamic historiography. Examines Lewis' interpretation of Islamic history, outlining his political and social views. (RW)

  13. Discovering Lewis and Clark

    ERIC Educational Resources Information Center

    Olsen, Ken

    2006-01-01

    Writer and historian Bernard DeVoto observed more than 50 years ago that a dismaying amount of American history has been written without regards to the Indians. Such disregard is glaring in many mainstream stories of Meriwether Lewis and William Clark. Lewis and Clark began preparing for their historic journey in 1803 and officially launched the…

  14. Arthritis in Lewis rats induced by the non-immunogenic adjuvant CP20961: an immunohistochemical analysis of the developing disease.

    PubMed Central

    Meacock, S C; Brandon, D R; Billingham, M E

    1994-01-01

    OBJECTIVES--The role of lymphocytes and macrophages in developing adjuvant arthritis induced by an injection of CP20961 in inbred Lewis rats was studied over a 32 day period using a novel biotin-avidin immunoperoxidase histochemical technique. METHODS--Fresh frozen sections of hind paws and spleens, as well as lymph nodes draining the site of the injected adjuvant were immunostained using a panel of monoclonal antibodies specific for subsets of lymphocytes and macrophages and for MHC Class II antigen. RESULTS--An increase in the numbers of activated T-lymphocytes was detected early in the draining lymph nodes before hind paw swelling had begun. The presence of these cells in significant numbers was only observed in the vicinity of the joint after joint swelling and damage had begun. Macrophages were among the first cells to invade the swollen paws and later were found with T-lymphocytes and cells bearing the MHC class II antigen at the face of eroding and re-organising bone. CONCLUSIONS--The activity of T-lymphocytes in initiating arthritis appeared to occur early in lymph nodes. Joint destruction was more closely associated with the arrival of macrophages but later arrival of T-lymphocytes may have contributed to the maintenance of chronic inflammation. Images PMID:7979577

  15. Body temperature variability (Part 2): masking influences of body temperature variability and a review of body temperature variability in disease.

    PubMed

    Kelly, Gregory S

    2007-03-01

    This is the second of a two-part review on body temperature variability. Part 1 discussed historical and modern findings on average body temperatures. It also discussed endogenous sources of temperature variability, including variations caused by site of measurement; circadian, menstrual, and annual biological rhythms; fitness; and aging. Part 2 reviews the effects of exogenous masking agents - external factors in the environment, diet, or lifestyle that can be a significant source of body temperature variability. Body temperature variability findings in disease states are also reviewed.

  16. The neuromythology of Parkinson's Disease.

    PubMed

    Calne, Donald B; Mizuno, Yoshikuni

    2004-07-01

    Over the last century three central points have become the orthodox dogma accepted and taught by those who study Parkinson's Disease. These are: Parkinson's Disease is one disease. Lewy bodies in the substantia nigra are an acceptable hallmark of Parkinson's Disease. Lewy bodies are responsible for the death of nigral neurons in Parkinson's Disease. Each of these tenets now present difficulties, and we are beginning to enter an era in which we must look critically at the current evidence to decide whether each dictum can be sustained.

  17. Abnormal blood rheology and chronic low grade inflammation: possible risk factors for accelerated atherosclerosis and coronary artery disease in Lewis negative subjects

    PubMed Central

    Alexy, Tamas; Pais, Eszter; Wenby, Rosalinda B.; Mack, Wendy J.; Hodis, Howard N.; Kono, Naoko; Wang, Jun; Baskurt, Oguz K.; Fisher, Timothy C.; Meiselman, Herbert J.

    2015-01-01

    Objective To test the hypothesis that abnormal hemorheology and chronic low-grade inflammation are more prevalent in Lewis negative individuals, possibly contributing to premature atherosclerosis. Methods and Results We enrolled 223 healthy subjects (154 females, mean age: 64yrs). Conventional risk factors, markers of inflammation and hemorheological profiles were measured; Lewis blood group was determined by serology. Conventional risk factors (age, gender, BMI, blood pressure, lipid profile, smoking habit) did not differ among Lewis phenotypes. However, markers of inflammation (WBC, hs-CRP, ESR) were significantly elevated and rheological parameters (RBC aggregation, plasma viscosity) were abnormal in Lewis negative subjects, especially when compared to the Le(a−b+) group. Conclusions With a prevalence of 33% in select populations, our data support the hypothesis that Le(a−b−) represents a pro-inflammatory phenotype that may contribute to the elevated cardiovascular risk in this group. PMID:25626016

  18. Mechanisms of body weight fluctuations in Parkinson's disease.

    PubMed

    Kistner, Andrea; Lhommée, Eugénie; Krack, Paul

    2014-01-01

    Typical body weight changes are known to occur in Parkinson's disease (PD). Weight loss has been reported in early stages as well as in advanced disease and malnutrition may worsen the clinical state of the patient. On the other hand, an increasing number of patients show weight gain under dopamine replacement therapy or after surgery. These weight changes are multifactorial and involve changes in energy expenditure, perturbation of homeostatic control, and eating behavior modulated by dopaminergic treatment. Comprehension of the different mechanisms contributing to body weight is a prerequisite for the management of body weight and nutritional state of an individual PD patient. This review summarizes the present knowledge and highlights the necessity of evaluation of body weight and related factors, as eating behavior, energy intake, and expenditure in PD.

  19. Mechanisms of Body Weight Fluctuations in Parkinson’s Disease

    PubMed Central

    Kistner, Andrea; Lhommée, Eugénie; Krack, Paul

    2014-01-01

    Typical body weight changes are known to occur in Parkinson’s disease (PD). Weight loss has been reported in early stages as well as in advanced disease and malnutrition may worsen the clinical state of the patient. On the other hand, an increasing number of patients show weight gain under dopamine replacement therapy or after surgery. These weight changes are multifactorial and involve changes in energy expenditure, perturbation of homeostatic control, and eating behavior modulated by dopaminergic treatment. Comprehension of the different mechanisms contributing to body weight is a prerequisite for the management of body weight and nutritional state of an individual PD patient. This review summarizes the present knowledge and highlights the necessity of evaluation of body weight and related factors, as eating behavior, energy intake, and expenditure in PD. PMID:24917848

  20. Increase in body weight after pramipexole treatment in Parkinson's disease.

    PubMed

    Kumru, Hatice; Santamaria, Joan; Valldeoriola, Francesc; Marti, Maria J; Tolosa, Eduardo

    2006-11-01

    Body weight changes occur during the clinical course of Parkinson's disease (PD) and with surgical treatment, but the effect of dopaminergic treatment on weight is unknown. Body mass index (BMI), Hamilton depression scale score (HDS), and Unified Parkinson's Disease Rating Scale III (UPRS-III) were measured before and 3 months after starting pramipexole in 28 PD patients. Pramipexole produced a significant weight increase, as well as motor and mood improvement (P <0.001). HDS and BMI changes were mildly related (P = 0.05). A direct effect of pramipexole on limbic D(3) receptors involved in the control of feeding may be responsible for weight gain in PD.

  1. Modifications to Ivor Lewis esophagectomy.

    PubMed

    David, Elizabeth A; Marshall, M Blair

    2010-11-01

    The surgical approach to esophagectomy is variable. A number of factors are considered when determining the optimal approach to esophagectomy: location and extent of disease, fibrosis, additional patient factors and surgeon preference. One of the disadvantages to some approaches is the need for a change in position, which increases operative time. Also, because typically the abdomen is initially explored, patients may later be deemed unresectable at thoracotomy. We describe time saving modifications to the standard Ivor Lewis esophagectomy that eliminate the need for repositioning and facilitate a stapled end-to-end anastomosis.

  2. Population pharmacokinetic-pharmacodynamic-disease progression model for effects of anakinra in Lewis rats with collagen-induced arthritis.

    PubMed

    Liu, Dongyang; Lon, Hoi-Kei; Dubois, Debra C; Almon, Richard R; Jusko, William J

    2011-12-01

    A population pharmacokinetic-pharmacodynamic-disease progression (PK/PD/DIS) model was developed to characterize the effects of anakinra in collagen-induced arthritic (CIA) rats and explore the role of interleukin-1β (IL-1β) in rheumatoid arthritis. The CIA rats received either vehicle, or anakinra at 100 mg/kg for about 33 h, 100 mg/kg for about 188 h, or 10 mg/kg for about 188 h by subcutaneous infusion. Plasma concentrations of anakinra were assayed by enzyme-linked immunosorbent assay. Swelling of rat hind paws was measured. Population PK/PD/DIS parameters were computed for the various groups using non-linear mixed-effects modeling software (NONMEM® Version VI). The final model was assessed using visual predictive checks and nonparameter stratified bootstrapping. A two-compartment PK model with two sequential absorption processes and linear elimination was used to capture PK profiles of anakinra. A transduction-based feedback model incorporating logistic growth rate captured disease progression and indirect response model I captured drug effects. The PK and paw swelling versus time profiles in CIA rats were fitted well. Anakinra has modest effects (I ( max ) = 0.28) on paw edema in CIA rats. The profiles are well-described by our PK/PD/DIS model which provides a basis for future mechanism-based assessment of anakinra dynamics in rheumatoid arthritis.

  3. Mind-Body Interventions for Pediatric Inflammatory Bowel Disease.

    PubMed

    Yeh, Ann Ming; Wren, Anava; Golianu, Brenda

    2017-04-03

    Pediatric inflammatory bowel disease is an autoimmune disease that causes chronic inflammation of the gastrointestinal mucosa. There is emerging evidence that the brain-gut connection affects inflammatory bowel disease (IBD) patients more than previously thought. This is evidenced by comorbid mood disorders, irritable bowel symptoms concurrent with quiescent IBD, and the potential of psychosocial stressors to trigger IBD flares. Mind-body interventions such as psychotherapy, relaxation, mindfulness, biofeedback, yoga, and clinical hypnosis offer an adjunct to standard medical treatment for IBD. We will review the current evidence base for these mind- body interventions in the treatment of pediatric IBD, illustrate a case study, and offer suggestions for future research for this promising field.

  4. The thymus in myasthenia gravis. Changes typical for the human disease are absent in experimental autoimmune myasthenia gravis of the Lewis rat.

    PubMed Central

    Meinl, E.; Klinkert, W. E.; Wekerle, H.

    1991-01-01

    In human myasthenia gravis (MG) formation of autoantibodies against acetylcholine receptor (AChR) is commonly associated with thymic changes termed lymphofollicular hyperplasia (LFH). To learn whether the thymic lesions of human MG are primary changes in the autoimmune pathogenesis, or rather secondary events caused by peripheral autoimmunization, the authors compared the pathologic changes of MG thymuses with the thymuses of Lewis rats with experimental autoimmune myasthenia gravis (EAMG). EAMG was induced either actively by immunization with AChR, or transferred passively with monoclonal antibodies (mAb) binding to AChR. The clinical diagnosis of EAMG was confirmed by electromyography. Germinal centers, which are typical for human MG thymuses, were not detectable in the thymus of EAMG rats. Scattered B cells were seen as normal components of the thymic medulla. In EAMG their number was not augmented, nor were they accumulated focally. The perivascular spaces (PVS) were not distended and the amount of reticulin was not increased. Thymic myoid cells were identified in EAMG as well as in control thymuses; their cellular microenvironment was inconspicuous. Both in normal and in EAMG thymuses, a subpopulation of myoid cells expressed the main immunogenic region of the AChR. Heavily affected rats showed a severe cortical involution, but no specific changes of the medulla. The fact that none of the thymic lesions characteristic for human MG was found in EAMG is compatible with the concept that the thymic changes in MG are primary events in the autoimmune pathogenesis of this disease. Images Figure 1 Figure 2 Figure 3 Figure 4 Figure 5 Figure 6 Figure 7 PMID:1951638

  5. Targeting ADAM12 in human disease: head, body or tail?

    PubMed

    Jacobsen, J; Wewer, U M

    2009-01-01

    ADAM12/meltrin alpha is a type I transmembrane multidomain protein involved in tumor progression and other severe diseases, including osteoarthritis, and as such could be considered as a potential drug target. In addition to protease activity, ADAM12 possesses cell binding and cell signaling properties. This functional trinity is reflected in the structure of ADAM12, which can be divided into head, body, and tail. The head of the protein (consisting of the pro and catalytic domains) mediates processing of growth factors and cytokines and has been implicated in epidermal growth factor (EGF) and insulin-like growth factor receptor signaling. The body of the protein (consisting of the disintegrin, cysteine-rich, and EGF-like domains) is involved in contacts with the extracellular matrix and other cells through interactions with integrins and syndecans. Finally, the tail of the protein (consisting of the cytoplasmic domain) is engaged in interactions with intracellular signaling molecules. In many studies, ADAM12 overexpression has been correlated with disease, and ADAM12 has been shown to promote tumor growth and progression in cancer. On the other hand, protective effects of ADAM12 in disease have also been reported. Future investigations should address the precise mechanisms of ADAM12 in disease and biology in order to counterbalance the benefits from targeting ADAM12 therapeutically with possible side effects. This review describes the biology of ADAM12, its association with disease, and evaluates the possible approaches to targeting ADAM12 in human disease.

  6. Body composition and calcium metabolism in adult treated coeliac disease.

    PubMed Central

    Bodé, S; Hassager, C; Gudmand-Høyer, E; Christiansen, C

    1991-01-01

    Twenty two treated adult patients with coeliac disease (aged 20-70 years) were examined. Body composition was assessed from anthropometry and directly measured by dual photon absorptiometry. Bone mineral content was measured in the spine (dual photon absorptiometry) and at two forearm sites (single photon absorptiometry). Compared with age matched healthy subjects, treated coeliac patients had lower body mass index (-5%, p less than 0.05) and lower directly measured total body fat mass (-30%, p less than 0.001). They also had decreased bone mineral content (-9 to -13%, p less than 0.01) in the spine and in the forearms. The serum concentrations of albumin, D vitamin binding protein, and iron were reduced (-6 to -22%, p less than 0.01), but otherwise blood and urine analyses were normal. We conclude that this group of treated adult coeliac patients had a reduced fat mass and bone mineral content compared with the general population. PMID:1752465

  7. A Novel Human Body Area Network for Brain Diseases Analysis.

    PubMed

    Lin, Kai; Xu, Tianlang

    2016-10-01

    Development of wireless sensor and mobile communication technology provide an unprecedented opportunity for realizing smart and interactive healthcare systems. Designing such systems aims to remotely monitor the health and diagnose the diseases for users. In this paper, we design a novel human body area network for brain diseases analysis, which is named BABDA. Considering the brain is one of the most complex organs in the human body, the BABDA system provides four function modules to ensure the high quality of the analysis result, which includes initial data collection, data correction, data transmission and comprehensive data analysis. The performance evaluation conducted in a realistic environment with several criteria shows the availability and practicability of the BABDA system.

  8. Body mass index is reduced early in Parkinson's disease.

    PubMed

    Cheshire, William P; Wszolek, Zbigniew K

    2005-01-01

    Mean body mass index (BMI) in 100 cases of idiopathic Parkinson's disease (PD) was found to be 9% reduced in comparison to that in patients with either essential tremor or no neurologic disease. A similar reduction in BMI was also discovered among the 24 cases of PD in whom retrospective BMI data were available from their presymptomatic years. These results suggest that alterations in nutrient intake or metabolism could reflect early changes in the central autonomic network preceding the emergence of classical extrapyramidal manifestations of PD.

  9. 123I-Meta-iodobenzylguanidine Sympathetic Imaging: Standardization and Application to Neurological Diseases

    PubMed Central

    Yamada, Masahito

    2016-01-01

    123I-meta-iodobenzylguanidine (MIBG) has become widely applied in Japan since its introduction to clinical cardiology and neurology practice in the 1990s. Neurological studies found decreased cardiac uptake of 123I-MIBG in Lewy-body diseases including Parkinson's disease and dementia with Lewy bodies. Thus, cardiac MIBG uptake is now considered a biomarker of Lewy body diseases. Although scintigraphic images of 123I-MIBG can be visually interpreted, an average count ratio of heart-to-mediastinum (H/M) has commonly served as a semi-quantitative marker of sympathetic activity. Since H/M ratios significantly vary according to acquisition and processing conditions, quality control should be appropriate, and quantitation should be standardized. The threshold H/M ratio for differentiating Lewy-body disease is 2.0-2.1, and was based on standardized H/M ratios to comparable values of medium-energy collimators. Parkinson's disease can be separated from various types of parkinsonian syndromes using cardiac 123I-MIBG, whereas activity is decreased on images of Lewy-body diseases using both 123I-ioflupane for the striatum and 123I-MIBG. Despite being a simple index, the H/M ratio of 123I-MIBG uptake is reproducible and can serve as an effective tool to support a diagnosis of Lewy-body diseases in neurological practice. PMID:27689024

  10. [An old "new" disease: body dysmorphic disorder (dysmorphophobia)].

    PubMed

    Szabó, Pál

    2010-10-31

    Body dysmorphic disorder causes significant suffering and serious impairment in psychosocial functions. However, this disease with dangerous risks is scarcely mentioned in the Hungarian medical literature. The objective of the author is to give a detailed review about this almost unknown, but relatively common disorder. The serious disorder of body perception is in the centre of symptoms, leading to social isolation, anxiety, depression and obsessive-compulsive phenomena. The disorder often remains unrecognized because of the lack of insight of disease. Comorbidity with affective disorders, anxiety disorders, personality disorders, eating disorders, alcoholism and substance use disorders is common. The life quality of affected patients is bad, the risk of suicide or violence is high. Biological, psychological and sociocultural factors play an important role in the etiopathogenesis of the disorder. Imaging techniques and neuropsychological measures revealed changes characteristic for the disease. Childhood abuse and neglect, appearance-related critical remarks, stressors and the impact of media are also supposed to have role in the development of the disorder. The point prevalence is 0.7-2.5% in the general population, however, in special groups such as in tertiary students, psychiatric, dermatological and cosmetic surgery patients the prevalence rates may be much higher. Typically, the disease begins in early adolescence, and it persists and deteriorates without treatment, showing a chronic course. By means of pharmacotherapy and/or psychotherapy long-during improvement or full recovery can be achieved within a relatively short period of time.

  11. Body mass index in Parkinson's disease: a meta-analysis.

    PubMed

    van der Marck, Marjolein A; Dicke, Heleen C; Uc, Ergun Y; Kentin, Zippora H A; Borm, George F; Bloem, Bastiaan R; Overeem, Sebastiaan; Munneke, Marten

    2012-03-01

    Prior work suggested that patients with Parkinson's disease (PD) have a lower Body Mass Index (BMI) than controls, but evidence is inconclusive. We therefore conducted a meta-analysis on BMI in PD. We searched MEDLINE, EMBASE, Cinahl and Scopus to identify cohort studies on BMI in PD, published before February 2011. Studies that reported mean BMI for PD patients and healthy controls were eligible. Twelve studies were included, with a total of 871 patients and 736 controls (in three studies controls consisted of subjects from other published studies). Our primary aim was to assess differences in BMI between patients and controls; this was analyzed with random effects meta-analysis. Our secondary aim was to evaluate the relation with disease severity (Hoehn and Yahr stage) and disease duration, using random effects meta-regression. PD patients had a significantly lower BMI than controls (overall effect 1.73, 95% CI 1.11-2.35, P<0.001). Pooled data of seven studies showed that patients with Hoehn and Yahr stage 3 had a lower BMI than patients with stage 2 (3.9, 95% CI 0.1-7.7, P<0.05). Disease duration was not associated with BMI. Because a low body weight is associated with negative health effects and a poorer prognosis, monitoring weight and nutritional status should be part of PD management.

  12. Edwin W. Lewis, Jr.

    NASA Technical Reports Server (NTRS)

    1999-01-01

    Edwin W. Lewis Jr. is a research pilot in the Airborne Science program, Flight Crew Branch, Dryden Flight Research Center, Edwards, California. He currently flies the DC-8, F/A-18, Lear Jet 24, King Air, and T-34C in support of Dryden's flight operations and is mentor pilot for the King Air and the Lear Jet. Prior to accepting this assignment Lewis was a pilot for eight years at NASA's Ames Research Center, Moffett Field, California, flying 10 different aircraft - C-130B, DC-8-72, UH-1, SH-3, King Air, Lear 24, T-38A, T-39G and YO-3A - in support of NASA flight missions. Lewis also flew the Kuiper Airborne Observatory (a modified civilian version of the Lockheed C-141 Starlifter). He was project pilot for Ames' 747 and T-38 programs. Lewis was born in New York City on May 19, 1936, and began flight training as a Civil Air Patrol cadet in 1951, ultimately earning his commercial pilot's certificate in 1958. He received a bachelor of arts degree in biology from Hobart College, Geneva, N.Y., and entered the U.S. Air Force through the Reserve Officer Training Corps. Following pilot training he was assigned to Moody Air Force Base, Ga., as an instructor pilot, for both the T-33 and T-37 aircraft. He served in Vietnam in 1965 and 1966, where he was a forward air controller, instructor and standardization/evaluation pilot, flying more than 1,000 hours in the O-1 'Bird Dog.' Lewis separated from the regular Air Force and joined Pan American World Airways and the 129th Air Commando Group, California Air National Guard (ANG) based in Hayward, California. During his 18-year career with the California ANG he flew the U-6, U-10, C-119, HC-130 aircraft and the HH-3 helicopter. He retired as commander, 129th Air Rescue and Recovery Group, a composite combat rescue group, in the grade of colonel. During his 22 years as an airline pilot, he flew the Boeing 707, 727 and 747. He took early retirement from Pan American in 1989 to become a pilot with NASA.

  13. Weibel-Palade bodies: a window to von Willebrand disease.

    PubMed

    Valentijn, K M; Eikenboom, J

    2013-04-01

    Weibel-Palade bodies (WPBs) are the storage organelles for von Willebrand factor (VWF) in endothelial cells. VWF forms multimers that assemble into tubular structures in WPBs. Upon demand, VWF is secreted into the blood circulation, where it unfolds into strings that capture platelets during the onset of primary hemostasis. Numerous mutations affecting VWF lead to the bleeding disorder von Willebrand disease. This review reports the recent findings on the effects of VWF mutations on the biosynthetic pathway of VWF and its storage in WPBs. These new findings have deepened our understanding of VWF synthesis, storage, secretion, and function.

  14. Lewis base activation of Lewis acids: development of a Lewis base catalyzed selenolactonization.

    PubMed

    Denmark, Scott E; Collins, William R

    2007-09-13

    The concept of Lewis base activation of Lewis acids has been applied to the selenolactonization reaction. Through the use of substoichiometric amounts of Lewis bases with "soft" donor atoms (S, Se, P) significant rate enhancements over the background reaction are seen. Preliminary mechanistic investigations have revealed the resting state of the catalyst as well as the significance of a weak Brønsted acid promoter.

  15. [Dobutamine stress body surface mapping in Kawasaki disease].

    PubMed

    Seki, T; Zhang, J; Ogawa, S; Hirayama, T

    1994-11-01

    The dobutamine (DOB) stress body surface mapping tests were carried out to detect myocardial ischemia in 23 patients who had Kawasaki disease previously. Eight of 23 patients (group A) had coronary stenosis of 75% or more diameter reduction in major coronary arteries without sufficient collateral flow, as shown by the coronary angiography, but without myocardial infarction. Nine patients (group B) showed no ischemic change exercised 201Tl myocardial scintigram. Six patients (group C) had myocardial infarction due to Kawasaki disease. ST segment potential mapping (0.04 sec after the J point in QRS) and ST-T Isointegral mapping were performed using CVM-3000 system (87 leads), and the following calculations were made: number of leads with horizontal or down-sloping ST depression of 0.10 mV or more, lasting 0.08 sec (nST); row number of the minimum lead in the Isointegral map (Imin); number of positive leads on the seventh row in Isointegral mapping (I-7); number of positive leads on the first row in Isointegral mapping (I-1) and I-7/I-1 ratio. Based on these calculations the criteria for detecting myocardial ischemia (nST < or = 2, Imin < or = 2, I-7/I-1 > or = 1) were created and their usefulness was tested using findings of coronary angiography and exercised 201Tl myocardial scintigram as the golden standard. For the diagnosis of ischemic lesion, the DOB stress body surface mapping test in group A had higher specificity (nST: 100%, Imin: 89%, I-7/I-1: 100% vs. 78%) and higher sensitivity (75%, 50%, 63% vs. 38%), than those by the Treadmill test, while ischemic changes were not detected in group C by this test. From these results it is concluded that it is useful in evaluating ischemic heart disease in children who can not perform Treadmill exercised test adequately.

  16. Chronic disease trends due to excess body weight in Australia.

    PubMed

    Atlantis, E; Lange, K; Wittert, G A

    2009-09-01

    Trends in chronic diseases provide insights into strategies required to improve population health. The authors determined prevalence and multiple-adjusted population attributable risk (PAR) estimates of chronic diseases because of lifestyle factors among Australian adults between 1989-90 and 2004-5, accounting for demographic factors. Between 1989-90 and 2004-5, prevalence increased for diabetes (3.8-6.0%, P < 0.001) and high cholesterol (11.3-13.9%, P < 0.001), but decreased for high blood pressure (21.4-20.4%, P = 0.003) and cardiovascular disease (CVD, 6.2-5.4%, P < 0.001). Prevalence increased for body mass index (BMI) 25-29.9 (30.3-34.9%, P < 0.001), BMI 30-34.9 (7.4-13.5%, P < 0.001) and BMI 35+ (2.1-5.4%, P < 0.001), but decreased for metabolic equivalent-hours per week (MET-hr/week) 0 (36.8-33.1%, P < 0.001) and current smokers (27.6-24.4%, P < 0.001). Diabetes, high cholesterol and high blood pressure burden increased mostly for 60+ years, lowest income quintiles and high BMI (30-34.9 and 35+). Diabetes and CVD burden increased mostly for MET-hr/week 0. Many chronic disease cases would have been theoretically prevented if adults had no prior exposure to BMI 25-29.9 (PAR 9-17%), BMI 30+ (PAR 1-14%) and MET-hr/week 0 (PAR 6-14%). Reducing exposure to lifestyle hazards across the lifespan is required for reversing the rising burden of chronic diseases. Decreases in CVD and high blood pressure prevalence were likely due to targeted improvements in health care, indicating that more can and should be done.

  17. A disease resembling inclusion body disease of boid snakes in captive palm vipers (Bothriechis marchi).

    PubMed

    Raymond, J T; Garner, M M; Nordhausen, R W; Jacobson, E R

    2001-01-01

    Between April 1998 and June 1999, 8 palm vipers (Bothriechis marchi) were diagnosed with a disease similar to inclusion body disease (IBD) of boids. Six palm vipers were captive bred, and 2 were wild caught. All of the vipers were adults at the time of death. Three palm vipers were found dead with no premonitory clinical signs, and 5 had anorexia plus possibly 1 of the following clinical signs: regurgitation, paresis, and dehydration. Histologically, all snakes had intracytoplasmic, round to oval, single to multiple eosinophilic inclusion bodies in hepatocytes and renal tubular epithelial cells. Inclusion bodies were distributed among other organs with varying frequency. Common concurrent histologic lesions were urate nephrosis, septic thrombi, and hepatocellular degeneration. Ultrastructurally, inclusions had features similar to inclusions in boid snakes with IBD.

  18. Lewis Incubator for Technology (LIFT)

    NASA Technical Reports Server (NTRS)

    Zeman, Wayne P.; King, Joseph B.; Jankura, Richard E., Jr.

    2004-01-01

    This report summarizes the work done to operate the Lewis Incubator for Technology for the period October 2000 through September 2004. The Lewis Incubator helped the startup and growth of technology based businesses with the potential to incorporate technology from the NASA Glenn Research Center.

  19. Meriwether Lewis: Was it Suicide?

    ERIC Educational Resources Information Center

    Westefeld, John S.; Less, Aaron

    2004-01-01

    Even 200 years following the conclusion of the Lewis and Clark Expedition, questions remain about whether Meriwether Lewis' death was a suicide. The purpose of this article is to consider this issue by examining historical evidence from a psychological perspective. A risk factor model for suicide assessment (Sanchez, 2001) is employed to evaluate…

  20. Body weight, diet and water intake in preventing stone disease.

    PubMed

    Meschi, Tiziana; Schianchi, Tania; Ridolo, Erminia; Adorni, Giuditta; Allegri, Franca; Guerra, Angela; Novarini, Almerico; Borghi, Loris

    2004-01-01

    Nutrition plays a major role in the pathogenesis of the most widespread forms of nephrolithiasis, i.e. calcium (calcium oxalate and phosphate) and uric acid stone disease. For this reason, dietary measures are the first level of intervention in primary prevention, as well as in secondary prevention of recurrences. An unbalanced diet or particular sensitivity to various foods in stone formers can lead to urinary alterations such as hypercalciuria, hyperoxaluria, hyperuricosuria, hypocitraturia and an excessively acid urinary pH. Over the course of time, these conditions contribute to the formation or recurrence of kidney stones, due to the effect they exert on the lithogenous salt profile. The fundamental aspects of the nutritional approach to the treatment of idiopathic nephrolithiasis are body weight, diet and water intake. This paper will present data resulting from our own investigations and the most significant evidence in literature.

  1. Esophageal body motility in achalasia and Chagas' disease.

    PubMed

    Abrahão, L J; de Oliveira Lemme, E M

    2011-07-01

    Previous studies have correlated esophageal body motility findings in idiopathic (IdAc) achalasia and achalasia secondary to Chagas' disease (ChAc) with degree of megaesophagus. The aim of this study was to compare esophageal body manometric data in patients with IdAc and achalasia secondary to Chagas' disease and correlate it with the degree of megaesophagus and symptom duration. One hundred nontreated patients with achalasia, 79% IdAc and 21% secondary to ChAc were compared with regards to age of presentation, duration of symptoms, amplitude and duration of simultaneous contractions, frequency of failed contractions, and degree of megaesophagus. Seventy-one percent of patients were classified as nonadvanced megaesophagus (60 [76%] with IdAc and 11 [52%] with ChAc) and 29% as advanced megaesophagus (19 [24%] with IdAc and 10 [48%] with ChAc, P= 0.04). In IdAc but not in ChAc, the symptom duration was significantly longer in advanced megaesophagus (A) compared with nonadvanced megaesophagus (NA) (34.8 ± 6.3 months vs. 95.4 ± 22.2 months, P= 0.001). There was no difference in amplitude and duration of simultaneous contractions in both achalasia groups (P > 0.05). Duration of contractions were longer in IdAc compared with ChAc in (NA) (P < 0.05), but not in (A). In IdAc but not in ChAc the amplitude of simultaneous contractions decreased with increased esophageal dilatation (P < 0.05). In ChAc but not in IdAC, the duration of contractions increased with esophageal dilatation (P < 0.05). Failed contractions were more frequent in ChAc group (28.6%) than in IdAc (10% -P= 0.03). Patients with ChAc have a higher prevalence of advanced megaesophagus compared with IdAc at diagnosis. In IdAc there was a strong correlation between advanced megaesophagus and longer symptom duration, suggesting disease progression over time, not observed in ChAc in which a more extensive denervation occurs earlier in the disease process.

  2. Lewy Body Digest eNewsletter

    MedlinePlus

    ... Host a LBD5K fundraise First Giving Fundraising Everyday Hero raise awareness awareness month photos raise LBD awareness ... LBDA December 2016 Newsletter A Father and Son Journey Giving is Easy with Amazon Resources Available to ...

  3. Body composition and dietary intake in neoplasic disease

    SciTech Connect

    Cohn, S.H.; Gartenhaus, W.; Vartsky, D.; Sawitsky, A.; Zanzi, I.; Vaswani, A. Yasummure, S.; Rai, K.; Cartes, E.; Ellis, K.J.

    1981-10-01

    Changes in body composition in 37 cancer patients were studied over a period of 6 months. Initially, the patients were divided into two groups: those who lost body weight (over 10%) and those who maintained or gained body weight before the study. Analysis of body composition indicated that patients who lost body weight has caloric and protein intakes markedly below ''normal'' levels at the beginning of the study. There also appears to be a direct relationship between the protein intake and the total body potassium/total body water ratio in the cancer patients. At the end of the 6-month study, the patients were again placed into two groups on the basis of weight loss or gain (and maintenance). Changes in body composition over the period were analyzed in terms of lean body mass, its protein constituent, water, and fat. Weight loss was found to reflect primarily the loss of fat, water, lean body mass (potassium), and only to a minor extent the protein component of lean body mass (nitrogen). Further, on the basis of the values of the ratios of total body nitrogen/total body potassium/total body water, it was possible to ascertain the relative normalcy of the body tissue gained or lost in the 6-month period. The results of the study suggest that the ratio total body nitrogen/total body potassium may serve as the best indicator of recent or ongoing catabolism or anabolism of the neoplastic process. By means of the application of the techniques used for the determination of body composition, it should be possible to assess regimes of hyperalimentation of cancer patients who lose body weight. (JMT)

  4. Carotid body, insulin, and metabolic diseases: unraveling the links

    PubMed Central

    Conde, Sílvia V.; Sacramento, Joana F.; Guarino, Maria P.; Gonzalez, Constancio; Obeso, Ana; Diogo, Lucilia N.; Monteiro, Emilia C.; Ribeiro, Maria J.

    2014-01-01

    The carotid bodies (CB) are peripheral chemoreceptors that sense changes in arterial blood O2, CO2, and pH levels. Hypoxia, hypercapnia, and acidosis activate the CB, which respond by increasing the action potential frequency in their sensory nerve, the carotid sinus nerve (CSN). CSN activity is integrated in the brain stem to induce a panoply of cardiorespiratory reflexes aimed, primarily, to normalize the altered blood gases, via hyperventilation, and to regulate blood pressure and cardiac performance, via sympathetic nervous system (SNS) activation. Besides its role in the cardiorespiratory control the CB has been proposed as a metabolic sensor implicated in the control of energy homeostasis and, more recently, in the regulation of whole body insulin sensitivity. Hypercaloric diets cause CB overactivation in rats, which seems to be at the origin of the development of insulin resistance and hypertension, core features of metabolic syndrome and type 2 diabetes. Consistent with this notion, CB sensory denervation prevents metabolic and hemodynamic alterations in hypercaloric feed animal. Obstructive sleep apnea (OSA) is another chronic disorder characterized by increased CB activity and intimately related with several metabolic and cardiovascular abnormalities. In this manuscript we review in a concise manner the putative pathways linking CB chemoreceptors deregulation with the pathogenesis of insulin resistance and arterial hypertension. Also, the link between chronic intermittent hypoxia (CIH) and insulin resistance is discussed. Then, a final section is devoted to debate strategies to reduce CB activity and its use for prevention and therapeutics of metabolic diseases with an emphasis on new exciting research in the modulation of bioelectronic signals, likely to be central in the future. PMID:25400585

  5. Kainate Receptors in the Striatum: Implications for Excitotoxicity in Huntington’s Disease

    DTIC Science & Technology

    2005-08-01

    disease, Lewy bodies are found in CM-PF, pants switch from a relaxed awake state to an attention- and in PSP, abundant intracellular neurofibrillary and...Award from Merck/Center for Neurodegenerative Diseases at Emory University. 6. REFERENCES Bevan, M.D., Magill, P.J., Terman , D., Bolam, J. P., and...Gating of information flow within the limbic system and the pathophysiology of schizophrenia. Brain Res Rev 2000; 31:330-341. 6. Lewis DA, Gonzalez

  6. An interview with Lewis Wolpert.

    PubMed

    Wolpert, Lewis; Vicente, Catarina

    2015-08-01

    Lewis Wolpert is a retired developmental biologist who, over his long career, has made many important contributions to the field, from his French Flag model and the concept of positional information to the famous quote that it is "not birth, marriage or death, but gastrulation which is truly the most important time in your life." In addition to his scientific contributions, Lewis is also a prolific writer, from the textbook 'Developmental Biology' to books about popular science, religion and his battle with depression. Although born in South Africa, it was in the United Kingdom that Lewis spent most of his scientific career. We met Lewis at the Spring Meeting of the British Society for Developmental Biology, where he was awarded the Waddington Medal.

  7. [Update on the pathophysiology of Parkinson' disease].

    PubMed

    Duyckaerts, Charles; Sazdovitch, Véronique; Seilhean, Danielle

    2010-10-01

    Changes in the substantia nigra of patients with Parkinson's disease were suspected by Brissaud in the late 19th century. They were subsequently confirmed by Tretiakoff but neglected by Lewy, who described the inclusion bodies that bear his name. The experimental Parkinsonian syndrome caused by reserpine led Carlsson to discover the neuromediatory role of dopamine, a finding at the origin of L-DOPA therapy. Identification of a mutation of the alpha-synuclein gene in cases of familial Parkinson's disease with autosomal dominant transmission was followed by the detection of the protein product in Lewy bodies and neurites. Alpha-synuclein is now recognized as being the main constituent of Lewy bodies. Alpha-synuclein immunohistochemistry has revealed that lesions can extend from the autonomous nervous system to the cortex (in Lewy body dementia). The Lewy body itself does not appear to be the direct cause of symptoms, which correlate better with neuronal death. Neuronal death could be due to metabolic disturbances related to alpha-synuclein accumulation, ubiquitin-proteasome system dysfunction, or oxidative stress. Non-autonomous cell death, caused by neuro-inflammation or gliosis, has also been incriminated.

  8. Serotonergic mediated body mass index changes in Parkinson's disease.

    PubMed

    Politis, Marios; Loane, Clare; Wu, Kit; Brooks, David J; Piccini, Paola

    2011-09-01

    More than 50% of patients with Parkinson's disease (PD) are expected to show abnormalities with their weight in a process that starts several years before the diagnosis. The serotonergic (5-HT) system has been proposed to regulate appetite and the 5-HT transporter (SERT) is a key modulator of 5-HT metabolism. Here, we hypothesized that a dysfunctional 5-HT system could be responsible for alterations of weight in PD and we sought to investigate this in vivo. Thirty four PD patients had Body Mass Index (BMI) changes monitored over a 12-month period and one positron emission tomography (PET) brain scan with (11)C-DASB, a selective marker of SERT availability, during their second clinical assessment. Results were compared with those of a group of 10 normal controls. Half (17) of the PD patients showed abnormal BMI changes over the 12-month period; 12 lost while 5 gained weight. PD patients with abnormal BMI changes showed significantly raised (11)C-DASB binding in rostral raphe nuclei, hypothalamus, caudate nucleus and ventral striatum compared to cases with no significant BMI changes. (11)C-DASB binding in other regions was similarly decreased in the PD BMI subgroups compared to normal controls. BMI gainers showed significantly raised (11)C-DASB binding in anterior cingulate cortex (ACC) compared to BMI losers. Our findings suggest that abnormal BMI changes over a 12-month period are linked with relatively raised SERT availability in PD on an overall background of decreased 5-HT function. The regions implicated are the rostral raphe nuclei and its connections to limbic and cognitive areas. It is conceivable that 5-HT agents could help alleviate abnormal changes in BMI in PD.

  9. Biomarkers, ketone bodies, and the prevention of Alzheimer's disease.

    PubMed

    VanItallie, Theodore B

    2015-03-01

    Sporadic Alzheimer's disease (spAD) has three successive phases: preclinical, mild cognitive impairment, and dementia. Individuals in the preclinical phase are cognitively normal. Diagnosis of preclinical spAD requires evidence of pathologic brain changes provided by established biomarkers. Histopathologic features of spAD include (i) extra-cellular cerebral amyloid plaques and intracellular neurofibrillary tangles that embody hyperphosphorylated tau; and (ii) neuronal and synaptic loss. Amyloid-PET brain scans conducted during spAD's preclinical phase have disclosed abnormal accumulations of amyloid-beta (Aβ) in cognitively normal, high-risk individuals. However, this measure correlates poorly with changes in cognitive status. In contrast, MRI measures of brain atrophy consistently parallel cognitive deterioration. By the time dementia appears, amyloid deposition has already slowed or ceased. When a new treatment offers promise of arresting or delaying progression of preclinical spAD, its effectiveness must be inferred from intervention-correlated changes in biomarkers. Herein, differing tenets of the amyloid cascade hypothesis (ACH) and the mitochondrial cascade hypothesis (MCH) are compared. Adoption of the ACH suggests therapeutic research continue to focus on aspects of the amyloid pathways. Adoption of the MCH suggests research emphasis be placed on restoration and stabilization of mitochondrial function. Ketone ester (KE)-induced elevation of plasma ketone body (KB) levels improves mitochondrial metabolism and prevents or delays progression of AD-like pathologic changes in several AD animal models. Thus, as a first step, it is imperative to determine whether KE-caused hyperketonemia can bring about favorable changes in biomarkers of AD pathology in individuals who are in an early stage of AD's preclinical phase.

  10. Body mass index and risk of Parkinson's disease: a prospective cohort study.

    PubMed

    Logroscino, Giancarlo; Sesso, Howard D; Paffenbarger, Ralph S; Lee, I-Min

    2007-11-15

    High body mass index has been associated with increased risk of several chronic diseases, including cardiovascular disease, and, recently, Alzheimer's disease. There are few data on the association of body mass index with Parkinson's disease, and results have been inconsistent. The authors conducted a prospective study among 10,812 men in the Harvard Alumni Health Study, followed from 1988 to 1998 (mean age at baseline: 67.7 years), to test the hypothesis that body mass index is associated with Parkinson's disease risk. Among 106 incident cases of Parkinson's disease, body mass index at baseline was not associated with Parkinson's disease risk (for body mass index <22.5, 22.5-<24.9, and > or =25.0 kg/m2: multivariate relative risks = 1.51 (95% confidence interval: 0.95, 2.40), 1.00 (referent), and 0.86 (95% confidence interval: 0.53, 1.41)). The authors had information on body mass index during late adolescence, when men entered college; this was unrelated to Parkinson's disease risk as well. Subjects who lost at least 0.5 units of body mass index per decade between college entry and 1988 had a significantly increased Parkinson's disease risk, compared with men having stable body mass index (multivariate relative risk = 2.60, 95% confidence interval: 1.10, 6.10). The authors conclude that body mass index is unrelated to Parkinson's disease risk and speculate that the observation of increased risk with body mass index loss since late adolescence may reflect weight loss due to Parkinson's disease that preceded clinical diagnosis.

  11. Lewis & Clark: An Interdisciplinary Expedition

    ERIC Educational Resources Information Center

    Brugar, Kristy

    2004-01-01

    On January 18, 1803 President Thomas Jefferson asked Congress to fund an expedition to the source of the Missouri River. This expedition would become known as the Corps of Discovery, which would spend twenty-eight months exploring, studying, and documenting the wonders of the western frontier. Led by Captains Meriwether Lewis and William Clark,…

  12. Lewis and Clark as Naturalists.

    ERIC Educational Resources Information Center

    Smithsonian Institution, Washington, DC. National Museum of Natural History.

    Intended for use in elementary and high school education, this Web site includes a teacher's guide and three lesson plans. The site contains images of museum specimens, scientific drawings, and field photos of the plant and animal species observed by Meriwether Lewis and William Clark, along with journal excerpts, historical notes, and references…

  13. Action Learning in John Lewis

    ERIC Educational Resources Information Center

    Spencer, Chris

    2005-01-01

    A small group of training professionals within the John Lewis Partnership set up an action learning group about 2 years ago. The main aim was to explore the technique for our own learning and development. The timing and lifespan of the group reflected the generally strategic and long-term nature of our projects. One of these was to introduce…

  14. Measurement of body fat and hydration of the fat-free body in health and disease

    SciTech Connect

    Streat, S.J.; Beddoe, A.H.; Hill, G.L.

    1985-06-01

    Body fat mass, fat-free body mass and body water are basic components of body composition which are used in nutritional and metabolic studies and in patient care. A method of measuring total body fat (TBF), fat-free mass (FFM) and its hydration (TBW/FFM) involving prompt gamma in vivo neutron activation analysis (IVNAA) and tritium dilution has been compared with the more traditional methods of densitometry and skinfold anthropometry in 36 normal volunteers, and with skinfold anthropometry in 56 patients presenting for nutritional support. While the mean values of TBF were in reasonable agreement for the three methods in normals it was founds that skinfold anthropometry underestimated TBF relative to the IVNAA/tritium method by, on average, 3.0 kg (19%) in patients. Furthermore, the ranges of values in normals of the ratio TBW/FFM for the anthropometric (0.62 to 0.80) and densitometric (0.65 to 0.80) methods were much wider than the range for the IVNAA/tritium method (0.69 to 0.76), in which TBW was measured by tritium dilution in all cases. In the patients, the ranges of this ratio were 0.52 to 0.90 for the anthropometric method and 0.67 to 0.82 for the IVNAA/tritium method; clearly anthropometry yields values of TBW/FFM which are outside accepted biological limits. On the basis of these findings, ranges of TBW/FFM are suggested for both normal adults (0.69 to 0.75) and patients requiring nutritional support (0.67 to 0.83). Finally it is concluded that the IVNAA/tritium method is a suitable method for measuring TBF and FFM and particularly so when body composition is abnormal.

  15. Carotid body disease and the physician--chronic carotid glomitis.

    PubMed Central

    Heath, D.; Khan, Q.; Nash, J.; Smith, P.

    1989-01-01

    There are three types of histological change in the carotid bodies which appear to have physiological and clinical associations. A prominence of the dark variant of chief cells with their contents of met-enkephalin and other peptides appears to be associated with acute exposure to hypoxia. Proliferation of sustentacular cells around the clusters of chief cells appears to be related to ageing and also to systemic hypertension. Recently we have described a new condition of chronic carotid glomitis which is characterized by follicles of lymphocytes and may have a basis in auto-immunity. In the present review we report for the first time plasma cell activity in the carotid bodies of an elderly man, especially around nerve fibrils and unmyelinated axons ensheathed in sustentacular cells. Such appearances are consistent with the view that ageing nerve fibrils may be the antigenic stimulus for the development of chronic carotid glomitis. Images Figure 1 Figure 2 Figure 3 Figure 4 Figure 5 PMID:2692011

  16. Idiopathic REM sleep behaviour disorder in the development of Parkinson's disease.

    PubMed

    Boeve, Bradley F

    2013-05-01

    Parkinson's disease is a progressive neurodegenerative disorder associated with Lewy body disease pathology in central and peripheral nervous system structures. Although the cause of Parkinson's disease is not fully understood, clinicopathological analyses have led to the development of a staging system for Lewy body disease-associated pathological changes. This system posits a predictable topography of progression of Lewy body disease in the CNS, beginning in olfactory structures and the medulla, then progressing rostrally from the medulla to the pons, then to midbrain and substantia nigra, limbic structures, and neocortical structures. If this topography and temporal evolution of Lewy body disease does occur, other manifestations of the disease as a result of degeneration of olfactory and pontomedullary structures could theoretically begin many years before the development of prominent nigral degeneration and the associated parkinsonian features of Parkinson's disease. One such manifestation of prodromal Parkinson's disease is rapid eye movement (REM) sleep behaviour disorder, which is a parasomnia manifested by vivid dreams associated with dream enactment behaviour during REM sleep. Findings from animal and human studies have suggested that lesions or dysfunction in REM sleep and motor control circuitry in the pontomedullary structures cause REM sleep behaviour disorder phenomenology, and degeneration of these structures might explain the presence of REM sleep behaviour disorder years or decades before the onset of parkinsonism in people who develop Parkinson's disease.

  17. EveryBody[TM]: Preventing HIV and Other Sexually Transmitted Diseases among Young Teens.

    ERIC Educational Resources Information Center

    Schoeberlein, Deborah

    EveryBody is a curriculum that emphasizes prevention of human immunodeficiency virus (HIV) and other sexually transmitted diseases (STDs) among early adolescents. It fosters active learning and facilitates communication about HIV/STD prevention and promotes safer behaviors. EveryBody incorporates current research on adolescent development so it…

  18. Body-self unity and self-esteem in patients with rheumatic diseases.

    PubMed

    Bode, Christina; van der Heij, Anouk; Taal, Erik; van de Laar, Mart A F J

    2010-12-01

    Perceptions and evaluations of the own body are important sources of self-esteem. Having a rheumatic disease challenges maintenance of positive self-esteem due to consequences of the disease such as unfavorable sensations as pain and limited (physical) functioning. We expect that a positive experience of the own body in spite of a rheumatic disease (body-self harmony) will be associated with higher levels of self-esteem and that experiencing the body as unworthy part of the own person or as disabler for own strivings (body-self alienation) will result in lower levels of self-esteem. For this explorative study, the body experience questionnaire (BEQ) measuring body-self unity was developed and piloted. One hundred sixty-eight patients visiting the outpatient rheumatology clinic of the Medisch Spectrum Twente, Enschede, The Netherlands, completed a questionnaire on touchscreen computers to measure body-self unity (BEQ), illness cognitions (illness cognition questionnaire), pain intensity, functional limitations (health assessment questionnaire disability index), self-esteem (Rosenberg Self-Esteem Scale) and demographics. To analyze predictors of self-esteem, hierarchical regression analyses were employed. The BEQ revealed a two-factor structure with good reliability (subscale harmony, four items, Cronbach's α = 0.76; subscale alienation, six items, Cronbach's α = 0.84). The final model of the hierarchical regression analyses showed that self-esteem can be predicted by the illness cognitions helplessness and acceptance, by harmony and most strongly by alienation from the body. R(2) of the final model was 0.50. The relationship between functional limitations and self-esteem was totally mediated by the psychological constructs body-self unity and illness cognitions. This explorative study showed the importance of the unity of body and self for self-esteem in patients with a rheumatic disease.

  19. [A comparative analysis of cognitive disturbances in dementia with Levy's bodies and Alzheimer's disease].

    PubMed

    Preobrazhenskaia, I S; Mkhitarian, E A; Iakhno, N N

    2005-01-01

    Basing on a neuropsychological study of 50 patients with dementia with Levy's bodies (DLB) and 50 patients with Alzheimer's disease (AD), peculiarities of cognitive impairment in these diseases are discussed. In similar severity of dementia, patients with DLB demonstrated a greater impairment of executive and visual-spatial functions as well as neurodynamic disturbances and patients with AD had more severe memory impairment.

  20. Of sound mind and body: depression, disease, and accelerated aging

    PubMed Central

    M. Wolkowitz, Owen; I. Reus, Victor; H. Mellon, Synthia

    2011-01-01

    Major depressive disorder (MDD) is associated with a high rate of developing serious medical comorbidities such as cardiovascular disease, stroke, dementia, osteoporosis, diabetes, and the metabolic syndrome. These are conditions that typically occur late in life, and it has been suggested that MDD may be associated with “accelerated aging.” We review several moderators and mediators that may accompany MDD and that may give rise to these comorbid medical conditions. We first review the moderating effects of psychological styles of coping, genetic predisposition, and epigenetic modifications (eg, secondary to childhood adversity). We then focus on several interlinked mediators occurring in MDD (or at least in subtypes of MDD) that may contribute to the medical comorbidity burden and to accelerated aging: limbic-hypothalamic-pituitary-adrenal axis alterations, diminution in glucocorticoid receptor function, altered glucose tolerance and insulin sensitivity, excitotoxicity, increases in intracellular calcium, oxidative stress, a proinflammatory milieu, lowered levels of “counter-regulatory” neurosteroids (such as allopregnanolone and dehydroepiandrosterone), diminished neurotrophic activity, and accelerated cell aging, manifest as alterations in telomerase activity and as shortening of telomeres, which can lead to apoptosis and cell death. In this model, MDD is characterized by a surfeit of potentially destructive mediators and an insufficiency of protective or restorative ones. These factors interact in increasing the likelihood of physical disease and of accelerated aging at the cellular level. We conclude with suggestions for novel mechanism-based therapeutics based on these mediators. PMID:21485744

  1. Inclusion body disease of cranes: comparison of pathologic findings in cranes with acquired vs. experimentally induced disease

    USGS Publications Warehouse

    Schuh, J.C.; Sileo, L.; Siegfried, L.M.; Yuill, Thomas M.

    1986-01-01

    Inclusion body disease of cranes was the cause of death in 17 immature and mature cranes of 5 different species in Wisconsin. A herpesvirus of unknown origin was the apparent cause. An isolate of this herpesvirus was used to experimentally infect 3 species of cranes. Macroscopic and microscopic lesions associated with naturally acquired and experimentally induced disease were essentially identical. Multifocal hepatic and splenic necrosis was found in all cranes evaluated. Necrosis of the gastrointestinal tract, thymus, and bursa of Fabricius also was seen in some of the cranes. Eosinophilic intranuclear inclusion bodies often were commonly associated with hepatic lesions, sometimes with the splenic lesions, and rarely with the thymic or gastrointestinal tract lesions. The lesions of this inclusion body disease were similar to those reported for cranes in Austria from which a crane herpesvirus was isolated.

  2. Inclusion body myopathy and Paget disease is linked to a novel mutation in the VCP gene.

    PubMed

    Haubenberger, D; Bittner, R E; Rauch-Shorny, S; Zimprich, F; Mannhalter, C; Wagner, L; Mineva, I; Vass, K; Auff, E; Zimprich, A

    2005-10-25

    Mutations in the valosin-containing protein (VCP) on chromosome 9p13-p12 were recently found to be associated with hereditary inclusion body myopathy, Paget disease of the bone, and frontotemporal dementia (IBMPFD). We identified a novel missense mutation in the VCP gene (R159H; 688G>A) segregating with this disease in an Austrian family of four affected siblings, who exhibited progressive proximal myopathy and Paget disease of the bone but without clinical signs of dementia.

  3. Validating Diagnostic and Screening Procedures for Pre-Motor Parkinson’s Disease

    DTIC Science & Technology

    2014-04-01

    motor; Parkinson’s Disease; Lewy Body Disease; REM Behavior Disorder (RBD); Cardiac dysautonomia; Electrocardiogram; Heart Rate Variability (HRV...four objectives: 1) to develop the required internal and collaborative infrastructure to establish a large cohort with idiopathic REM behavior...Establish collaborative relationships with all San Francisco Bay Area sleep medicine clinics ii) Develop physician outreach methods and materials

  4. Diagnostic value of minor salivary glands biopsy for the detection of Lewy pathology.

    PubMed

    Folgoas, Emmanuelle; Lebouvier, Thibaud; Leclair-Visonneau, Laurène; Cersosimo, Maria-Graciela; Barthelaix, Annick; Derkinderen, Pascal; Letournel, Franck

    2013-09-13

    The recent demonstration of the presence of Lewy pathology in the submandibular glands of Parkinson's disease (PD) patients prompted us to evaluate the diagnostic performance of minor salivary gland biopsy for PD. Minor salivary glands were examined for Lewy pathology using phosphorylated alpha-synuclein antibody in 16 patients with clinically diagnosed PD and 11 control subjects with other neurological disorders. Abnormal accumulation of alpha-synuclein was found in 3 out of 16 PD patients. Two control subjects exhibited weak phosphorylated alpha-synuclein immunoreactivity. Our results do not support the use of minor salivary glands biopsy for the detection of Lewy pathology in living subjects.

  5. Rice body mass formation mimicking a neoplastic disease around the trochanteric bursae of the hip.

    PubMed

    Uludağ, Serkan; Seyahi, Aksel; Ege, Yaman; Tetik, Onur

    2010-01-01

    Multiple rice body formation is an uncommon inflammatory process. Sometimes it leads to a big mass in unusual locations. Although sometimes associated with bursitis and systemic diseases, such as rheumatoid arthritis, the pathophysiology of this rare entity is still obscure. We present a 29-year-old woman with multiple rice body mass formation in the trochanteric bursa of the left hip. She was operated, and had no recurrence at 18 months after the surgery.

  6. Polar body genome transfer for preventing the transmission of inherited mitochondrial diseases.

    PubMed

    Wang, Tian; Sha, Hongying; Ji, Dongmei; Zhang, Helen L; Chen, Dawei; Cao, Yunxia; Zhu, Jianhong

    2014-06-19

    Inherited mtDNA diseases transmit maternally and cause severe phenotypes. Currently, there is no effective therapy or genetic screens for these diseases; however, nuclear genome transfer between patients' and healthy eggs to replace mutant mtDNAs holds promises. Considering that a polar body contains few mitochondria and shares the same genomic material as an oocyte, we perform polar body transfer to prevent the transmission of mtDNA variants. We compare the effects of different types of germline genome transfer, including spindle-chromosome transfer, pronuclear transfer, and first and second polar body transfer, in mice. Reconstructed embryos support normal fertilization and produce live offspring. Importantly, genetic analysis confirms that the F1 generation from polar body transfer possesses minimal donor mtDNA carryover compared to the F1 generation from other procedures. Moreover, the mtDNA genotype remains stable in F2 progeny after polar body transfer. Our preclinical model demonstrates polar body transfer has great potential to prevent inherited mtDNA diseases.

  7. The cell biology of disease: Acute promyelocytic leukemia, arsenic, and PML bodies.

    PubMed

    de Thé, Hugues; Le Bras, Morgane; Lallemand-Breitenbach, Valérie

    2012-07-09

    Acute promyelocytic leukemia (APL) is driven by a chromosomal translocation whose product, the PML/retinoic acid (RA) receptor α (RARA) fusion protein, affects both nuclear receptor signaling and PML body assembly. Dissection of APL pathogenesis has led to the rediscovery of PML bodies and revealed their role in cell senescence, disease pathogenesis, and responsiveness to treatment. APL is remarkable because of the fortuitous identification of two clinically effective therapies, RA and arsenic, both of which degrade PML/RARA oncoprotein and, together, cure APL. Analysis of arsenic-induced PML or PML/RARA degradation has implicated oxidative stress in the biogenesis of nuclear bodies and SUMO in their degradation.

  8. Periodic electroencephalogram discharges in a case of Lafora body disease: An unusual finding

    PubMed Central

    Jain, Rajendra Singh; Gupta, Arti; Gupta, Pankaj Kumar; Agrawal, Rakesh

    2016-01-01

    Lafora body disease (LBD) is a form of progressive myoclonic epilepsy, characterized by seizures, myoclonic jerks, cognitive decline, ataxia, and intracellular polyglucosan inclusion bodies (Lafora bodies) in the neurons, heart, skeletal muscle, liver, and sweat gland duct cells. Electroencephalogram (EEG) findings in LBD may include multiple spikes and wave discharges, photosensitivity, multifocal epileptiform discharges, and progressive slowing in background activity. Periodicity in epileptiform discharges has not been frequently depicted in LBD. We herein report an unusual case of LBD who showed generalized periodic epileptiform discharges in EEG. PMID:27293346

  9. Using body diagrams and disease protocols as part of an integrated approach to the medical consultation in Nepal.

    PubMed

    McKellar, Angus T; Rutland-Brown, Wesley

    2004-07-01

    Neither medical assistants nor doctors in Nepal receive adequate training in medical consultation techniques. Patients often leave the consultation with poor understanding of their disease. Moreover, disease management counselling and preventative health counselling are rarely done. In order to address these issues, simple body diagrams and disease protocols were developed and tested in a random cohort survey of 300 outpatients. While 72% of patients who were shown a body diagram achieved basic understanding of their disease, only 38% of patients who were not shown a body diagram understood their disease. This improvement was significant and independent of other factors. Satisfactory disease management counselling was given in 38% of cases, and preventative health counselling in 36%. There was correlation between use of body diagrams and provision of disease management counselling and preventative health counselling. These findings emphasize the need for simple consultation tools such as body diagrams and disease management protocols in developing countries.

  10. Fort Lewis Exceptional Family Member Program (EFMP)

    ERIC Educational Resources Information Center

    Hebdon, Heather

    2007-01-01

    Located in the shadow of Mt. Rainier, Fort Lewis is the home of the highest per capita exceptional family member population in the Army. Ideally located on the Northwest coast of Washington State, Fort Lewis is home to the Strykers and First Brigade. Combined with its close proximity to McChord Air Force Base, the installation is ideally suited to…

  11. Simplified Lewis Structure Drawing for Nonscience Majors.

    ERIC Educational Resources Information Center

    Miburo, Barnabe B.

    1998-01-01

    Argues that Lewis diagrams can be easily done by students using a minimal number of clues. Presents a method to draw the Lewis structure of molecules, polyatomic ions, and radicals whereby students no longer need to move bonds or lone pairs of electrons. (DDR)

  12. Streptococcal cell wall-induced arthritis and adjuvant arthritis in F344----Lewis and in Lewis----F344 bone marrow chimeras

    SciTech Connect

    van Bruggen, M.C.; van den Broek, M.F.; van den Berg, W.B. )

    1991-09-01

    Streptococcal cell wall (SCW)-induced arthritis and adjuvant arthritis (AA) are rat models for chronic, erosive polyarthritis. Both models can be induced in susceptible Lewis rats, whereas F344 rats are resistant. In AA as well as in SCW arthritis, antigen-specific T lymphocytes have been demonstrated to be crucial for chronic disease. In this communication the authors describe their studies to probe the cellular mechanism responsible for the difference in susceptibility of Lewis and F344, using bone marrow chimeras. By transplanting bone marrow cells from F344 into lethally irradiated Lewis recipients, Lewis rats were rendered resistant to SCW arthritis induction. F344 rats reconstituted with Lewis bone marrow, i.e., Lewis----F344 chimeras, develop an arthritis upon SCW injection. For AA comparable results were obtained. These data suggest that both resistance and susceptibility to bacterium-induced chronic arthritis are mediated by hemopoietic/immune cells and that the recipiental environment does not influence the susceptibility to chronic joint inflammation.

  13. Body composition and cardiometabolic disease risk factors in captive baboons (Papio hamadryas sp.): sexual dimorphism.

    PubMed

    Higgins, Paul B; Rodriguez, Perla J; Voruganti, V Saroja; Mattern, Vicki; Bastarrachea, Raul A; Rice, Karen; Raabe, Timothy; Comuzzie, Anthony G

    2014-01-01

    Baboons (Papio hamadryas sp.) exhibit significant sexual dimorphism in body size. Sexual dimorphism is also exhibited in a number of circulating factors associated with risk of cardiometabolic disease. We investigated whether sexual dimorphism in body size and composition underlie these differences. We examined data from 28 male and 24 female outdoor group-housed young adult baboons enrolled in a longitudinal observational study of cardiometabolic disease risk factors. Animals were sedated with ketamine HCl (10 mg/kg) before undergoing venous blood draws, basic body measurements, and dual-energy X-ray absorptiometry body composition scans. Percentage glycated hemoglobin A1c (%HbA1c ) was measured in whole blood. Serum samples were analyzed for glucose, insulin, C-peptide, high-density lipoprotein, and triglyceride concentrations. Males were heavier and had greater body length and lean tissue mass than females. Females had a greater body fat percentage relative to males (10.8 ± 6.4 vs. 6.9 ± 4.0, P = 0.01). Although C-peptide, fasting glucose, and %HbA1c did not differ between the sexes, females had greater fasting insulin and triglyceride compared to their male counterparts. Insulin and percentage body fat were significantly correlated in males (r = 0.61, P = 0.001) and to a lesser extent in females (r = 0.43, P = 0.04). Overall, relations between adiposity and fasting insulin and fasting triglyceride were stronger in males. After accounting for differences in percentage body fat, fasting insulin and triglyceride were no longer statistically different between males and females. Despite stronger correlations between relative adiposity and insulin and triglyceride in males, the higher fasting insulin and triglyceride of female baboons may be underlain by their greater relative body fat masses.

  14. Human noroviruses recognize sialyl Lewis x neoglycoprotein.

    PubMed

    Rydell, Gustaf E; Nilsson, Jonas; Rodriguez-Diaz, Jesus; Ruvoën-Clouet, Nathalie; Svensson, Lennart; Le Pendu, Jacques; Larson, Göran

    2009-03-01

    The carbohydrate binding characteristics of a norovirus GII.3 (Chron1) and a GII.4 (Dijon) strain were investigated using virus-like particles (VLPs) and saliva samples from 81 individuals genotyped for FUT2 (secretor) and FUT3 (Lewis) and phenotyped for ABO and Lewis blood groups. The two VLPs showed a typical secretor-gene-dependent binding and bound significantly stronger to saliva from A, B, and AB than from O individuals (P < 0.0001 and P < 0.001) but did not bind to any samples from secretor-negative individuals. The GII.3 strain showed larger interindividual variation and bound stronger to saliva from B than from A(2) secretors (P < 0.01). When assaying for binding to neoglycoproteins, the GII.3 and GII.4 strains were compared with the Norwalk GI.1 prototype strain. Although all three strains bound to Lewis b (and H type 1 chain) glycoconjugates, only the two GII strains showed an additional binding to sialyl Lewis x. This novel binding was specific since the VLPs did not bind to structural analogs, e.g., Lewis x or sialyl Lewis a, but only to sialyl Lewis x, sialyl diLewis x and sialylated type 2 chain conjugates. In inhibition experiments, the sialyl Lewis x conjugate was the most potent inhibitor. The minimal requirement for this potential receptor structure is Neu5Ac alpha 3Gal beta 4(Fuc alpha 3)GlcNAc beta 3Gal beta- where Fuc is not absolutely necessary for binding. Our study shows that some human norovirus GII strains have at least two binding specificities: one secretor-gene-dependent related to alpha1,2-fucosylated carbohydrates and another related to alpha2,3-sialylated carbohydrates of the type 2 chain, e.g., sialyl Lewis x.

  15. Body mass index, muscle and fat in chronic kidney disease: questions about survival.

    PubMed

    Mafra, D; Guebre-Egziabher, F; Fouque, D

    2008-08-01

    The human body can be roughly divided into two major compartments, fat mass and lean body mass. Adipose tissue is now considered to be a highly active tissue and, in addition to storing calories as triglycerides, it also secretes a large variety of compounds, including cytokines, chemokines and hormone-like factors such as leptin, adiponectin and resistin. On the other hand, muscle plays a central role in whole-body protein metabolism by serving as the principal provider for amino acids to maintain protein synthesis in vital tissues and organs and by providing hepatic gluconeogenic precursors. Although not a good indicator of body composition, the Quetelet index, also called body mass index (BMI), is often used for practical reasons. It is well known that high BMI predicts mortality and cardiovascular disease (CVD) in the general population. However, observational reports in the dialysis population have suggested that obesity is associated with improved survival, a phenomenon that is not well understood and subject to controversies. This review describes the characteristics of BMI in the general population and in chronic kidney disease (CKD) patients, as well as the respective role of muscle, whole body fat and fat distribution towards mortality, with particular emphasis on patients with CKD.

  16. Bodies in skin: a philosophical and theological approach to genetic skin diseases.

    PubMed

    Walser, Angelika

    2010-03-01

    This contribution evolved from my work in a European network and is dedicated to the rare genetic skin diseases. To gain a deeper knowledge about the question, what it means to suffer from a genetic skin disease, I have discussed the concepts of skin in philosophical and theological anthropology. Presuming that ancient interpretations of skin diseases (moral and cultical impurity) are still relevant today, feminist Christian theology shows the ways of deconstructing stigmatizing paradigma by using the body as a hermeneutic category. Skin becomes the "open borderline" of the human being, pointing out both the social vulnerability and the transcendent capacity of the human person.

  17. Motor asymmetry and estimation of body-scaled aperture width in Parkinson's disease.

    PubMed

    Smith, J G; Harris, J P; Khan, S; Atkinson, E A; Fowler, M S; Ewins, D; D'Souza, S; Gregory, R P; Kean, R J

    2011-09-01

    The present study examined how asymmetrical motor symptomatology helps predict the pattern of perceptual judgements of body-scaled aperture width in lateralised Parkinson's disease (PD). Eleven patients with PD predominantly affecting the left side of their body (LPD), 16 patients with PD predominantly affecting their right side (RPD), and 16 healthy controls made forced-choice judgements about whether or not they would fit without turning their shoulders through a life-sized schematic doorway shown on a large screen. Whereas control and LPD groups made accurate estimations of body-scaled aperture width, RPD patients significantly underestimated aperture width relative to their body, perceiving doorways on average that were 12% narrower than their bodies as wide enough to allow them to pass through without rotation. Across all patients, estimates of body-scaled aperture width correlated with ratio of right-to-left symptom severity. These perceptual errors may indicate a mismatch between the neural representation of external space and that of body size in PD.

  18. More than a Rumor Spreads in Parkinson's Disease

    PubMed Central

    Prymaczok, Natalia C.; Riek, Roland; Gerez, Juan

    2016-01-01

    As Parkinson's disease progresses, a massive loss of dopaminergic neurons is accompanied by accumulation of alpha-Synuclein (αSyn) neuronal inclusions called Lewy bodies and Lewy neurites. Inclusions first appear in olfactory bulb and enteric neurons then in ascendant neuroanatomical interconnected areas, and finally, in late stages of the disease, Lewy bodies are observed in a substantia nigra pars compacta with clear signs of neuronal loss. It is believed that the spreading of Lewy bodies through the nervous system is a consequence of the cell-to-cell propagation of αSyn, that can occur via sequential steps of secretion and uptake. Certain pathological forms of transmitted αSyn are able to seed endogenous counterparts in healthy recipient cells, thus promoting the self-sustained cycle of inclusion formation, amplification and spreading, that ultimately underlies disease progression. Here we review the cell-to-cell propagation of αSyn focusing on its role in the progression of Parkinson's disease. PMID:27994545

  19. More than a Rumor Spreads in Parkinson's Disease.

    PubMed

    Prymaczok, Natalia C; Riek, Roland; Gerez, Juan

    2016-01-01

    As Parkinson's disease progresses, a massive loss of dopaminergic neurons is accompanied by accumulation of alpha-Synuclein (αSyn) neuronal inclusions called Lewy bodies and Lewy neurites. Inclusions first appear in olfactory bulb and enteric neurons then in ascendant neuroanatomical interconnected areas, and finally, in late stages of the disease, Lewy bodies are observed in a substantia nigra pars compacta with clear signs of neuronal loss. It is believed that the spreading of Lewy bodies through the nervous system is a consequence of the cell-to-cell propagation of αSyn, that can occur via sequential steps of secretion and uptake. Certain pathological forms of transmitted αSyn are able to seed endogenous counterparts in healthy recipient cells, thus promoting the self-sustained cycle of inclusion formation, amplification and spreading, that ultimately underlies disease progression. Here we review the cell-to-cell propagation of αSyn focusing on its role in the progression of Parkinson's disease.

  20. Imaging methods for analyzing body composition in human obesity and cardiometabolic disease.

    PubMed

    Seabolt, Lynn A; Welch, E Brian; Silver, Heidi J

    2015-09-01

    Advances in the technological qualities of imaging modalities for assessing human body composition have been stimulated by accumulating evidence that individual components of body composition have significant influences on chronic disease onset, disease progression, treatment response, and health outcomes. Importantly, imaging modalities have provided a systematic method for differentiating phenotypes of body composition that diverge from what is considered normal, that is, having low bone mass (osteopenia/osteoporosis), low muscle mass (sarcopenia), high fat mass (obesity), or high fat with low muscle mass (sarcopenic obesity). Moreover, advances over the past three decades in the sensitivity and quality of imaging not just to discern the amount and distribution of adipose and lean tissue but also to differentiate layers or depots within tissues and cells is enhancing our understanding of distinct mechanistic, metabolic, and functional roles of body composition within human phenotypes. In this review, we focus on advances in imaging technologies that show great promise for future investigation of human body composition and how they are being used to address the pandemic of obesity, metabolic syndrome, and diabetes.

  1. Cation affinity numbers of Lewis bases.

    PubMed

    Lindner, Christoph; Tandon, Raman; Maryasin, Boris; Larionov, Evgeny; Zipse, Hendrik

    2012-01-01

    Using selected theoretical methods the affinity of a large range of Lewis bases towards model cations has been quantified. The range of model cations includes the methyl cation as the smallest carbon-centered electrophile, the benzhydryl and trityl cations as models for electrophilic substrates encountered in Lewis base-catalyzed synthetic procedures, and the acetyl cation as a substrate model for acyl-transfer reactions. Affinities towards these cationic electrophiles are complemented by data for Lewis-base addition to Michael acceptors as prototypical neutral electrophiles.

  2. Frustrated Lewis pair chemistry: development and perspectives.

    PubMed

    Stephan, Douglas W; Erker, Gerhard

    2015-05-26

    Frustrated Lewis pairs (FLPs) are combinations of Lewis acids and Lewis bases in solution that are deterred from strong adduct formation by steric and/or electronic factors. This opens pathways to novel cooperative reactions with added substrates. Small-molecule binding and activation by FLPs has led to the discovery of a variety of new reactions through unprecedented pathways. Hydrogen activation and subsequent manipulation in metal-free catalytic hydrogenations is a frequently observed feature of many FLPs. The current state of this young but rapidly expanding field is outlined in this Review and the future directions for its broadening sphere of impact are considered.

  3. Body lice

    MedlinePlus

    ... Body lice are tiny insects (scientific name is Pediculus humanus corporis ) that are spread through close contact ... disease Images Body louse Lice, body with stool (Pediculus humanus) Body louse, female and larvae Head louse ...

  4. Total glutamine synthetase levels in cerebrospinal fluid of Alzheimer's disease patients are unchanged.

    PubMed

    Timmer, Nienke M; Herbert, Megan K; Claassen, Jurgen A H R; Kuiperij, H Bea; Verbeek, Marcel M

    2015-03-01

    Decreased cerebral protein and activity levels of glutamine synthetase (GS) have been reported for Alzheimer's disease (AD) patients. Using a recently established method, we quantified total GS levels in cerebrospinal fluid (CSF) from AD patients and control subjects. Furthermore, we investigated if total GS levels in CSF could differentiate AD from frontotemperal dementia and dementia with Lewy bodies patients. As we found no significantly altered total GS levels in any of the patient groups compared with control subjects, we conclude that levels of total GS in CSF have no diagnostic value for AD, dementia with Lewy bodies, or frontotemperal dementia.

  5. Glucocorticoid-Related Changes in Body Mass Index among Children and Adolescents with Rheumatic Diseases

    PubMed Central

    Shiff, Natalie J; Brant, Rollin; Guzman, Jaime; Cabral, David A; Huber, Adam M.; Miettunen, Paivi M.; Roth, Johannes; Scuccimarri, Rosie; Alos, Nathalie; Atkinson, Stephanie A.; Collet, Jean Paul; Couch, Robert; Cummings, Elizabeth A.; Dent, Peter B.; Ellsworth, Janet; Hay, John; Houghton, Kristin; Jurencak, Roman; Lang, Bianca; Larche, Maggie; LeBlanc, Claire; Rodd, Celia; Saint-Cyr, Claire; Stein, Robert; Stephure, David; Taback, Shayne; Rauch, Frank; Ward, Leanne M.

    2014-01-01

    Objective To examine the temporal and dose-related effect of glucocorticoids (GCs) on body mass index (BMI) in children with rheumatic diseases. Methods Children initiating GCs for a rheumatic disease (n=130) were assessed every 3 months for 18 months. BMI, weight and height Z-score trajectories were described according to GC starting dosage in prednisone equivalents: high (≥1.0 mg/kg/day), low (<0.2 mg/kg/day to a maximum of 7.5 mg/d), and moderate (between high and low) dosage. The impact of GC dosing, underlying diagnosis, pubertal status, physical and disease activity on BMI Z-scores and on percent body fat was assessed with longitudinal mixed effects growth curve models. Results The GC starting dose was high in 59% and moderate in 39% of patients. The peak BMI Z score was +1.29 at 4 months with high-dose GCs and +0.69 at 4.2 months with moderate-dose GCs (p<0.001). Overall, 50% (95% confidence interval 41–59%) of children returned to within +0.25 standard deviations (SD) of their baseline BMI Z score. Oral GC dose over the preceding 3 months was the most significant determinant of BMI Z-score and percent body fat. The proportion of days in receipt of GCs, disease activity, and a diagnosis of systemic-onset juvenile idiopathic arthritis were also associated with BMI Z scores. The correlation between changes in BMI and changes in percent body fat was 0.09. Conclusions In children with rheumatic disease starting moderate and high doses of GCs, BMI Z score peaked at 4 months and only half returned to within +0.25 SD of their baseline BMI Z-score by 18 months. PMID:22826190

  6. Compensatory activity in the extrastriate body area of Parkinson's disease patients.

    PubMed

    van Nuenen, Bart F L; Helmich, Rick C; Buenen, Noud; van de Warrenburg, Bart P C; Bloem, Bastiaan R; Toni, Ivan

    2012-07-11

    Compensatory mechanisms are a crucial component of the cerebral changes triggered by neurodegenerative disorders. Identifying such compensatory mechanisms requires at least two complementary approaches: localizing candidate areas using functional imaging, and showing that interference with these areas has behavioral consequences. Building on recent imaging evidence, we use this approach to test whether a visual region in the human occipito-temporal cortex-the extrastriate body area-compensates for altered dorsal premotor activity in Parkinson's disease (PD) during motor-related processes. We separately inhibited the extrastriate body area and dorsal premotor cortex in 11 PD patients and 12 healthy subjects, using continuous theta burst stimulation. Our goal was to test whether these areas are involved in motor compensatory processes. We used motor imagery to isolate a fundamental element of motor planning, namely subjects' ability to incorporate the current state of their body into a motor plan (mental hand rotation). We quantified this ability through a posture congruency effect (i.e., the improvement in subjects' performance when their current body posture is congruent to the imagined movement). Following inhibition of the right extrastriate body area, the posture congruency effect was lost in PD patients, but not in healthy subjects. In contrast, inhibition of the left dorsal premotor cortex reduced the posture congruency effect in healthy subjects, but not in PD patients. These findings suggest that the right extrastriate body area plays a compensatory role in PD by supporting a function that is no longer performed by the dorsal premotor cortex.

  7. Development of a Lewis Base Catalyzed Selenocyclization Reaction

    ERIC Educational Resources Information Center

    Collins, William

    2009-01-01

    The concept of Lewis base activation of selenium Lewis acids has been effectively reduced to practice in the Lewis base catalyzed selenofunctionalization of unactivated olefins. In this reaction, the weakly acidic species, "N"-phenylselenyl succinimide, is cooperatively activated by the addition of a "soft" Lewis base donor (phosphine sulfides,…

  8. The Use of C. S. Lewis's "Poems" for Oral Interpretation.

    ERIC Educational Resources Information Center

    Keefe, Carolyn

    Suggestions are offered in this paper for adapting C. S. Lewis's poems for oral interpretation. A discussion of Lewis's lifelong correspondence with his friend Arthur Greeves provides insights into Lewis's perceptions of his own writing. Eighty poems selected from Lewis's "Poems" as appropriate for oral interpretation are classified…

  9. G. N. Lewis and the Chemical Bond.

    ERIC Educational Resources Information Center

    Pauling, Linus

    1984-01-01

    Discusses the contributions of G. N. Lewis to chemistry, focusing on his formulation of the basic principle of the chemical bond--the idea that the chemical bond consists of a pair of electrons held jointly by two atoms. (JN)

  10. Pueblo Pottery: Continuity and Change. Lucy Lewis.

    ERIC Educational Resources Information Center

    Herzog, Melanie

    1991-01-01

    Describes Lucy Lewis' ceramic work which is inspired by the ancient pottery of her Acoma Pueblo artistic heritage. Discusses concepts of tradition, artistic heritage, and change over time. Outlines related ceramic and discussion activities for elementary and secondary students. (KM)

  11. 90 Seconds of Discovery: Frustrated Lewis Pairs

    SciTech Connect

    Kathmann, Shawn; Schenter, Greg; Autrey, Tom

    2014-02-14

    Hydrogen activating catalysts play an important role in producing valuable chemicals, such as biofuels and ammonia. As a part of efforts to develop the next generation of these catalysts, PNNL researchers have found potential in Frustrated Lewis Pairs.

  12. Abegg, Lewis, Langmuir, and the Octet Rule.

    ERIC Educational Resources Information Center

    Jensen, William B.

    1984-01-01

    Discusses major events leading to the development of the octet rule. Three conclusions based on the work of Mendeleev, Abegg, Thompson, Kossel, Lewis, and Langmuir are considered as is the debate over the rule's validity. (JN)

  13. 90 Seconds of Discovery: Frustrated Lewis Pairs

    ScienceCinema

    Kathmann, Shawn; Schenter, Greg; Autrey, Tom

    2016-07-12

    Hydrogen activating catalysts play an important role in producing valuable chemicals, such as biofuels and ammonia. As a part of efforts to develop the next generation of these catalysts, PNNL researchers have found potential in Frustrated Lewis Pairs.

  14. Lewis Research Center: Commercialization Success Stories

    NASA Technical Reports Server (NTRS)

    Heyward, Ann O.

    1996-01-01

    The NASA Lewis Research Center, located in Cleveland, Ohio, has a portfolio of research and technology capabilities and facilities that afford opportunities for productive partnerships with industry in a broad range of industry sectors. In response to the President's agenda in the area of technology for economic growth (Clinton/Gore 1993), the National Performance Review (1993), NASA's Agenda for Change (1994), and the needs of its customers, NASA Lewis Research Center has sought and achieved significant successes in technology transfer and commercialization. This paper discusses a sampling of Lewis Research Center's successes in this area, and lessons learned that Lewis Research Center is applying in pursuit of continuous improvement and excellence in technology transfer and commercialization.

  15. Investigation of Lewis acid versus Lewis base catalysis in asymmetric cyanohydrin synthesis.

    PubMed

    North, Michael; Omedes-Pujol, Marta; Williamson, Courtney

    2010-10-04

    The asymmetric addition of trimethylsilyl cyanide to aldehydes can be catalysed by Lewis acids and/or Lewis bases, which activate the aldehyde and trimethylsilyl cyanide, respectively. It is not always apparent from the structure of the catalyst whether Lewis acid or Lewis base catalysis predominates. To investigate this in the context of using salen complexes of titanium, vanadium and aluminium as catalysts, a Hammett analysis of asymmetric cyanohydrin synthesis was undertaken. When Lewis acid catalysis is dominant, a significantly positive reaction constant is observed, whereas reactions dominated by Lewis base catalysis give much smaller reaction constants. [{Ti(salen)O}(2)] was found to show the highest degree of Lewis acid catalysis, whereas two [VO(salen)X] (X=EtOSO(3) or NCS) complexes both displayed lower degrees of Lewis acid catalysis. In the case of reactions catalysed by [{Al(salen)}(2)O] and triphenylphosphine oxide, a non-linear Hammett plot was observed, which is indicative of a change in mechanism with increasing Lewis base catalysis as the carbonyl compound becomes more electron-deficient. These results suggested that the aluminium complex/triphenylphosphine oxide catalyst system should also catalyse the asymmetric addition of trimethylsilyl cyanide to ketones and this was found to be the case.

  16. The scent of disease: human body odor contains an early chemosensory cue of sickness.

    PubMed

    Olsson, Mats J; Lundström, Johan N; Kimball, Bruce A; Gordon, Amy R; Karshikoff, Bianka; Hosseini, Nishteman; Sorjonen, Kimmo; Olgart Höglund, Caroline; Solares, Carmen; Soop, Anne; Axelsson, John; Lekander, Mats

    2014-03-01

    Observational studies have suggested that with time, some diseases result in a characteristic odor emanating from different sources on the body of a sick individual. Evolutionarily, however, it would be more advantageous if the innate immune response were detectable by healthy individuals as a first line of defense against infection by various pathogens, to optimize avoidance of contagion. We activated the innate immune system in healthy individuals by injecting them with endotoxin (lipopolysaccharide). Within just a few hours, endotoxin-exposed individuals had a more aversive body odor relative to when they were exposed to a placebo. Moreover, this effect was statistically mediated by the individuals' level of immune activation. This chemosensory detection of the early innate immune response in humans represents the first experimental evidence that disease smells and supports the notion of a "behavioral immune response" that protects healthy individuals from sick ones by altering patterns of interpersonal contact.

  17. The grey area of effort syndrome and hyperventilation: from Thomas Lewis to today.

    PubMed

    Nixon, P G

    1993-10-01

    Lewis used the diagnosis 'effort syndrome' for subjects whose ability to make and sustain effort had been reduced by homeostatic failure. A major element was depletion of the body's capacity for buffering the acids produced by exercise. In his view this systems disorder was not to be regarded as a specific organ disease, and losing sight of the metabolic element would foster the invention of fanciful, unphysiological diagnoses. His views were dismissed because normal resting plasma bicarbonate levels were considered by others in that era to exclude serious depletion of the body's total capacity for buffering the effects of exertion. Today, effort syndrome is still a useful diagnosis for a condition of exhaustion and failure of performance associated with depletion of the body's buffering systems. Other elements associated with homeostatic failure are now recognised, principally emotional hyperarousal and hyperventilation. Their physiological interrelationships are described. Effort syndrome is amenable to recovery through rehabilitation, and it may be a mistake to treat chronic fatigue syndrome and unspecific illness without including it in the differential diagnosis.

  18. Arenavirus Coinfections Are Common in Snakes with Boid Inclusion Body Disease

    PubMed Central

    Salmenperä, P.; Sironen, T.; Hetzel, U.; Korzyukov, Y.; Kipar, A.; Vapalahti, O.

    2015-01-01

    Recently, novel arenaviruses were found in snakes with boid inclusion body disease (BIBD); these form the new genus Reptarenavirus within the family Arenaviridae. We used next-generation sequencing and de novo sequence assembly to investigate reptarenavirus isolates from our previous study. Four of the six isolates and all of the samples from snakes with BIBD contained at least two reptarenavirus species. The viruses sequenced comprise four novel reptarenavirus species and a representative of a new arenavirus genus. PMID:26041290

  19. Association of body mass index and the depletion of nigrostriatal dopamine in Parkinson's disease.

    PubMed

    Lee, Jae Jung; Oh, Jungsu S; Ham, Jee H; Lee, Dong H; Lee, Injoo; Sohn, Young H; Kim, Jae S; Lee, Phil Hyu

    2016-02-01

    Several antecedent studies had reported close relationship between low body weight and Parkinson's disease (PD). However, there have been few investigations about the role of body weight to nigrostriatal dopaminergic neurodegeneration. This study enrolled 398 de novo patients with PD whom underwent [18F] N-(3-Fluoropropyl)-2β-carbon ethoxy-3β-(4-iodophenyl) nortropane positron emission tomography scan and body mass index (BMI) measurement. The relationships between BMI and dopamine transporter (DAT) activity were analyzed using linear regression analysis. A multivariate analysis adjusted for age, gender, disease duration, smoking status, coffee and tea consumption, and residence area revealed that BMI remained independently and significantly associated with DAT activity in all striatal subregions. Moreover, multiple logistic regression analyses showed that BMI was a significant predictor for the lowest quartile of DAT activity in the anterior putamen, ventral striatum, caudate nucleus, and total striatum. The present findings suggest that a low BMI might be closely associated with low density of nigrostriatal dopaminergic neurons in PD, which could support the evidence for the role of low body weight to PD-related pathologies.

  20. In vivo neutron activation analysis: body composition studies in health and disease

    SciTech Connect

    Ellis, K.J.; Cohn, S.H.

    1984-01-01

    In vivo analysis of body elements by neutron activation is an important tool in medical research. It has provided a direct quantitative measure of body composition of human beings in vivo. Basic physiological differences related to age, sex, race, and body size have been assessed by this noninvasive technique. The diagnosis and management of patients with various metabolic disorders and diseases has also been demonstrated. Two major facilities at Brookhaven are being utilized exclusively for in vivo neutron activation analysis (IVNAA) of calcium, phosphorus, sodium, chlorine, nitrogen, hydrogen, and potassium. These elements serve as the basis for a four compartment model of body composition: protein, water, mineral ash, and fat. Variations in these compartments are demonstrated in clinical research programs investigating obesity, anorexia, cancer, renal failure, osteoporosis, and normal aging. IVNAA continues to provide a unique approach to the evaluation of clinical diagnosis, efficacy of therapeutic regimens, and monitoring of the aging process. Classical balance studies usually require the patient to be admitted to a hospital for extended periods of confinement. IVNAA, however, allows for clinical management of the patient on an out-patient basis, an important aspect for treatment of chronic diseases. 25 references, 3 figures, 5 tables.

  1. Body weight gain rate in patients with Parkinson's disease and deep brain stimulation.

    PubMed

    Barichella, Michela; Marczewska, Agnieszka M; Mariani, Claudio; Landi, Andrea; Vairo, Antonella; Pezzoli, Gianni

    2003-11-01

    We evaluated body weight changes in patients with Parkinson's disease (PD) after electrode implantation for deep brain stimulation (DBS) in the subthalamic nucleus (STN) in relation to clinical improvement. Thirty PD patients who received STN DBS were included (22 men, 8 women; mean age, 60.0 +/- 7.1 years; mean PD duration, 13.5 +/- 3.7 years; mean body mass index [BMI], 21.6 +/- 3.0 kg/m2). Body weight, physical activity, and Unified Parkinson's Disease Rating Scale (UPDRS) scores were noted before and 3 and 12 months after the procedure. Significant weight gain occurred in 29 patients; the mean increase was 14.8 +/- 9.8% of initial body weight in 1 year. Of the patients, 46.5% reported weight gain in the first 3 months, 21.4% gradual weight gain in the first 6 months, and 32.1% a slow increase for 1 year. Mean BMI increased up to 24.7 +/- 3.7 kg/m2. After 1 year, mean UPDRS motor score improved significantly in off and in on; and therapy complications improved by 91.0 +/- 17.0%. BMI changes at 3 and 12 months were significantly correlated to dyskinesia score changes, and levodopa dosage was not. In PD, STN DBS produces not only symptom control, but also weight gain. DBS candidates should be given nutritional counseling before the intervention to prevent rapid and/or excessive weight gain.

  2. [Body composition and heart rate variability in patients with chronic obstructive pulmonary disease pulmonary rehabilitation candidates].

    PubMed

    Curilem Gatica, Cristian; Almagià Flores, Atilio; Yuing Farías, Tuillang; Rodríguez Rodríguez, Fernando

    2014-07-01

    Body composition is a non-invasive method, which gives us information about the distribution of tissues in the body structure, it is also an indicator of the risk of mortality in patients with chronic obstructive pulmonary disease. The heart rate variability is a technique that gives us information of autonomic physiological condition, being recognized as an indicator which is decreased in a number of diseases. The purpose of this study was to assess body composition and heart rate variability. The methodology used is that of Debora Kerr (1988) endorsed by the International Society for advances in Cineantropometría for body composition and heart rate variability of the guidelines described by the American Heart Association (1996). Roscraff equipment, caliper Slimguide and watch Polar RS 800CX was used. , BMI 26.7 ± 3.9 kg / m²; Muscle Mass 26.1 ± 6.3 kg ; Bone Mass 1.3 kg ± 8.1 76 ± 9.9 years Age : 14 candidates for pulmonary rehabilitation patients were evaluated , Adipose mass 16.4 ± 3.6 kg ; FEV1 54 ± 14%. Increased waist circumference and waist hip ratio was associated with a lower overall heart rate variability. The bone component was positively related to the variability of heart rate and patients with higher forced expiratory volume in one second had lower high frequency component in heart rate variability. In these patients, the heart rate variability is reduced globally and is associated with cardiovascular risk parameters.

  3. [Inclusion Body Disease (IBD of Boids)--a haematological, histological and electron microscopical study].

    PubMed

    Keilwerth, Melanie; Bühler, Ilina; Hoffmann, Rudolf; Soliman, Hatem; El-Matbouli, Mansour

    2012-01-01

    Our objective was to evaluate diagnostic tools for the detection of Inclusion Body Disease (IBD) in bold snakes. The aetiology of IBD is unknown, and the disease has non-specific clinical signs, hence there is a need for a clinically-applicable, specific diagnostic method. We examined blood smears and liver biopsies from 26 bold snakes (17 boas and nine pythons; some of which were suspected of having IBD) for the presence of characteristic inclusion bodies. We used haematology, histology and electron microscopy to characterise samples as IBD-positive or -negative. Our results indicate that examination of a simple blood smear is sufficient to diagnose IBD in boas. Inclusion bodies in lymphocytes, erythrocytes and thrombocytes were observed. In both, boas and pythons, we detected inclusion bodies within hepatocytes. We demonstrated also that IBD was more common in boas than in pythons: only samples from two Ball Pythons (Python regius) tested positive, whereas no other Pythonidae were positive. We consider that blood smears represents a rapid, non-invasive technique for detection of IBD.

  4. Research and technology, Lewis Research Center

    NASA Technical Reports Server (NTRS)

    1985-01-01

    The NASA Lewis Research Center's research and technology accomplishments for fiscal year 1985 are summarized. The report is organized into five major sections covering aeronautics, aerospace technology, spaceflight systems, space station systems, and computational technology support. This organization of the report roughly parallels the organization of the Center into directorates. Where appropriate, subheadings are used to identify special topics under the major headings. Results of all research and technology work performed during the fiscal year are contained in Lewis-published technical reports and presentations prepared either by Lewis scientists and engineers or by contractor personnel. In addition, significant results are presented by university faculty or graduate students in technical sessions and in journals of the technical societies. For the reader who desires more information about a particular subject, the Lewis contact will provide that information or references. In 1985, five Lewis products were selected by Research and Development Magazine for IR-100 awards. All are described and identified. In addition, the Lewis Distinguished Paper for 1984 to 1985, which was selected by the Chief Scientist and a research advisory board, is included and so identified.

  5. Obesity as Assessed by Body Adiposity Index and Multivariable Cardiovascular Disease Risk

    PubMed Central

    Dhaliwal, Satvinder S.; Welborn, Timothy A.; Goh, Louise G. H.; Howat, Peter A.

    2014-01-01

    To assess the role of body adiposity index (BAI) in predicting cardiovascular disease (CVD) and coronary heart disease (CHD) mortality, in comparison with body mass index (BMI), waist circumference (WC), and the waist circumference to hip circumference ratio (WHR). This study was a prospective 15 year mortality follow-up of 4175 Australian males, free of heart disease, diabetes and stroke. The Framingham Risk Scores (FRS) for CHD and CVD death were calculated at baseline for all subjects. Multivariable logistic regression was used to assess the effects of the measures of obesity on CVD and CHD mortality, before adjustment and after adjustment for FRS. The predictive ability of BAI, though present in the unadjusted analyses, was generally not significant after adjustment for age and FRS for both CVD and CHD mortality. BMI behaved similarly to BAI in that its predictive ability was generally not significant after adjustments. Both WC and WHR were significant predictors of CVD and CHD mortality and remained significant after adjustment for covariates. BAI appeared to be of potential interest as a measure of % body fat and of obesity, but was ineffective in predicting CVD and CHD. PMID:24714547

  6. Objective Biomarkers of Balance and Gait for Parkinson’s Disease using Body-worn Sensors

    PubMed Central

    Horak, Fay B; Mancini, Martina

    2014-01-01

    Balance and gait impairments characterize progression of Parkinson’s disease (PD), predict fall risk, and are important contributors to reduced quality of life. Advances in technology of small, body-worn inertial sensors have made it possible to develop quick, objective measures of balance and gait impairments in the clinic for research trials and clinical practice. Objective balance and gait metrics may eventually provide useful biomarkers for PD. In fact, objective balance and gait measures are already being used as surrogate end-points for demonstrating clinical efficacy of new treatments, in place of counting falls from diaries, using stop-watch measures of gait speed, or clinical balance rating scales. This review summarizes the types of objective measures available from body-worn sensors. We organize the metrics based on the neural control system for mobility affected by PD: postural stability in stance, postural responses, gait initiation, gait (temporal-spatial lower and upper body coordination and dynamic equilibrium), postural transitions, and freezing of gait. However, the explosion of metrics derived by wearable sensors during prescribed balance and gait tasks that are abnormal in people with PD do not yet qualify as behavioral biomarkers because many balance and gait impairments observed in PD are not specific to the disease, nor shown to be related to specific pathophysiologic biomarkers. In the future, the most useful balance and gait biomarkers for PD will be those that are sensitive and specific for early PD and related to the underlying disease process. PMID:24132842

  7. Objective biomarkers of balance and gait for Parkinson's disease using body-worn sensors.

    PubMed

    Horak, Fay B; Mancini, Martina

    2013-09-15

    Balance and gait impairments characterize the progression of Parkinson's disease (PD), predict the risk of falling, and are important contributors to reduced quality of life. Advances in technology of small, body-worn, inertial sensors have made it possible to develop quick, objective measures of balance and gait impairments in the clinic for research trials and clinical practice. Objective balance and gait metrics may eventually provide useful biomarkers for PD. In fact, objective balance and gait measures are already being used as surrogate endpoints for demonstrating clinical efficacy of new treatments, in place of counting falls from diaries, using stop-watch measures of gait speed, or clinical balance rating scales. This review summarizes the types of objective measures available from body-worn sensors. The metrics are organized based on the neural control system for mobility affected by PD: postural stability in stance, postural responses, gait initiation, gait (temporal-spatial lower and upper body coordination and dynamic equilibrium), postural transitions, and freezing of gait. However, the explosion of metrics derived by wearable sensors during prescribed balance and gait tasks, which are abnormal in individuals with PD, do not yet qualify as behavioral biomarkers, because many balance and gait impairments observed in PD are not specific to the disease, nor have they been related to specific pathophysiologic biomarkers. In the future, the most useful balance and gait biomarkers for PD will be those that are sensitive and specific for early PD and are related to the underlying disease process.

  8. Neuropathology of Parkinson's disease with the R1441G mutation in LRRK2.

    PubMed

    Martí-Massó, José-Félix; Ruiz-Martínez, Javier; Bolaño, Maria J; Ruiz, Irune; Gorostidi, Ana; Moreno, Fermin; Ferrer, Isidre; López de Munain, Adolfo

    2009-10-15

    We report the neuropathological findings in a patient with Parkinson's disease (PD) associated with Basque R1441G-LRRK2/dardarin mutation. The patient was a man with disease onset at 68 years of age, with unilateral rest tremor; the Parkinsonism was well controlled with medication for 15 years. He died at the age of 86, after 18 years of evolution. The neuropathological examination disclosed mild neuronal loss in the substantia nigra pars compacta without alpha-synuclein, tau, LRRK2, or ubiquitin cytoplasmic inclusions. Lewy bodies and Lewy neurites were absent. This is the first neuropathological study of PD associated with brain with the R1441G mutation in LRRK2.

  9. Gender, body mass index and rheumatoid arthritis disease activity: results from the QUEST-RA study

    PubMed Central

    Jawaheer, Damini; Olsen, Jørn; Lahiff, Maureen; Forsberg, Sinikka; Lähteenmäki, Jukka; Silveira, Ines Guimaraes da; Rocha, Francisco Airton; Laurindo, Ieda Maria Magalhães; Mota, Licia Maria Henrique da; Drosos, Alexandros A.; Murphy, Eithne; Sheehy, Claire; Quirke, Edel; Cutolo, Maurizio; Rexhepi, Sylejman; Dadoniene, Jolanta; Verstappen, Suzan M.M.; Sokka, Tuulikki

    2010-01-01

    Objective To investigate whether body mass index (BMI), as a proxy for body fat, influences rheumatoid arthritis (RA) disease activity in a gender-specific manner. Methods Consecutive patients with RA were enrolled from 25 countries into the QUEST-RA program between 2005 and 2008. Clinical and demographic data were collected by treating rheumatologists and by patient self-report. Distributions of Disease Activity Scores (DAS28), BMI, age, and disease duration were assessed for each country and for the entire dataset; mean values between genders were compared using Student’s t-tests. An association between BMI and DAS28 was investigated using linear regression, adjusting for age, disease duration and country. Results A total of 5,161 RA patients (4,082 women and 1,079 men) were included in the analyses. Overall, women were younger, had longer disease duration, and higher DAS28 scores than men, but BMI was similar between genders. The mean DAS28 scores increased with increasing BMI from normal to overweight and obese, among women, whereas the opposite trend was observed among men. Regression results showed BMI (continuous or categorical) to be associated with DAS28. Compared to the normal BMI range, being obese was associated with a larger difference in mean DAS28 (0.23, 95% CI: 0.11, 0.34) than being overweight (0.12, 95% CI: 0.03, 0.21); being underweight was not associated with disease activity. These associations were more pronounced among women, and were not explained by any single component of the DAS28. Conclusion BMI appears to be associated with RA disease activity in women, but not in men. PMID:20810033

  10. Weight and Body Composition Compartments do Not Predict Therapeutic Thiopurine Metabolite Levels in Inflammatory Bowel Disease

    PubMed Central

    Holt, Darcy Q; Strauss, Boyd JG; Moore, Gregory T

    2016-01-01

    OBJECTIVES: Thiopurine drugs are the most commonly used steroid-sparing therapies in moderate-to-severe inflammatory bowel disease (IBD). Their complex metabolism and their narrow therapeutic windows means that optimal dosing is difficult. However, weight-based dosing is the norm. Similar antimetabolites are dosed by body composition parameters. In IBD, treatment response and toxicity has been shown to correlate with thiopurine metabolite levels. We sought to determine whether weight or body composition parameters predicted therapeutic 6-thioguanine nucleotide (6TGN) or toxic 6-methylmercaptopurine (6MMP) levels. METHODS: This single-center retrospective cohort study identified 66 IBD patients who had body composition analysis and thiopurine metabolite levels tested. Statistical analysis was performed using Spearman correlation, Kruskal–Wallis, Mann–Whitney, and unpaired t tests and receiver-operator operating characteristic curves. A P value of <0.05 was considered significant. RESULTS: No correlation was identified between 6TGN and any body composition parameters, absolute drug dose or drug dose/kg of fat mass, fat-free mass (FFM), subcutaneous adipose tissue area, or visceral adipose tissue area. However, 6MMP correlated with azathioprine dose, thiopurine dose/kg of body weight, and with several body composition parameters. CONCLUSIONS: No relationship was found between therapeutic metabolite levels and weight or body composition compartments. Higher thiopurine doses, especially in relation to FFM, are associated with higher levels of potentially hepatotoxic 6MMP and shunting toward this metabolite. Conventional weight-based dosing to attain therapeutic metabolite levels appears unreliable and may be replaced by metabolite level testing. PMID:27787512

  11. Imaging biomarkers in Parkinson's disease.

    PubMed

    Brooks, David J; Pavese, Nicola

    2011-12-01

    Parkinson's disease (PD) is characterized by a progressive loss of nigrostriatal dopaminergic neurons associated with intracellular Lewy inclusion bodies. The result is poverty of movement, increased muscle rigidity, and tremor at rest and on posture. Midbrain/nigral structural abnormalities can be demonstrated in vivo with both transcranial sonography (TCS) and diffusion tensor magnetic resonance imaging (DTI) while positron emission tomography (PET) and single photon emission computed tomography (SPECT) ligands exist to demonstrate dopamine terminal dysfunction. These radiotracers are markers of dopamine storage capacity, vesicular monoamine and dopamine transporter availability. While loss of putamen dopaminergic function leads to motor disability, Lewy bodies not only target dopamine neurons but have also been observed in serotoninergic, noradrenergic, and cholinergic neurons. As a consequence, non-dopaminergic neurotransmission is also impaired resulting in non-motor symptoms including sleep disturbance, fatigue, depression, dementia, and autonomic dysfunction. PET and SPECT ligands exist to interrogate the function of monoaminergic and cholinergic neurons. Cortical and limbic Lewy body disease is seen in more advanced PD and this can be detected with FDG PET as abnormal covariance between levels of resting brain metabolism in these regions. Additionally, widespread microglial activation can be detected in PD with PET. This review discusses the role of structural and functional imaging for understanding parkinsonian syndromes and aiding in their diagnosis and management.

  12. Adult polyglucosan body disease: clinical and histological heterogeneity of a large Italian family.

    PubMed

    Colombo, I; Pagliarani, S; Testolin, S; Salsano, E; Napoli, L M; Bordoni, A; Salani, S; D'Adda, E; Morandi, L; Farina, L; Magri, F; Riva, M; Prelle, A; Sciacco, M; Comi, G P; Moggio, M

    2015-05-01

    Adult Polyglucosan Body Disease (APBD) is a rare inherited leukodystrophy associated with axonal polyneuropathy, mainly reported in persons of Ashkenazi-Jewish descent. We describe three Italian siblings at disease onset, presenting in their fifties with a combination of pyramidal and ataxic signs, mild demyelinating neuropathy on neurophysiological investigation (1/3 cases) and transient symptoms (1/3). A leucoencephalopathy with infratentorial lesions without enhancement and medullary/spine atrophy was demonstrated on brain/spine MRI (3/3). Muscle biopsy was normal in 2/3; both muscle and nerve biopsy showed polyglucosan bodies in the sibling with polyneuropathy. This indicated a need for GBE1 sequencing, which revealed a novel missense mutation (c.1064G>A; p.Arg355His) and one previously described (c.1604A>G; p.Tyr535Cys) in all siblings. We highlight that peripheral neuropathy, deemed as disease hallmark, may be missing and that transient symptoms are confirmed as early disease manifestations. The pattern of damage at neuro-imaging described recurs irrespective of clinical presentation, constituting a unifying diagnostic clue.

  13. Impact of nutritional status on body functioning in chronic obstructive pulmonary disease and how to intervene

    PubMed Central

    Aniwidyaningsih, Wahju; Varraso, Raphaëlle; Cano, Noel; Pison, Christophe

    2008-01-01

    Purpose of review Chronic obstructive pulmonary disease (COPD) is the fifth cause of mortality in the world. This article reviews diet as a risk or protective factor for COPD, mechanisms of malnutrition, undernutrition consequences on body functioning and how to modulate nutritional status of COPD patients. Recent findings Different dietary factors (dietary pattern, foods, nutrients) have been associated with COPD and the course of the disease. Mechanical disadvantage, energy imbalance, disuse muscle atrophy, hypoxemia, systemic inflammation and oxidative stress have been reported to cause systemic consequences such as cachexia and compromise whole body functioning. Nutritional intervention makes it possible to modify the natural course of the disease provide that it is included in respiratory rehabilitation combining bronchodilators optimization, infection control, exercise and in some patients correction of hypogonadism. Summary Diet, as a modifiable risk factor, appears more as an option to prevent and modify the course of COPD. Reduction of mechanical disadvantage, physical training and anabolic agents should be used conjointly with oral nutrition supplements to overcome undernutrition and might change the prognosis of the disease in some cases. Major research challenges address the role of systemic inflammation and the best interventions for control it besides smoking cessation. PMID:18542004

  14. Monistic dualism and the body electric: An ontology of disease, patient and clinician for person-centred healthcare.

    PubMed

    Pârvan, Alexandra

    2016-08-01

    Ontology is involved in medical care, because what both doctors and patients think the disease, the patient and the doctor are affects the giving and receiving of care, and hence the definition of medical care as profession. Going back to ancient philosophical views of disease as 'bounded entity' or as 'relation' (still echoed in contemporary theories and mindsets), I propose a way to think ontologically about disease that places it in necessary connection with the patient as person. Drawing on Augustine's views on disease, bodily integrity, and the human person as mind-body unit, I speak of 'monistic dualism' as the view where the unit and health of the person is continuously and personally generated by the mind's attention to and action on the body, whether the body is impaired or not. Monistic dualism is identified as the ontological position of both patients who are (or can become) healthy within illness and clinicians who are 'healthy' in their profession. It is what guides both to create what their body is in a personal state of integrity or health. This 'metaphysical body' is termed 'the body electric' in patients, and I argue that clinicians can attend properly to the diseased body by attending to patients' metaphysical body. As clinicians offer metaphysical care to themselves, employing monistic dualism to create their metaphysical body, they should not deny it to patients. Ontology cannot be part of medical care without making metaphysical care a requirement.

  15. Are Upper-Body Axial Symptoms a Feature of Early Parkinson’s Disease?

    PubMed Central

    Moreau, Caroline; Baille, Guillaume; Delval, Arnaud; Tard, Céline; Perez, Thierry; Danel-Buhl, Nicolas; Seguy, David; Labreuche, Julien; Duhamel, Alain; Delliaux, Marie; Dujardin, Kathy; Defebvre, Luc

    2016-01-01

    Background Axial disorders are considered to appear late in the course of Parkinson’s disease (PD). The associated impact on quality of life (QoL) and survival and the lack of an effective treatment mean that understanding and treating axial disorders is a key challenge. However, upper-body axial disorders (namely dysarthria, swallowing and breathing disorders) have never been prospectively assessed in early-stage PD patients. Objectives To characterize upper-body axial symptoms and QoL in consecutive patients with early-stage PD. Methods We prospectively enrolled 66 consecutive patients with early-stage PD (less than 3 years of disease progression) and assessed dysarthria, dysphagia and respiratory function (relative to 36 controls) using both objective and patient-reported outcomes. Results The mean disease duration was 1.26 years and the mean UPDRS motor score was 19.4 out of 108. 74% of the patients presented slight dysarthria (primarily dysprosodia). Men appeared to be more severely affected (i.e. dysphonia). This dysfunction was strongly correlated with low swallowing speed (despite the absence of complaints about dysphagia), respiratory insufficiency and poor QoL. Videofluorography showed that oral-phase swallowing disorders affected 60% of the 31 tested patients and that pharyngeal-phase disorders affected 21%. 24% of the patients reported occasional dyspnea, which was correlated with anxiety in women but not in men. Marked diaphragmatic dysfunction was suspected in 42% of the patients (predominantly in men). Conclusion Upper body axial symptoms were frequent in men with early-stage PD, whereas women presented worst non-motor impairments. New assessment methods are required because currently available tools do not reliably detect these upper-body axial disorders. PMID:27654040

  16. Disordered Eating and Body Esteem Among Individuals with Glycogen Storage Disease.

    PubMed

    Flanagan, Theresa B; Sutton, Jill A; Brown, Laurie M; Weinstein, David A; Merlo, Lisa J

    2015-01-01

    Glycogen storage disease (GSD) is an inherited disorder that requires a complex medical regimen to maintain appropriate metabolic control. Previous research has suggested the disease is associated with decreased quality of life, and clinical experience suggests that patients are at risk for disordered eating behaviors that may significantly compromise their health. The current study assessed eating attitudes, eating disorder symptoms, and body image among 64 patients with GSD ranging from 7-52 years old (M = 18.5 years old). About half the participants were male (n = 33, 51.6%). Most participants were diagnosed with GSD Type I (n = 52, 81.3%). Quantitative and qualitative analyses were utilized. Results indicated that 14.8% of children and 11.1% of adolescents/adults with GSD met the clinical cutoff for dysfunctional attitudes toward eating, suggesting high likelihood for presence of an eating disorder. However, traditional eating disorder symptoms (e.g., binging, purging, fasting, etc.) were less prevalent in the GSD sample compared to population norms (t = -6.45, p < 0.001). Body esteem was generally lower for both children and adolescents/adults with GSD compared to population norms. These results were consistent with interview responses indicating that GSD patients experience negative feedback from peers regarding their bodies, especially during childhood and adolescence. However, they reported growing acceptance of their bodies with age and reported less negative attitudes and behaviors. Assessing mental health, including symptoms of disordered eating and low body esteem, among individuals with GSD should be an important component of clinical care.

  17. Appearance of monoclonal plasma cell diseases in whole-body magnetic resonance imaging and correlation with parameters of disease activity.

    PubMed

    Kloth, Jost K; Hillengass, Jens; Listl, Karin; Kilk, Kerstin; Hielscher, Thomas; Landgren, Ola; Delorme, Stefan; Goldschmidt, Hartmut; Kauczor, Hans-Ulrich; Weber, Marc-André

    2014-11-15

    The aim of our study was to assess in which way different infiltration patterns of monoclonal plasma cell diseases in whole-body (wb) magnetic resonance imaging (MRI) are associated with clinical stages, plasma cell content in bone marrow samples and established serum markers of disease activity. Institutional review board approval was obtained. We performed wb-MRI in 547 consecutive, unselected and untreated patients with monoclonal gammopathy of undetermined significance (MGUS, n=138), smoldering myeloma (SMM, n=157) and multiple myeloma (MM, n=252) on two 1.5 T MRI-scanners with body array coils. The studies were evaluated in consensus by two experienced radiologists blinded to the diagnosis. We observed focal lesions in 23.9% (MGUS), 34.4% (SMM) and 81.3% (MM), respectively. A diffuse infiltration pattern was detected in 38.4%, 45.9% and 71%, respectively. The differences between all infiltration patterns were significant (p<0.0001). The presence of focal lesions and the presence of a diffuse bone marrow infiltration was associated with an increased plasma cell percentage in bone marrow samples (median 22% vs. 14%, 26% vs. 10%, both p<0.0001) and monoclonal protein concentration (median 18 g/dl vs. 13 g/dl, p=0.003, 20 g/dl vs. 11 g/dl, p<0.0001). Further categorization of the diffuse infiltration patterns in wb-MRI into "salt-and-pepper," moderate and severe identified significant associations with M-protein (median g/dl for S+P/moderate/severe 23/18/25, p=0.04), plasma cell percentage in the bone marrow (median 25%/24%/40%, p=0.02), and age (median years 67/60/57, p<0.0001). Bone marrow infiltration in wb-MRI is significantly different between the various stages of plasma cell disease and correlates well with established markers of disease activity.

  18. Experimental evaluation of blockage ratio and plenum evacuation system flow effects on pressure distribution for bodies of revolution in 0.1 scale model test section of NASA Lewis Research Center's proposed altitude wind tunnel

    NASA Technical Reports Server (NTRS)

    Burley, Richard R.; Harrington, Douglas E.

    1987-01-01

    An experimental investigation was conducted in the slotted test section of the 0.1-scale model of the proposed Altitude Wind Tunnel to evaluate wall interference effects at tunnel Mach numbers from 0.70 to 0.95 on bodies of revolution with blockage rates of 0.43, 3, 6, and 12 percent. The amount of flow that had to be removed from the plenum chamber (which surrounded the slotted test section) by the plenum evacuation system (PES) to eliminate wall interference effects was determined. The effectiveness of tunnel reentry flaps in removing flow from the plenum chamber was examined. The 0.43-percent blockage model was the only one free of wall interference effects with no PES flow. Surface pressures on the forward part of the other models were greater than interference-free results and were not influenced by PES flow. Interference-free results were achieved on the aft part of the 3- and 6-percent blockage models with the proper amount of PES flow. The required PES flow was substantially reduced by opening the reentry flaps.

  19. Isolation, Identification, and Characterization of Novel Arenaviruses, the Etiological Agents of Boid Inclusion Body Disease

    PubMed Central

    Hetzel, Udo; Sironen, Tarja; Laurinmäki, Pasi; Liljeroos, Lassi; Patjas, Aino; Henttonen, Heikki; Vaheri, Antti; Artelt, Annette; Kipar, Anja; Butcher, Sarah J.; Vapalahti, Olli

    2013-01-01

    Boid inclusion body disease (BIBD) is a progressive, usually fatal disease of constrictor snakes, characterized by cytoplasmic inclusion bodies (IB) in a wide range of cell types. To identify the causative agent of the disease, we established cell cultures from BIBD-positive and -negative boa constrictors. The IB phenotype was maintained in cultured cells of affected animals, and supernatants from these cultures caused the phenotype in cultures originating from BIBD-negative snakes. Viruses were purified from the supernatants by ultracentrifugation and subsequently identified as arenaviruses. Purified virus also induced the IB phenotype in naive cells, which fulfilled Koch's postulates in vitro. One isolate, tentatively designated University of Helsinki virus (UHV), was studied in depth. Sequencing confirmed that UHV is a novel arenavirus species that is distinct from other known arenaviruses including those recently identified in snakes with BIBD. The morphology of UHV was established by cryoelectron tomography and subtomographic averaging, revealing the trimeric arenavirus spike structure at 3.2-nm resolution. Immunofluorescence, immunohistochemistry, and immunoblotting with a polyclonal rabbit antiserum against UHV and reverse transcription-PCR (RT-PCR) revealed the presence of genetically diverse arenaviruses in a large cohort of snakes with BIBD, confirming the causative role of arenaviruses. Some snakes were also found to carry arenavirus antibodies. Furthermore, mammalian cells (Vero E6) were productively infected with UHV, demonstrating the potential of arenaviruses to cross species barriers. In conclusion, we propose the newly identified lineage of arenaviruses associated with BIBD as a novel taxonomic entity, boid inclusion body disease-associated arenaviruses (BIBDAV), in the family Arenaviridae. PMID:23926354

  20. Isolation, identification, and characterization of novel arenaviruses, the etiological agents of boid inclusion body disease.

    PubMed

    Hetzel, Udo; Sironen, Tarja; Laurinmäki, Pasi; Liljeroos, Lassi; Patjas, Aino; Henttonen, Heikki; Vaheri, Antti; Artelt, Annette; Kipar, Anja; Butcher, Sarah J; Vapalahti, Olli; Hepojoki, Jussi

    2013-10-01

    Boid inclusion body disease (BIBD) is a progressive, usually fatal disease of constrictor snakes, characterized by cytoplasmic inclusion bodies (IB) in a wide range of cell types. To identify the causative agent of the disease, we established cell cultures from BIBD-positive and -negative boa constrictors. The IB phenotype was maintained in cultured cells of affected animals, and supernatants from these cultures caused the phenotype in cultures originating from BIBD-negative snakes. Viruses were purified from the supernatants by ultracentrifugation and subsequently identified as arenaviruses. Purified virus also induced the IB phenotype in naive cells, which fulfilled Koch's postulates in vitro. One isolate, tentatively designated University of Helsinki virus (UHV), was studied in depth. Sequencing confirmed that UHV is a novel arenavirus species that is distinct from other known arenaviruses including those recently identified in snakes with BIBD. The morphology of UHV was established by cryoelectron tomography and subtomographic averaging, revealing the trimeric arenavirus spike structure at 3.2-nm resolution. Immunofluorescence, immunohistochemistry, and immunoblotting with a polyclonal rabbit antiserum against UHV and reverse transcription-PCR (RT-PCR) revealed the presence of genetically diverse arenaviruses in a large cohort of snakes with BIBD, confirming the causative role of arenaviruses. Some snakes were also found to carry arenavirus antibodies. Furthermore, mammalian cells (Vero E6) were productively infected with UHV, demonstrating the potential of arenaviruses to cross species barriers. In conclusion, we propose the newly identified lineage of arenaviruses associated with BIBD as a novel taxonomic entity, boid inclusion body disease-associated arenaviruses (BIBDAV), in the family Arenaviridae.

  1. Whole-body FDG-PET imaging for staging of Hodgkin`s disease and lymphoma

    SciTech Connect

    Hoh, C.K.; Glaspy, J.; Rosen, P.

    1997-03-01

    Accurate staging of Hodgkin`s disease (HD) and non-Hodgkin`s lymphoma (NHL) is important for treatment management. In this study, the utility of 2-[{sup 18}F]fluoro-2-deoxy-D-glucose (FDG) wholebody PET was evaluated as an imaging modality for initial staging or restaging of 7 HD and 11 NHL patients. Whole-body PET-based staging results were compared to the patient`s clinical stage based on conventional staging studies, which included combinations of CT of the chest, abdomen and pelvis, MRI scans, gallium scans, lymphangiograms, staging laparatomies and bone scans. Accurate staging was performed in 17 of 18 patients using a whole-body PET-based staging algorithm compared to the conventional staging algorithm in 15 of 18 patients. In 5 of 18 patients, whole-body PET-based staging showed additional lesions not detected by conventional staging modalities, whereas conventional staging demonstrated additional lesions in 4 of 18 patients not detected by whole-body PET. The total cost of conventional staging was $66,292 for 16 CT chest scans, 16 CT abdominal/pelvis scans, three limited MRI scans, four bone scans, give gallium scans, two laparotomies and one lymphangiogram. In contrast, scans cost $36,250 for 18 whole-body PET studies and additional selected correlative studies: one plain film radiograph, one limited CT, one bone marrow san, one upper GI and one endoscopy. A whole-body FDG-PET-based staging algorithm may be an accurate and cost-effective method for staging or restaging HD and NHL. 10 refs., 7 figs., 2 tabs.

  2. Body Fat Composition Assessment Using Analytic Morphomics Predicts Infectious Complications After Bowel Resection in Crohn's Disease

    PubMed Central

    Waljee, Akbar K.; Day, Nicholas M.; Bergmans, Carrie L.; Zahn, Katelin M.; Higgins, Peter D. R.; Wang, Stewart C.; Su, Grace L.

    2015-01-01

    Background: Decisions between medical and surgical management of Crohn's disease (CD) incorporate risk assessments for potential complications of each therapy. Analytic morphomics is a novel method of image analysis providing quantifiable measurements of body tissue composition, characterizing body fat more comprehensively than body mass index alone. The aim of this study was to determine the risk factors associated with postoperative complications in CD, incorporating fat composition analysis using analytic morphomics. Methods: We performed a retrospective review of adults undergoing bowel resection for CD between 2004 and 2011 at a single center. Computed tomography obtained within 30 days prior to surgery underwent morphomic analysis for fat characterization. Postoperative infectious complications were defined as the need for a postoperative abdominal drain, intravenous antibiotics, or reoperation within 30 days. Bivariate and multivariate analyses using logistic regression were used to generate a prediction model of infectious complications. Results: A total of 269 subjects met selection criteria; 27% incurred postoperative infectious complications. Bivariate analysis showed hemoglobin, albumin, surgical urgency, high-dose prednisone use, and subcutaneous-to-visceral fat volume distribution as predictors of complications. Body mass index, anti-tumor necrosis factor alpha therapies, and immunomodulator use were not predictors of complication. Multivariate modeling demonstrated a c-statistic of 0.77 and a negative predictive value of 81.1% with surgical urgency (odds ratio = 2.78; 95% confidence interval, 1.46–6.02; P = 0.004), subcutaneous-to-visceral fat distribution (odds ratio = 2.01; 95% confidence interval, 1.20–3.19; P = 0.006), and hemoglobin (odds ratio = 0.69; 95% confidence interval, 0.55–0.85; P = 0.001) as predictors of infectious complication. Conclusions: Fat subtype and distribution are predictive of postoperative infectious complications

  3. Association of Fluid Status and Body Composition with Physical Function in Patients with Chronic Kidney Disease

    PubMed Central

    Hsiao, Shih-Ming; Tsai, Yi-Chun; Chen, Hui-Mei; Lin, Ming-Yen; Chiu, Yi-Wen; Chen, Tzu-Hui; Wang, Shu-Li; Hsiao, Pei-Ni; Kung, Lan-Fang; Hwang, Shang-Jyh; Huang, Mei-Feng; Yeh, Yi-Chun; Chen, Cheng-Sheng; Kuo, Mei-Chuan

    2016-01-01

    Background Impairment of physical function and abnormal body composition are the major presentations in patients with chronic kidney disease (CKD). The aim of this study is to investigate the relationship between body composition and physical function in CKD patients. Methods This cross-sectional study enrolled 172 of CKD stages 1–5 from February 2013 to September 2013. Handgrip strength (upper extremity muscle endurance), 30-second chair-stand test (lower extremity muscle endurance) and 2-minute step test (cardiorespiratory endurance) were used as indices of physical function. Body composition, including fluid status (extracellular water/total body water, ECW/TBW), lean tissue index (LTI), and fat tissue index (FTI), was measured using a bioimpedance spectroscopy method. Results All patients with high ECW/TBW had lower handgrip strength and 30-second chair-stand than those with low ECW/TBW (P<0.001 and P = 0.002). CKD patients with high FTI had lower handgrip strength and 30-second chair-stand than those with low FTI (P<0.001 and P = 0.002). These patients with low LTI had lower handgrip strength than those with high LTI (P = 0.04). In multivariate analysis, high ECW/TBW was positively associated with decreased handgrip strength (β = -41.17, P = 0.03) in CKD patients. High FTI was significantly correlated with decreased times of 30-second chair-stand (β = -0.13, P = 0.01). There was no significant relationship between body composition and 2-minute step test. Conclusions Our results show a significant association of impaired upper and lower extremity muscle endurance with high fluid status and fat tissue. Evaluation of body composition may assist in indentifying physical dysfunction earlier in CKD patients. PMID:27798648

  4. Structural diversity and biological importance of ABO, H, Lewis and secretor histo-blood group carbohydrates.

    PubMed

    de Mattos, Luiz Carlos

    ABO, H, secretor and Lewis histo-blood system genes control the expression of part of the carbohydrate repertoire present in areas of the body occupied by microorganisms. These carbohydrates, besides having great structural diversity, act as potential receptors for pathogenic and non-pathogenic microorganisms influencing susceptibility and resistance to infection and illness. Despite the knowledge of some structural variability of these carbohydrate antigens and their polymorphic levels of expression in tissue and exocrine secretions, little is known about their biological importance and potential applications in medicine. This review highlights the structural diversity, the biological importance and potential applications of ABO, H, Lewis and secretor histo-blood carbohydrates.

  5. Scales of Lewis basicities toward C-centered Lewis acids (carbocations).

    PubMed

    Mayr, Herbert; Ammer, Johannes; Baidya, Mahiuddin; Maji, Biplab; Nigst, Tobias A; Ofial, Armin R; Singer, Thomas

    2015-02-25

    Equilibria for the reactions of benzhydryl cations (Ar2CH(+)) with phosphines, tert-amines, pyridines, and related Lewis bases were determined photometrically in CH2Cl2 and CH3CN solution at 20 °C. The measured equilibrium constants can be expressed by the sum of two parameters, defined as the Lewis Acidity (LA) of the benzhydrylium ions and the Lewis basicity (LB) of the phosphines, pyridines, etc. Least-squares minimization of log K = LA + LB with the definition LA = 0 for (4-MeOC6H4)2CH(+) gave a Lewis acidity scale for 18 benzhydrylium ions covering 18 orders of magnitude in CH2Cl2 as well as Lewis basicities (with respect to C-centered Lewis acids) for 56 bases. The Lewis acidities correlated linearly with the quantum chemically calculated (B3LYP/6-311++G(3df,2pd)//B3LYP/6-31G(d,p) level) methyl anion affinities of the corresponding benzhydrylium ions, which can be used as reference compounds for characterizing a wide variety of Lewis bases. The equilibrium measurements were complemented by isothermal titration calorimetry studies. Rates of SN1 solvolyses of benzhydryl chlorides, bromides, and tosylates derived from E(13-33)(+), i.e., from highly reactive carbocations, correlate excellently with the corresponding Lewis acidities and the quantum chemically calculated methyl anion affinities. This correlation does not hold for solvolyses of derivatives of the better stabilized amino-substituted benzhydrylium ions E(1-12)(+). In contrast, the correlation between electrophilic reactivities and Lewis acidities (or methyl anion affinities) is linear for all donor-substituted benzhydrylium ions E(1-21)(+), while the acceptor-substituted benzhydrylium ions E(26-33)(+) react more slowly than expected from their thermodynamic stabilities. The boundaries of linear rate-equilibrium relationships were thus defined.

  6. Five-year incidence of periodontal disease is related to body mass index.

    PubMed

    Morita, I; Okamoto, Y; Yoshii, S; Nakagaki, H; Mizuno, K; Sheiham, A; Sabbah, W

    2011-02-01

    Numerous cross-sectional epidemiological studies suggest that obesity is associated with periodontal disease. This longitudinal study tested whether body mass index (BMI) was related to the development of periodontal disease in a sample of employed Japanese participants. Data are from the statutory medical checkups routinely collected for employees in and around Nagoya, Japan. The authors tested the relationship between BMI at baseline and the 5-year incidence of periodontal disease in a sample of 2787 males and 803 females. The hazard ratios for developing periodontal disease after 5 years were 1.30 (P < .001) and 1.44 (P = .072) in men and 1.70 (P < .01) and 3.24 (P < .05) in women for those with BMIs of 25-30 and ≥ 30, respectively, compared to those with BMI < 22, after adjusting for age, smoking status, and clinical history of diabetes mellitus. These findings demonstrate a dose-response relationship between BMI and the development of periodontal disease in a population of Japanese individuals.

  7. Weight and body mass index in Parkinson's disease patients after deep brain stimulation surgery.

    PubMed

    Tuite, Paul J; Maxwell, Robert E; Ikramuddin, Sayeed; Kotz, Catherine M; Kotzd, Catherine M; Billington, Charles J; Billingtond, Charles J; Laseski, Maggie A; Thielen, Scott D

    2005-06-01

    A retrospective chart review characterizing changes in 17 male and 10 female Parkinson's disease (PD) patients undergoing deep brain stimulation (DBS) surgery indicated that 6 mo before surgery, patients lost a mean of 5.1 lbs, whereas in the 6 mo after surgery, subjects gained a mean of 10.1 lbs; 22% gained more than 14 lbs. In 10 patients followed an additional 6 mo, weight gain continued. This weight gain may be associated with decreased energy expenditure due to subsidence of chronic tremor. The magnitude of gain underscores the need for proactive management of body weight in PD patients undergoing DBS.

  8. Rocket Propulsion Research at Lewis Research Center

    NASA Technical Reports Server (NTRS)

    Dawson, Virginia P.

    1992-01-01

    A small contingent of engineers at NASA Lewis Research Center pioneered in basic research on liquid propellants for rockets shortly after World War II. Carried on through the 1950s, this work influenced the important early decisions made by Abe Silverstein when he took charge of the Office of Space Flight Programs for NASA. He strongly supported the development of liquid hydrogen as a propulsion fuel in the face of resistance from Wernher von Braun. Members of the Lewis staff played an important role in bringing liquid hydrogen technology to the point of reliability through their management of the Centaur Program. This paper demonstrates how the personality and engineering intuition of Abe Silverstein shaped the Centaur program and left a lasting imprint on the laboratory research tradition. Many of the current leaders of Lewis Research Center received their first hands-on engineering experience when they worked on the Centaur program in the 1960s.

  9. NASA Lewis Wind Tunnel Model Systems Criteria

    NASA Technical Reports Server (NTRS)

    Soeder, Ronald H.; Haller, Henry C.

    1994-01-01

    This report describes criteria for the design, analysis, quality assurance, and documentation of models or test articles that are to be tested in the aeropropulsion facilities at the NASA Lewis Research Center. The report presents three methods for computing model allowable stresses on the basis of the yield stress or ultimate stress, and it gives quality assurance criteria for models tested in Lewis' aeropropulsion facilities. Both customer-furnished model systems and in-house model systems are discussed. The functions of the facility manager, project engineer, operations engineer, research engineer, and facility electrical engineer are defined. The format for pretest meetings, prerun safety meetings, and the model criteria review are outlined Then, the format for the model systems report (a requirement for each model that is to be tested at NASA Lewis) is described, the engineers that are responsible for developing the model systems report are listed, and the time table for its delivery to the facility manager is given.

  10. New loci for body fat percentage reveal link between adiposity and cardiometabolic disease risk

    PubMed Central

    Lu, Yingchang; Day, Felix R.; Gustafsson, Stefan; Buchkovich, Martin L.; Na, Jianbo; Bataille, Veronique; Cousminer, Diana L.; Dastani, Zari; Drong, Alexander W.; Esko, Tõnu; Evans, David M.; Falchi, Mario; Feitosa, Mary F.; Ferreira, Teresa; Hedman, Åsa K.; Haring, Robin; Hysi, Pirro G.; Iles, Mark M.; Justice, Anne E.; Kanoni, Stavroula; Lagou, Vasiliki; Li, Rui; Li, Xin; Locke, Adam; Lu, Chen; Mägi, Reedik; Perry, John R. B.; Pers, Tune H.; Qi, Qibin; Sanna, Marianna; Schmidt, Ellen M.; Scott, William R.; Shungin, Dmitry; Teumer, Alexander; Vinkhuyzen, Anna A. E.; Walker, Ryan W.; Westra, Harm-Jan; Zhang, Mingfeng; Zhang, Weihua; Zhao, Jing Hua; Zhu, Zhihong; Afzal, Uzma; Ahluwalia, Tarunveer Singh; Bakker, Stephan J. L.; Bellis, Claire; Bonnefond, Amélie; Borodulin, Katja; Buchman, Aron S.; Cederholm, Tommy; Choh, Audrey C.; Choi, Hyung Jin; Curran, Joanne E.; de Groot, Lisette C. P. G. M.; De Jager, Philip L.; Dhonukshe-Rutten, Rosalie A. M.; Enneman, Anke W.; Eury, Elodie; Evans, Daniel S.; Forsen, Tom; Friedrich, Nele; Fumeron, Frédéric; Garcia, Melissa E.; Gärtner, Simone; Han, Bok-Ghee; Havulinna, Aki S.; Hayward, Caroline; Hernandez, Dena; Hillege, Hans; Ittermann, Till; Kent, Jack W.; Kolcic, Ivana; Laatikainen, Tiina; Lahti, Jari; Leach, Irene Mateo; Lee, Christine G.; Lee, Jong-Young; Liu, Tian; Liu, Youfang; Lobbens, Stéphane; Loh, Marie; Lyytikäinen, Leo-Pekka; Medina-Gomez, Carolina; Michaëlsson, Karl; Nalls, Mike A.; Nielson, Carrie M.; Oozageer, Laticia; Pascoe, Laura; Paternoster, Lavinia; Polašek, Ozren; Ripatti, Samuli; Sarzynski, Mark A.; Shin, Chan Soo; Narančić, Nina Smolej; Spira, Dominik; Srikanth, Priya; Steinhagen-Thiessen, Elisabeth; Sung, Yun Ju; Swart, Karin M. A.; Taittonen, Leena; Tanaka, Toshiko; Tikkanen, Emmi; van der Velde, Nathalie; van Schoor, Natasja M.; Verweij, Niek; Wright, Alan F.; Yu, Lei; Zmuda, Joseph M.; Eklund, Niina; Forrester, Terrence; Grarup, Niels; Jackson, Anne U.; Kristiansson, Kati; Kuulasmaa, Teemu; Kuusisto, Johanna; Lichtner, Peter; Luan, Jian'an; Mahajan, Anubha; Männistö, Satu; Palmer, Cameron D.; Ried, Janina S.; Scott, Robert A.; Stancáková, Alena; Wagner, Peter J.; Demirkan, Ayse; Döring, Angela; Gudnason, Vilmundur; Kiel, Douglas P.; Kühnel, Brigitte; Mangino, Massimo; Mcknight, Barbara; Menni, Cristina; O'Connell, Jeffrey R.; Oostra, Ben A.; Shuldiner, Alan R.; Song, Kijoung; Vandenput, Liesbeth; van Duijn, Cornelia M.; Vollenweider, Peter; White, Charles C.; Boehnke, Michael; Boettcher, Yvonne; Cooper, Richard S.; Forouhi, Nita G.; Gieger, Christian; Grallert, Harald; Hingorani, Aroon; Jørgensen, Torben; Jousilahti, Pekka; Kivimaki, Mika; Kumari, Meena; Laakso, Markku; Langenberg, Claudia; Linneberg, Allan; Luke, Amy; Mckenzie, Colin A.; Palotie, Aarno; Pedersen, Oluf; Peters, Annette; Strauch, Konstantin; Tayo, Bamidele O.; Wareham, Nicholas J.; Bennett, David A.; Bertram, Lars; Blangero, John; Blüher, Matthias; Bouchard, Claude; Campbell, Harry; Cho, Nam H.; Cummings, Steven R.; Czerwinski, Stefan A.; Demuth, Ilja; Eckardt, Rahel; Eriksson, Johan G.; Ferrucci, Luigi; Franco, Oscar H.; Froguel, Philippe; Gansevoort, Ron T.; Hansen, Torben; Harris, Tamara B.; Hastie, Nicholas; Heliövaara, Markku; Hofman, Albert; Jordan, Joanne M.; Jula, Antti; Kähönen, Mika; Kajantie, Eero; Knekt, Paul B.; Koskinen, Seppo; Kovacs, Peter; Lehtimäki, Terho; Lind, Lars; Liu, Yongmei; Orwoll, Eric S.; Osmond, Clive; Perola, Markus; Pérusse, Louis; Raitakari, Olli T.; Rankinen, Tuomo; Rao, D. C.; Rice, Treva K.; Rivadeneira, Fernando; Rudan, Igor; Salomaa, Veikko; Sørensen, Thorkild I. A.; Stumvoll, Michael; Tönjes, Anke; Towne, Bradford; Tranah, Gregory J.; Tremblay, Angelo; Uitterlinden, André G.; van der Harst, Pim; Vartiainen, Erkki; Viikari, Jorma S.; Vitart, Veronique; Vohl, Marie-Claude; Völzke, Henry; Walker, Mark; Wallaschofski, Henri; Wild, Sarah; Wilson, James F.; Yengo, Loïc; Bishop, D. Timothy; Borecki, Ingrid B.; Chambers, John C.; Cupples, L. Adrienne; Dehghan, Abbas; Deloukas, Panos; Fatemifar, Ghazaleh; Fox, Caroline; Furey, Terrence S.; Franke, Lude; Han, Jiali; Hunter, David J.; Karjalainen, Juha; Karpe, Fredrik; Kaplan, Robert C.; Kooner, Jaspal S.; McCarthy, Mark I.; Murabito, Joanne M.; Morris, Andrew P.; Bishop, Julia A. N.; North, Kari E.; Ohlsson, Claes; Ong, Ken K.; Prokopenko, Inga; Richards, J. Brent; Schadt, Eric E.; Spector, Tim D.; Widén, Elisabeth; Willer, Cristen J.; Yang, Jian; Ingelsson, Erik; Mohlke, Karen L.; Hirschhorn, Joel N.; Pospisilik, John Andrew; Zillikens, M. Carola; Lindgren, Cecilia; Kilpeläinen, Tuomas Oskari; Loos, Ruth J. F.

    2016-01-01

    To increase our understanding of the genetic basis of adiposity and its links to cardiometabolic disease risk, we conducted a genome-wide association meta-analysis of body fat percentage (BF%) in up to 100,716 individuals. Twelve loci reached genome-wide significance (P<5 × 10−8), of which eight were previously associated with increased overall adiposity (BMI, BF%) and four (in or near COBLL1/GRB14, IGF2BP1, PLA2G6, CRTC1) were novel associations with BF%. Seven loci showed a larger effect on BF% than on BMI, suggestive of a primary association with adiposity, while five loci showed larger effects on BMI than on BF%, suggesting association with both fat and lean mass. In particular, the loci more strongly associated with BF% showed distinct cross-phenotype association signatures with a range of cardiometabolic traits revealing new insights in the link between adiposity and disease risk. PMID:26833246

  11. Experimental infection of Boa constrictor with an orthoreovirus isolated from a snake with inclusion body disease.

    PubMed

    Darke, Sabina; Marschang, Rachel E; Hetzel, Udo; Reinacher, Manfred

    2014-06-01

    Orthoreoviruses have been associated with disease in reptiles, but have not previously been isolated from snakes with inclusion body disease (IBD). An orthoreovirus was isolated from a Boa constrictor diagnosed with IBD and then used to conduct a transmission study to determine the clinical importance of this virus. For the transmission study, 10 juvenile boas were experimentally infected with the isolated orthoreovirus and compared to 5 sham-infected control animals. Orthoreovirus was reisolated for a period of 18 wk after infection and weight gain was reduced in infected snakes. Histological examination showed a mild hepatitis in three of four virologically positive snakes up to 12 wk after infection. Results indicated that the orthoreovirus was moderately pathogenic, but, no evidence was found to indicate that it was the causal agent of IBD. In the light of the discovery of Arenaviruses in some snakes with IBD, it was proposed that orthoreoviruses may play a role in synergistic infection.

  12. New loci for body fat percentage reveal link between adiposity and cardiometabolic disease risk.

    PubMed

    Lu, Yingchang; Day, Felix R; Gustafsson, Stefan; Buchkovich, Martin L; Na, Jianbo; Bataille, Veronique; Cousminer, Diana L; Dastani, Zari; Drong, Alexander W; Esko, Tõnu; Evans, David M; Falchi, Mario; Feitosa, Mary F; Ferreira, Teresa; Hedman, Åsa K; Haring, Robin; Hysi, Pirro G; Iles, Mark M; Justice, Anne E; Kanoni, Stavroula; Lagou, Vasiliki; Li, Rui; Li, Xin; Locke, Adam; Lu, Chen; Mägi, Reedik; Perry, John R B; Pers, Tune H; Qi, Qibin; Sanna, Marianna; Schmidt, Ellen M; Scott, William R; Shungin, Dmitry; Teumer, Alexander; Vinkhuyzen, Anna A E; Walker, Ryan W; Westra, Harm-Jan; Zhang, Mingfeng; Zhang, Weihua; Zhao, Jing Hua; Zhu, Zhihong; Afzal, Uzma; Ahluwalia, Tarunveer Singh; Bakker, Stephan J L; Bellis, Claire; Bonnefond, Amélie; Borodulin, Katja; Buchman, Aron S; Cederholm, Tommy; Choh, Audrey C; Choi, Hyung Jin; Curran, Joanne E; de Groot, Lisette C P G M; De Jager, Philip L; Dhonukshe-Rutten, Rosalie A M; Enneman, Anke W; Eury, Elodie; Evans, Daniel S; Forsen, Tom; Friedrich, Nele; Fumeron, Frédéric; Garcia, Melissa E; Gärtner, Simone; Han, Bok-Ghee; Havulinna, Aki S; Hayward, Caroline; Hernandez, Dena; Hillege, Hans; Ittermann, Till; Kent, Jack W; Kolcic, Ivana; Laatikainen, Tiina; Lahti, Jari; Mateo Leach, Irene; Lee, Christine G; Lee, Jong-Young; Liu, Tian; Liu, Youfang; Lobbens, Stéphane; Loh, Marie; Lyytikäinen, Leo-Pekka; Medina-Gomez, Carolina; Michaëlsson, Karl; Nalls, Mike A; Nielson, Carrie M; Oozageer, Laticia; Pascoe, Laura; Paternoster, Lavinia; Polašek, Ozren; Ripatti, Samuli; Sarzynski, Mark A; Shin, Chan Soo; Narančić, Nina Smolej; Spira, Dominik; Srikanth, Priya; Steinhagen-Thiessen, Elisabeth; Sung, Yun Ju; Swart, Karin M A; Taittonen, Leena; Tanaka, Toshiko; Tikkanen, Emmi; van der Velde, Nathalie; van Schoor, Natasja M; Verweij, Niek; Wright, Alan F; Yu, Lei; Zmuda, Joseph M; Eklund, Niina; Forrester, Terrence; Grarup, Niels; Jackson, Anne U; Kristiansson, Kati; Kuulasmaa, Teemu; Kuusisto, Johanna; Lichtner, Peter; Luan, Jian'an; Mahajan, Anubha; Männistö, Satu; Palmer, Cameron D; Ried, Janina S; Scott, Robert A; Stancáková, Alena; Wagner, Peter J; Demirkan, Ayse; Döring, Angela; Gudnason, Vilmundur; Kiel, Douglas P; Kühnel, Brigitte; Mangino, Massimo; Mcknight, Barbara; Menni, Cristina; O'Connell, Jeffrey R; Oostra, Ben A; Shuldiner, Alan R; Song, Kijoung; Vandenput, Liesbeth; van Duijn, Cornelia M; Vollenweider, Peter; White, Charles C; Boehnke, Michael; Boettcher, Yvonne; Cooper, Richard S; Forouhi, Nita G; Gieger, Christian; Grallert, Harald; Hingorani, Aroon; Jørgensen, Torben; Jousilahti, Pekka; Kivimaki, Mika; Kumari, Meena; Laakso, Markku; Langenberg, Claudia; Linneberg, Allan; Luke, Amy; Mckenzie, Colin A; Palotie, Aarno; Pedersen, Oluf; Peters, Annette; Strauch, Konstantin; Tayo, Bamidele O; Wareham, Nicholas J; Bennett, David A; Bertram, Lars; Blangero, John; Blüher, Matthias; Bouchard, Claude; Campbell, Harry; Cho, Nam H; Cummings, Steven R; Czerwinski, Stefan A; Demuth, Ilja; Eckardt, Rahel; Eriksson, Johan G; Ferrucci, Luigi; Franco, Oscar H; Froguel, Philippe; Gansevoort, Ron T; Hansen, Torben; Harris, Tamara B; Hastie, Nicholas; Heliövaara, Markku; Hofman, Albert; Jordan, Joanne M; Jula, Antti; Kähönen, Mika; Kajantie, Eero; Knekt, Paul B; Koskinen, Seppo; Kovacs, Peter; Lehtimäki, Terho; Lind, Lars; Liu, Yongmei; Orwoll, Eric S; Osmond, Clive; Perola, Markus; Pérusse, Louis; Raitakari, Olli T; Rankinen, Tuomo; Rao, D C; Rice, Treva K; Rivadeneira, Fernando; Rudan, Igor; Salomaa, Veikko; Sørensen, Thorkild I A; Stumvoll, Michael; Tönjes, Anke; Towne, Bradford; Tranah, Gregory J; Tremblay, Angelo; Uitterlinden, André G; van der Harst, Pim; Vartiainen, Erkki; Viikari, Jorma S; Vitart, Veronique; Vohl, Marie-Claude; Völzke, Henry; Walker, Mark; Wallaschofski, Henri; Wild, Sarah; Wilson, James F; Yengo, Loïc; Bishop, D Timothy; Borecki, Ingrid B; Chambers, John C; Cupples, L Adrienne; Dehghan, Abbas; Deloukas, Panos; Fatemifar, Ghazaleh; Fox, Caroline; Furey, Terrence S; Franke, Lude; Han, Jiali; Hunter, David J; Karjalainen, Juha; Karpe, Fredrik; Kaplan, Robert C; Kooner, Jaspal S; McCarthy, Mark I; Murabito, Joanne M; Morris, Andrew P; Bishop, Julia A N; North, Kari E; Ohlsson, Claes; Ong, Ken K; Prokopenko, Inga; Richards, J Brent; Schadt, Eric E; Spector, Tim D; Widén, Elisabeth; Willer, Cristen J; Yang, Jian; Ingelsson, Erik; Mohlke, Karen L; Hirschhorn, Joel N; Pospisilik, John Andrew; Zillikens, M Carola; Lindgren, Cecilia; Kilpeläinen, Tuomas Oskari; Loos, Ruth J F

    2016-02-01

    To increase our understanding of the genetic basis of adiposity and its links to cardiometabolic disease risk, we conducted a genome-wide association meta-analysis of body fat percentage (BF%) in up to 100,716 individuals. Twelve loci reached genome-wide significance (P<5 × 10(-8)), of which eight were previously associated with increased overall adiposity (BMI, BF%) and four (in or near COBLL1/GRB14, IGF2BP1, PLA2G6, CRTC1) were novel associations with BF%. Seven loci showed a larger effect on BF% than on BMI, suggestive of a primary association with adiposity, while five loci showed larger effects on BMI than on BF%, suggesting association with both fat and lean mass. In particular, the loci more strongly associated with BF% showed distinct cross-phenotype association signatures with a range of cardiometabolic traits revealing new insights in the link between adiposity and disease risk.

  13. Columbid herpesvirus-1 in two Cooper's hawks (Accipiter cooperii) with fatal inclusion body disease.

    PubMed

    Pinkerton, Marie E; Wellehan, James F X; Johnson, April J; Childress, April L; Fitzgerald, Scott D; Kinsel, Michael J

    2008-07-01

    We report two separate naturally occurring cases of fatal herpesviral disease in Cooper's Hawks (Accipiter cooperii). Gross lesions included splenomegaly and hepatomegaly, with diffuse pale mottling or scattered small white foci. Histologic lesions included splenic and hepatic necrosis associated with eosinophilic intranuclear inclusion bodies characteristic of herpesvirus. In one case, necrosis and inclusions were also noted in bone marrow, thymus, bursa of Fabricius, thyroid gland, parathyroid gland, ceca, and the enteric system. Transmission electron microscopy demonstrated viral particles typical of herpesvirus within hepatocyte nuclei and budding from the nuclear membrane. Herpesviral DNA was amplified via polymerase chain reaction (PCR) of paraffin-embedded liver and spleen, and sequence data were consistent with columbid herpesvirus-1, an alphaherpesvirus of Rock Pigeons (Columba livia). PCR results provide evidence that this disease is transmitted to raptors via Rock Pigeons, most likely through ingestion of Rock Pigeons as prey.

  14. Lewis hybrid computing system, users manual

    NASA Technical Reports Server (NTRS)

    Bruton, W. M.; Cwynar, D. S.

    1979-01-01

    The Lewis Research Center's Hybrid Simulation Lab contains a collection of analog, digital, and hybrid (combined analog and digital) computing equipment suitable for the dynamic simulation and analysis of complex systems. This report is intended as a guide to users of these computing systems. The report describes the available equipment' and outlines procedures for its use. Particular is given to the operation of the PACER 100 digital processor. System software to accomplish the usual digital tasks such as compiling, editing, etc. and Lewis-developed special purpose software are described.

  15. Serum albumin and body weight as biomarkers for the antemortem identification of bone and gastrointestinal disease in the common marmoset.

    PubMed

    Baxter, Victoria K; Shaw, Gillian C; Sotuyo, Nathaniel P; Carlson, Cathy S; Olson, Erik J; Zink, M Christine; Mankowski, Joseph L; Adams, Robert J; Hutchinson, Eric K; Metcalf Pate, Kelly A

    2013-01-01

    The increasing use of the common marmoset (Callithrix jacchus) in research makes it important to diagnose spontaneous disease that may confound experimental studies. Bone disease and gastrointestinal disease are two major causes of morbidity and mortality in captive marmosets, but currently no effective antemortem tests are available to identify affected animals prior to the terminal stage of disease. In this study we propose that bone disease and gastrointestinal disease are associated disease entities in marmosets and aim to establish the efficacy of several economical antemortem tests in identifying and predicting disease. Tissues from marmosets were examined to define affected animals and unaffected controls. Complete blood count, serum chemistry values, body weight, quantitative radiographs, and tissue-specific biochemical markers were evaluated as candidate biomarkers for disease. Bone and gastrointestinal disease were associated, with marmosets being over seven times more likely to have either concurrent bone and gastrointestinal disease or neither disease as opposed to lesions in only one organ system. When used in tandem, serum albumin <3.5 g/dL and body weight <325 g identified 100% of the marmosets affected with concurrent bone and gastrointestinal disease. Progressive body weight loss of 0.05% of peak body weight per day predicted which marmosets would develop disease prior to the terminal stage. Bone tissue-specific tests, such as quantitative analysis of radiographs and serum parathyroid hormone levels, were effective for distinguishing between marmosets with bone disease and those without. These results provide an avenue for making informed decisions regarding the removal of affected marmosets from studies in a timely manner, preserving the integrity of research results.

  16. The role of nutrition and body composition in peripheral arterial disease

    PubMed Central

    Brostow, Diana P.; Hirsch, Alan T.; Collins, Tracie C.; Kurzer, Mindy S.

    2015-01-01

    Peripheral arterial disease (PAD) has not been as extensively investigated as other cardiovascular diseases. However, the available data suggest that nutrition-based treatment strategies have the potential to reduce the cost-economic burden of PAD substantially. Abdominal obesity is associated with PAD and prospective and cross-sectional studies have shown that a low dietary intake of folate and reduced synthesis of vitamin D are associated with an increased risk of PAD and severe walking impairment in patients who have the disease. However, dietary patterns that are associated with decreased cardiovascular risk might protect against PAD. A small number of clinical trials have provided evidence that increased intakes of niacin and insoluble fiber might be associated with decreased levels of LDL cholesterol and thrombogenic biomarkers, as well as increased serum levels of HDL cholesterol in patients with PAD. However, little evidence that antioxidants, vitamins B6 and B12, or essential fatty acid supplements improve clinical outcomes in these patients exists. Overall, data on the effects of nutrition, body composition, and nutritional supplementation on the risk, progression, and prognosis of PAD are scarce. Further research into these areas is required to allow the development of evidence-based nutritional guidelines for the prevention and treatment of the disease. PMID:22922595

  17. Impaired intracellular trafficking defines early Parkinson's disease.

    PubMed

    Hunn, Benjamin H M; Cragg, Stephanie J; Bolam, J Paul; Spillantini, Maria-Grazia; Wade-Martins, Richard

    2015-03-01

    Parkinson's disease (PD) is an insidious and incurable neurodegenerative disease, and represents a significant cost to individuals, carers, and ageing societies. It is defined at post-mortem by the loss of dopamine neurons in the substantia nigra together with the presence of Lewy bodies and Lewy neurites. We examine here the role of α-synuclein and other cellular transport proteins implicated in PD and how their aberrant activity may be compounded by the unique anatomy of the dopaminergic neuron. This review uses multiple lines of evidence from genetic studies, human tissue, induced pluripotent stem cells, and refined animal models to argue that prodromal PD can be defined as a disease of impaired intracellular trafficking. Dysfunction of the dopaminergic synapse heralds trafficking impairment.

  18. Leg muscle activation during gait in Parkinson's disease: influence of body unloading.

    PubMed

    Dietz, V; Leenders, K L; Colombo, G

    1997-10-01

    The effect of body unloading (75, 50 and 25% of body weight) on upper and lower leg muscle activation during stepping on a treadmill was investigated in groups of patients with Parkinson's disease and age-matched healthy subjects. The aim of the study was to test the hypothesis that impaired extensor load receptor function exists in the patients. A strong load sensitivity was found for the gastrocnemius (GM) electromyographic (EMG) activity (i.e. EMG amplitude decreased with unloading during stepping in both groups of subjects). The change in the EMG amplitude of the rectus femoris was less dependent upon the load but was observed to be more pronounced in the patients. Upper and lower leg flexor muscles were relatively load-insensitive. The absolute GM EMG amplitude during the stance phase of stepping with normal body loading was significantly smaller in the patients than in the healthy subjects. It is suggested that the latter observation is due to a change in the threshold or bias of the extensor load reflex mechanism in the patients. The slope or gain of this reflex appears to be preserved.

  19. Body composition and exercise performance in patients with chronic obstructive pulmonary disease.

    PubMed Central

    Schols, A M; Mostert, R; Soeters, P B; Wouters, E F

    1991-01-01

    To investigate whether a compromised nutritional state may limit exercise performance in patients with chronic obstructive pulmonary disease we studied 54 such patients (FEV1 less than 50% and arterial oxygen tension (PaO2) greater than 7.3 kPa) whose clinical condition was stable and who were admitted to a pulmonary rehabilitation centre. Fat free mass was assessed anthropometrically (from skinfold measurements at four sites) and by bioelectrical impedance; creatinine height index and arm muscle circumference were also assessed. The mean (SD) distance walked in 12 minutes was 845 (178) m. No association was established between the distance walked and spirometric measures. A good correlation was found between the distance walked and fat free mass in the whole group (r = 0.73 for impedance measurements and 0.65 for skinfold thickness) and in a subgroup of 23 lean patients (body weight less than 90% of ideal weight; r = 0.66 for impedance measurements and 0.46 for skinfold thickness). Body weight correlated with the distance walked only in the whole group (r = 0.61). On stepwise regression analysis fat free mass measured by bioelectrical impedance, maximal inspiratory mouth pressure, and PaO2 accounted for 60% of the variation in the distance walked in 12 minutes. We conclude that fat free mass, independently of airflow obstruction, is an important determinant of exercise performance in patients with severe chronic obstructive pulmonary disease. PMID:1750015

  20. Downsizing of lean body mass is a key determinant of Alzheimer's disease.

    PubMed

    Ingenbleek, Yves; Bernstein, Larry H

    2015-01-01

    Lean body mass (LBM) encompasses all metabolically active organs distributed into visceral and structural tissue compartments and collecting the bulk of N and K stores of the human body. Transthyretin (TTR) is a plasma protein mainly secreted by the liver within a trimolecular TTR-RBP-retinol complex revealing from birth to old age strikingly similar evolutionary patterns with LBM in health and disease. TTR is also synthesized by the choroid plexus along distinct regulatory pathways. Chronic dietary methionine (Met) deprivation or cytokine-induced inflammatory disorders generates LBM downsizing following differentiated physiopathological processes. Met-restricted regimens downregulate the transsulfuration cascade causing upstream elevation of homocysteine (Hcy) safeguarding Met homeostasis and downstream drop of hydrogen sulfide (H2S) impairing anti-oxidative capacities. Elderly persons constitute a vulnerable population group exposed to increasing Hcy burden and declining H2S protection, notably in plant-eating communities or in the course of inflammatory illnesses. Appropriate correction of defective protein status and eradication of inflammatory processes may restore an appropriate LBM size allowing the hepatic production of the retinol circulating complex to resume, in contrast with the refractory choroidal TTR secretory process. As a result of improved health status, augmented concentrations of plasma-derived TTR and retinol may reach the cerebrospinal fluid and dismantle senile amyloid plaques, contributing to the prevention or the delay of the onset of neurodegenerative events in elderly subjects at risk of Alzheimer's disease.

  1. Ketone body β-hydroxybutyrate blocks the NLRP3 inflammasome-mediated inflammatory disease

    PubMed Central

    Youm, Yun-Hee; Nguyen, Kim Y.; Grant, Ryan W.; Goldberg, Emily L.; Bodogai, Monica; Kim, Dongin; D'Agostino, Dominic; Planavsky, Noah; Lupfer, Christopher; Kanneganti, Thirumala D.; Kang, Seokwon; Horvath, Tamas L.; Fahmy, Tarek M.; Crawford, Peter A.; Biragyn, Arya; Alnemri, Emad; Dixit, Vishwa Deep

    2015-01-01

    Ketone bodies , β-hydroxybutyrate (BHB) and acetoacetate support mammalian survival during states of energy deficit by serving as alternative source of ATP1. BHB levels are elevated during starvation, high-intensity exercise or by the low carbohydrate ketogenic diet2. Prolonged caloric restriction or fasting reduces inflammation as immune system adapts to low glucose supply and energy metabolism switches towards mitochondrial fatty acid oxidation, ketogenesis and ketolysis2-6. However, role of ketones bodies in regulation of innate immune response is unknown. We report that BHB, but neither acetoacetate nor structurally-related short chain fatty acids, butyrate and acetate, suppresses activation of the NLRP3 inflammasome in response to several structurally unrelated NLRP3 activators, without impacting NLRC4, AIM2 or non-canonical caspase-11 inflammasome activation. Mechanistically, BHB inhibits NLRP3 inflammasome by preventing K+ efflux and reducing ASC oligomerization and speck formation. The inhibitory effects of BHB on NLRP3 were not dependent on chirality or classical starvation regulated mechanisms like AMPK, reactive oxygen species (ROS), autophagy or glycolytic inhibition. BHB blocked NLRP3 inflammasome without undergoing oxidation in TCA cycle, independently of uncoupling protein-2 (UCP2), Sirt2, receptor Gpr109a and inhibition of NLRP3 did not correlate with magnitude of histone acetylation in macrophages. BHB reduced the NLRP3 inflammasome mediated IL-1β and IL-18 production in human monocytes. In vivo, BHB attenuates caspase-1 activation and IL-1β secretion in mouse models of NLRP3-mediated diseases like Muckle-Wells Syndrome (MWS), Familial Cold Autoinflammatory syndrome (FCAS) and urate crystal induce body cavity inflammation. Taken together, these findings suggest that the anti-inflammatory effects of caloric restriction or ketogenic diets may be mechanistically linked to BHB-mediated inhibition of the NLRP3 inflammasome, and point to the potential

  2. Herpesviral inclusion body disease in owls and falcons is caused by the pigeon herpesvirus (columbid herpesvirus 1).

    PubMed

    Gailbreath, Katherine L; Oaks, J Lindsay

    2008-04-01

    A herpesviral disease of Rock Pigeons (Columba livia), called "inclusion body disease" or "inclusion body hepatitis," was first described in the 1940s. The disease involves hepatic and splenic necrosis with associated intranuclear inclusion bodies and occurs primarily in young squabs. A similar herpesviral disease occurs in falcons and owls. Serologic and restriction endonuclease digestion studies indicate that herpesviruses from pigeons, falcons, and owls are very closely related and that most reported cases of disease in falcons and owls involve prior documented or possible ingestion of pigeons. These findings led to the hypothesis that an endemic herpesvirus of pigeons may be causing disease in falcons and owls. In order to test this hypothesis, we sequenced a fragment of the herpesviral DNA polymerase gene from naturally infected owls, falcons, and pigeons with inclusion body disease collected between 1991 and 2006. Sequences from all three sources were almost identical, and we therefore propose that the usual agent of inclusion body hepatitis in owls and falcons is columbid herpesvirus 1.

  3. A Case Report of Improvement in Crohn's Disease-related Symptoms Following Participation in a Comprehensive Mind-Body Program.

    PubMed

    Dossett, Michelle L; Korzenik, Joshua R; Baim, Margaret; Denninger, John W; Mehta, Darshan H

    2016-01-01

    Stress is widely believed to play a role in the development and pathogenesis of inflammatory bowel disease (IBD), and several studies of mind-body programs have suggested benefits in this patient population. Here we describe a case report of a young man with a flare in Crohn's disease-related symptoms that improved in response to a comprehensive, multi-modal, mind-body program and the development of a novel IBD treatment center that incorporates mind-body approaches, nutrition, and other modalities to provide more holistic and patient-centered care for individuals with IBD.

  4. Recommendations of the Alzheimer's disease-related dementias conference.

    PubMed

    Montine, Thomas J; Koroshetz, Walter J; Babcock, Debra; Dickson, Dennis W; Galpern, Wendy R; Glymour, M Maria; Greenberg, Steven M; Hutton, Michael L; Knopman, David S; Kuzmichev, Andrey N; Manly, Jennifer J; Marder, Karen S; Miller, Bruce L; Phelps, Creighton H; Seeley, William W; Sieber, Beth-Anne; Silverberg, Nina B; Sutherland, Margaret; Torborg, Christine L; Waddy, Salina P; Zlokovic, Berislav V; Corriveau, Roderick A

    2014-08-26

    The National Alzheimer's Project Act, signed into law in 2011, mandates a National Plan to Address Alzheimer's Disease that is updated annually. In the Plan, the term Alzheimer disease includes not only Alzheimer disease (AD) proper, but also several specified related dementias, namely, frontotemporal, Lewy body, vascular, and mixed dementia. In response to a specific action item in the 2012 National Plan, the National Institute of Neurological Disorders and Stroke, in collaboration with the National Institute on Aging, convened panels of experts and conducted a 2-day public conference to develop research priorities and timelines for addressing Alzheimer disease-related dementias (ADRD) in 5 topic areas: multiple etiology dementias, health disparities, Lewy body dementias including dementia with Lewy bodies and Parkinson disease dementia, frontotemporal dementia and related tauopathies, and vascular contributions to ADRD. By design, the product was up to 8 prioritized research recommendations in each topic area including estimated timelines from when work on a recommendation is started to completion or to full implementation of an ongoing activity, and recognition of shared research themes across recommendations. These included increased education and training of both researchers and health care professionals, addressing health disparities, fundamental neurobiology research, advanced diagnostics, collaborative biosample repositories, and a focus on developing effective interventions to prevent or treat ADRD by the year 2025 as targeted by the National Plan.

  5. Abnormal Weight and Body Mass Index in Children with Juvenile Huntington’s Disease

    PubMed Central

    Lee, Jessica K.; Gonzalez-Alegre, Pedro; Crane, Kaitlin; Dawson, Jeffrey; Nopoulos, Peg

    2016-01-01

    Objectives To evaluate anthropometric measures of growth and development (height, weight, body mass index (BMI)) in a group of children, adolescents, and young adults diagnosed with Juvenile Onset Huntington’s Disease (JHD). Methods Growth measures for 18 JHD patients, documented prior to or shortly after diagnosis, were obtained through medical records. JHD growth measures were compared to a large sample (n=274) of healthy children, as well as the Center for Disease Control (CDC) growth norms. Results After controlling for sex and age, the JHD subjects had no significant differences in height. However, they were an average of 10% lower than controls in weight and BMI. Using CDC norms, the JHD subjects had the same pattern of normal height but decrement in weight. Length of cytosine-adenine-guanine (CAG) repeat in the huntingtin gene was significantly correlated to measures of weight with longer CAG repeats being associated with more severe weight reduction. A subset of 4 subjects had measures that pre-dated onset of any symptom and were therefore prodromal JHD (preJHD). These subjects also had a significant decrement in BMI compared to CDC norms. Conclusions Children with JHD have normal height, but significantly reduced weight and BMI, indicative of a specific deficit in body weight. As the preJHD subjects were also low in BMI, this suggests that these changes are directly due to the effect of the mutated gene on development, rather than symptom manifestation of the disease itself. Potential mechanisms of the weight decrement include energy deficiency due to mitochondrial dysfunction during development. PMID:26443925

  6. Celebrating the Bicentennial of Lewis and Clark

    ERIC Educational Resources Information Center

    Morris, Ronald V.; McNeely, Jean

    2005-01-01

    Lewis, Clark, and the Corps of Discovery traveled westward from 1803 to 1806; therefore, the bicentennial of the expedition is being celebrated from 2003 until 2006. Students and teachers celebrating the bicentennial and Jefferson's Louisiana Purchase in 1803 can use social studies classes to help them connect with their community and to reach a…

  7. Lewis and Clark--Indiana Connections.

    ERIC Educational Resources Information Center

    Bennett, Pamela J., Ed.

    2003-01-01

    The state of Indiana has an important, recognized connection to the Lewis and Clark Expedition. That connection is reinforced with a National Signature Event in Clarksville (Indiana) during October 2003. Until the expedition party left its winter camp in May 1804, it remained in Indiana Territory, governed from Vincennes (Indiana) by William Henry…

  8. Lewis Mumford and the Ecology of Technics.

    ERIC Educational Resources Information Center

    Strate, Lance; Lum, Casey Man Kong

    2000-01-01

    Examines Lewis Mumford's scholarship and his contribution to the emergence of media ecology as both an intellectual tradition and a theoretical perspective on the study of technology, media, and culture. Focuses on Mumford's epochal historiography of technology, the techno-organicism in his thinking about technology and human development, and his…

  9. Playing around in Lewis Carroll's "Alice" Books

    ERIC Educational Resources Information Center

    Susina, Jan

    2010-01-01

    Mathematician Charles Dodgson's love of play and his need for rules came together in his use of popular games as part of the structure of the two famous children's books, "Alice in Wonderland" and "Through the Looking-Glass," he wrote under the pseudonym Lewis Carroll. The author of this article looks at the interplay between…

  10. Reply to Tone Kvernbekk and Ann Lewis

    ERIC Educational Resources Information Center

    Tangen, Reidun

    2008-01-01

    The purpose of this reply to Kvernbekk and Lewis's comments regarding the discussion on epistemological and ethical problems of listening to children's voices, is not to propose a coherent foundation free from any epistemological tensions. Rather, Tangen's intent is primarily to explore different perspectives in order to disclose some of their…

  11. Composites research at NASA Lewis Research Center

    NASA Technical Reports Server (NTRS)

    Levine, Stanley R.; Duffy, Stephen; Vary, Alex; Nathal, Michael V.; Miner, Robert V.; Arnold, Steven M.; Castelli, Michael G.; Hopkins, Dale A.; Meador, Michael A.

    1994-01-01

    Composites research at NASA Lewis is focused on their applications in aircraft propulsion, space propulsion, and space power, with the first being predominant. Research on polymer-, metal-, and ceramic-matrix composites is being carried out from an integrated materials and structures viewpoint. This paper outlines some of the topics being pursued from the standpoint of key technical issues, current status, and future directions.

  12. Teaching a Model for Writing Lewis Structures.

    ERIC Educational Resources Information Center

    Pardo, Juan Quilez

    1989-01-01

    Presents a didactic model to improve the teaching/learning process in the representation of Lewis structures. Places special emphasis on the calculation and reduction of formal charges, and in the representation of molecules in which the central atom has expanded its valence shell. (MVL)

  13. A pilot study on the impact of body composition on bone and mineral metabolism in Parkinson's disease.

    PubMed

    Fernández, María C; Parisi, Muriel S; Díaz, Sergio P; Mastaglia, Silvina R; Deferrari, Juan M; Seijo, Mariana; Bagur, Alicia; Micheli, Federico; Oliveri, Beatriz

    2007-08-01

    The impact of body composition on bone and mineral metabolism in Parkinson's disease (PD) was evaluated. Body fat mass, lean mass, bone mineral content, and bone mineral density (BMD) were measured by DXA in 22 PD patients and 104 controls. Female patients exhibited reduced body mass index, fat mass, and BMD compared to controls (p<0.05). Significant positive correlation was found between 25 OHD levels and BMC. Diminished bone mass in women with PD was found to be associated with alterations in body composition and low 25 OHD levels.

  14. Body mass index, abdominal fatness and the risk of gallbladder disease.

    PubMed

    Aune, Dagfinn; Norat, Teresa; Vatten, Lars J

    2015-09-01

    Epidemiological studies have indicated a positive association between adiposity and gallbladder disease risk, however, the shape of the dose-response relationship and differences between overall and abdominal adiposity remains to be clarified. We conducted a systematic review and dose-response meta-analysis of cohort studies of body mass index (BMI), waist circumference and waist-to-hip ratio and risk of gallbladder disease. PubMed and Embase databases were searched up to January 9th 2015. Summary relative risks were calculated using a random effects model. Seventeen prospective studies of BMI and gallbladder disease risk with 55,670 cases among 1,921,103 participants were included. The summary relative risk (RR) for a 5 unit increment in BMI was 1.63 (95 % CI 1.49-1.78, I(2) = 98 %). There was evidence of a nonlinear association overall and among women, p(nonlinearity) < 0.0001, but not among men, p(nonlinearity) = 0.99, with a slight flattening of the curve at very high BMI levels (BMI 40-45), however, the risk of gallbladder disease increased almost twofold even within the "normal" BMI range. The summary RR for a 10 cm increase in waist circumference was 1.46 (95 % CI 1.24-1.72, I(2) = 98 %, n = 5) and for a 0.1 unit increment in waist-to-hip ratio was 1.44 (95 % CI 1.26-1.64, I(2) = 92 %, n = 4). Associations were attenuated, but still significant, when BMI and abdominal adiposity measures were mutually adjusted. Our results confirm a positive association between both general and abdominal fatness and the risk of gallbladder disease. There is an almost twofold increase in the risk even within the "normal" BMI range, suggesting that even moderate increases in BMI may increase risk.

  15. Teaching Beginning Chemistry Students Simple Lewis Dot Structures

    ERIC Educational Resources Information Center

    Nassiff, Peter; Czerwinski, Wendy A.

    2015-01-01

    Students beginning their initial study of chemistry often have a difficult time mastering simple Lewis dot structures. Textbooks show students how to manipulate Lewis structures by moving valence electron dots around the chemical structure so each atom has an octet or duet. However, an easier method of teaching Lewis structures for simple…

  16. An Overview of Lewis Basicity and Affinity Scales

    ERIC Educational Resources Information Center

    Laurence, Christian; Graton, Jerome; Gal, Jean-Francois

    2011-01-01

    The impossibility of establishing a universal scale of Lewis basicity does not prevent the determination of the quantitative behavior of Lewis bases, thanks to scales constructed against particular Lewis acids: BF[subscript 3], 4-FC[subscript 6]H[subscript 4]OH, I[subscript 2], Li[superscript +], Na[superscript +], K[superscript +], Al[superscript…

  17. Mechanisms of body weight gain in patients with Parkinson's disease after subthalamic stimulation.

    PubMed

    Montaurier, C; Morio, B; Bannier, S; Derost, P; Arnaud, P; Brandolini-Bunlon, M; Giraudet, C; Boirie, Y; Durif, F

    2007-07-01

    decreased significantly in both men and women (-7.3 +/- 2.2% and -13.1 +/- 1.7%, respectively, P < 0.01) but there was no correlation between daily EE changes and body weight gain. Parkinson's disease is associated with profound alterations in the central control of energy metabolism. Normalization of energy metabolism after DBS-STN implantation may favour body weight gain, of which quality was gender specific. As men gained primarily fat-free mass, a reasonable weight gain may be tolerated, in contrast with women who gained only fat. Other factors such as changes in free-living physical activity may help to limit body weight gain in some patients.

  18. Disease, risk, and contagion: French colonial and postcolonial constructions of "African" bodies.

    PubMed

    Sargent, Carolyn; Larchanché, Stéphanie

    2014-12-01

    In this article, we explore how sub-Saharan African immigrant populations in France have been constructed as risk groups by media sources, in political rhetoric, and among medical professionals, drawing on constructs dating to the colonial period. We also examine how political and economic issues have been mirrored and advanced in media visibility and ask why particular populations and the diseases associated with them in the popular imagination have received more attention at certain historical moments. In the contemporary period we analyze how the bodies of West African women and men have become powerful metaphors in the politics of discrimination prevalent in France, in spite of Republican precepts that theoretically disavow cultural and social difference.

  19. Fractured bodies and diseased societies: medicalizing Quebec in Cité libre.

    PubMed

    Robert, Julie

    2011-01-01

    This essay seeks to rationalize and explain the evolution of medical rhetoric in Cité libre by looking at trends in the journal's use of tropes of illness and disease. Through a combination of broad content analysis and close readings, it contrasts how individual metaphors create the impression of a sickening nation and the manner in which these metaphors collectively, albeit paradoxically, act as a national allegory of cure for mid-twentieth-century Quebec's social ills in general, and specifically for its pathological inferiority complex. By examining how the journal uses medical metaphors and specifically how the writers employed the trope of the body politic to illustrate Quebec's national failings, the essay demonstrates how Quebec challenges the rhetorical stability of the age-old metaphor as it attempts to solve, but also creates, problems within Quebec's articulation of its own nationhood.

  20. Reduced body mass index in Parkinson's disease: contribution of comorbid depression.

    PubMed

    Pilhatsch, Maximilian; Kroemer, Nils B; Schneider, Christine; Ebersbach, Georg; Jost, Wolfgang H; Fuchs, Gerd; Odin, Per; Reifschneider, Gerd; Bauer, Michael; Reichmann, Heinz; Storch, Alexander

    2013-01-01

    Courses of Parkinson's disease (PD) that are complicated by weight loss result in poorer overall treatment outcome and lower quality of life. To determine the contribution of depression, which has not yet been specified in the etiology of weight loss in PD, symptomatology and anamnesis from 215 outpatients diagnosed with PD were assessed using a comprehensive battery of neuropsychiatric scales. A percentage of 31 comorbid depressed patients and a comparison with a control population allowed an accurate characterization of effect sizes, sex differences, and patterns of the contribution of comorbid depression to weight loss. Our study showed that comorbid depression had a clinically relevant effect concerning reduced body mass index in male (0.3; Hedges' g) but not in female PD patients. Although some possible confounders are not controlled here, our results support the need of monitoring depressive symptoms in the courses of PD, particularly in male patients.

  1. Research note: the isolation of a herpes virus from captive cranes with an inclusion body disease

    USGS Publications Warehouse

    Docherty, D.E.; Henning, D.J.

    1980-01-01

    A viral agent, identified as a herpesvirus and tentatively called 'inclusion body disease of cranes' (IBDC), was isolated from captive cranes involved in a die-off at the International Crane Foundation near Baraboo, Wisconsin. Preliminary animal susceptibility tests, based on experimental infections, suggested that White Pekin ducklings up to 17 days old and adult coots were susceptible to the IBDC virus whereas 16-day-old White Leghorn chicks and 64-day-old Muscovy ducks were not. No serum antibody to IBDC virus was detected in 95 wild sandhill cranes collected in Wisconsin or Indiana in 1976 and 1977. However, 9 of 11 captive cranes in the affected area at the ICF had antibody to this agent.

  2. From loose body to osteochondritis dissecans: a historical account of disease definition

    PubMed Central

    TARABELLA, VITTORIO; FILARDO, GIUSEPPE; DI MATTEO, BERARDO; ANDRIOLO, LUCA; TOMBA, PATRIZIA; VIGANÒ, ANNA; MARCACCI, MAURILIO

    2016-01-01

    Osteochondritis dissecans (OCD) is a rare yet fascinating disease affecting young, active patients. It remains a ‘mysterious disease’ whose etiopathology, still unclear, is the subject of ongoing studies aiming improving the knowledge of this condition and, therefore, treatment options, too. Even though the first descriptions of intra-articular loose bodies date back to very ancient times, it is only relatively recently that, thanks to the contribution of some very eminent physicians, it became recognized as a specific orthopaedic condition. The aim of the present manuscript is to trace the main steps in the journey that led to the acknowledgement of OCD as an autonomous clinical entity, and to recall the prominent figures involved. PMID:27900309

  3. Detection of novel divergent arenaviruses in boid snakes with inclusion body disease in The Netherlands.

    PubMed

    Bodewes, R; Kik, M J L; Raj, V Stalin; Schapendonk, C M E; Haagmans, B L; Smits, S L; Osterhaus, A D M E

    2013-06-01

    Arenaviruses are bi-segmented negative-stranded RNA viruses, which were until recently only detected in rodents and humans. Now highly divergent arenaviruses have been identified in boid snakes with inclusion body disease (IBD). Here, we describe the identification of a new species and variants of the highly divergent arenaviruses, which were detected in tissues of captive boid snakes with IBD in The Netherlands by next-generation sequencing. Phylogenetic analysis of the complete sequence of the open reading frames of the four predicted proteins of one of the detected viruses revealed that this virus was most closely related to the recently identified Golden Gate virus, while considerable sequence differences were observed between the highly divergent arenaviruses detected in this study. These findings add to the recent identification of the highly divergent arenaviruses in boid snakes with IBD in the United States and indicate that these viruses also circulate among boid snakes in Europe.

  4. Effects of random whole-body vibration on postural control in Parkinson's disease.

    PubMed

    Turbanski, Stephan; Haas, Christian T; Schmidtbleicher, Dietmar; Friedrich, Antje; Duisberg, Petra

    2005-01-01

    We investigated spontaneous effects of random whole-body vibration (rWBV) on postural control in Parkinsonian subjects. Effects were examined in biomechanical tests from a total of 52 patients divided equally into one experimental and one control group. Postural control was tested pre- and post-treatment in two standardized conditions (narrow standing and tandem standing). The intervention was based on rWBV (ŷ: 3 mm, f: 6 Hz 1 Hz/sec) consisting of 5 series lasting 60 seconds each. The main findings from this study were that (1) rWBV can improve postural stability in Parkinson's disease (PD) spontaneously (2) these effects depend on the test condition. Based on the results of this study, rWBV can be regarded as an additional device in physical therapy in PD.

  5. The role of body position and gravity in the symptoms and treatment of various medical diseases.

    PubMed

    Martin-Du Pan, Rémy C; Benoit, Raymond; Girardier, Lucia

    2004-09-18

    Postural medicine studies the effects of gravity on human body functions and the ability to influence various diseases by changing the body's position. Orthostasis requires numerous cardiovascular and neurohumoral adaptations to prevent hypotension and a resulting decrease in cerebral perfusion. Sitting upright or in a semi-sitting position reduces venous return in patients with heart failure, intracranial pressure in patients with intracranial hypertension, intraocular pressure in glaucoma patients and may decrease gastro-oesophageal reflux. A left recumbent posture also decreases reflux. A right lateral position results in a lower sympathetic tone than lying on the left side and is beneficial in patients with heart failure or after an infarction without bradycardia. A 40 to 70% decreased prevalence of the sudden infant death syndrome has been observed since the recommendation to avoid laying infants to sleep in a prone position. Sleeping in a supine posture increases the severity of sleep apnoea compared to a lateral position. In patients with acute respiratory distress syndrome, a prone position can rapidly improve blood oxygenation. Idiopathic oedema, orthostatic proteinuria, intradiscal pressure and venous circulation in legs are improved in the decubitus position, whereas arterial flow is reduced. Health risks due to microgravity and prolonged bed rest, such as osteoporosis, venous thrombosis or pressure sores, are discussed.

  6. Investigating the Lewis acidity of aluminium fluoride surfaces

    NASA Astrophysics Data System (ADS)

    Bailey, C. L.; Mukhopadhyay, S.; Wander, A.; Harrison, N. M.

    2008-03-01

    The current study employs state of the art hybrid-exchange density functional theory (DFT) to investigate the Lewis acidic sites on the β-AlF3 (100) surface. It is shown that the strong Lewis base, NH3, binds to the surface with a binding energy of up to 1.9 eV. This demonstrates that the material is strongly Lewis acidic. We also consider the binding of the weak Lewis base CO to the surface. We calculate the shift in its stretch frequency compared to the gas phase molecule. Shifts are compared to experimental data and are shown to be typical of strong Lewis acidity.

  7. Modern Exploration of the Lewis and Clark Expedition

    NASA Technical Reports Server (NTRS)

    2006-01-01

    The Lewis and Clark Geosystem is an online collection of private, state, local, and Federal data resources associated with the geography of the Lewis and Clark Expedition. Data were compiled from key partners including NASA s Stennis Space Center, the U.S. Army Corps of Engineers, the U.S. Fish and Wildlife Service, the U.S. Geological Survey (USGS), the University of Montana, the U.S. Department of Agriculture Forest Service, and from a collection of Lewis and Clark scholars. It combines modern views of the landscape with historical aerial photography, cartography, and other geographical data resources and historical sources, including: The Journals of the Lewis and Clark Expedition, the Academy of Natural Science's Lewis and Clark Herbarium, high-resolution copies of the American Philosophical Society s primary-source Lewis and Clark Journals, The Library of Congress Lewis and Clark cartography collection, as well as artifacts from the Smithsonian Institution and other sources.

  8. Advanced glycation end products induce in vitro cross-linking of alpha-synuclein and accelerate the process of intracellular inclusion body formation.

    PubMed

    Shaikh, Shamim; Nicholson, Louise F B

    2008-07-01

    Cross-linking of alpha-synuclein and Lewy body formation have been implicated in the dopaminergic neuronal cell death observed in Parkinson's disease (PD); the mechanisms responsible, however, are not clear. Reactive oxygen species and advanced glycation end products (AGEs) have been found in the intracellular, alpha-synuclein-positive Lewy bodies in the brains of both PD as well as incidental Lewy body disease patients, suggesting a role for AGEs in alpha-synuclein cross-linking and Lewy body formation. The aims of the present study were to determine 1) whether AGEs can induce cross-linking of alpha-synuclein peptides, 2) the progressive and time-dependent intracellular accumulation of AGEs and inclusion body formation, and 3) the effects of extracellular or exogenous AGEs on intracellular inclusion formation. We first investigated the time-dependent cross-linking of recombinant human alpha-synuclein in the presence of AGEs in vitro, then used a cell culture model based on chronic rotenone treatment of human dopaminergic neuroblastoma cells (SH-SY5Y) over a period of 1-4 weeks, in the presence of different doses of AGEs. Cells (grown on coverslips) and cell lysates, collected at the end of every week, were analyzed for the presence of intracellular reactive oxygen species, AGEs, alpha-synuclein proteins, and intracellular alpha-synuclein- and AGE-positive inclusion bodies by using immunocytochemical, biochemical, and Western blot techniques. Our results show that AGEs promote in vitro cross-linking of alpha-synuclein, that intracellular accumulation of AGEs precedes alpha-synuclein-positive inclusion body formation, and that extracellular AGEs accelerate the process of intracellular alpha-synuclein-positive inclusion body formation.

  9. Validating Diagnostic and Screening Procedures for Pre-Motor Parkinson’s Disease

    DTIC Science & Technology

    2013-04-01

    motor; Parkinson’s Disease; Lewy Body Disease; REM Behavior Disorder (RBD); Cardiac dysautonomia; Electrocardiogram; Heart Rate Variability (HRV...has four objectives: 1) to develop the required internal and collaborative infrastructure to establish a large cohort with idiopathic REM behavior...established collaborative relationships with San Francisco Bay Area sleep medicine clinics and neurologists in order to recruit study subjects. After pre-IRB

  10. Incipient intranuclear inclusion body disease in a 78-year-old woman.

    PubMed

    Mori, Fumiaki; Miki, Yasuo; Tanji, Kunikazu; Ogura, Eriko; Yagihashi, Norito; Jensen, Poul H; Wakabayashi, Koichi

    2011-04-01

    We report an incipient case of intranuclear inclusion body disease (INIBD) in a 78-year-old woman. No apparent neurological symptoms were noticed during the clinical course. Post mortem examination revealed widespread occurrence of eosinophilic intranuclear inclusions in neuronal and glial cells of the central and peripheral nervous systems, as well as in parenchymal cells of the visceral organs. The inclusions were observed more frequently in glial cells than in neuronal cells. Ultrastructurally, the inclusions consisted of granular and filamentous material. Immunohistochemically, the inclusions were positive for ubiquitin, ubiquitin-related proteins (NEDD8 ultimate buster 1, small ubiquitin modifier-1, small ubiquitin modifier-2 and p62), promyelocytic leukemia protein and abnormally expanded polyglutamine. Consistent with previous studies, the vast majority of inclusion-bearing glial cells were astrocytes. Furthermore, p25α-positive oligodendrocytes rarely contained intranuclear inclusions. These findings suggest that INIBD may occur in non-demented elderly individuals and that oligodendrocyte is also involved in the disease process of INIBD.

  11. Alpha-Synuclein in Parkinson's Disease: From Pathogenetic Dysfunction to Potential Clinical Application.

    PubMed

    Xu, Lingjia; Pu, Jiali

    2016-01-01

    Parkinson's disease is a neurodegenerative disease/synucleinopathy that develops slowly; however, there is no efficient method of early diagnosis, nor is there a cure. Progressive dopaminergic neuronal cell loss in the substantia nigra pars compacta and widespread aggregation of the α-synuclein protein (encoded by the SNCA gene) in the form of Lewy bodies and Lewy neurites are the neuropathological hallmarks of Parkinson's disease. The SNCA gene has undergone gene duplications, triplications, and point mutations. However, the specific mechanism of α-synuclein in Parkinson's disease remains obscure. Recent research showed that various α-synuclein oligomers, pathological aggregation, and propagation appear to be harmful in certain areas in Parkinson's disease patients. This review summarizes our current knowledge of the pathogenetic dysfunction of α-synuclein associated with Parkinson's disease and highlights current approaches that seek to develop this protein as a possible diagnostic biomarker and therapeutic target.

  12. A Biography of Distinguished Scientist Gilbert Newton Lewis (by Edward S. Lewis)

    NASA Astrophysics Data System (ADS)

    Harris, Reviewed By Harold H.

    1999-11-01

    The Edward Mellen Press: Lewiston, NY, 1998. 114 pp + index. ISBN 0-7734-8284-9. $69.95. There may not be a surname better known to students of chemistry than Lewis, from the Lewis electron-dot diagrams and the Lewis theory of acids and bases. More advanced students may know of the groundbreaking textbook Thermodynamics, by Lewis and Randall. Yet few Americans know much about this remarkable U.S.-born scholar, whose contributions equal those of the greatest scientists. He is a chemist-educator of whom we should be as proud and as well informed as we are of Linus Pauling, who was part of the westward movement of science in this country that G. N. Lewis began, or of the recently deceased Glenn Seaborg, who was one of the many students of Lewis who achieved renown. Gilbert N. Lewis was born in Weymouth, Massachusetts, in 1875, but his family moved to near Lincoln, Nebraska, in 1884. He spent two years at the University of Nebraska, but then moved to Harvard when his father became an executive at Merchants Trust Company in Boston. Young Lewis (then only 17) was also said to have been disappointed with the quality of education in Nebraska, and this may have been part of the impetus for the family's move east. After earning his baccalaureate at Harvard, he taught for a year at Phillips Andover Academy before returning to Harvard to study for his doctorate, which he completed 100 years ago, in 1899, under T. W. Richards. Lewis's doctoral work was on the thermodynamics of zinc and cadmium amalgams. At that time, physical chemistry was only beginning to achieve recognition as a branch of science, and its boundaries were ill defined. Edward Lewis quotes his father as often saying, "Physical chemistry is anything interesting." Like many chemists of his time, Lewis went to Europe to complete his preparation for a career; he was in the laboratories of Ostwald in Leipzig and Nernst in Göttingen in 1900-1901. On his return to the United States, he was an instructor at Harvard

  13. Does body mass index (BMI) influence the Ankylosing Spondylitis Disease Activity Score in axial spondyloarthritis?

    PubMed Central

    Rubio Vargas, Roxana; van den Berg, Rosaline; van Lunteren, Miranda; Ez-Zaitouni, Zineb; Bakker, Pauline A C; Dagfinrud, Hanne; Ramonda, Roberta; Landewé, Robert; Molenaar, Esmeralda; van Gaalen, Floris A; van der Heijde, Désirée

    2016-01-01

    Objective Obesity is associated with elevated C reactive protein (CRP) levels. The Ankylosing Spondylitis Disease Activity Score (ASDAS) combines patient-reported outcomes (PROs) and CRP. We evaluated the effect of body mass index (BMI) on CRP and on ASDAS, and studied if ASDAS can be used in obese axial spondyloarthritis (axSpA) patients to assess disease activity. Methods Baseline data of patients with chronic back pain of short duration included in the SPondyloArthritis Caught Early (SPACE) cohort were used. Collected data included BMI and ASDAS. Patients were classified according to the ASAS axSpA classification criteria and BMI (overweight ≥25 and obese ≥30). Correlation and linear regression analyses were performed to assess the relation between BMI and ASDAS. Linear regression models were performed to assess if age or gender were effect modifiers in the relation between BMI and CRP, and between BMI and ASDAS. Results In total, 428 patients were analysed (n=168 axSpA; n=260 no-axSpA). The mean age was 31.1 years, 36.9% were male, 26.4% were overweight and 13.3% obese, median CRP was 3 mg/L and the mean ASDAS was 2.6. Gender was the only factor modifying the relationship between BMI and CRP as BMI had an influence on CRP only in females (β=0.35; p<0.001). Correlations between BMI and CRP or PROs were generally weak, and only significant for CRP in female patients. BMI was not related to ASDAS in axSpA patients. Conclusions ASDAS is not affected by BMI in axSpA patients. Therefore, based on our data it is not necessary to take BMI in consideration when assessing disease activity using ASDAS in axSpA patients. PMID:27403336

  14. Nutritional status and body composition in patients with peripheral arterial disease: A cross-sectional examination of disease severity and quality of life.

    PubMed

    Brostow, Diana P; Hirsch, Alan T; Pereira, Mark A; Bliss, Robin L; Kurzer, Mindy S

    2016-01-01

    Nutritional and body weight recommendations for cardiovascular diseases are well established, yet there are no equivalent guidelines for peripheral arterial disease (PAD). This cross-sectional study measured the prevalence of cardiovascular-related nutritional and body composition risk factors in sixty PAD patients and their association with PAD severity. A diet that exceeds daily recommended intake of fat and that falls short of recommended intakes of fiber, folate, and vitamin D was associated with increased leg pain and walking difficulty. Increased body fat and waist circumference were associated with diminished walking ability and poorer psychosocial quality of life. Future prospective investigations are merited to inform both PAD clinical care and disease management guidelines.

  15. Body mass index and incident coronary heart disease in women: a population-based prospective study

    PubMed Central

    2013-01-01

    Background A high body mass index (BMI) is associated with an increased risk of mortality from coronary heart disease (CHD); however, a low BMI may also be associated with an increased mortality risk. There is limited information on the relation of incident CHD risk across a wide range of BMI, particularly in women. We examined the relation between BMI and incident CHD overall and across different risk factors of the disease in the Million Women Study. Methods 1.2 million women (mean age = 56 years) participants without heart disease, stroke, or cancer (except non-melanoma skin cancer) at baseline (1996 to 2001) were followed prospectively for 9 years on average. Adjusted relative risks and 20-year cumulative incidence from age 55 to 74 years were calculated for CHD using Cox regression. Results After excluding the first 4 years of follow-up, we found that 32,465 women had a first coronary event (hospitalization or death) during follow-up. The adjusted relative risk for incident CHD per 5 kg/m2 increase in BMI was 1.23 (95% confidence interval (CI) 1.22 to 1.25). The cumulative incidence of CHD from age 55 to 74 years increased progressively with BMI, from 1 in 11 (95% CI 1 in10 to 12) for BMI of 20 kg/m2, to 1 in 6(95% CI 1 in 5 to 7) for BMI of 34 kg/m2. A 10 kg/m2 increase in BMI conferred a similar risk to a 5-year increment in chronological age. The 20 year cumulative incidence increased with BMI in smokers and non-smokers, alcohol drinkers and non-drinkers, physically active and inactive, and in the upper and lower socioeconomic classes. In contrast to incident disease, the relation between BMI and CHD mortality (n = 2,431) was J-shaped. For the less than 20 kg/m2 and ≥35 kg/m2 BMI categories, the respective relative risks were 1.27 (95% CI 1.06 to 1.53) and 2.84 (95% CI 2.51 to 3.21) for CHD deaths, and 0.89 (95% CI 0.83 to 0.94) and 1.85 (95% CI 1.78 to 1.92) for incident CHD. Conclusions CHD incidence in women increases progressively with BMI, an

  16. Immunohistochemical and ultrastructural changes in the brain in probable adult glycogenosis type IV: adult polyglucosan body disease.

    PubMed

    Wierzba-Bobrowicz, Teresa; Lewandowska, Eliza; Stepień, Tomasz; Modzelewska, Joanna

    2008-01-01

    Glycogenosis type IV is caused by a deficiency of glycogen branching enzyme (alpha-1,4 glucan 6-transglucosylase). Adult polyglucosan body disease (APBD) may represent a neuropathological hallmark of the adult form of this storage disease of the central nervous system. We analysed a case of a 45-year-old unconscious woman who died three days after admission to the hospital. Neuropathological examination revealed massive accumulation of polyglucosan bodies (PBs) in the cortex and white matter of the whole brain. PBs were located in the processes of neurons, astrocytes and microglial cells. The storage material in the cytoplasm of neurons and glial cells was visible as fine granules. Ultrastructurally, PBs consisted of non-membrane-bound deposits of branched and densely packed filaments, measuring about 7-10 nm in diameter, typical of polyglucosan bodies. APBD patients develop upper and lower neuron disease and dementia, probably secondary to the disruption of neuron and astrocyte functions.

  17. alpha-Synucleinopathy in the human olfactory system in Parkinson's disease: involvement of calcium-binding protein- and substance P-positive cells.

    PubMed

    Ubeda-Bañon, Isabel; Saiz-Sanchez, Daniel; de la Rosa-Prieto, Carlos; Argandoña-Palacios, Lucia; Garcia-Muñozguren, Susana; Martinez-Marcos, Alino

    2010-06-01

    Hyposmia is an early symptom of idiopathic Parkinson's disease but the pathological bases of such dysfunction are largely unknown. The distribution of alpha-synuclein, which forms Lewy bodies and Lewy neurites, and the types of neurons (based on their neurotransmitters) affected by alpha-synucleinopathy were investigated in the olfactory system in Parkinson's disease. Immunohistochemical distribution of alpha-synuclein and its co-localization with tyrosine hydroxylase, somatostatin, calbindin, calretinin, parvalbumin and substance P in the olfactory bulb, anterior olfactory nucleus, olfactory tubercle and piriform, periamygdaloid and rostral entorhinal cortices of idiopathic Parkinson's disease cases (n = 11) and age-matched controls (n = 11) were investigated. Lewy bodies and Lewy neurites were present in the olfactory bulb, particularly in mitral cells and in the inner plexiform layer. alpha-synuclein was particularly abundant in the different divisions of the anterior olfactory nucleus (bulbar, intrapeduncular, retrobulbar and cortical). In contrast, Lewy bodies and Lewy neurites were less abundant in the olfactory tubercle and olfactory cortices. In the olfactory bulb, anterior olfactory nucleus and olfactory cortices, cells affected by alpha-synucleinopathy rarely co-localized tyrosine hydroxylase or somatostatin, but they frequently co-localized calbindin, calretinin, parvalbumin and substance P. The present data provide evidence that alpha-synucleinopathy affects neurons along the olfactory pathway. Dopamine- and somatostatin-positive cells are rarely affected; whereas the cell types most vulnerable to neurodegeneration include glutamate- (mitral cells), calcium-binding protein- and substance P-positive cells. These results provide data on the distribution and cell types involved by alpha-synucleinopathy in the human olfactory system during Parkinson disease that may be useful for future clinical investigation.

  18. Anionic Lewis Acids. A Chemical Oxymoron.

    DTIC Science & Technology

    1995-10-17

    NUMBER OF PAGES12 anionic lewis acid ab initio synthesis 1 2 methide FT NMR 16. PRICE CODE imide multi-nule r 17. SECURITY CLASSIFICATION 18...chemically robust, thermally stable, non-toxic, environmentally safe, and cost-effective. One of our current areas of interest involves the synthesis and...developing a predictive knowledge base that can be used to guide the synthesis of new locally electron-deficient anions. Additionally, we proposed to

  19. Calcium-based Lewis acid catalysts.

    PubMed

    Begouin, Jeanne-Marie; Niggemann, Meike

    2013-06-17

    Recently, Lewis acidic calcium salts bearing weakly coordinating anions such as Ca(NTf₂)₂, Ca(OTf)₂, CaF₂ and Ca[OCH(CF₃)₂]₂ have been discovered as catalysts for the transformation of alcohols, olefins and carbonyl compounds. High stability towards air and moisture, selectivity and high reactivity under mild reaction conditions render these catalysts a sustainable and mild alternative to transition metals, rare-earth metals or strong Brønsted acids.

  20. Polymerization by classical and frustrated Lewis pairs.

    PubMed

    Chen, Eugene Y-X

    2013-01-01

    Main-group classical and frustrated Lewis pairs (CLPs and FLPs) comprising strong Lewis acids (LAs) and strong Lewis bases (LBs) are highly active for polymerization of conjugated polar alkenes, affording typically high molecular weight polymers with relatively narrow molecular weight distributions. Especially effective systems are the Lewis pairs (LPs) consisting of the strong LA Al(C6F5)3 and strong LBs, such as achiral phosphines and chiral chelating diphosphines, N-heterocyclic carbenes, and phosphazene superbases, for polymerization of methacrylates and acrylamides as well as renewable α-methylene-γ-butyrolactones. Chain initiation involves cooperative addition of LPs to the monomer to generate zwitterionic active species, and chain propagation proceeds via a bimetallic, activated-monomer addition mechanism. Transition metal nucleophile/electrophile pairs comprising neutral metallocene bis(ester enolate)s and strong LAs E(C6F5)3 (E = Al, B) generate two drastically different polymerization systems, depending on the LA. With E = Al, catalyst activation and chain initiating events lead to dually active ion-pairs, thereby effecting ion-pairing polymerization that affords polymers with unique stereo-multiblock microstructures. With E = B, on the other hand, the FLP-induced catalyst activation generates metallacyclic cations paired with the hydridoborate anion [HB(C6F5)3](-); uniquely, such ion-pairs effect catalytic polymerization of conjugated polar alkenes by an H-shuttling mechanism, with the cation catalyzing chain growth and the anion promoting chain transfer by shuttling the hydride between the cation and anion centers through the neutral borane.

  1. NASA Lewis' IITA K-12 Program

    NASA Technical Reports Server (NTRS)

    1996-01-01

    The NASA Lewis Research Center's Information Infrastructure Technology and Applications for Kindergarten to 12th Grade (IITA K-12) Program is designed to introduce into school systems computing and communications technology that benefits math and science studies. By incorporating this technology into K-12 curriculums, we hope to increase the proficiency and interest in math and science subjects by K-12 students so that they continue to study technical subjects after their high school careers are over.

  2. A Lewis acid-mediated conformational switch.

    PubMed

    Knipe, Peter C; Lingard, Hannah; Jones, Ian M; Thompson, Sam; Hamilton, Andrew D

    2014-10-28

    Molecules that change conformation in response to a stimulus have numerous uses, such as artificial chemoreceptors, novel drug delivery strategies and liquid crystal technology. Here we describe the design, synthesis and conformational behaviour of an isonicotinamide-substituted diphenylacetylene upon recognition of Lewis acids, including metalloporphyrins. Binding of these at a remote site - the pyridyl nitrogen - increases hydrogen-bond donor ability of the proximal amide NH, causing an increased preference for the alkyne rotamer in which this hydrogen bond is maintained.

  3. Maudlin's challenge refuted: A reply to Lewis

    NASA Astrophysics Data System (ADS)

    Kastner, Ruth E.

    2014-08-01

    Lewis has recently argued that Maudlin's contingent absorber experiment remains a significant problem for the Transactional Interpretation (TI). He argues that the only straightforward way to resolve the challenge is by describing the absorbers as offer waves, and asserts that this is a previously unnoticed aspect of the challenge for TI. This argument is refuted in two basic ways: (i) it is noted that the Maudlin experiment cannot be meaningfully recast with absorbers described by quantum states; instead the author replaces it with an ordinary which-way experiment; and (ii) the extant rebuttals to the Maudlin challenge in its original form are not in fact subject to the alleged flaws that Lewis ascribes to them. This paper further seeks to clarify the issues raised in Lewis' presentation concerning the distinction between quantum systems and macroscopic objects in TI. It is noted that the latest, possibilist version of TI (PTI) has no ambiguity concerning macroscopic absorbers. In particular, macroscopic objects are not subject to indeterminate trajectories, since they are continually undergoing collapse. It is concluded that the Maudlin challenge poses no significant problem for the transactional interpretation.

  4. Lewis' Educational and Research Collaborative Internship Program

    NASA Technical Reports Server (NTRS)

    Heyward, Ann; Gott, Susan (Technical Monitor)

    2004-01-01

    The Lewis Educational and Research Collaborative Internship Program (LERCIP) is a collaborative undertaking by the Office of Educational Programs at NASA Glenn Research Center at Lewis Field (formerly NASA Lewis Research Center) and the Ohio Aerospace Institute. This program provides 10-week internships in addition to summer and winter extensions if funding is available and/or is requested by mentor (no less than 1 week no more than 4 weeks) for undergraduate/graduate students and secondary school teachers. Students who meet the travel reimbursement criteria receive up to $500 for travel expenses. Approximately 178 interns are selected to participate in this program each year and begin arriving the fourth week in May. The internships provide students with introductory professional experiences to complement their academic programs. The interns are given assignments on research and development projects under the personal guidance of NASA professional staff members. Each intern is assigned a NASA mentor who facilitates a research assignment. In addition to the research assignment, the summer program includes a strong educational component that enhances the professional stature of the participants. The educational activities include a research symposium and a variety of workshops, and lectures. An important aspect of the program is that it includes students with diverse social, cultural and economic backgrounds. The purpose of this report is to document the program accomplishments for 2004.

  5. Lewis Information Network (LINK): Background and overview

    NASA Technical Reports Server (NTRS)

    Schulte, Roger R.

    1987-01-01

    The NASA Lewis Research Center supports many research facilities with many isolated buildings, including wind tunnels, test cells, and research laboratories. These facilities are all located on a 350 acre campus adjacent to the Cleveland Hopkins Airport. The function of NASA-Lewis is to do basic and applied research in all areas of aeronautics, fluid mechanics, materials and structures, space propulsion, and energy systems. These functions require a great variety of remote high speed, high volume data communications for computing and interactive graphic capabilities. In addition, new requirements for local distribution of intercenter video teleconferencing and data communications via satellite have developed. To address these and future communications requirements for the next 15 yrs, a project team was organized to design and implement a new high speed communication system that would handle both data and video information in a common lab-wide Local Area Network. The project team selected cable television broadband coaxial cable technology as the communications medium and first installation of in-ground cable began in the summer of 1980. The Lewis Information Network (LINK) became operational in August 1982 and has become the backbone of all data communications and video.

  6. Structure of an anti-Lewis X Fab fragment in complex with its Lewis X antigen.

    PubMed

    van Roon, Anne-Marie M; Pannu, Navraj S; de Vrind, Johannes P M; van der Marel, Gijs A; van Boom, Jacques H; Hokke, Cornelis H; Deelder, André M; Abrahams, Jan Pieter

    2004-07-01

    The Lewis X trisaccharide is pivotal in mediating specific cell-cell interactions. Monoclonal antibody 291-2G3-A, which was generated from mice infected with schistosomes, has been shown to recognize the Lewis X trisaccharide. Here we describe the structure of the Fab fragment of 291-2G3-A, with Lewis X, to 1.8 A resolution. The crystallographic analysis revealed that the antigen binding site is a rather shallow binding pocket, and residues from all six complementary determining regions of the antibody contact all sugar residues. The high specificity of the binding pocket does not result in high affinity; the K(D) determined by isothermal calorimetry is 11 microM. However, this affinity is in the same range as for other sugar-antibody complexes. The detailed understanding of the antibody-Lewis X interaction revealed by the crystal structure may be helpful in the design of better diagnostic tools for schistosomiasis and for studying Lewis X-mediated cell-cell interactions by antibody interference.

  7. Dual Lewis Acid/Lewis Base Catalyzed Acylcyanation of Aldehydes: A Mechanistic Study.

    PubMed

    Laurell Nash, Anna; Hertzberg, Robin; Wen, Ye-Qian; Dahlgren, Björn; Brinck, Tore; Moberg, Christina

    2016-03-07

    A mechanistic investigation, which included a Hammett correlation analysis, evaluation of the effect of variation of catalyst composition, and low-temperature NMR spectroscopy studies, of the Lewis acid-Lewis base catalyzed addition of acetyl cyanide to prochiral aldehydes provides support for a reaction route that involves Lewis base activation of the acyl cyanide with formation of a potent acylating agent and cyanide ion. The cyanide ion adds to the carbonyl group of the Lewis acid activated aldehyde. O-Acylation by the acylated Lewis base to form the final cyanohydrin ester occurs prior to decomplexation from titanium. For less reactive aldehydes, the addition of cyanide is the rate-determining step, whereas, for more reactive, electron-deficient aldehydes, cyanide addition is rapid and reversible and is followed by rate-limiting acylation. The resting state of the catalyst lies outside the catalytic cycle and is believed to be a monomeric titanium complex with two alcoholate ligands, which only slowly converts into the product.

  8. Association between body energy content in the dry period and post-calving production disease status in dairy cattle.

    PubMed

    Smith, G L; Friggens, N C; Ashworth, C J; Chagunda, M G G

    2017-02-15

    The transition from gestation to lactation is marked by significant physiological changes for the individual cow such that disease incidence is highest in early lactation. Around the time of calving, cows rely on mobilisation of body energy reserves to fill the energy deficit created by an increase in nutrient demands at a time of restricted feed intake. It is well established that monitoring of body energy reserves in lactation is an important component of herd health management. However, despite their influence on future health and productivity, monitoring of body energy reserves in the dry period is often sparse. Further, there is increasing concern that current dry off management is inappropriate for modern cattle and may influence future disease risk. This study aimed to identify candidate indicators of early lactation production disease from body energy data collected in the dry period and production data recorded at the time of dry off. Retrospective analysis was performed on 482 cow-lactations collected from a long-term Holstein-Friesian genetic and management systems project, the Langhill herd in Scotland. Cow-lactations were assigned to one of four health groups based on health status in the first 30 days of lactation. These four groups were as follows: healthy, reproductive tract disorders (retained placenta and metritis), subclinical mastitis and metabolic disorders (ketosis, hypocalcaemia, hypomagnesaemia and left displaced abomasum). ANOVA, employing a GLM was used to determine effects for the candidate indicator traits. Cows which were diagnosed with a reproductive tract disorder in the first 30 days of lactation experienced a significantly greater loss in body energy content, body condition score and weight in the preceding dry period than healthy cows. The rate of change in body energy content during the first 15 days of the dry period was -18.26 MJ/day for cows which developed reproductive tract disorder compared with +0.63 MJ/day for healthy cows

  9. Steroid-responsive Encephalopathy Subsequently Associated with Alzheimer Disease Pathology: A Case Series

    PubMed Central

    Mateen, Farrah J.; Josephs, Keith A.; Parisi, Joseph E.; Drubach, Daniel A.; Caselli, Richard J.; Kantarci, Kejal; Lennon, Vanda; Jack, Clifford; Boeve, Bradley F.

    2011-01-01

    Background Steroid-responsive encephalopathies can considered vasculitic or nonvasculitic. Clinicopathological studies of nonvasculitic steroid-responsive encephalopathy are unusual, but can explain the range of diagnoses consistent with a steroid responsive presentation in life. Objective To extend the range of clinical features and pathological findings consistent with steroid-responsive encephalopathy. Design, Methods, and Patients A clinicopathological case series of four patients (ages 54–71 years, 2 women) with steroid-responsive encephalopathy followed at this institution until the time of death. Results Clinical features were suggestive of Creutzfeld-Jakob disease, dementia with Lewy Bodies, and parkinsonism, but pathological examination revealed only Alzheimer’s Disease-related findings without evidence of Lewy bodies or prion disease in all cases. All patients demonstrated marked, sustained improvement following steroid treatment, based on clinical, magnetic resonance imaging, and/or electroencephalogram studiesAlzheimer’s Disease was not diagnosed in life due to a lack of hippocampal atrophy on brain imaging and a dramatic symptomatic response to steroids. Conclusions Steroid-responsive encephalopathy is the clinical presentation of some patients with Alzheimer’s Disease related pathology at autopsy, and can be consistent with the clinical diagnoses of parkisonism, dementia with Lewy Bodies, or Creutzfeld-Jakob Disease in life. PMID:21714739

  10. Body-Worn Sensors in Parkinson's Disease: Evaluating Their Acceptability to Patients

    PubMed Central

    Hammerla, Nils Y.; Rochester, Lynn; Andras, Peter; Walker, Richard W.

    2016-01-01

    Abstract Background: Remote monitoring of symptoms in Parkinson's disease (PD) using body-worn sensors would assist treatment decisions and evaluation of new treatments. To date, a rigorous, systematic evaluation of the acceptability of body-worn sensors in PD has not been undertaken. Materials and Methods: Thirty-four participants wore bilateral wrist-worn sensors for 4 h in a research facility and then for 1 week at home. Participants' experiences of wearing the sensors were evaluated using a Likert-style questionnaire after each phase. Qualitative data were collected through free-text responses. Differences in responses between phases were assessed by using the Wilcoxon rank-sum test. Content analysis of qualitative data was undertaken. “Non–wear time” was estimated via analysis of accelerometer data for periods when sensors were stationary. Results: After prolonged wearing there was a negative shift in participants' views on the comfort of the sensor; problems with the sensor's strap were highlighted. However, accelerometer data demonstrated high patient concordance with wearing of the sensors. There was no evidence that participants were less likely to wear the sensors in public. Most participants preferred wearing the sensors to completing symptom diaries. Conclusions: The finding that participants were not less likely to wear the sensors in public provides reassurance regarding the ecological validity of the data captured. The validity of our findings was strengthened by “triangulation” of data sources, enabling patients to express their agenda and repeated assessment after prolonged wearing. Long-term monitoring with wrist-worn sensors is acceptable to this cohort of PD patients. Evaluation of the wearer's experience is critical to the development of remote monitoring technology. PMID:26186307

  11. Body Mass Index Is Associated with Inflammatory Bowel Disease: A Systematic Review and Meta-Analysis

    PubMed Central

    Tang, Yuchen; Xu, Fei; Yu, Chaohui; Li, Youming; Pankaj, Prasoon; Dai, Ning

    2015-01-01

    Background Prior work suggested that patients with inflammatory bowel diseases (IBD) have lower body mass index (BMI) than controls and patients with lower BMI have more serious complications. Goal The study was aimed to find relationship between BMI in patients with and without IBD, investigate effects of medicine therapy and disease stages on patients’ BMI. Methods Potentially eligible studies were identified through searching PubMed, Cochrane and Embase databases. Outcome measurements of mean BMI and the number of patients from each study were pooled by a random-effect model. Publication bias test, sensitivity analysis and subgroup analysis were conducted. Results A total of 24 studies containing 1442 patients and 2059 controls were included. Main results were as follows: (1) BMI in Crohn’s disease (CD) patients was lower than that in health controls (-1.88, 95% CI -2.77 to -1.00, P< 0.001); (2) Medical therapy significantly improved BMI of CD patients (with therapy: -1.58, -3.33 to 0.16; without: -2.09, 95% CI -3.21 to -0.98) while on the contrary not significantly improving BMI of UC patients (with therapy: -0.24, 95% CI -3.68 to 3.20; without: -1.34, 95% CI -2.87 to 0.20, P = 0.57); (3) Both CD and UC patients in active phase showed significantly greater BMI difference compared with controls than those in remission (CD patients: remission: -2.25, 95% CI -3.38 to -1.11; active phase: -4.25, 95% CI -5.58 to -2.92, P = 0.03; UC patients: remission: 0.4, 95% CI -2.05 to 2.84; active phase: -5.38, -6.78 to -3.97, P = 0.001). Conclusions BMI is lower in CD patients; medical therapy couldn’t improve BMI of IBD patients; the state of disease affects BMI of CD patients and UC patients. PMID:26658675

  12. Frustrated Lewis pairs: from concept to catalysis.

    PubMed

    Stephan, Douglas W

    2015-02-17

    CONSPECTUS: Frustrated Lewis pair (FLP) chemistry has emerged in the past decade as a strategy that enables main-group compounds to activate small molecules. This concept is based on the notion that combinations of Lewis acids and bases that are sterically prevented from forming classical Lewis acid-base adducts have Lewis acidity and basicity available for interaction with a third molecule. This concept has been applied to stoichiometric reactivity and then extended to catalysis. This Account describes three examples of such developments: hydrogenation, hydroamination, and CO2 reduction. The most dramatic finding from FLP chemistry was the discovery that FLPs can activate H2, thus countering the long-existing dogma that metals are required for such activation. This finding of stoichiometric reactivity was subsequently evolved to employ simple main-group species as catalysts in hydrogenations. While the initial studies focused on imines, subsequent studies uncovered FLP catalysts for a variety of organic substrates, including enamines, silyl enol ethers, olefins, and alkynes. Moreover, FLP reductions of aromatic anilines and N-heterocycles have been developed, while very recent extensions have uncovered the utility of FLP catalysts for ketone reductions. FLPs have also been shown to undergo stoichiometric reactivity with terminal alkynes. Typically, either deprotonation or FLP addition reaction products are observed, depending largely on the basicity of the Lewis base. While a variety of acid/base combinations have been exploited to afford a variety of zwitterionic products, this reactivity can also be extended to catalysis. When secondary aryl amines are employed, hydroamination of alkynes can be performed catalytically, providing a facile, metal-free route to enamines. In a similar fashion, initial studies of FLPs with CO2 demonstrated their ability to capture this greenhouse gas. Again, modification of the constituents of the FLP led to the discovery of reaction

  13. A focused review of the role of ketone bodies in health and disease.

    PubMed

    Akram, Muhammad

    2013-11-01

    Ketone bodies are produced in the liver and are utilized in other tissues in the body as an energy source when hypoglycemia occurs in the body. There are three ketone bodies: acetoacetate, beta hydroxy butyrate, and acetone. Ketone bodies are usually present in the blood, and their level increases during fasting and starvation. They are also found in the blood of neonates and pregnant women. In diabetic ketoacidosis, high levels of ketone bodies are produced in response to low insulin levels and high levels of counter-regulatory hormones.

  14. [Depiction of the structure of the vitreous body in horses without ocular diseases and in horses with equine recurrent uveitis (ERU) using transmission electron microscopy].

    PubMed

    Niedermaier, G; Wollanke, B; Hoffmann, R; Matiasek, K; Gerhards, H

    2006-06-01

    Neither the ultrastructure of the vitreous body from horses without ocular diseases, nor the pathomorphological changes in the vitreous body associated with equine recurrent uveitis (ERU) have been described. However, the vitreous body plays an important role in the pathogenesis of ERU. Ten vitreous body samples obtained from 5 horses without ocular disease, and 38 vitreous body samples from horses with ERU (collected during vitrectomy) were examined by transmission electron microscopy. The vitreous body samples of horses without ocular diseases were characterized by a loose network of unbranched fibrils 10-12 nm in width. In the vitreous body samples of horses with ERU numerous dense bundles of fibrils, mononuclear inflammatory cells and necrotic cells represent the destruction of the vitreous fibrillar network. In this study, equine vitreous body ultrastructure was described for the first time. Thus, demonstrating ultramorphologically, the clinically apparent changes of the vitreous body associated with ERU.

  15. Differences in nutrition status by body mass index in patients with peripheral artery disease.

    PubMed

    Oka, Roberta K; Alley, Hugh F

    2012-09-01

    Peripheral Arterial Disease (PAD) is most prevalent in the elderly and associated with increased cardio vascular disease (CVD) morbidity and mortality. Treatment focuses on improving functional capacity and reducing CVD risk factors. To date, little is understood about dietary habits and weight in this patient population. Nutritional and weight recommendations are based on heart health, and little is known about the unique needs of elderly PAD patients with multiple comorbidities. This prospective study compared 1) the dietary intake of nonobese PAD patients in comparison with those who were obese and; 2) dietary intake of those patients with the Estimated Average Requirement (EAR) based on age, gender and BMI. Nutritional intake was assessed with the Block 98 Food Frequency Questionnaire. Body mass index (BMI) was calculated in accordance with the National Heart, Lung, and Blood Institute (NHLBI) guidelines.The study population was divided into obese (BMI ≥ 30) and nonobese (NO) groups. Comparisons between groups were performed using the Mann-Whitney U test for continuous variables and the Chi-square test for ordinal variables. All tests were two-tailed and P < 0.05 was considered significant. The Estimated Average Requirement (EAR) cut-point method was used to compare nutritional variables with Dietary Reference Intakes (DRI). The study population included 189 NO (BMI < 30) and 111 obese (BMI > 30) individuals. Obese participants reported greater intake of foods containing cholesterol and trans-fatty acids and more frequent intake of B vitamins in comparison with the NO BMI group. Additionally, the nutrient intake of all participants by age, gender and BMI was lower than the EAR for magnesium, folate, and Vitamin E. These results suggest that the nutritional intake of PAD patients differs based on gender and BMI. Additionally, EAR was lower for specific nutrients than recommended. Further investigation is needed to examine the association between nutritional

  16. Coronary heart disease incidence in women by waist circumference within categories of body mass index.

    PubMed

    Canoy, Dexter; Cairns, Benjamin J; Balkwill, Angela; Wright, F Lucy; Green, Jane; Reeves, Gillian; Beral, Valerie

    2013-10-01

    High body mass index (BMI) and large waist circumference are separately associated with increased coronary heart disease (CHD) risk but these measures are highly correlated. Their separate associations with incident CHD, cross-classifying one variable by the other, are less investigated in large-scale studies. We examined these associations in a large UK cohort (the Million Women Study), which is a prospective population-based study. We followed 496,225 women (mean age 60 years) with both waist circumference and BMI measurements who had no vascular disease or cancer. Adjusted relative risk and 20-year cumulative CHD incidence (first coronary hospitalization or death) from age 55 to 74 years were calculated using Cox regression. Plasma apolipoproteins were assayed in 6295 randomly selected participants. There were 10,998 incident coronary events after mean follow up of 5.1 years. Within each BMI category (<25, 25-29.9, ≥30 kg/m(2)), CHD risk increased with increasing waist circumference; within each waist circumference category (<70, 70-79.9, ≥79 cm), CHD risk increased with increasing BMI. The cumulative CHD incidence was lowest in women with BMI <25 kg/m(2) and waist circumference <70 cm, with 1 in 14 (95% confidence interval 1 in 12 to 16) women developing CHD in the 20 years from age 55 to 74 years, and highest in women with BMI ≥30 kg/m(2) and waist circumference ≥80 cm, with 1 in 8 (95% confidence interval 1 in 7 to 9) women developing CHD over the same period. Similar associations for apolipoprotein B to A1 ratio across adiposity categories were observed, particularly in non-obese women. Our conclusions were that both waist circumference and BMI are independently associated with incident CHD.

  17. Glucose sensing by carotid body glomus cells: potential implications in disease

    PubMed Central

    Gao, Lin; Ortega-Sáenz, Patricia; García-Fernández, María; González-Rodríguez, Patricia; Caballero-Eraso, Candela; López-Barneo, José

    2014-01-01

    The carotid body (CB) is a key chemoreceptor organ in which glomus cells sense changes in blood O2, CO2, and pH levels. CB glomus cells have also been found to detect hypoglycemia in both non-primate mammals and humans. O2 and low-glucose responses share a common final pathway involving membrane depolarization, extracellular calcium influx, increase in cytosolic calcium concentration, and neurotransmitter secretion, which stimulates afferent sensory fibers to evoke sympathoadrenal activation. On the other hand, hypoxia and low glucose induce separate signal transduction pathways. Unlike O2 sensing, the response of the CB to low glucose is not altered by rotenone, with the low glucose-activated background cationic current unaffected by hypoxia. Responses of the CB to hypoglycemia and hypoxia can be potentiated by each other. The counter-regulatory response to hypoglycemia by the CB is essential for the brain, an organ that is particularly sensitive to low glucose. CB glucose sensing could be altered in diabetic patients, particularly those under insulin treatment, as well as in other medical conditions such as sleep apnea or obstructive pulmonary diseases, where chronic hypoxemia presents with plastic modifications in CB structure and function. The current review will focus on the following main aspects: (1) the CB as a low glucose sensor in both in vitro and in vivo models; (2) molecular and ionic mechanisms of low glucose sensing by glomus cells, (3) the interplay between low glucose and O2 sensing in CB, and (4) the role of CB low glucose sensing in the pathophysiology of cardiorespiratory and metabolic diseases, and how this may serve as a potential therapeutic target. PMID:25360117

  18. Glucose sensing by carotid body glomus cells: potential implications in disease.

    PubMed

    Gao, Lin; Ortega-Sáenz, Patricia; García-Fernández, María; González-Rodríguez, Patricia; Caballero-Eraso, Candela; López-Barneo, José

    2014-01-01

    The carotid body (CB) is a key chemoreceptor organ in which glomus cells sense changes in blood O2, CO2, and pH levels. CB glomus cells have also been found to detect hypoglycemia in both non-primate mammals and humans. O2 and low-glucose responses share a common final pathway involving membrane depolarization, extracellular calcium influx, increase in cytosolic calcium concentration, and neurotransmitter secretion, which stimulates afferent sensory fibers to evoke sympathoadrenal activation. On the other hand, hypoxia and low glucose induce separate signal transduction pathways. Unlike O2 sensing, the response of the CB to low glucose is not altered by rotenone, with the low glucose-activated background cationic current unaffected by hypoxia. Responses of the CB to hypoglycemia and hypoxia can be potentiated by each other. The counter-regulatory response to hypoglycemia by the CB is essential for the brain, an organ that is particularly sensitive to low glucose. CB glucose sensing could be altered in diabetic patients, particularly those under insulin treatment, as well as in other medical conditions such as sleep apnea or obstructive pulmonary diseases, where chronic hypoxemia presents with plastic modifications in CB structure and function. The current review will focus on the following main aspects: (1) the CB as a low glucose sensor in both in vitro and in vivo models; (2) molecular and ionic mechanisms of low glucose sensing by glomus cells, (3) the interplay between low glucose and O2 sensing in CB, and (4) the role of CB low glucose sensing in the pathophysiology of cardiorespiratory and metabolic diseases, and how this may serve as a potential therapeutic target.

  19. Objective Radiological Assessment of Body Composition in Patients with End-Stage Liver Disease: Going Beyond the BMI

    PubMed Central

    Cruz, Ruy J.; Dew, Mary Amanda; Myaskovsky, Larissa; Goodpaster, Bret; Fox, Kristen; Fontes, Paulo; DiMartini, Andrea

    2015-01-01

    Body Mass Index is a commonly used but likely inexact measure of body composition for patients with end-stage liver disease. For this reason, we examined whether body composition measurements from direct visualization on computerized tomography (CT) scans provide new insights both into the degree of malnutrition and also discordant combinations such as obesity with muscle mass loss. This technology is widely used in other medically ill populations but not yet in liver transplantation. Methods We examined actual body composition using abdominal CT scan data and software designed to measure fat and muscle compartments. Results In 234 liver transplant candidates we found BMI was highly and significantly correlated to subcutaneous and visceral fat. However we additionally found that even among obese patients, cachexia, as defined by muscle mass, was common with 56% of those with BMIs over 30 being cachexic. We also found that patients with non-alcoholic steatohepatitis, compared to other types of liver diseases, were significantly more likely to have larger amounts of visceral fat while also having less muscle. In an exploratory analysis muscle mass corrected for height was a significant predictor of post-transplant survival. Conclusions Body composition by CT scan data provides a specific method to identify obesity and muscle wasting for end-stage liver disease patients. Whether these data can aid in the prognostication of outcomes and survival requires further investigation. PMID:23348896

  20. Cajal bodies and their role in plant stress and disease responses.

    PubMed

    Love, Andrew J; Yu, Chulang; Petukhova, Natalia V; Kalinina, Natalia O; Chen, Jianping; Taliansky, Michael E

    2016-10-11

    Cajal bodies (CBs) are distinct sub-nuclear structures that are present in eukaryotic living cells and are often associated with the nucleolus. CBs play important roles in RNA metabolism and formation of RNPs involved in transcription, splicing, ribosome biogenesis, and telomere maintenance. Besides these primary roles, CBs appear to be involved in additional functions that may not be directly related to RNA metabolism and RNP biogenesis. In this review, we assess possible roles of plant CBs in RNA regulatory pathways such as nonsense-mediated mRNA decay and RNA silencing. We also summarize recent progress and discuss new non-canonical functions of plant CBs in responses to stress and disease. It is hypothesized that CBs can regulate these responses via their interaction with poly(ADP ribose)polymerase (PARP), which is known to play an important role in various physiological processes including responses to biotic and abiotic stresses. It is suggested that CBs and their components modify PARP activities and functions.

  1. Body mass index, weight change, and clinical progression in mild cognitive impairment and Alzheimer disease.

    PubMed

    Besser, Lilah M; Gill, Dawn P; Monsell, Sarah E; Brenowitz, Willa; Meranus, Dana H; Kukull, Walter; Gustafson, Deborah R

    2014-01-01

    The speed and severity of clinical progression after Alzheimer disease (AD) diagnosis varies and depends on multiple factors, most not well elucidated. We assessed whether body mass index (BMI) and 1-year weight change (WC) are associated with clinical progression in amnestic mild cognitive impairment (aMCI) and early-stage AD. Longitudinal data comprising 2268 aMCI and 1506 AD participants in the National Alzheimer's Coordinating Center's Uniform Data Set were used to examine nuances of clinical progression by BMI and WC, as well as potential variations in associations by age, sex, BMI (WC model), or apolipoprotein E genotype. In aMCI, high BMI (vs. moderate BMI) was associated with slower progression; weight loss (vs. no WC) was associated with faster progression. In AD, no significant differences were observed in clinical progression by BMI or WC. The association between BMI and clinical progression varied significantly by apolipoprotein E genotype in AD, and the association between WC and clinical progression varied significantly by sex and BMI in aMCI. Baseline BMI and 1-year WC in late life may serve as early prognostic indicators in aMCI and early-stage AD. If replicated, these results may help in counseling patients on anticipated clinical progression and suggest windows of opportunity for intervention.

  2. Short and long interval cortical inhibition in patients with Unverricht-Lundborg and Lafora body disease.

    PubMed

    Canafoglia, Laura; Ciano, Claudia; Visani, Elisa; Anversa, Paola; Panzica, Ferruccio; Viri, Maurizio; Gennaro, Elena; Zara, Federico; Madia, Francesca; Franceschetti, Silvana

    2010-05-01

    Myoclonus has different clinical and neurophysiological features in patients with Unverricht-Lundborg (ULD) and Lafora body disease (LBD), probably because of a different cortical hyperexcitability profile. To investigate the role of intracortical inhibition in such different presentations, we used paired-pulse transcranial magnetic stimulation (TMS) in ten ULD and five LBD patients, all with a positive molecular diagnosis. All of the patients were treated with antiepileptic drugs (AEDs). In comparison with healthy subjects, both patient groups had significantly defective short intracortical inhibition (SICI), however LBD patients, but not ULD and healthy subjects, had a clear inhibition at ISI 6 ms and ISI 10 ms. Moreover, defective long interval cortical inhibition (LICI) was found in LBD but not ULD patients. The substantial reduction in SICI suggests that both ULD and LBD patients have impaired inhibitory interneuron pools which are involved in the generation of cortical reflex myoclonus, whereas the inhibition found in LBD patients at ISI 6 and 10 ms, as well the reduced inhibition found at long intervals, suggest a more complex circuitry dysfunction possibly involving both excitatory and inhibitory systems. These findings are probably related to the high epileptogenic propensity characterizing LBD with respect to ULD and to the more severely distorted neuronal network resulting from the pathogenesis of LBD.

  3. Contributions of pediatrics and pediatric pathology to the body of knowledge regarding human disease.

    PubMed

    Nezelof, Christian; Seemayer, Thomas A; Bridge, Julia A

    2010-03-01

    A century or so ago, pediatrics and pediatric pathology did not exist. Then, many fetuses/newborns died in utero or shortly after birth. With time, the issue of sepsis was addressed, and a greater number of newborns survived. Gradually, in this soil, the disciplines of pediatrics and pediatric nursing arose, as some recognized that infants were not merely small adults but were, in fact, quite different. Years later, pediatric pathology developed as a field of exploration. Today, pediatric pathology is a specialty, as witnessed by training programs, societies devoted to research and education, an expanding number of textbooks and innovative research. Pediatric pathology is distinct from adult pathology, as seen by the diversity of malformations and metabolic diseases stemming from mutations, the immaturity of the newborn's immune system, and the types of neoplasms germane to infants and children. Much of the progress in these areas was facilitated by the simultaneous emergence of cytogenetics and molecular biology and their powerful tools of investigation. The latter were applied in a synergistic fashion to a major extent in maternity clinics and children's hospitals by, among others, molecular biologists, clinical geneticists, cytogeneticists, pediatricians, and pediatric pathologists. This article describes a select but small number of the many contributions of pediatrics and pediatric pathology to the current body of medical knowledge.

  4. Carotid body: a new target for rescuing neural control of cardiorespiratory balance in disease.

    PubMed

    Fitzgerald, Robert S

    2014-01-01

    Significant insight into the mechanisms involved in chronic heart failure (CHF) have been provided by Schultz and his associates at the University of Nebraska Medical Center with the use of pacing-induced heart failure rabbits. Critical among the CHF mechanisms was the role of the carotid body (CB). The stimulated CB produces a wide array of systemic reflex responses; certainly those in the cardiopulmonary (CP) system are the most important in CHF. This generates a question as to whether the CB could serve as a target for some kind of treatment to reestablish control of cardiorespiratory balance in CHF. Any treatment would have to be based on a solid understanding of the mechanisms of chemosensing by the CB as well as the transducing of that sensing into neural activity sent to the medullary centers and regions of autonomic outflow to the periphery. Two avenues of treatment could be to (1) silence or attenuate the CB's neural output pharmacologically and (2) excise the CBS. There is a long history of CB removal mostly as a remedy for chronic obstructive lung disease. Results have been inconclusive as to the effectiveness of this procedure. But if carefully planned, the procedure might be a helpful treatment.

  5. A monoclonal antibody to inclusion body disease of cranes virus enabling specific immunohistochemistry and competitive ELISA

    USGS Publications Warehouse

    Letchworth, G.J.; Fishel, J.R.; Hansen, W.R.

    1997-01-01

    Inclusion body disease of cranes (IBDC) herpesvirus kills some infected cranes and persists in convalescent animals. To enable further study and rapid identification of carrier animals, we developed a monoclonal antibody (MAb) to IBDC virus and used it in immunohistochemistry and a competitive enzyme-linked immunosorbent assay (ELISA). We used conventional techniques to make murine MAbs directed against IBDC virus purified from infected duck embryo cells. Hybridomas reacting in an ELISA with IBDC virus but not uninfected duck embryo cells were characterized by radioimmunoprecipitation, in situ immunohistochemistry, and competitive ELISA with neutralizing and nonneutralizing crane sera. MAb 2C11 immunoprecipitated 59-, 61-, and 110-kD proteins from IBDC virus-infected but not uninfected cells and stained glutaraldehyde-fixed IBDC virus plaques but not surrounding uninfected duck embryo cells in vitro. Antibody 2C11 did not react with duck embryo cells infected with falcon herpesvirus, psittacine herpesvirus, infectious laryngotracheitis, pigeon herpesvirus, or duck plague virus. A competitive ELISA using antibody 2C11 identified most sera that were positive in the neutralization test. This antibody will be useful in further characterizing IBDC virus, its pathogenesis, and its natural history.

  6. Stress and body condition in a population of largemouth bass: implications for red-sore disease

    SciTech Connect

    Esch, G.W.; Hazen, T.C.

    1980-09-01

    The body conditions, K = 10/sup 5/(weight, g)/(standard length)/sup 3/, and various hematological characters were examined for largemouth bass (Micropterus salmoides) taken from Par Pond, a reservoir heated by effluent from a nuclear production reactor at the Savannah River Plant near Aiken, South Carolina. Largemouth bass with K less than 2.0 had significantly lower (P < 0.05) hematocrits, hemoglobin concentrations, total red blood cell counts, total white blood cell counts, and lymphocyte fractions, and significantly higher granulocyte fractions and cortisol concentrations, than those with K greater than 2.0; monocyte, thrombocyte, and reticulocyte fractions were not different between the two K-factor groupings. When data were pooled, all blood variables except the reticulocyte fraction were significantly correlated with K. Hematocrit, the lymphocyte fraction, and cortisol concentration account for 20.5% of the variation in K. These data support a previous hypothesis that elevated water temperature promotes stress. Stress within the Par Pond largemouth bass population may play an important role in the epizootiology of red-sore disease caused by the gram-negative bacterium, Aeromonas hydrophila.

  7. Body mass index is associated with biological CSF markers of core brain pathology of Alzheimer's disease.

    PubMed

    Ewers, Michael; Schmitz, Susanne; Hansson, Oskar; Walsh, Cathal; Fitzpatrick, Annette; Bennett, David; Minthon, Lennart; Trojanowski, John Q; Shaw, Leslie M; Faluyi, Yetunde O; Vellas, Bruno; Dubois, Bruno; Blennow, Kaj; Buerger, Katharina; Teipel, Stefan J; Weiner, Michael; Hampel, Harald

    2012-08-01

    Weight changes are common in aging and Alzheimer's disease (AD) and postmortem findings suggest a relation between lower body mass index (BMI) and increased AD brain pathology. In the current multicenter study, we tested whether lower BMI is associated with higher core AD brain pathology as assessed by cerebrospinal fluid (CSF)-based biological markers of AD in 751 living subjects: 308 patients with AD, 296 subjects with amnestic mild cognitive impairment (MCI), and 147 elderly healthy controls (HC). Based upon a priori cutoff values on CSF concentration of total tau and beta-amyloid (Aβ(1-42)), subjects were binarized into a group with abnormal CSF biomarker signature (CSF+) and those without (CSF-). Results showed that BMI was significantly lower in the CSF+ when compared with the CSF- group (F = 27.7, df = 746, p < 0.001). There was no interaction between CSF signature and diagnosis or apolipoprotein E (ApoE) genotype. In conclusion, lower BMI is indicative of AD pathology as assessed with CSF-based biomarkers in demented and nondemented elderly subjects.

  8. The Relationship of Body Fat to Metabolic Disease: Influence of Sex and Ethnicity

    PubMed Central

    Sumner, Anne E.

    2012-01-01

    Clinical investigations designed to determine risk profiles for the development of cardiovascular disease (CVD) and type 2 diabetes mellitus (DM) are usually performed in homogenous populations and often focus on body mass index (BMI), waist circumference (WC), and fasting triglyceride (TG) levels. However, there are major ethnic differences in the relationship of these risk factors to outcomes. For example, the BMI risk threshold may be higher in blacks than in whites and higher in women than in men. Furthermore, a WC that predicts an obese BMI in white women only predicts a BMI in the overweight category in black women. In addition, overweight black men have a greater risk of developing type 2 DM than do overweight black women. Although TG levels are excellent predictors of insulin resistance in whites, they are not effective markers of insulin resistance in blacks. Among the criteria sets currently available to predict the development of CVD and type 2 DM, the most well known is the metabolic syndrome. The metabolic syndrome has 5 criteria: central obesity, hypertriglyceridemia, low high-density lipoprotein (HDL) levels, fasting hyperglycemia, and hypertension. To make the diagnosis of the metabolic syndrome, 3 of the 5 factors must be present. For central obesity and low HDL, the metabolic syndrome guidelines are sex specific. Diagnostic guidelines should also take ethnic differences into account, particularly in the diagnosis of central obesity and hypertriglyceridemia. PMID:19108808

  9. Gender difference in relationship between body mass index and development of chronic kidney disease

    PubMed Central

    2013-01-01

    Background An epidemiological approach to preventing the development or progression of chronic kidney disease (CKD) is necessary, while few effective preventive measures are currently available. We conducted a community-based, cohort study to identify the factors associated with the development of CKD in the general population. Methods We examined 1876 local residents of a Japanese community who had an annual health check-up and, of those, 1506 residents judged not to have CKD (473 men and 1033 women) were followed for the development of CKD over 10 years. Results The numbers of male and female residents who developed CKD during the follow-up period were 167 (35.3%) and 299 (28.9%), respectively. As compared to those without CKD development, the residents who developed CKD were older, and had a higher body mass index (BMI), systolic blood pressure, and creatinine in both genders. The rate of CKD development in obese female residents was higher than in non-obese women, but such a difference was not noted in male residents. In addition to age and serum creatinine, we identified BMI as an independently significant factor for the development of CKD in women, but not in men. Conclusions Increased BMI is a significant risk factor for the development of CKD in women, and there seems to be a gender difference in the association between increased BMI and the development of CKD in the general population. PMID:24225117

  10. Experimental allergic encephalomyelitis in pituitary-grafted Lewis rats

    PubMed Central

    Esquifino, Ana I; Cano, Pilar; Zapata, Agustín; Cardinali, Daniel P

    2006-01-01

    Treatment of susceptible rats with dopaminergic agonists that reduce prolactin release decreases both severity and duration of clinical signs of experimental allergic encephalomyelitis (EAE). To assess to what extent the presence of an ectopic pituitary (that produces an increase in plasma prolactin levels mainly derived from the ectopic gland) affects EAE, 39 male Lewis rats were submitted to pituitary grafting from littermate donors. Another group of 38 rats was sham-operated by implanting a muscle fragment similar in size to the pituitary graft. All rats received subcutaneous (s.c.) injections of complete Freund's adjuvant (CFA) plus spinal cord homogenate (SCH) and were monitored daily for clinical signs of EAE. Animals were killed by decapitation on days 1, 4, 7, 11 or 15 after immunization and plasma was collected for prolactin RIA. In a second experiment, 48 rats were immunized by s.c. injection of a mixture of SCH and CFA, and then received daily s.c. injections of bromocriptine (1 mg/kg) or saline. Groups of 8 animals were killed on days 8, 11 or 15 after immunization and plasma prolactin was measured. Only sham-operated rats exhibited clinical signs of the disease when assessed on day 15 after immunization. A progressive decrease in plasma prolactin levels was observed in pituitary-grafted rats, attaining a minimum 15 days after immunization, whereas plasma prolactin levels were increased during the course of the disease in sham-operated rats. Plasma prolactin levels were higher in pituitary-grafted rats than in sham-operated rats 1 day after immunization, but lower on days 7, 11 and 15 after immunogen injection. Further supporting a correlation of suppressed prolactin levels with absence of clinical signs of EAE, rats that were administered the dopaminergic agonist bromocriptine showed very low plasma prolactin levels and did not exhibit any clinical sign of EAE. These results indicate that low circulating prolactin levels coincide with absence of

  11. Advanced selective non-invasive ketone body detection sensors based on new ionophores

    NASA Astrophysics Data System (ADS)

    Sathyapalan, A.; Sarswat, P. K.; Zhu, Y.; Free, M. L.

    2014-12-01

    New molecules and methods were examined that can be used to detect trace level ketone bodies. Diseases such as type 1 diabetes, childhood hypo-glycaemia-growth hormone deficiency, toxic inhalation, and body metabolism changes are linked with ketone bodies concentration. Here we introduce, selective ketone body detection sensors based on small, environmentally friendly organic molecules with Lewis acid additives. Density functional theory (DFT) simulation of the sensor molecules (Bromo-acetonaphthone tungstate (BANT) and acetonaphthophenyl ether propiono hydroxyl tungstate (APPHT)), indicated a fully relaxed geometry without symmetry attributes and specific coordination which enhances ketone bodies sensitivity. A portable sensing unit was made in which detection media containing ketone bodies at low concentration and new molecules show color change in visible light as well as unique irradiance during UV illumination. RGB analysis, electrochemical tests, SEM characterization, FTIR, absorbance and emission spectroscopy were also performed in order to validate the ketone sensitivity of these new molecules.

  12. Methods for determining healthy body weight in end stage renal disease.

    PubMed

    Harvey, Kathy Schiro

    2006-07-01

    Several formulas for calculating desirable body weight are used in chronic kidney failure patients. Ideal body weight (IBW) derived from Metropolitan Life Insurance tables has been available since the 1950s. The Hamwi formula was proposed in the 1960s as a simple tool for quickly estimating desirable body weight, especially in people with diabetes. Since the 1970s, National Health and Nutrition Evaluation Surveys I, II, and III have provided an in-depth evaluation of the average body weights of Americans. These standard body weights (SBW) are often interpreted to be normal and healthy weight goals. Body mass index (BMI) has also been studied for decades and is used internationally as the standard for determining healthy weight, especially in relationship to obesity. These 4 methods are discussed and compared along with a brief review of the history of using the adjusted body weight (ABW) formulas, followed by recommendations for clinical practice.

  13. The lived experience of Huntington's disease: A phenomenological perspective on genes, the body and the lived experience of a genetic disease.

    PubMed

    Hagen, Niclas

    2017-01-01

    The purpose of this article is to explore the intersections between genes, the body and the lived experience of a genetic disease. This article is based on empirical material from a study on how individuals affected by Huntington's disease experience their everyday life. This study identified two themes that represent and capture the experience of the affected individuals. The themes are (1) noticing symptoms in everyday life and (2) neither health nor disease. The analysis of the empirical material was performed by employing a theoretical framework based on phenomenology. The findings of this study showed that the lived experiences among individuals affected by Huntington's disease were both fluid and dynamic in their nature. Furthermore, the analysis of the empirical material suggests that this fluid and dynamic character can be linked to a dimension that revolves around the intersections between genetics and the body. Following phenomenologist Drew Leder's outline of the divergence between the invisible and the visible features of the body, the analysis of the empirical material suggests that the mutated gene that causes Huntington's disease can be seen as a phenomenological nullpoint. It is important that the healthcare system acknowledges and addresses the lived experiences that are discussed in this article, particularly, as the use of genetics and genetic testing becomes more widespread usage within medicine.

  14. NASA Lewis Research Center Futuring Workshop

    NASA Technical Reports Server (NTRS)

    Boroush, Mark; Stover, John; Thomas, Charles

    1987-01-01

    On October 21 and 22, 1986, the Futures Group ran a two-day Futuring Workshop on the premises of NASA Lewis Research Center. The workshop had four main goals: to acquaint participants with the general history of technology forecasting; to familiarize participants with the range of forecasting methodologies; to acquaint participants with the range of applicability, strengths, and limitations of each method; and to offer participants some hands-on experience by working through both judgmental and quantitative case studies. Among the topics addressed during this workshop were: information sources; judgmental techniques; quantitative techniques; merger of judgment with quantitative measurement; data collection methods; and dealing with uncertainty.

  15. Immunohistochemical detection of a unique protein within cells of snakes having inclusion body disease, a world-wide disease seen in members of the families Boidae and Pythonidae.

    PubMed

    Chang, Li-Wen; Fu, Ann; Wozniak, Edward; Chow, Marjorie; Duke, Diane G; Green, Linda; Kelley, Karen; Hernandez, Jorge A; Jacobson, Elliott R

    2013-01-01

    Inclusion body disease (IBD) is a worldwide disease in captive boa constrictors (boa constrictor) and occasionally in other snakes of the families Boidae and Pythonidae. The exact causative agent(s) and pathogenesis are not yet fully understood. Currently, diagnosis of IBD is based on the light microscopic identification of eosinophilic intracytoplasmic inclusion bodies in hematoxylin and eosin stained tissues or blood smears. An antigenically unique 68 KDa protein was identified within the IBD inclusion bodies, called IBD protein. A validated immuno-based ante-mortem diagnostic test is needed for screening snakes that are at risk of having IBD. In this study, despite difficulties in solubilizing semi-purified inclusion bodies, utilizing hybridoma technology a mouse anti-IBD protein monoclonal antibody (MAB) was produced. The antigenic specificity of the antibody was confirmed and validated by western blots, enzyme-linked immunosorbent assay, immuno-transmission electron microscopy, and immunohistochemical staining. Paraffin embedded tissues of IBD positive and negative boa constrictors (n=94) collected from 1990 to 2011 were tested with immunohistochemical staining. In boa constrictors, the anti-IBDP MAB had a sensitivity of 83% and specificity of 100% in detecting IBD. The antibody also cross-reacted with IBD inclusion bodies in carpet pythons (Morelia spilota) and a ball python (python regius). This validated antibody can serve as a tool for the development of ante-mortem immunodiagnostic tests for IBD.

  16. Immunohistochemical Detection of a Unique Protein within Cells of Snakes Having Inclusion Body Disease, a World-Wide Disease Seen in Members of the Families Boidae and Pythonidae

    PubMed Central

    Chang, Li-Wen; Fu, Ann; Wozniak, Edward; Chow, Marjorie; Duke, Diane G.; Green, Linda; Kelley, Karen; Hernandez, Jorge A.; Jacobson, Elliott R.

    2013-01-01

    Inclusion body disease (IBD) is a worldwide disease in captive boa constrictors (boa constrictor) and occasionally in other snakes of the families Boidae and Pythonidae. The exact causative agent(s) and pathogenesis are not yet fully understood. Currently, diagnosis of IBD is based on the light microscopic identification of eosinophilic intracytoplasmic inclusion bodies in hematoxylin and eosin stained tissues or blood smears. An antigenically unique 68 KDa protein was identified within the IBD inclusion bodies, called IBD protein. A validated immuno-based ante-mortem diagnostic test is needed for screening snakes that are at risk of having IBD. In this study, despite difficulties in solubilizing semi-purified inclusion bodies, utilizing hybridoma technology a mouse anti-IBD protein monoclonal antibody (MAB) was produced. The antigenic specificity of the antibody was confirmed and validated by western blots, enzyme-linked immunosorbent assay, immuno-transmission electron microscopy, and immunohistochemical staining. Paraffin embedded tissues of IBD positive and negative boa constrictors (n=94) collected from 1990 to 2011 were tested with immunohistochemical staining. In boa constrictors, the anti-IBDP MAB had a sensitivity of 83% and specificity of 100% in detecting IBD. The antibody also cross-reacted with IBD inclusion bodies in carpet pythons (Morelia spilota) and a ball python (python regius). This validated antibody can serve as a tool for the development of ante-mortem immunodiagnostic tests for IBD. PMID:24340066

  17. [Multifocal demyelinating polyneuropathy with persistent conduction block (Lewis-Sumner syndrome)].

    PubMed

    Mezaki, T; Kaji, R; Hamano, T; Kimura, J; Kameyama, M

    1990-11-01

    Multifocal demyelinating neuropathy with persistent conduction block (Lewis-Sumner syndrome) is a variant of chronic inflammatory demyelinating polyradiculoneuropathy (CIDP), which often clinically simulates a motor neuron disease (MND). We report here three patients initially suspected to have MND, who later were diagnosed as a Lewis-Sumner syndrome. One of them showed a remarkable clinical improvement after immunoglobulin therapy. The definitive diagnosis of this syndrome rests upon nerve conduction studies, uncovering multiple sites of persistent conduction block. Technically, it is important to exclude insufficient stimulus which may lead to an erroneous impression of conduction block. Magnetic stimulation, as compared to electric current, elicited larger responses possibly because of deeper current penetration. We found this mode of stimulation useful especially in testing focal demyelination requiring full activation of a diseased nerve at a most proximal segment.

  18. A zwitterionic carbanion frustrated by boranes--dihydrogen cleavage with weak Lewis acids via an "inverse" frustrated Lewis pair approach.

    PubMed

    Li, Hui; Aquino, Adelia J A; Cordes, David B; Hung-Low, Fernando; Hase, William L; Krempner, Clemens

    2013-10-30

    The synthesis, structural characterization, and acid-base chemistry of [C(SiMe2OCH2CH2OMe)3]Na (2), a sterically encumbered zwitterionic organosodium compound, is reported. 2 is a strong Brønsted base that forms frustrated Lewis pairs (FLPs) with a number of boron-containing Lewis acids ranging from weakly Lewis acidic aryl and alkyl boranes to various alkyl borates. These intermolecular FLPs readily cleave H2, which confirms that even poor Lewis acids can engage in FLP-mediated H2 cleavage provided that the present bulky base is of sufficiently high Brønsted basicity.

  19. Structural characterization of the DC-SIGN-Lewis(X) complex.

    PubMed

    Pederson, Kari; Mitchell, Daniel A; Prestegard, James H

    2014-09-09

    Dendritic cell-specific intracellular adhesion molecule-3-grabbing nonintegrin (DC-SIGN) is a C-type lectin highly expressed on the surface of antigen-presenting dendritic cells. DC-SIGN mediates interactions among dendritic cells, pathogens, and a variety of epithelia, myeloid cells, and endothelia by binding to high mannose residues on pathogenic invaders or fucosylated residues on the membranes of other immune cells. Although these interactions are normally beneficial, they can also contribute to disease. The structural characterization of binding geometries is therefore of interest as a basis for the construction of mimetics that can mediate the effects of abnormal immune response. Here, we report the structural characteristics of the interaction of the DC-SIGN carbohydrate recognition domain (CRD) with a common fucosylated entity, the Lewis(X) trisaccharide (Le(X)), using NMR methods. Titration of the monomeric DC-SIGN CRD with Le(X) monitored by 2D NMR revealed significant perturbations of DC-SIGN cross-peak positions in (1)H-(15)N heteronuclear single quantum coherence (HSQC) spectra and identified residues near the binding site. Additionally, saturation transfer difference (STD) and transferred nuclear Overhauser effect (trNOE) NMR experiments, using a tetrameric form of DC-SIGN, identified binding epitopes and bound conformations of the Le(X) ligand. The restraints derived from these multiple experiments were used to generate models for the binding of Le(X) to the DC-SIGN CRD. Ranking of the models based on the fit of model-based simulations of the trNOE data and STD buildup curves suggested conformations distinct from those seen in previous crystal structures. The new conformations offer insight into how differences between binding of Lewis(X) and mannose-terminated saccharides may be propagated.

  20. 4 Tesla Whole Body MRI MRSI System for Investigation of Neurodegenerative Diseases

    DTIC Science & Technology

    2004-10-01

    tools for data processing. 14. SUBJECT TERMS 15. NUMBER OF PAGES Magnetic resonance imaging, gulf war syndrome, alzheimer’s disease , 9 brain 16. PRICE...imaging system fully dedicated to study neurodegenerative disorders of the brain, including Alzheimer’s disease , Parkinson’s disease, Posttraumatic...resolution (0.5 x 0.4 x 2mm) Turbo Spin Echo image showing subfieldshave found that certain diseases, such as of the hippocampus Alzheimer’s disease and

  1. Body weight and food intake in Parkinson's disease. A review of the association to non-motor symptoms.

    PubMed

    Aiello, Marilena; Eleopra, Roberto; Rumiati, Raffella I

    2015-01-01

    Research on eating behaviours has extensively highlighted that cognitive systems interact with the metabolic system in driving food intake and in influencing body weight regulation. Parkinson's disease is a good model for studying these complex interactions since alterations in both body weight and cognitive domains have been frequently reported among these patients. Interestingly, even if different non-motor symptoms may characterize the course of the disease, their contribution to weight and food preference has been poorly investigated. This review describes body weight alterations and eating habits in patients with Parkinson's disease, including those who underwent deep brain stimulation surgery. In particular, the review considers the link between non-motor symptoms, affecting sensory perception, cognition, mood and motivation, and food intake and weight alterations. The take home message is twofold. First, we recommend a comprehensive approach in order to develop effective strategies in the management of patients' weight. Second, we also suggest that investigating this issue in patients with Parkinson's disease may provide some useful information about the mechanisms underlying food and weight regulation in healthy subjects.

  2. Brain PET in the Diagnosis of Alzheimer’s Disease

    PubMed Central

    Marcus, Charles; Mena, Esther; Subramaniam, Rathan M.

    2015-01-01

    Objectives The aim of this article was to review the current role of brain PET in the diagnosis of Alzheimer dementia. The characteristic patterns of glucose metabolism on brain FDG-PET can help in differentiating Alzheimer’s disease from other causes of dementia such as frontotemporal dementia and dementia of Lewy body. Amyloid brain PET may exclude significant amyloid deposition and thus Alzheimer’s disease in appropriate clinical setting. Conclusions FDG-PET and amyloid PET imaging are valuable in the assessment of patients with Alzheimer’s disease. PMID:25199063

  3. Cyclosporin a. Inhibition of experimental autoimmune uveitis in Lewis rats.

    PubMed Central

    Nussenblatt, R B; Rodrigues, M M; Wacker, W B; Cevario, S J; Salinas-Carmona, M C; Gery, I

    1981-01-01

    Cyclosporin A (CS-A), a selective inhibitor of T lymphocytes, is reported here to prevent S antigen (S-Ag) induced uveitis in Lewis rats. The S-Ag, found in all mammalian retinas, is uveitogenic under experimental conditions and patients with certain uveitic entities demonstrate cell mediated responses to this antigen. Daily treatment with CS-A (10 mg/kg) begun on the same day as S-Ag immunization totally inhibited the development of the uveitis in this experimental autoimmune model. Moreover a greater CS-A dose (40 mg/kg) efficiently prevented the disease process when therapy was started 7 d after S-Ag immunization. Anti-S-Ag antibody titers were observed to be similar in rats either protected or not protected with CS-A. Our data support strongly the need for T cell participation in this disease model. Since ocular inflammatory disease is an important cause of visual impairment, the data further suggest that CS-A may be useful in the treatment of patients with intractable uveitis. Images PMID:7204576

  4. Body, gender, and disease: the female breast in late imperial Chinese medicine.

    PubMed

    Wu, Yi-Li

    2011-01-01

    This paper examines the diverse ways in which Chinese medical experts historically gendered breast disease as a female ailment. By comparing representations of the female breast from the "Imperially-Compiled Golden Mirror of Medical Learning (Yuzuan yizong jinjian, 1742)" to those from earlier and contemporary texts, this paper analyzes how breast disease was alternately categorized as an ailment of childbearing and as a disease rooted in pathological female emotion. Medical awareness of breast disease in men did somewhat challenge these connections between womanhood and disease. Nevertheless, medical illustrations of women helped to reinforce the idea that breast disease was a characteristically female problem.

  5. 32 CFR 552.168 - Fort Lewis Area Access Office.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... 32 National Defense 3 2014-07-01 2014-07-01 false Fort Lewis Area Access Office. 552.168 Section 552.168 National Defense Department of Defense (Continued) DEPARTMENT OF THE ARMY MILITARY..., Yakima Training Center, and Camp Bonneville § 552.168 Fort Lewis Area Access Office. (a) DPTM...

  6. 32 CFR 552.168 - Fort Lewis Area Access Office.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... 32 National Defense 3 2010-07-01 2010-07-01 true Fort Lewis Area Access Office. 552.168 Section 552.168 National Defense Department of Defense (Continued) DEPARTMENT OF THE ARMY MILITARY..., Yakima Training Center, and Camp Bonneville § 552.168 Fort Lewis Area Access Office. (a) DPTM...

  7. 32 CFR 552.168 - Fort Lewis Area Access Office.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... 32 National Defense 3 2012-07-01 2009-07-01 true Fort Lewis Area Access Office. 552.168 Section 552.168 National Defense Department of Defense (Continued) DEPARTMENT OF THE ARMY MILITARY..., Yakima Training Center, and Camp Bonneville § 552.168 Fort Lewis Area Access Office. (a) DPTM...

  8. Interview with Smithsonian NASM Spacesuit Curator Dr. Cathleen Lewis

    NASA Technical Reports Server (NTRS)

    Lewis, Cathleen; Wright, Rebecca

    2012-01-01

    Dr. Cathleen Lewis was interviewed by Rebecca Wright during the presentation of an "Interview with Smithsonian NASM Spacesuit Curator Dr. Cathleen Lewis" on May 14, 2012. Topics included the care, size, and history of the spacesuit collection at the Smithsonian and the recent move to the state-of-the-art permanent storage facility at the Udvar-Hazy facility in Virginia.

  9. 32 CFR 552.168 - Fort Lewis Area Access Office.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... RESERVATIONS AND NATIONAL CEMETERIES REGULATIONS AFFECTING MILITARY RESERVATIONS Land Use Policy for Fort Lewis, Yakima Training Center, and Camp Bonneville § 552.168 Fort Lewis Area Access Office. (a) DPTM Range Division operates the Area Access Section to issue permits and grant non-training access to the...

  10. 32 CFR 552.168 - Fort Lewis Area Access Office.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... RESERVATIONS AND NATIONAL CEMETERIES REGULATIONS AFFECTING MILITARY RESERVATIONS Land Use Policy for Fort Lewis, Yakima Training Center, and Camp Bonneville § 552.168 Fort Lewis Area Access Office. (a) DPTM Range Division operates the Area Access Section to issue permits and grant non-training access to the...

  11. New entries to water-compatible Lewis acids.

    PubMed

    Kobayashi, Shu; Ogawa, Chikako

    2006-08-07

    Lewis acid catalysis has attracted much attention in organic synthesis as it often affords access to unique reactivity and selectivity under mild conditions. Although various kinds of Lewis acids have been developed and applied in industry, these Lewis acids must be generally used under strictly anhydrous conditions, as the presence of even a small amount of water interferes with the reactions due to preferential reaction of the Lewis acids with water rather than the substrates. In contrast to this, rare earth and other metal complexes have been found to be water-compatible. Furthermore, Bi(OTf)(3)- and Ga(OTf)(3)-basic ligand complexes have also been found to be stable in water, and have been used as water-compatible Lewis acids. This application is particularly significant, as Bi(OTf)(3) and Ga(OTf)(3) themselves are unstable in the presence of water, but are stabilized by the basic ligands. This observation has led to the development of a new approach to Lewis acid catalysis in which Lewis acids that are generally unstable in the presence of water are rendered amenable to aqueous systems when combined with basic ligands. In particular, the use of chiral basic ligands leading to new types of water-compatible chiral Lewis acids may enable a wide range of asymmetric catalysis in aqueous media.

  12. Thoughts on Teaching: John L. Lewis, Jesus, and President Bush.

    ERIC Educational Resources Information Center

    Starnes, Bobby Ann

    2004-01-01

    Bobby Ann Starnes, the author of this article, grew up with portraits of two important people displayed prominently in her home, Jesus, and John L. Lewis. Lewis, a giant among American leaders in the first half of the twentieth century, sent hundreds of organizers to help create some of the nation's leading labor unions, including the United…

  13. Body Mass Index Is Associated With Mucosal Disease in Crohn’s: Results of a Case-Control Study

    PubMed Central

    Malik, Talha A.; Kaslow, Richard A.; Cofield, Stacey S.; Mannon, Peter J.

    2014-01-01

    Background Recent studies have suggested that increased body mass index (BMI) may have an adverse effect on treatment outcomes and natural history in Crohn’s disease (CD). We aimed to test the hypothesis that CD patients with higher BMI would be more likely than those with lower BMI to have persistent active mucosal disease. Methods We designed a case-control study. Sample population comprised CD patients with active disease at the beginning of observation. At the end of observation, cases had persistent active mucosal disease and controls had entered remission. With multivariable logistic regression models, we evaluated the effect of baseline BMI as a continuous variable and a categorical variable on persistent active mucosal disease. Results We analyzed data from 104 patients (36 cases and 68 controls). In a model containing BMI as a continuous variable, higher BMI was significantly associated with persistent active mucosal disease (odds ratio (OR) = 1.09 per unit increase; 95% confidence interval (CI), 1.02 - 1.17; P = 0.012). In a model containing BMI as a categorical variable, obese patients were 2.7 times more likely to have persistent active mucosal disease compared to non-obese patients (OR = 2.72; 95% CI, 1.00 - 7.35; P = 0.049). Conclusion Excessive weight measured both quantitatively as BMI and categorically as obesity in CD patients is associated with persistent active mucosal disease. PMID:27785280

  14. Epitope recognition and T cell receptors in recurrent autoimmune anterior uveitis in Lewis rats immunized with myelin basic protein.

    PubMed

    Adamus, G; Manczak, M; Sugden, B; Arendt, A; Hargrave, P A; Offner, H

    2000-08-01

    Lewis rats immunized with myelin basic protein (MBP) develop experimental autoimmune encephalomyelitis (EAE) and associated anterior uveitis (AU). Rats recover and become resistant to further reinduction of EAE. We investigated whether the resistance to reinduction of EAE was associated with the resistance to AU in LEW rats reinjected with MBP. We demonstrated that while rats remained resistant to EAE, they become susceptible to uveitis after recovery, and suffered a second episode of disease. The susceptibility to reinduced disease was associated with the recognition of new MBP epitopes. In contrast to the initial episode of AU, TCR Vbeta8.2 predominance was not observed in the iris/ciliary body. Our results suggest that T cells specific for MBP, which are rapidly reactivated when re-exposed to antigen, are sufficient to induce clinical uveitis in LEW rats. This process may involve a shifting of T cell specificity from the major encephalitogenic peptide utilizing the Vbeta8.2 receptor to a more diverse cell repertoire.

  15. Whole Body Plethysmography Reveals Differential Ventilatory Responses to Ozone in Rat Models of Cardiovascular Disease

    EPA Science Inventory

    Increasingly, urban air pollution is recognized as an important determinant of cardiovascular disease. Host susceptibility to air pollution can vary due to genetic predisposition and underlying disease. To elucidate key factors of host ...

  16. Lymphoblastic lymphoma and leukemic blood profile in a red-tail boa (Boa constrictor constrictor) with concurrent inclusion body disease.

    PubMed

    Schilliger, Lionel; Selleri, Paolo; Frye, Fredric L

    2011-01-01

    An adult male wild-caught true red-tail boa (Boa constrictor constrictor), imported from Surinam, was presented for anorexia, extreme lethargy, and coelomic swelling in the cranial third of the body, in the anatomic location of the thymus. The snake died a few minutes after blood sampling via cardiocentesis. Hematology revealed anemia and extreme leukocytosis (820 × 10(3)/ml) characterized by a predominance (95%) of lymphocytes. Necropsy revealed enlargement of most of the visceral organs. Histology confirmed lymphoblastic lymphoma with a leukemic blood profile and diffuse infiltration of some of the heart, thymus, bone marrow, kidney, spleen, lung, and liver. Several large intracytoplasmic eosinophilic inclusion bodies surrounded by narrow clear "halos" were identified within gastric mucosal cells, proximal and distal convoluted tubule epithelial cells, and splenic cells. The final diagnosis was lymphoblast lymphoma with a leukemic blood profile and concurrent inclusion body disease.

  17. Genetic variants and animal models in SNCA and Parkinson disease.

    PubMed

    Deng, Hao; Yuan, Lamei

    2014-05-01

    Parkinson disease (PD; MIM 168600) is the second most common progressive neurodegenerative disorder characterized by a variety of motor and non-motor features. To date, at least 20 loci and 15 disease-causing genes for parkinsonism have been identified. Among them, the α-synuclein (SNCA) gene was associated with PARK1/PARK4. Point mutations, duplications and triplications in the SNCA gene cause a rare dominant form of PD in familial and sporadic PD cases. The α-synuclein protein, a member of the synuclein family, is abundantly expressed in the brain. The protein is the major component of Lewy bodies and Lewy neurites in dopaminergic neurons in PD. Further understanding of its role in the pathogenesis of PD through various genetic techniques and animal models will likely provide new insights into our understanding, therapy and prevention of PD.

  18. Body side and predominant motor features at the onset of Parkinson's disease are linked to motor and nonmotor progression.

    PubMed

    Baumann, Christian R; Held, Ulrike; Valko, Philipp O; Wienecke, Miriam; Waldvogel, Daniel

    2014-02-01

    Patients with Parkinson's disease most often have asymmetric motor features at onset, and specific motor signs (ie, tremor versus bradykinesia and rigidity) frequently characterize the first few years of disease evolution. Some previous clinical evidence has suggested that body side and a predominance of motor manifestations at disease onset are linked to long-term evolution and disease progression. We prospectively analyzed 206 patients with Parkinson's disease according to the most affected side and predominant motor signs at onset. Patients were divided into left-side rigid-akinetic (n = 71), right-side rigid-akinetic (n = 59), left-side tremor (n = 41), and right-side tremor (n = 35) subgroups. These subgroups were compared in terms of motor and cognitive functions, mean motor deterioration per year (calculated as the motor score divided by disease duration), total equivalent doses of dopaminergic drugs, and the presence of hallucinations and rapid eye movement sleep behavior disorder. Disease duration was similar in all groups. Motor fluctuations were more likely to occur in rigid-akinetic patients. In a multiple model analysis adjusted for potential confounders, faster disease progression was associated with right-side (P = 0.045) and rigid-akinetic onset (P = 0.001). With respect to nonmotor symptoms, the rigid-akinetic type was associated with increased risk of cognitive decline (P = 0.004) compared with the tremor type. A trend was noticed toward an increased risk of developing visual hallucinations in rigid-akinetic patients and toward an increased frequency of rapid eye movement sleep behavior disorder in those who had left-sided onset of symptoms. Our findings corroborate that body side and type of motor signs at the time of diagnosis affect the evolution of motor severity and may also have an impact on some nonmotor manifestations.

  19. Differentiating the associations of waist circumference and body mass index with cardiovascular disease risk in a Chinese population.

    PubMed

    Li, Rui; Shi, Liang; Jia, Jian; Li, Yanyun; Yang, Qundi; Ruan, Ye; Chen, Renjie; Kan, Haidong

    2015-03-01

    It is not known which obesity index best explains variations in cardiovascular disease risk across populations. The objective of this study was to differentiate the associations of waist circumference (WC) and body mass index (BMI) with cardiovascular disease risk in a Chinese population. Cardiovascular risk factors, WC, and BMI were measured in 13 817 adults aged more than 18 years in Shanghai. Higher WC tertiles were associated with higher blood pressure and higher cholesterol, triacylglycerol, and glucose concentrations within each tertile of BMI and vice versa. The odds ratios (ORs) of hypertension, dyslipidemia, and metabolic syndrome increased with successive WC (or BMI) tertiles after adjustment for BMI (or WC) and several covariates. However, BMI tertiles were not associated with the ORs of diabetes after adjustment for WC. WC may be better than BMI as an alternative measure of body fatness or fat distribution for predicting diabetic risks in Chinese adults.

  20. Detection of arenavirus in a peripheral odontogenic fibromyxoma in a red tail boa (Boa constrictor constrictor) with inclusion body disease.

    PubMed

    Hellebuyck, Tom; Pasmans, Frank; Ducatelle, Richard; Saey, Veronique; Martel, An

    2015-03-01

    A captive bred red tail boa (Boa constrictor constrictor) was presented with a large intraoral mass originating from the buccal gingiva, attached to the right dentary teeth row. Based on the clinical features and histological examination, the diagnosis of a peripheral odontogenic fibromyxoma was made. Sections of liver biopsies and circulating lymphocytes contained relatively few eosinophilic intracytoplasmic inclusion bodies, indistinguishable from those observed in inclusion body disease-affected snakes. Inclusion bodies were not observed in cells comprising the neoplastic mass. Using reverse transcription polymerase chain reaction (RT-PCR), arenavirus was detected in the neoplastic tissue. Two years after surgical removal of the mass, recurrence of the neoplastic lesion was observed. Numerous large inclusion body disease inclusions were abundantly present in the neoplastic cells of the recurrent fibromyxoma. Sections of liver biopsies and circulating lymphocytes contained relatively few intracytoplasmic inclusions. The RT-PCR revealed the presence of arenavirus in blood, a liver biopsy, and neoplastic tissue. The present case describes the co-occurrence of an arenavirus infection and an odontogenic fibromyxoma in a red tail boa.

  1. Using body temperature, food and water consumption as biomarkers of disease progression in mice with Eμ-myc lymphoma

    PubMed Central

    Hunter, J E; Butterworth, J; Perkins, N D; Bateson, M; Richardson, C A

    2014-01-01

    Background: Non-invasive biomarkers of disease progression in mice with cancer are lacking making it challenging to implement appropriate humane end points. We investigated whether body temperature, food and water consumption could be used to predict tumour burden. Methods: Thirty-six male, wild-type C57Bl/6 mice were implanted with subcutaneous RFID temperature sensors and inoculated with Eμ-myc tumours that infiltrate lymphoid tissue. Results: Decrease in body temperature over the course of the study positively predicted post-mortem lymph node tumour burden (R2=0.68, F(1,22)=44.8, P<0.001). At experimental and humane end points, all mice that had a mean decrease in body temperature of 0.7 °C or greater had lymph nodes heavier than 0.5 g (100% sensitivity), whereas a mean decrease in body temperature <0.7 °C always predicted lymph nodes lighter than 0.5 g (100% specificity). The mean decrease in food consumption in each cage also predicted mean post-mortem lymph node tumour burden at 3 weeks (R2=0.89, F(1,3)=23.2, P=0.017). Conclusion: Temperature, food and water consumption were useful biomarkers of disease progression in mice with lymphoma and could potentially be used more widely to monitor mice with other forms of cancer. PMID:24407190

  2. Prevalence of asbestos bodies in a necropsy series in East London: association with disease, occupation, and domiciliary address.

    PubMed

    Doniach, I; Swettenham, K V; Hathorn, M K

    1975-02-01

    The prevalence of asbestos bodies was measured in lung sections in a necropsy series carried out at the London Hospital (1965-66) after exclusion of all known asbestos factory workers and cases of asbestosis and of mesothelioma. Associations were sought between the presence and number of asbestos bodies with the patients' sex, domiciliary address, occupation, industry, and diseases recorded at necropsy. Asbestos bodies were present in 42% of the 216 men in the series and in 30% of the 178 women. The number of bodies in the positive cases was small in comparison with the numbers seen typically in asbestosis; thus there were less than 6 asbestos bodies per 6-75 mm-3 lung tissue in 107 of the total 145 positive cases in contrast to 1 000 or more in asbestosis. In comparison with the overall series, an increased number of asbestos body positives was present in males with carcinoma of stomach and females with carcinoma of breast. In view of this finding lung sections were counted in further post-mortem examples of these carcinomas making a total of 50 males with carcinoma stomach and 82 females with carcinoma breast. Thirty-five positive cases were found in the carcinoma stomach group as against 22-7 expected and 38 in the carcinoma breast group against 26-35 expected. There was no excess of observed over expected asbestos body positives in 51 males with carcinoma of bronchus. There was an excess of asbestos body positives (60-9%) in heavy manual workers and in both heavy and light manual male workers in the shipping (61%), electrical and engineering (56%), and transport (54%) industries. The incidence in male clerical workers was 12-8%. The incidence of asbestos body positives according to home address was highest (53% in males, 45% in females) in patients living in the industrial and cockland area due east of the hospital. The incidence fell in the less industrial areas north-east of the hospital. Consideration of possible environmental sources of the inhaled asbestos

  3. Alpha Synuclein Aggregation in a Neurotoxic Model of Parkinson’s Disease

    DTIC Science & Technology

    2001-08-01

    The cause of Parkinson’s disease (PD) is not known but the pattern of neurodegeneration can be replicated by the systemic administration of the neurotoxin 1-methyl-4-phenyl-tetrahydropyridine (MPTP). MPTP inhibits mitochondrial oxidative phosphorylation and causes oxidative injury leading to cell death. Neurons that degenerate in PD develop inclusions called Lewy bodies that are composed of aggregates of a synaptic protein, alpha synuclein. The purpose of this study is

  4. [Movement disorders is psychiatric diseases].

    PubMed

    Hidasi, Zoltan; Salacz, Pal; Csibri, Eva

    2014-12-01

    Movement disorders are common in psychiatry. The movement disorder can either be the symptom of a psychiatric disorder, can share a common aetiological factor with it, or can be the consequence of psychopharmacological therapy. Most common features include tic, stereotypy, compulsion, akathisia, dyskinesias, tremor, hypokinesia and disturbances of posture and gait. We discuss characteristics and clinical importance of these features. Movement disorders are frequently present in mood disorders, anxiety disorders, schizophrenia, catatonia, Tourette-disorder and psychogenic movement disorder, leading to differential-diagnostic and therapeutical difficulties in everyday practice. Movement disorders due to psychopharmacotherapy can be classified as early-onset, late-onset and tardive. Frequent psychiatric comorbidity is found in primary movement disorders, such as Parkinson's disease, Wilson's disease, Huntington's disease, diffuse Lewy-body disorder. Complex neuropsychiatric approach is effective concerning overlapping clinical features and spectrums of disorders in terms of movement disorders and psychiatric diseases.

  5. Lewis morris rutherfurd 1816-1892.

    PubMed

    Devons, S

    1976-07-01

    Lewis M. Rutherfurd (1816-1892) was a wealthy amateur practitioner of science, making notable contributions to the optics of astronomy and spectroscopy. He graduated from Williams College at the age of 18 and soon began a career in law. Not long thereafter he was fortunate enough to acquire sufficient wealth through marriage to permit him to pursue scientific activity, for which he had gained interest. He soon became interested in photographing the heavens to obtain quantitative data regarding star motions. A few years later he developed a spectrometer with which he obtained some of the best attainable stellar spectra of the time. Rutherfurd is not widely known because he did not fully report his work; but through correspondence and instrument development he had a profound influence on his contemporaries. He was made a trustee of Columbia College in 1858, and in 1881 he helped to found a department of Geodesy and Practical Astronomy there.

  6. Aluminium Diphosphamethanides: Hidden Frustrated Lewis Pairs.

    PubMed

    Styra, Steffen; Radius, Michael; Moos, Eric; Bihlmeier, Angela; Breher, Frank

    2016-07-04

    The synthesis and characterisation of two aluminium diphosphamethanide complexes, [Al(tBu)2 {κ(2) P,P'-Mes*PCHPMes*}] (3) and [Al(C6 F5 )2 {κ(2) P,P'-Mes*PCHPMes*}] (4), and the silylated analogue, Mes*PCHP(SiMe3 )Mes* (5), are reported. The aluminium complexes feature four-membered PCPAl core structures consisting of diphosphaallyl ligands. The silylated phosphine 5 was found to be a valuable precursor for the synthesis of 4 as it cleanly reacts with the diaryl aluminium chloride [(C6 F5 )2 AlCl]2 . The aluminium complex 3 reacts with molecular dihydrogen at room temperature under formation of the acyclic σ(2) λ(3) ,σ(3) λ(3) -diphosphine Mes*PCHP(H)Mes* and the corresponding dialkyl aluminium hydride [tBu2 AlH]3 . Thus, 3 belongs to the family of so-called hidden frustrated Lewis pairs.

  7. Superconducting Microwave Electronics at Lewis Research Center

    NASA Technical Reports Server (NTRS)

    Warner, Joseph D.; Bhasin, Kul B.; Leonard, Regis F.

    1991-01-01

    Over the last three years, NASA Lewis Research Center has investigated the application of newly discovered high temperature superconductors to microwave electronics. Using thin films of YBa2Cu3O7-delta and Tl2Ca2Ba2Cu3Ox deposited on a variety of substrates, including strontium titanate, lanthanum gallate, lanthanum aluminate and magnesium oxide, a number of microwave circuits have been fabricated and evaluated. These include a cavity resonator at 60 GHz, microstrip resonators at 35 GHz, a superconducting antenna array at 35 GHz, a dielectric resonator at 9 GHz, and a microstrip filter at 5 GHz. Performance of some of these circuits as well as suggestions for other applications are reported.

  8. Toward a Theoretical Model of Women's Body Image Resilience

    ERIC Educational Resources Information Center

    Choate, Laura Hensley

    2005-01-01

    This article discusses women's body image resilience. Body image dissatisfaction is prevalent among girls and women. Girls as young as 6 years old experience negative body image, and there is evidence that women struggle with body concerns throughout the life cycle (Lewis & Cachelin, 2001; Smolak, 2002; Striegel-Moore & Franko, 2002). In fact,…

  9. Large Lewis No. Edge-Flame Instabilities

    NASA Technical Reports Server (NTRS)

    Buckmaster, J.

    2001-01-01

    Edge-flames play an important role in a number of microgravity investigations, and in the general study of flames. Examples include the candle-flame experiments carried out on board both the Space Shuttle and the Mir Space Station; the flame-spread-over-liquid work carried out by H. Ross and W. Sirignano amongst others and lifted turbulent diffusion flames. In all of these configurations a local two-dimensional flame structure can be identified which looks like a flame-sheet with an edge, and these structures exhibit dynamical behavior which characterizes them and distinguishes them from ad hoc 2D flame structures. Edge-flames can exist in both a non-premixed context (edges of diffusion flames) and in a premixed context (edges of deflagrations), but the work reported here deals with the edges of diffusion flames. It is particularly relevant, we believe, to oscillations that have been seen in both the candle-flame context, and the flame-spread-over-liquid context. These oscillations are periodic edge-oscillations (in an appropriate reference frame), sans oscillation of the trailing diffusion flame. It is shown that if the Lewis number of the fuel is sufficiently large (the Lewis number of the oxidizer is taken to be 1), and the Damkohler number is sufficiently small, oscillating-edge solutions can be found. Oscillations are encouraged by an on-edge convective flow and the insertion of a cold probe, discouraged by an off-edge convective flow. In the present work, the nature of these oscillations is examined in more depth, using a variety of numerical strategies.

  10. Chiral organoborane Lewis pairs derived from pyridylferrocene.

    PubMed

    Chen, Jiawei; Lalancette, Roger A; Jäkle, Frieder

    2014-07-14

    In an effort to develop a new class of redox-active chiral Lewis pairs, pyridine and borane moieties with different steric and electronic properties were introduced onto a planar chiral 1,2-disubstituted ferrocene framework. Metathesis of lithiated, stannylated, or mercuriated pyridylferrocenes with boron halides afforded (pR)-2-[bis(pentafluorophenyl)boryl]-1-(3,5-dimethylpyrid-2-yl)ferrocene (4-Pf), (pR)-2-[dimesitylboryl]-1-(3,5-dimethylpyrid-2-yl)ferrocene (4-Mes), (pS)-2-(bis(pentafluorophenyl)boryl)-1-(2-trimethylsilylpyrid-6-yl)ferrocene (5-Pf), or (pS)-2-[dimesitylboryl]-1-(2-trimethylsilylpyrid-6-yl)ferrocene (5-Mes). The borylated products were analyzed by multinuclear NMR spectroscopy, HRMS, and single-crystal X-ray diffraction. Chiral HPLC and optical-rotation measurements were employed to assess the stereoselectivity of the borylation process and to establish the correct stereochemical assignments. The strength of the B-N interactions were investigated in solution and in the solid state. Compounds 4-Pf and 4-Mes formed robust 'closed' B-N heterocyclic systems that proved to be perfectly stable to air and moisture, whereas 5-Pf established a dynamic equilibrium, in which the B-N heterocycle was observed exclusively at room temperature, but opened up at high temperature according to (19)F NMR exchange spectroscopy data. As a consequence, 5-Pf reacted readily with a molecule of water to generate a ring-opened pyridinium borate. The combination of bulky borane and bulky pyridyl groups in 5-Mes led to a completely 'open' frustrated Lewis pair system with uncomplexed pyridine and borane groups, even at room temperature. Electrochemical studies were performed and the effect of preparative ferrocene oxidation on the structural features was also explored.

  11. Lewis-Sumner syndrome and multifocal motor neuropathy.

    PubMed

    Verschueren, Annie; Azulay, Jean Philippe; Attarian, Shahram; Boucraut, José; Pellissier, Jean François; Pouget, Jean

    2005-01-01

    We compared the clinical, electrophysiological, laboratory, and pathological features of 13 patients with Lewis-Sumner syndrome (LSS) with those of 20 patients with multifocal motor neuropathy (MMN). LSS and MMN patients have several common clinical features: age at onset, weakness in the distribution of individual peripheral nerves, mild wasting, cramps and fasciculations, partial areflexia, and frequent stepwise disease course. Cerebrospinal fluid protein level was normal or slightly elevated, but always less than 100 mg/dl. Conduction blocks are the electrophysiological hallmarks of these two neuropathies, and no differences in distribution and number of blocks were found. Contrary to MMN, lower-limb involvement at onset was frequent in LSS but extension to the upper limbs was a frequent later feature of the disease. Cranial nerve involvement was noted in 4 LSS patients during relapses and absent in all MMN patients. The major distinguishing features were the clinical and electrophysiological sensory involvement in LSS, and the lack of anti-GM1 antibodies in LSS, whereas IgM anti-GM1 were found in 40% of MMN patients. Some LSS patients responded to steroid therapy, whereas this was ineffective in MMN. From these features, LSS can be considered an entity distinct from MMN, with its own clinical, laboratory, and electrophysiological characteristics, and as an intermediate link between chronic inflammatory demyelinating polyneuropathy and MMN.

  12. Targeting of Neutrophil Lewis X Blocks Transepithelial Migration and Increases Phagocytosis and Degranulation.

    PubMed

    Brazil, Jennifer C; Sumagin, Ronen; Cummings, Richard D; Louis, Nancy A; Parkos, Charles A

    2016-02-01

    Polymorphonuclear leukocytes (PMNs) are innate immune cells whose principal function is to migrate from the blood to sites of inflammation, where they exert crucial anti-infectious and immunomodulatory effects. However, dysregulated migration of PMNs into mucosal epithelial tissues is characteristic of chronic inflammatory disorders, including inflammatory bowel disease. Carbohydrate-mediated binding interactions between PMN Lewis glycans and endothelial glycan-binding proteins are critical for initial migration of PMN out of the vasculature. However, the role of Lewis glycans during transepithelial migration (TEM) has not been well characterized. Herein, we show that antibody blockade of Lewis X (Le(x)) displayed as terminal glycan residues on the PMN surface blocks chemotaxis and TEM while enhancing PMN-adhesive interactions with intestinal epithelia. Unexpectedly, targeting of subterminal Le(x) residues within glycan chains had no effect on PMN migration or adhesive interactions. There was increased surface expression of Le(x) on PMN after TEM, and blockade of terminal Le(x) regulated post-migratory PMN functions, increasing PMN phagocytosis and the surface mobilization of azurophilic (CD63, myeloperoxidase, and neutrophil elastase) and specific (CD66b and lactoferrin) granule markers. These findings suggest that terminal Le(x) represents a potential target for regulating PMN trafficking and function in inflamed mucosa. Furthermore, given its abundant expression on migrating PMN, Le(x) may be a rational target for modulating inflammation in diseases where dysregulated PMN influx is associated with host tissue damage.

  13. The neuropsychological profile of Alzheimer disease.

    PubMed

    Weintraub, Sandra; Wicklund, Alissa H; Salmon, David P

    2012-04-01

    Neuropsychological assessment has featured prominently over the past 30 years in the characterization of dementia associated with Alzheimer disease (AD). Clinical neuropsychological methods have identified the earliest, most definitive cognitive and behavioral symptoms of illness, contributing to the identification, staging, and tracking of disease. With increasing public awareness of dementia, disease detection has moved to earlier stages of illness, at a time when deficits are both behaviorally and pathologically selective. For reasons that are not well understood, early AD pathology frequently targets large-scale neuroanatomical networks for episodic memory before other networks that subserve language, attention, executive functions, and visuospatial abilities. This chapter reviews the pathognomonic neuropsychological features of AD dementia and how these differ from "normal," age-related cognitive decline and from other neurodegenerative diseases that cause dementia, including cortical Lewy body disease, frontotemporal lobar degeneration, and cerebrovascular disease.

  14. The Neuropsychological Profile of Alzheimer Disease

    PubMed Central

    Weintraub, Sandra; Wicklund, Alissa H.; Salmon, David P.

    2012-01-01

    Neuropsychological assessment has featured prominently over the past 30 years in the characterization of dementia associated with Alzheimer disease (AD). Clinical neuropsychological methods have identified the earliest, most definitive cognitive and behavioral symptoms of illness, contributing to the identification, staging, and tracking of disease. With increasing public awareness of dementia, disease detection has moved to earlier stages of illness, at a time when deficits are both behaviorally and pathologically selective. For reasons that are not well understood, early AD pathology frequently targets large-scale neuroanatomical networks for episodic memory before other networks that subserve language, attention, executive functions, and visuospatial abilities. This chapter reviews the pathognomonic neuropsychological features of AD dementia and how these differ from “normal,” age-related cognitive decline and from other neurodegenerative diseases that cause dementia, including cortical Lewy body disease, frontotemporal lobar degeneration, and cerebrovascular disease. PMID:22474609

  15. Neuroimaging Biomarkers of Neurodegenerative Diseases and Dementia

    PubMed Central

    Risacher, Shannon L.; Saykin, Andrew J.

    2014-01-01

    Neurodegenerative disorders leading to dementia are common diseases that affect many older and some young adults. Neuroimaging methods are important tools for assessing and monitoring pathological brain changes associated with progressive neurodegenerative conditions. In this review, the authors describe key findings from neuroimaging studies (magnetic resonance imaging and radionucleotide imaging) in neurodegenerative disorders, including Alzheimer’s disease (AD) and prodromal stages, familial and atypical AD syndromes, frontotemporal dementia, amyotrophic lateral sclerosis with and without dementia, Parkinson’s disease with and without dementia, dementia with Lewy bodies, Huntington’s disease, multiple sclerosis, HIV-associated neurocognitive disorder, and prion protein associated diseases (i.e., Creutzfeldt-Jakob disease). The authors focus on neuroimaging findings of in vivo pathology in these disorders, as well as the potential for neuroimaging to provide useful information for differential diagnosis of neurodegenerative disorders. PMID:24234359

  16. Total body nitrogen in health and disease: effects of age, weight, height, and sex

    SciTech Connect

    Ellis, K.J.; Yasumura, S.; Vartsky, D.; Vaswani, A.N.; Cohn, S.H.

    1982-06-01

    Total body levels of nitrogen were measured by prompt-gamma neutron activation analysis in 136 healthy adults in the general population (age 20 to 80 years), in 55 cancer patients, and in 20 obese subjects. In order to evaluate the TBN values for the patients, it was necessary to normalize the data for possible differences due to body habitus. This normalization was defined as the ratio of the measured nitrogen level to a predicted nitrogen level derived from the normal population. The parameters of sex, age, height, weight, and fat were used to calculate expected normal values of nitrogen. For the cancer patients, an average TBN deficit of less than 10% was observed. Individual patients, however, showed deviations from the TBN/sub p/ value as large as 28%. For obese patients, the TBN values were normal to slightly high. When adjusted for body size, the deficit of TBN in the cancer patients was approximately half that observd for TBK.

  17. Alpha-synuclein in motor neuron disease: an immunohistologic study.

    PubMed

    Doherty, M J; Bird, T D; Leverenz, J B

    2004-02-01

    Alpha-synuclein (ASN) has been implicated in neurodegenerative disorders characterized by Lewy body inclusions such as Parkinson's disease and dementia with Lewy bodies. Lewy body-like inclusions have also been observed in spinal neurons of patients with amyotrophic lateral sclerosis (ALS) and reports suggest possible ASN abnormalities in ALS patients. We assessed ASN immunoreactivity in spinal and brain tissues of subjects who had died of progressive motor neuron disorders (MND). Clinical records of subjects with MND and a comparison group were reviewed to determine the diagnosis according to El-Escariol Criteria of ALS. Cervical, thoracic and lumbar cord sections were stained with an antibody to ASN. A blinded, semiquantitative review of sections from both groups included examination for evidence of spheroids, neuronal staining, cytoplasmic inclusions, anterior horn granules, white and gray matter glial staining, corticospinal tract axonal fiber and myelin changes. MND cases, including ALS and progressive muscular atrophy, displayed significantly increased ASN staining of spheroids ( P< or =0.001), and glial staining in gray and white matter ( P< or =0.05). Significant abnormal staining of corticospinal axon tract fibers and myelin was also observed ( P< or =0.05 and 0.01). Detection of possible ASN-positive neuronal inclusions did not differ between groups. Significant ASN abnormalities were observed in MND. These findings suggest a possible role for ASN in MND; however, the precise nature of this association is unclear.

  18. VCP Associated Inclusion Body Myopathy and Paget Disease of Bone Knock-In Mouse Model Exhibits Tissue Pathology Typical of Human Disease

    PubMed Central

    Kitazawa, Masashi; Su, Hailing; Tanaja, Jasmin; Dec, Eric; Wallace, Douglas C.; Mukherjee, Jogeshwar; Caiozzo, Vincent; Warman, Matthew; Kimonis, Virginia E.

    2010-01-01

    Dominant mutations in the valosin containing protein (VCP) gene cause inclusion body myopathy associated with Paget's disease of bone and frontotemporal dementia (IBMPFD). We have generated a knock-in mouse model with the common R155H mutation. Mice demonstrate progressive muscle weakness starting approximately at the age of 6 months. Histology of mutant muscle showed progressive vacuolization of myofibrils and centrally located nuclei, and immunostaining shows progressive cytoplasmic accumulation of TDP-43 and ubiquitin-positive inclusion bodies in quadriceps myofibrils and brain. Increased LC3-II staining of muscle sections representing increased number of autophagosomes suggested impaired autophagy. Increased apoptosis was demonstrated by elevated caspase-3 activity and increased TUNEL-positive nuclei. X-ray microtomography (uCT) images show radiolucency of distal femurs and proximal tibiae in knock-in mice and uCT morphometrics shows decreased trabecular pattern and increased cortical wall thickness. Bone histology and bone marrow derived macrophage cultures in these mice revealed increased osteoclastogenesis observed by TRAP staining suggestive of Paget bone disease. The VCPR155H/+ knock-in mice replicate the muscle, bone and brain pathology of inclusion body myopathy, thus representing a useful model for preclinical studies. PMID:20957154

  19. Primary Prevention of Chronic Disease among Children: The School-Based "Know Your Body" Intervention Trials.

    ERIC Educational Resources Information Center

    Walter, Heather J.

    1989-01-01

    The classroom-based Know Your Body program focuses on diet, physical activity, and smoking prevention in elementary schools. Longitudinal testing in two New York City schools found significant favorable changes in blood cholesterol, dietary intake of fat and carbohydrates, health knowledge, and reduction in the initiation of smoking. (SK)

  20. DNAJC13 mutations in Parkinson disease.

    PubMed

    Vilariño-Güell, Carles; Rajput, Alex; Milnerwood, Austen J; Shah, Brinda; Szu-Tu, Chelsea; Trinh, Joanne; Yu, Irene; Encarnacion, Mary; Munsie, Lise N; Tapia, Lucia; Gustavsson, Emil K; Chou, Patrick; Tatarnikov, Igor; Evans, Daniel M; Pishotta, Frederick T; Volta, Mattia; Beccano-Kelly, Dayne; Thompson, Christina; Lin, Michelle K; Sherman, Holly E; Han, Heather J; Guenther, Bruce L; Wasserman, Wyeth W; Bernard, Virginie; Ross, Colin J; Appel-Cresswell, Silke; Stoessl, A Jon; Robinson, Christopher A; Dickson, Dennis W; Ross, Owen A; Wszolek, Zbigniew K; Aasly, Jan O; Wu, Ruey-Meei; Hentati, Faycal; Gibson, Rachel A; McPherson, Peter S; Girard, Martine; Rajput, Michele; Rajput, Ali H; Farrer, Matthew J

    2014-04-01

    A Saskatchewan multi-incident family was clinically characterized with Parkinson disease (PD) and Lewy body pathology. PD segregates as an autosomal-dominant trait, which could not be ascribed to any known mutation. DNA from three affected members was subjected to exome sequencing. Genome alignment, variant annotation and comparative analyses were used to identify shared coding mutations. Sanger sequencing was performed within the extended family and ethnically matched controls. Subsequent genotyping was performed in a multi-ethnic case-control series consisting of 2928 patients and 2676 control subjects from Canada, Norway, Taiwan, Tunisia, and the USA. A novel mutation in receptor-mediated endocytosis 8/RME-8 (DNAJC13 p.Asn855Ser) was found to segregate with disease. Screening of cases and controls identified four additional patients with the mutation, of which two had familial parkinsonism. All carriers shared an ancestral DNAJC13 p.Asn855Ser haplotype and claimed Dutch-German-Russian Mennonite heritage. DNAJC13 regulates the dynamics of clathrin coats on early endosomes. Cellular analysis shows that the mutation confers a toxic gain-of-function and impairs endosomal transport. DNAJC13 immunoreactivity was also noted within Lewy body inclusions. In late-onset disease which is most reminiscent of idiopathic PD subtle deficits in endosomal receptor-sorting/recycling are highlighted by the discovery of pathogenic mutations VPS35, LRRK2 and now DNAJC13. With this latest discovery, and from a neuronal perspective, a temporal and functional ecology is emerging that connects synaptic exo- and endocytosis, vesicular trafficking, endosomal recycling and the endo-lysosomal degradative pathway. Molecular deficits in these processes are genetically linked to the phenotypic spectrum of parkinsonism associated with Lewy body pathology.

  1. Associations between body fat variability and later onset of cardiovascular disease risk factors

    PubMed Central

    Takahashi, Osamu; Arioka, Hiroko; Kobayashi, Daiki

    2017-01-01

    Objective There is current debate regarding whether body weight variability is associated with cardiovascular events. Recently, high body fat percentage (BF%) has been shown to be a cardiovascular risk factor. We therefore hypothesized that BF% variability would present a stronger cardiovascular risk than body weight variability. Methods A single-center retrospective cohort study of medical check-up examinees aged 20 years or older at baseline (2005) was performed. Examinees were followed in 2007, 2009, and 2013–2014. BF% variability in 2005, 2007 and 2009 was calculated as the root-mean square error (RMSE) using a simple linear regression model. Multiple logistic regression models estimated the association between BF%-RMSE and new diagnoses of cardiovascular risk factors occurring between the 2009 and 2013–2014 visits. Results In total, 11,281 participants (mean age: 51.3 years old, 48.8% were male) were included in this study. The average BF%-RMSE of our subjects was 0.63, and the average BMI-RMSE was 0.24. The high BF%-RMSE group (76-100th percentile) had a higher incidence of hypertension and a lower incidence of diabetes mellitus than the low BF%-RMSE group (1-25th percentile). This tendency was particularly evident in male participants. BMI-RMSE was not associated with any cardiovascular risks in our study. Conclusions This study indicates that body fat variability has contrasting effects on cardiovascular risk factors, while body weight variability has no significant effects. PMID:28369119

  2. Stress, Allostatic Load, Catecholamines, and Other Neurotransmitters in Neurodegenerative Diseases

    PubMed Central

    2017-01-01

    As populations age, the prevalence of geriatric neurodegenerative diseases will increase. These diseases generally are multifactorial, arising from complex interactions among genes, environment, concurrent morbidities, treatments, and time. This essay provides a concept for the pathogenesis of Lewy body diseases such as Parkinson disease, by considering them in the context of allostasis and allostatic load. Allostasis reflects active, adaptive processes that maintain apparent steady states, via multiple, interacting effectors regulated by homeostatic comparators—“homeostats.” Stress can be defined as a condition or state in which a sensed discrepancy between afferent information and a setpoint for response leads to activation of effectors, reducing the discrepancy. “Allostatic load” refers to the consequences of sustained or repeated activation of mediators of allostasis. From the analogy of an idling car, the revolutions per minute of the engine can be maintained at any of a variety of levels (allostatic states). Just as allostatic load (cumulative wear and tear) reflects design and manufacturing variations, byproducts of combustion, and time, eventually leading to engine breakdown, allostatic load in catecholaminergic neurons might eventually lead to Lewy body diseases. Central to the argument is that catecholaminergic neurons leak vesicular contents into the cytoplasm continuously during life and that catecholamines in the neuronal cytoplasm are autotoxic. These neurons therefore depend on vesicular sequestration to limit autotoxicity of cytosolic transmitter. Parkinson disease might be a disease of the elderly because of allostatic load, which depends on genetic predispositions, environmental exposures, repeated stress-related catecholamine release, and time. PMID:21615193

  3. Stress, Allostatic Load, Catecholamines, and Other Neurotransmitters in Neurodegenerative Diseases

    PubMed Central

    2016-01-01

    As populations age, the prevalence of geriatric neurodegenerative diseases will increase. These diseases generally are multifactorial, arising from complex interactions among genes, environment, concurrent morbidities, treatments, and time. This essay provides a concept for the pathogenesis of Lewy body diseases such as Parkinson disease, by considering them in the context of allostasis and allostatic load. Allostasis reflects active, adaptive processes that maintain apparent steady states, via multiple, interacting effectors regulated by homeostatic comparators—“homeostats.” Stress can be defined as a condition or state in which a sensed discrepancy between afferent information and a setpoint for response leads to activation of effectors, reducing the discrepancy. “Allostatic load” refers to the consequences of sustained or repeated activation of mediators of allostasis. From the analogy of an idling car, the revolutions per minute of the engine can be maintained at any of a variety of levels (allostatic states). Just as allostatic load (cumulative wear and tear) reflects design and manufacturing variations, byproducts of combustion, and time, eventually leading to engine breakdown, allostatic load in catecholaminergic neurons might eventually lead to Lewy body diseases. Central to the argument is that catecholaminergic neurons leak vesicular contents into the cytoplasm continuously during life and that catecholamines in the neuronal cytoplasm are autotoxic. These neurons therefore depend on vesicular sequestration to limit autotoxicity of cytosolic transmitter. Parkinson disease might be a disease of the elderly because of allostatic load, which depends on genetic predispositions, environmental exposures, repeated stress-related catecholamine release, and time. PMID:22297542

  4. Biomarkers for Cognitive Impairment in Parkinson Disease

    PubMed Central

    Shi, Min; Huber, Bertrand R.; Zhang, Jing

    2010-01-01

    Cognitive impairment, including dementia, is commonly seen in those afflicted with Parkinson disease (PD), particularly at advanced disease stages. Pathologically, PD with dementia (PD-D) is most often associated with the presence of cortical Lewy bodies, as is the closely related dementia with Lewy bodies (DLB). Both PD-D and DLB are also frequently complicated by the presence of neurofibrillary tangles and amyloid plaques, features most often attributed to Alzheimer disease. Biomarkers are urgently needed to differentiate among these disease processes and predict dementia in PD as well as monitor responses of patients to new therapies. A few clinical assessments, along with structural and functional neuroimaging, have been utilized in the last few years with some success in this area. Additionally, a number of other strategies have been employed to identify biochemical/molecular biomarkers associated with cognitive impairment and dementia in PD, e.g., targeted analysis of candidate proteins known to be important to PD pathogenesis and progression in cerebrospinal fluid or blood. Finally, interesting results are emerging from preliminary studies with unbiased and high throughput genomic, proteomic and metabolomic techniques. The current findings and perspectives of applying these strategies and techniques are reviewed in this article, together with potential areas of advancement. PMID:20522092

  5. Lewis Acid-Base, Molecular Modeling, and Isotopic Labeling in a Sophomore Inorganic Chemistry Laboratory

    ERIC Educational Resources Information Center

    Nataro, Chip; Ferguson, Michelle A.; Bocage, Katherine M.; Hess, Brian J.; Ross, Vincent J.; Swarr, Daniel T.

    2004-01-01

    An experiment to prepare a deuterium labeled adduct of a Lewis acid and Lewis base, to use computational methods allowing students to visualize the LUMO of Lewis acids, the HOMO of Lewis bases and the molecular orbitals of the adduct that is formed is developed. This allows students to see the interplay between calculated and experimental results.

  6. Neuropathology in transplants in Parkinson's disease: implications for disease pathogenesis and the future of cell therapy.

    PubMed

    Brundin, Patrik; Kordower, Jeffrey H

    2012-01-01

    Neural transplantation is over a century old, but the modern era encompasses only the last 30-40 years. For most of this time period, research has focused on reversing disability engendered by neurologic disease and brain damage. Only recently was it recognized that the underlying neurological disease itself might negatively impact the grafted neurons. We have found that a subset of neurons within embryonic neural grafts that survive more than 10 years in Parkinson patients display Lewy bodies, a classical feature of Parkinson's disease neuropathology. Additionally, the grafted cells placed in the Parkinson's disease brain eventually downregulate the expression of dopamine transporter and tyrosine hydroxylase in a manner similar to what is seen in the substantia nigra dopamine neurons that are degenerating due to the disease. We discuss these findings in terms of how they might improve our understanding of Parkinson's disease pathogenesis and the effects they may have on the future of neural cell replacement strategies.

  7. FEATURE B. MACHINE GUN POSITION WITH LEWIS MOUNT, VIEW FACING ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    FEATURE B. MACHINE GUN POSITION WITH LEWIS MOUNT, VIEW FACING NORTHWEST (with scale stick). - Naval Air Station Barbers Point, Battery-Machine Gun Positions, South of Point Cruz Road & west of Coral Sea Road, Ewa, Honolulu County, HI

  8. FEATURE B. MACHINE GUN POSITION WITH LEWIS MOUNT, VIEW FACING ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    FEATURE B. MACHINE GUN POSITION WITH LEWIS MOUNT, VIEW FACING NORTHWEST. - Naval Air Station Barbers Point, Battery-Machine Gun Positions, South of Point Cruz Road & west of Coral Sea Road, Ewa, Honolulu County, HI

  9. Distance Learning With NASA Lewis Research Center's Learning Technologies Project

    NASA Technical Reports Server (NTRS)

    Petersen, Ruth

    1998-01-01

    The NASA Lewis Research Center's Learning Technologies Project (LTP) has responded to requests from local school district technology coordinators to provide content for videoconferencing workshops. Over the past year we have offered three teacher professional development workshops that showcase NASA Lewis-developed educational products and NASA educational Internet sites. In order to determine the direction of our involvement with distance learning, the LTP staff conducted a survey of 500 U.S. schools. We received responses from 72 schools that either currently use distance learning or will be using distance learning in 98-99 school year. The results of the survey are summarized in the article. In addition, the article provides information on distance learners, distance learning technologies, and the NASA Lewis LTP videoconferencing workshops. The LTP staff will continue to offer teacher development workshops through videoconferencing during the 98-99 school year. We hope to add workshops on new educational products as they are developed at NASA Lewis.

  10. Sporadic Inclusion Body Myositis Manifesting as Isolated Muscle Weakness of the Finger Flexors Three Years after Disease Onset

    PubMed Central

    Suwa, Yuichi; Suzuki, Naoki; Soga, Temma; Harada, Ryuhei; Shibui, Aya; Kuroda, Hiroshi; Izumi, Rumiko; Tateyama, Maki; Nakashima, Ichiro; Sonoo, Masahiro; Aoki, Masashi

    2016-01-01

    Sporadic inclusion body myositis (sIBM) is a chronic progressive myopathy characterized by muscle weakness of both the quadriceps femoris and finger flexors. We herein present the case of a typical male patient with sIBM, which manifested as the isolated weakness of the finger flexors three years after the disease onset. We have identified several patients with sIBM in our cohort with muscle weakness of the flexors but not the quadriceps femoris. Examination of the flexor digitorum profundus muscle is important for the early and proper diagnosis of sIBM, even if a patient only presents with isolated finger flexor muscle weakness. PMID:27904121

  11. Postal survey of contacts between cattle farms on the Isle of Lewis.

    PubMed

    Vernon, M C; Webb, C R; Heath, M F

    2010-01-09

    The British Cattle Movement Service (BCMS) database contains an unprecedented quantity of data on the movement of cattle within the UK. These data may be used to construct models of the contact structure of the UK cattle herd, for epidemiological purposes. There are two significant potential sources of inaccuracy within such models: movements that are not reported or are reported inaccurately to the BCMS, and contacts between farms that might transmit infection, but are not animal movements. This field study addressed these issues. Cattle farmers on the Isle of Lewis were recruited with the assistance of the local veterinary surgeon, and asked to record a range of potential risk behaviours for a one-month period. They were also asked questions about husbandry practices on their farm. Comparison of the BCMS contact data with that reported by Lewis' farmers highlighted use of common grazing land as a significant source of contact, and potential disease transmission, between cattle that currently goes unreported; around half of responding holdings on Lewis use common grazing land at some point during the year, and these movements are not reported to the BCMS.

  12. Chemistry and Electrochemistry in Lewis Acid and Superacid Ionic Liquids

    DTIC Science & Technology

    1994-04-30

    LEWIS ACID AND SUPERACID IONIC LIQUIDS PRINCIPAL INVESTIGATOR: Dr. Robert A. Osteryoung Department of Chemistry North Carolina State University...Spectroscopic Study of Anthracene in a Mixed Lewis-Bronsted Acid Ambient Temperature Molten Salt System", Electrochim. Acta, 37, 2615-2628 (1992...investigated. In acidic melts, electrochemical oxidation of anthracene produces a cation radical which exhibits stability similar to that found in "Msuperdry

  13. Lewis Research Center space station electric power system test facilities

    NASA Technical Reports Server (NTRS)

    Birchenough, Arthur G.; Martin, Donald F.

    1988-01-01

    NASA Lewis Research Center facilities were developed to support testing of the Space Station Electric Power System. The capabilities and plans for these facilities are described. The three facilities which are required in the Phase C/D testing, the Power Systems Facility, the Space Power Facility, and the EPS Simulation Lab, are described in detail. The responsibilities of NASA Lewis and outside groups in conducting tests are also discussed.

  14. NASA Lewis Stirling engine computer code evaluation

    SciTech Connect

    Sullivan, T.J.

    1989-01-01

    In support of the US Department of Energy's Stirling Engine Highway Vehicle Systems program, the NASA Lewis Stirling engine performance code was evaluated by comparing code predictions without engine-specific calibration factors to GPU-3, P-40, and RE-1000 Stirling engine test data. The error in predicting power output was /minus/11 percent for the P-40 and 12 percent for the RE-1000 at design conditions and 16 percent for the GPU-3 at near-design conditions (2000 rpm engine speed versus 3000 rpm at design). The efficiency and heat input predictions showed better agreement with engine test data than did the power predictions. Concerning all data points, the error in predicting the GPU-3 brake power was significantly larger than for the other engines and was mainly a result of inaccuracy in predicting the pressure phase angle. Analysis into this pressure phase angle prediction error suggested that improvement to the cylinder hysteresis loss model could have a significant effect on overall Stirling engine performance predictions. 13 refs., 26 figs., 3 tabs.

  15. ISDN at NASA Lewis Research Center

    NASA Technical Reports Server (NTRS)

    Bakes, Catherine Murphy; Goldberg, Fredric; Eubanks, Steven W.

    1992-01-01

    An expository investigation of the potential impact of the Integrated Services Digital Network (ISDN) at NASA Lewis Research Center is described. To properly frame the subject, the paper contains a detailed survey of the components of Narrowband ISDN. The principles and objectives are presented as decreed by the Consultative Committee for International Telephone and Telegraph (CCITT). The various channel types are delineated and their associated service combinations are described. The subscriber-access network functions are explained pictorially via the ISDN reference configuration. A section on switching techniques is presented to enable the reader to understand the emergence of the concept of fast packet switching. This new technology is designed to operate over the high bandwidth, low error rate transmission media that characterizes the LeRC environment. A brief introduction to the next generation of networks is covered with sections on Broadband ISDM (B-ISDN), Asynchronous Transfer Mode (ATM), and Synchronous Optical Networks (SONET). Applications at LeRC are presented, first in terms of targets of opportunity, then in light of compatibility constraints. In-place pilot projects and testing are described that demonstrate actual usage at LeRC.

  16. Lewis Research Center R and D Facilities

    NASA Technical Reports Server (NTRS)

    1991-01-01

    The NASA Lewis Research Center (LeRC) defines and develops advanced technology for high priority national needs. The work of the Center is directed toward new propulsion, power, and communications technologies for application to aeronautics and space, so that U.S. leadership in these areas is ensured. The end product is knowledge, usually in a report, that is made fully available to potential users--the aircraft engine industry, the energy industry, the automotive industry, the space industry, and other NASA centers. In addition to offices and laboratories for almost every kind of physical research in such fields as fluid mechanics, physics, materials, fuels, combustion, thermodynamics, lubrication, heat transfer, and electronics, LeRC has a variety of engineering test cells for experiments with components such as compressors, pumps, conductors, turbines, nozzles, and controls. A number of large facilities can simulate the operating environment for a complete system: altitude chambers for aircraft engines; large supersonic wind tunnels for advanced airframes and propulsion systems; space simulation chambers for electric rockets or spacecraft; and a 420-foot-deep zero-gravity facility for microgravity experiments. Some problems are amenable to detection and solution only in the complete system and at essentially full scale. By combining basic research in pertinent disciplines and generic technologies with applied research on components and complete systems, LeRC has become one of the most productive centers in its field in the world. This brochure describes a number of the facilities that provide LeRC with its exceptional capabilities.

  17. NASA Lewis Stirling engine computer code evaluation

    NASA Technical Reports Server (NTRS)

    Sullivan, Timothy J.

    1989-01-01

    In support of the U.S. Department of Energy's Stirling Engine Highway Vehicle Systems program, the NASA Lewis Stirling engine performance code was evaluated by comparing code predictions without engine-specific calibration factors to GPU-3, P-40, and RE-1000 Stirling engine test data. The error in predicting power output was -11 percent for the P-40 and 12 percent for the Re-1000 at design conditions and 16 percent for the GPU-3 at near-design conditions (2000 rpm engine speed versus 3000 rpm at design). The efficiency and heat input predictions showed better agreement with engine test data than did the power predictions. Concerning all data points, the error in predicting the GPU-3 brake power was significantly larger than for the other engines and was mainly a result of inaccuracy in predicting the pressure phase angle. Analysis into this pressure phase angle prediction error suggested that improvements to the cylinder hysteresis loss model could have a significant effect on overall Stirling engine performance predictions.

  18. Hydatid disease involving some rare locations in the body: a pictorial essay.

    PubMed

    Yuksel, Murvet; Demirpolat, Gulen; Sever, Ahmet; Bakaris, Sevgi; Bulbuloglu, Ertan; Elmas, Nevra

    2007-01-01

    Hydatid disease (HD) is an endemic illness in many countries, and it poses an important public health problem that's influenced by peoples' socioeconomic status and migration that spreads this disease. Although rare, it may occur in any organ or tissue. The most common site is the liver (59-75%), followed in frequency by lung (27%), kidney (3%), bone (1-4%) and brain (1-2%). Other sites such as the heart, spleen, pancreas and muscles are very rarely affected. Unusual sites for this disease can cause diagnostic problems. This pictorial essay illustrates various radiological findings of HD in the liver, spleen, kidney, pancreas, peritoneal cavity, omentum, adrenal, ovary, lung, mediastinum and retroperitoneum. Familiarity with the imaging findings of HD may be helpful in making an accurate diagnosis and preventing potential complications.

  19. Vitamins mediate immunological homeostasis and diseases at the surface of the body.

    PubMed

    Kunisawa, Jun; Kiyono, Hiroshi

    2015-01-01

    The host immune system is regulated not only by endogenous factors, such as cytokines and chemokines, but also by exogenous factors, such as commensal bacteria and dietary materials. Vitamins are vital nutrients that are mainly derived from the diet and commensal bacteria. Accumulating evidence has revealed specific functions of vitamins in the control of host immunity. In agreement with their vital roles in the appropriate maintenance of immunity, excessive or insufficient intake of vitamins leads to the development of immune diseases or susceptibility to infection. In this review, we focus on the diverse but specific immunologic functions of vitamins in regulating host immune responses and their association with immune and infectious diseases.

  20. AN OUTBREAK OF PSITTACOSIS IN PIGEONS, INVOLVING THE PRODUCTION OF INCLUSION BODIES, AND TRANSFER OF THE DISEASE TO MAN

    PubMed Central

    Smadel, Joseph E.; Wall, M. J.; Gregg, Alan

    1943-01-01

    An epizootic disease in pigeons associated with atypical pneumonia in two persons handling the birds has been studied. Most of the observations made during the work were consistent with the idea that we were dealing with an infection caused by a member of the psittacosis-lymphogranuloma venereum group of viruses. The outbreak was peculiar, however, in that tissues of the diseased pigeons contained many intranuclear inclusions and that the viruses isolated from these birds produced both intranuclear inclusions and elementary bodies in the cytoplasm of cells of chorio-allantoic membranes of the developing egg. Whether the pigeons were