Science.gov

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. Lewy Body Disease

    MedlinePlus

    ... of symptoms, including Changes in alertness and attention Hallucinations Problems with movement and posture Muscle stiffness Confusion Loss of memory Lewy body disease can be hard to diagnose, because Parkinson's ...

  3. [Diffuse Lewy body disease].

    PubMed

    Kosaka, K

    1995-12-01

    Diffuse Lewy body disease (DLBD), which we have proposed since 1976, has received great attention among both researchers and clinicians. Recently, it was reported by some English and American research groups that DLBD is the second most frequent dementing illness in the elderly, following Alzheimer-type dementia (ATD). Our recent research of 79 autopsied dementia cases in a hospital disclosed that DLBD (15.4%) was the second most common degenerative dementia, following ATD (43.6%). In 1980 we proposed Lewy body disease, and classified it into three types: brain stem type, transitional type, and diffuse type. Diffuse type of LBD is now called DLBD. In 1990 we divided DLBD into two forms: common form and pure form. The common form of DLBD has more or less Alzheimer pathology, and pure form has none. Very recently, we proposed the cerebral type of LBD, in which numerous Lewy bodies are found in the cerebral cortex and amygdala, but no PD pathology is present in the brain stem. Therefore, LBD is now classified as follows: [table: see text] PMID:8752428

  4. Lewy body disease and dementia with Lewy bodies

    PubMed Central

    KOSAKA, Kenji

    2014-01-01

    In 1976 we reported our first autopsied case with diffuse Lewy body disease (DLBD), the term of which we proposed in 1984. We also proposed the term “Lewy body disease” (LBD) in1980. Subsequently, we classified LBD into three types according to the distribution pattern of Lewy bodies: a brain stem type, a transitional type and a diffuse type. Later, we added the cerebral type. As we have proposed since 1980, LBD has recently been used as a generic term to include Parkinson’s disease (PD), Parkinson’s disease with dementia (PDD) and dementia with Lewy bodies (DLB), which was proposed in 1996 on the basis of our reports of DLBD. DLB is now known to be the second most frequent dementia following Alzheimer’s disease (AD). In this paper we introduce our studies of DLBD and LBD. PMID:25311140

  5. Lewy Body Pathology in Familial Alzheimer Disease

    PubMed Central

    Leverenz, James B.; Fishel, Mark A.; Peskind, Elaine R.; Montine, Thomas J.; Nochlin, David; Steinbart, Ellen; Raskind, Murray A.; Schellenberg, Gerard D.; Bird, Thomas D.; Tsuang, Debby

    2006-01-01

    Background The origin and significance of Lewy bodies and neurites (Lewy body pathology [LBP]) in Alzheimer disease (AD) are poorly understood. Objective To examine LBP in the brainstem, limbic cortex, and neocortex of a large number of familial AD cases with mutations in 2 presenilin (PSEN) genes. Methods Twenty-five familial AD cases with 9 known PSEN 1 mutations and 14 familial AD cases with a single PSEN 2 mutation (N141I) were examined for LBP using α-synuclein immunohistochemistry and sampling of multiple brainstem and cortical regions. Results The amygdala was the most vulnerable site for LBP. In fact, virtually all (24 [96%] of 25 cases) of the PSEN 1 mutation cases had LBP in the amygdala. The PSEN 1 mutation cases also had more frequent LBP in the amygdala and neocortex than those with the PSEN 2 mutation. However, within families with a single mutation of either PSEN 1 or PSEN 2, there was frequent variability of the LBP. Conclusion These findings suggest that there are genetic influences on the presence of LBP in familial AD as demonstrated by the differences between PSEN 1 and PSEN 2 mutation cases. PMID:16533963

  6. 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. PMID:26355527

  7. Lewy Body Dementia Research

    MedlinePlus

    ... Alzheimer's when Lewy Bodies are present Lewy body pathology is found in up to 50% of cases ... between people who have autopsy-verified Alzheimer’s disease pathology alone versus those who have both Alzheimer’s and ...

  8. Lewy Body Dementia Diagnosis

    MedlinePlus

    ... individuals, it may also be due to the natural course of the disease. All Rights Reserved Lewy Body Dementia Association, Inc. 912 Killian Hill Road S.W., Lilburn, GA 30047 © 2016 Lewy Body Dementia Association, Inc. Connect ...

  9. The spectrum of cognitive impairment in Lewy body diseases

    PubMed Central

    Goldman, Jennifer G.; Williams-Gray, Caroline; Barker, Roger A.; Duda, John E.; Galvin, James E.

    2014-01-01

    Cognitive impairment represents an important and often defining component of the clinical syndromes of Lewy body disorders: Parkinson’s disease and dementia with Lewy bodies. The spectrum of cognitive deficits in these Lewy body diseases encompasses a broad range of clinical features, severity of impairment, and timing of presentation. Cognitive dysfunction is now recognized to occur not only in more advanced Parkinson’s disease, but also in early, untreated patients, and even in those patients with pre-motor syndromes such as REM behavior disorder and hyposmia. In recent years, the concept of “mild cognitive impairment” as a transitional or pre-dementia state in Parkinson’s disease has emerged. While this has led to much research regarding the diagnosis, prognosis, and underlying neurobiology of mild cognitive impairment in Parkinson’s disease, it has also raised questions regarding the usefulness of this concept and its application in clinical and research settings. In addition, the conundrum of whether Parkinson’s disease dementia and dementia with Lewy bodies represent the same or different entities remains unresolved. While these disorders overlap in many aspects of their presentations and pathophysiology, they differ in other aspects such as timing of cognitive, behavioral, and motor symptoms, medication responses, and neuropathological contributions. This article examines the spectrum and evolution of cognitive impairment in Lewy body disorders and debates these controversial issues in the field using point-counterpoint approaches. PMID:24757110

  10. Clinical Features of Alzheimer Disease With and Without Lewy Bodies

    PubMed Central

    Chung, Eun Joo; Babulal, Ganesh M.; Monsell, Sarah E.; Cairns, Nigel J.; Roe, Catherine M.; Morris, John C.

    2015-01-01

    IMPORTANCE Lewy bodies are a frequent coexisting pathology in late-onset Alzheimer disease (AD). Previous studies have examined the contribution of Lewy bodies to the clinical phenotype of late-onset AD with variable findings. OBJECTIVE To determine whether the presence of Lewy body pathology influences the clinical phenotype and progression of symptoms in longitudinally assessed participants with AD. DESIGN, SETTING, AND PARTICIPANTS Retrospective clinical and pathological cohort study of 531 deceased participants who met the neuropathologic criteria for intermediate or high likelihood of AD according to the National Institute on Aging–Ronald Reagan Institute guidelines for the neuropathologic diagnosis of AD. All participants had a clinical assessment within 2 years of death. The data were obtained from 34 AD centers maintained by the National Alzheimer Coordinating Center and spanned from September 12, 2005, to April 30, 2013. EXPOSURES Standardized neuropathologic assessment and then brain autopsy after death. MAIN OUTCOMES AND MEASURES Clinical and neuropsychiatric test scores. RESULTS The mean (SD) age at death was statistically significantly younger for participants who had AD with Lewy bodies (77.9 [9.5] years) than for participants who had AD without Lewy bodies (80.2 [11.1] years) (P = .01). The mean (SD) age at onset of dementia symptoms was also younger for participants who had AD with Lewy bodies (70.0 [9.9] years) than for participants who had AD without Lewy bodies (72.2 [12.3] years) (P = .03). More men than women had AD with Lewy bodies (P = .01). The frequency of having at least 1 APOE ε4 allele was higher for participants who had AD with Lewy bodies than for participants who had AD without Lewy bodies (P = .03). After adjusting for age, sex, education, frequency of plaques (neuritic and diffuse), and tangle stage, we found that participants who had AD with Lewy bodies had a statistically significantly higher mean (SD) Neuropsychiatric

  11. Diffuse Lewy body disease with immediate post-partum onset.

    PubMed

    Opeskin, K; Gonzales, M; Borenstein, R; Anderson, R

    1993-01-01

    A previously healthy 27 years-old woman developed psychotic depression and parkinsonism shortly after delivery of her first child. Her neuropsychiatric symptoms progressed to dementia and she died 5 years after onset. Diffuse Lewy body disease was found at autopsy. This case is unusual because of the early age of onset and the abrupt development of symptoms following pregnancy. PMID:8442413

  12. 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…

  13. Dementia with Lewy bodies: disease concept and genetics.

    PubMed

    Graeber, Manuel B; Müller, Ulrich

    2003-08-01

    Dementia with Lewy bodies (DLB) was first recognized as a clinicopathological entity about 20 years ago. It is the second most-common degenerative dementia after Alzheimer's disease. Clinically, DLB differs from Alzheimer's disease in that disease symptoms are prone to fluctuate and patients often suffer from visual hallucinations, while short-term memory is relatively preserved. As many as 70% of patients have parkinsonism and up to 50% are sensitive to the extrapyramidal side effects of neuroleptic drugs. About 3 million Europeans will be affected by DLB in 2020 if no cure or effective treatment is found. This article reviews the current disease concept, as well as existing problems concerning classification and delineation of DLB from other conditions with dementia. The literature on genetic findings in this complex disease is critically discussed. PMID:12898286

  14. Reduced striatal tyrosine hydroxylase in incidental Lewy body disease

    PubMed Central

    Adler, Charles H.; Sue, Lucia I.; Peirce, Jeffrey B.; Bachalakuri, Jyothi; Dalsing-Hernandez, Jessica E.; Lue, Lih Fen; Caviness, John N.; Connor, Donald J.; Sabbagh, Marwan N.; Walker, Douglas G.

    2009-01-01

    Incidental Lewy body disease (ILBD) is the term used when Lewy bodies are found in the nervous system of subjects without clinically documented parkinsonism or dementia. The prevalence of ILBD in the elderly population has been estimated at between 3.8 and 30%, depending on subject age and anatomical site of sampling. It has been speculated that ILBD represents the preclinical stage of Parkinson’s disease (PD) and/or dementia with Lewy bodies (DLB). Studies of ILBD could potentially identify early diagnostic signs of these disorders. At present, however, it is impossible to know whether ILBD is a precursor to PD or DLB or is just a benign finding of normal aging. We hypothesized that, if ILBD represents an early stage of PD or DLB, it should be associated with depletion of striatal dopaminergic markers. Eleven subjects with ILBD and 27 control subjects were studied. The ILBD subjects ranged in age from 74 to 96 years (mean 86.5) while the control subjects’ age ranged from 75 to 102 years (mean 86.7). Controls and subjects did not differ in terms of age, postmortem interval, gender distribution, medical history conditions, brain weight, neuritic plaque density or Braak neurofibrillary stage. Quantitative ELISA measurement of striatal tyrosine hydroxylase (TH), the principal enzyme for dopamine synthesis, showed a 49.8% (P = 0.01) reduction in ILBD cases, as compared with control cases. The finding suggests that ILBD is not a benign condition but is likely a precursor to PD and/or DLB. PMID:17985144

  15. Symptoms of Lewy Body Dementia

    MedlinePlus

    ... of the environment or personal interactions, and the natural progression of the disease. All Rights Reserved Lewy Body Dementia Association, Inc. 912 Killian Hill Road S.W., Lilburn, GA 30047 © 2016 Lewy Body Dementia Association, Inc. Connect ...

  16. 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

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

    PubMed

    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

  18. Motor and cognitive function in Lewy body dementia: comparison with Alzheimer's and Parkinson's diseases.

    PubMed Central

    Gnanalingham, K K; Byrne, E J; Thornton, A; Sambrook, M A; Bannister, P

    1997-01-01

    OBJECTIVE: Motor and cognitive function were compared in patients with Lewy body dementia, Parkinson's disease, or Alzheimer's disease, to identify features that may be clinically useful in differentiating Lewy body dementia from Alzheimer's disease and Parkinson's disease. METHODS: A range of neuropsychological function and extrapyrimidal signs (EPS) was assessed in 16 patients with Lewy body dementia, 15 with Parkinson's disease, 25 with Alzheimer's disease, and 22 control subjects. RESULTS: The severity of total motor disability scores increased in the following order: controls approximately = Alzheimer's disease << Parkinson's disease < Lewy body dementia. Compared with patients with Parkinson's disease, patients with Lewy body dementia had greater scores for rigidity and deficits in the finger tapping test, but rest tremor and left/right asymmetry in EPS were more evident in Parkinson's disease. Patients with Lewy body dementia were also less likely to present with left/right asymmetry in EPS at the onset of their parkinsonism. "Sensitivity" to neuroleptic drugs was noted in 33% of patients with Lewy body dementia. Alzheimer's disease and Lewy body dementia groups had greater severity of dementia compared with the Parkinson's disease group and controls. Neuropsychological evaluation disclosed severe but similar degrees of impaired performances in tests of attention (digit span), frontal lobe function (verbal fluency, category, and Nelson card sort test) and motor sequencing in both Lewy body dementia and Alzheimer's disease groups, than Parkinson's disease and controls. In the clock face test, improved performance was noted in the "copy" compared to "draw" part of the test in controls, patients with Alzheimer's disease, and those with Parkinson's disease, but not in the patients with Lewy body dementia, who achieved equally poor scores in both parts of the test. CONCLUSIONS: EPS in Lewy body dementia resemble those seen in idiopathic Parkinson's disease

  19. Prodromal clinical manifestations of neuropathologically confirmed Lewy body disease.

    PubMed

    Jicha, G A; Schmitt, F A; Abner, E; Nelson, P T; Cooper, G E; Smith, C D; Markesbery, W R

    2010-10-01

    The mild cognitive impairment (MCI) stage of dementia with Lewy bodies (MCI-DLB) has not yet been defined, but is likely to differ in the MCI stage of Alzheimer's disease (MCI-AD). To determine whether clinical features distinguish MCI-DLB and MCI-AD, 9 cases of neuropathologically confirmed MCI-DLB and 12 cases of MCI-AD were compared. No significant differences were found between MCI-DLB and MCI-AD cases in age at death, gender, ApoE status, education, time followed while clinically normal, or duration of MCI. MCI-DLB and MCI-AD cases differed clinically in the expression of Parkinsonism (P=0.012), provoked hallucinations or delirium (P=0.042), or the presence of any of these noncognitive symptoms of DLB (P<0.0001). Letter fluency (P=0.007) was significantly lower and Wechsler Logical Memory I (P=0.019) was significantly higher in MCI-DLB compared to MCI-AD cases. These data demonstrate the feasibility of differentiating underlying pathologic processes responsible for cognitive decline in the preclinical disease state and suggest that further refinement in diagnostic criteria may allow more accurate early detection of prodromal DLB and AD. PMID:19026468

  20. Dementia with lewy bodies.

    PubMed

    Posner, H; Chin, S; Marder, K

    2001-10-17

    In this case study, we describe the symptoms, neuropsychological testing, and brain pathology of a man with dementia with Lewy bodies. Dementia with Lewy bodies might be the second most common form of degenerative dementia in the elderly. Progressive cognitive decline, well-formed visual hallucinations, and parkinsonism are core features of this disease. This case was marked by preserved verbal expression despite impairment in memory, visuospatial skills, and attention span. Development of visual symptoms and parkinsonism occurred very early in the course of the disease. PMID:14602963

  1. Lewy body dementias.

    PubMed

    Walker, Zuzana; Possin, Katherine L; Boeve, Bradley F; Aarsland, Dag

    2015-10-24

    The broad importance of dementia is undisputed, with Alzheimer's disease justifiably getting the most attention. However, dementia with Lewy bodies and Parkinson's disease dementia, now called Lewy body dementias, are the second most common type of degenerative dementia in patients older than 65 years. Despite this, Lewy body dementias receive little attention and patients are often misdiagnosed, leading to less than ideal management. Over the past 10 years, considerable effort has gone into improving diagnostic accuracy by refining diagnostic criteria and using imaging and other biomarkers. Dementia with Lewy bodies and Parkinson's disease dementia share the same pathophysiology, and effective treatments will depend not only on successful treatment of symptoms but also on targeting the pathological mechanisms of disease, ideally before symptoms and clinical signs develop. We summarise the most pertinent progress from the past 10 years, outlining some of the challenges for the future, which will require refinement of diagnosis and clarification of the pathogenesis, leading to disease-modifying treatments. PMID:26595642

  2. 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

  3. 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

  4. 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

    2016-08-01

    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

  5. [Dementia with Lewy bodies].

    PubMed

    Orimo, Satoshi

    2016-03-01

    It is important to differentiate dementia with Lewy bodies (DLB) and other dementia, especially Alzheimer disease (AD), because the medical treatment, management, and the prognosis of these diseases are different. In regard to clinical features, DLB patients have relatively mild memory disturbance, fluctuating cognition, more severe disturbances of attention, executive function, visuospacial function, visual hallucination, depression, autonomic symptoms, REM sleep behavior disorder, and idiopathic parkinsonism compared to AD patients. In regard to imaging tools, DLB patients have milder atrophy of medial temporal lobe by brain MRI, reduced occipital activity by SPECT or PET, reduced MIBG uptake by MIBG cardiac scintigraphy, and low dopamine transporter activity in the basal ganglia by SPECT or PET. PMID:27025091

  6. Nightmares without atonia as an early symptom of diffuse Lewy bodies disease.

    PubMed

    de Brito-Marques, Paulo Roberto; de Mello, Roberto Vieira; Montenegro, Luciano

    2003-12-01

    A male 70 years old patient with diffuse or "pure" Lewy body disease is described. The diagnosis was made based on clinical features of nightmares with no atonia, attention deficits with fluctuation in cognitive function, incapacity to find his way around the neighbourhood and other formerly familiar environments and mild neuropsychiatric symptoms. Neuropsychological assessment showed memory deficits, visuospatial and visuo-constructive disturbances. He had neither parkinsonism nor recurrent visual hallucinations typically well formed and detailed. Neuroimaging (computed tomography and magnetic resonance spectroscopy) showed mild diffuse cortical atrophy, mostly on the left temporal lobe and a decrease of N-acetyl-aspartate levels. A cholinesterase inhibitor was prescribed to this patient during 6 months with clinically relevant behavioral effect. Diagnosis confirmation was made by post-mortem neuropathological findings. Macroscopical features were mild atrophy on the frontal, parietal and temporal lobes, notedly on the frontal lobes. Microscopically, there was neuronal loss and diffuse classic Lewy bodies. Brainstem (substantia nigra, raphe nucleus, locus coeruleus, pedunculopontine nucleus), limbic cortex, and neocortex (frontal, parietal and temporal) were the areas of predilection for Lewy bodies. Hematoxylin-eosin and Bielschowsky staining did not show neuronal swelling (ballooned cell), argyrophilic inclusion (Pick's bodies), neurofibrillary tangles nor senile plaques. Immunohistochemical staining for anti-tau, anti-beta-amyloid, and anti-prion protein were negative. Antiubiquitine reaction was positive for Lewy body in the cerebral cortex and brainstem. PMID:14762594

  7. Lewy body-like pathology in long-term embryonic nigral transplants in Parkinson's disease.

    PubMed

    Kordower, Jeffrey H; Chu, Yaping; Hauser, Robert A; Freeman, Thomas B; Olanow, C Warren

    2008-05-01

    Fourteen years after transplantation into the striatum of an individual with Parkinson's disease, grafted nigral neurons were found to have Lewy body-like inclusions that stained positively for alpha-synuclein and ubiquitin and to have reduced immunostaining for dopamine transporter. These pathological changes suggest that Parkinson's disease is an ongoing process that can affect grafted cells in the striatum in a manner similar to host dopamine neurons in the substantia nigra. These findings have implications for cell-based therapies and for understanding the cause of Parkinson's disease. PMID:18391962

  8. GBA mutations increase risk for Lewy body disease with and without Alzheimer disease pathology

    PubMed Central

    Leverenz, James B.; Lopez, Oscar L.; Hamilton, Ronald L.; Bennett, David A.; Schneider, Julie A.; Buchman, Aron S.; Larson, Eric B.; Crane, Paul K.; Kaye, Jeffrey A.; Kramer, Patricia; Woltjer, Randy; Kukull, Walter; Nelson, Peter T.; Jicha, Gregory A.; Neltner, Janna H.; Galasko, Doug; Masliah, Eliezer; Trojanowski, John Q.; Schellenberg, Gerard D.; Yearout, Dora; Huston, Haley; Fritts-Penniman, Allison; Mata, Ignacio F.; Wan, Jia Y.; Edwards, Karen L.; Montine, Thomas J.

    2012-01-01

    Objectives: Mutations in the GBA gene occur in 7% of patients with Parkinson disease (PD) and are a well-established susceptibility factor for PD, which is characterized by Lewy body disease (LBD) neuropathologic changes (LBDNCs). We sought to determine whether GBA influences risk of dementia with LBDNCs, Alzheimer disease (AD) neuropathologic changes (ADNCs), or both. Methods: We screened the entire GBA coding region for mutations in controls and in subjects with dementia and LBDNCs and no or low levels of ADNCs (pure dementia with Lewy bodies [pDLB]), LBDNCs and high-level ADNCs (LBD-AD), and high-level ADNCs but without LBDNCs (AD). Results: Among white subjects, pathogenic GBA mutations were identified in 6 of 79 pDLB cases (7.6%), 8 of 222 LBD-AD cases (3.6%), 2 of 243 AD cases (0.8%), and 3 of 381 controls (0.8%). Subjects with pDLB and LBD-AD were more likely to carry mutations than controls (pDLB: odds ratio [OR] = 7.6; 95% confidence interval [CI] = 1.8–31.9; p = 0.006; LBD-AD: OR = 4.6; CI = 1.2–17.6; p = 0.025), but there was no significant difference in frequencies between the AD and control groups (OR = 1.1; CI = 0.2–6.6; p = 0.92). There was a highly significant trend test across groups (χ2(1) = 19.3; p = 1.1 × 10−5), with the likelihood of carrying a GBA mutation increasing in the following direction: control/AD < LBD-AD < pDLB. Conclusions: GBA is a susceptibility gene across the LBD spectrum, but not in AD, and appears to convey a higher risk for PD and pDLB than for LBD-AD. PD and pDLB might be more similar to one another in genetic determinants and pathophysiology than either disease is to LBD-AD. PMID:23035075

  9. 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. PMID:26563477

  10. Dementia with Lewy bodies

    PubMed Central

    Graff-Radford, Jonathan; Murray, Melissa E.; Lowe, Val J.; Boeve, Bradley F.; Ferman, Tanis J.; Przybelski, Scott A.; Lesnick, Timothy G.; Senjem, Matthew L.; Gunter, Jeffrey L.; Smith, Glenn E.; Knopman, David S.; Jack, Clifford R.; Dickson, Dennis W.; Petersen, Ronald C.

    2014-01-01

    Objectives: To investigate clinical, imaging, and pathologic associations of the cingulate island sign (CIS) in dementia with Lewy bodies (DLB). Methods: We retrospectively identified and compared patients with a clinical diagnosis of DLB (n = 39); patients with Alzheimer disease (AD) matched by age, sex, and education (n = 39); and cognitively normal controls (n = 78) who underwent 18F-fluorodeoxyglucose (FDG) and C11 Pittsburgh compound B (PiB)-PET scans. Among these patients, we studied those who came to autopsy and underwent Braak neurofibrillary tangle (NFT) staging (n = 10). Results: Patients with a clinical diagnosis of DLB had a higher ratio of posterior cingulate to precuneus plus cuneus metabolism, cingulate island sign (CIS), on FDG-PET than patients with AD (p < 0.001), a finding independent of β-amyloid load on PiB-PET (p = 0.56). Patients with CIS positivity on visual assessment of FDG-PET fit into the group of high- or intermediate-probability DLB pathology and received clinical diagnosis of DLB, not AD. Higher CIS ratio correlated with lower Braak NFT stage (r = −0.96; p < 0.001). Conclusions: Our study found that CIS on FDG-PET is not associated with fibrillar β-amyloid deposition but indicates lower Braak NFT stage in patients with DLB. Identifying biomarkers that measure relative contributions of underlying pathologies to dementia is critical as neurotherapeutics move toward targeted treatments. PMID:25056580

  11. Parkinson's disease dementia – A diminished role for the Lewy body

    PubMed Central

    Libow, Leslie S.; Frisina, Pasquale G.; Haroutunian, Vahram; Perl, Daniel P.; Purohit, Dushyant P.

    2010-01-01

    The literature currently views Lewy bodies as central in the pathogenesis of Parkinson's disease dementia (PDD) when Alzheimer's disease (AD) or vascular pathology is not present. Because the neuropathology of PDD is not well understood, the pathological features of PDD were characterized in eighteen PD brain specimens using published criteria for AD, Diffuse Lewy Body Disease (DLBD), and Vascular Disease as a framework. Among the PD dementia (n = 16) subjects, 3 (19%) did not have LBs outside of the brain stem, nor AD or vascular pathology. In two additional cases, one did have rare LBs in the neocortex and cingulate gyrus. However, these two cases did not meet the diagnostic criteria for DLBD. Beyond these 5 cases, the remaining PD dementia subjects fitted a classical pathological profile consistent with AD (38%), vascular disease (12.5%), DLBD (6%), or a combination of these pathologies (12.5%). The findings from this study do not support the hypothesis that LBs are the main substrate for dementia in PD. More research with a larger sample size is needed to determine whether the LB may be a secondary phenomenon and/or an “innocent-bystander”. The entire role of the LB in PD dementia is again brought into question. PMID:19346154

  12. 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

  13. The brainstem pathologies of Parkinson's disease and dementia with Lewy bodies.

    PubMed

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

    2015-03-01

    Parkinson's disease (PD) and dementia with Lewy bodies (DLB) are among the human synucleinopathies, which show alpha-synuclein immunoreactive neuronal and/or glial aggregations and progressive neuronal loss in selected brain regions (eg, substantia nigra, ventral tegmental area, pedunculopontine nucleus). Despite several studies about brainstem pathologies in PD and DLB, there is currently no detailed information available regarding the presence of alpha-synuclein immunoreactive inclusions (i) in the cranial nerve, precerebellar, vestibular and oculomotor brainstem nuclei and (ii) in brainstem fiber tracts and oligodendroctyes. Therefore, we analyzed the inclusion pathologies in the brainstem nuclei (Lewy bodies, LB; Lewy neurites, LN; coiled bodies, CB) and fiber tracts (LN, CB) of PD and DLB patients. As 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. Additionally we were able to demonstrate 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 findings can contribute to a large variety of less well-explained PD and DLB symptoms (eg, 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 transneuronal spread of the underlying pathological processes of PD and DLB along anatomical pathways. PMID:24995389

  14. 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. PMID:26643944

  15. 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

  16. Dementia with Lewy bodies in Meige Syndrome

    PubMed Central

    Ho, Ho Yin; Yu, Chi Shing

    2012-01-01

    Meige syndrome is a rare form of segmental dystonia characterized by blepharospasm and oromandibular dystonia. A few case reports of Meige syndrome have been associated with Lewy body pathologies, and the syndrome was also proposed for inclusion in the spectrum of Lewy body disease. We report a case of an elderly gentleman with a history of Meige syndrome for more than 10 years who developed dementia with Lewy bodies. Updated clinical and pathological evidence of linkages between these two conditions is also presented. PMID:22984651

  17. RAB39B gene mutations are not a common cause of Parkinson's disease or dementia with Lewy bodies.

    PubMed

    Hodges, Kyndall; Brewer, Sheridan S; Labbé, Catherine; Soto-Ortolaza, Alexandra I; Walton, Ronald L; Strongosky, Audrey J; Uitti, Ryan J; van Gerpen, Jay A; Ertekin-Taner, Nilüfer; Kantarci, Kejal; Lowe, Val J; Parisi, Joseph E; Savica, Rodolfo; Graff-Radford, Jonathan; Jones, David T; Knopman, David S; Petersen, Ronald C; Murray, Melissa E; Graff-Radford, Neill R; Ferman, Tanis J; Dickson, Dennis W; Wszolek, Zbigniew K; Boeve, Bradley F; Ross, Owen A; Lorenzo-Betancor, Oswaldo

    2016-09-01

    Mutations in Ras-related protein Rab-39B (RAB39B) gene have been linked to X-linked early-onset Parkinsonism with intellectual disabilities. The aim of this study was to address the genetic contribution of RAB39B to Parkinson's disease (PD), dementia with Lewy bodies (DLB), and pathologically confirmed Lewy body dementia (pLBD) cases. A cohort of 884 PD, 399 DLB, and 379 pLBD patients were screened for RAB39B mutations, but no coding variants were found, suggesting RAB39B mutations are not a common cause of PD, DLB, or pLBD in Caucasian population. PMID:27459931

  18. Divergent brain functional network alterations in dementia with Lewy bodies and Alzheimer's disease

    PubMed Central

    Peraza, Luis R.; Taylor, John-Paul; Kaiser, Marcus

    2015-01-01

    The clinical phenotype of dementia with Lewy bodies (DLB) is different from Alzheimer's disease (AD), suggesting a divergence between these diseases in terms of brain network organization. To fully understand this, we studied functional networks from resting-state functional magnetic resonance imaging in cognitively matched DLB and AD patients. The DLB group demonstrated a generalized lower synchronization compared with the AD and healthy controls, and this was more severe for edges connecting distant brain regions. Global network measures were significantly different between DLB and AD. For instance, AD showed lower small-worldness than healthy controls, while DLB showed higher small-worldness (AD < controls < DLB), and this was also the case for global efficiency (DLB > controls > AD) and clustering coefficient (DLB < controls < AD). Differences were also found for nodal measures at brain regions associated with each disease. Finally, we found significant associations between network performance measures and global cognitive impairment and severity of cognitive fluctuations in DLB. These results show network divergences between DLB and AD which appear to reflect their neuropathological differences. PMID:26115566

  19. Lewy body pathology is associated with mitochondrial DNA damage in Parkinson's disease.

    PubMed

    Müller, Sarina K; Bender, Andreas; Laub, Christoph; Högen, Tobias; Schlaudraff, Falk; Liss, Birgit; Klopstock, Thomas; Elstner, Matthias

    2013-09-01

    Mitochondrial dysfunction has been strongly implicated in the pathogenesis of Parkinson's disease (PD) and Alzheimer's disease (AD), but its relation to protein aggregation is unclear. PD is characterized by synuclein aggregation (i.e., Lewy body [LB] formation). In AD, the abnormal accumulation of tau protein forms neurofibrillary tangles. In this study, we laser-dissected LB-positive and -negative neurons from the substantia nigra of postmortem PD brains, and tau-positive and -negative hippocampal neurons from AD brains. We quantified mitochondrial DNA deletions in relation to the cellular phenotype and in comparison with age-matched controls. Deletion levels were highest in LB-positive neurons of PD brains (40.5 ± 16.8%), followed by LB-negative neurons of PD cases (31.8 ± 14.4%) and control subjects (25.6 ± 17.5%; analysis of variance p < 0.005). In hippocampal neurons, deletion levels were 25%-30%, independent of disease status and neurofibrillary tangles. The presented findings imply increased mitochondrial DNA damage in LB-positive midbrain neurons, but do not support a direct causative link of respiratory chain dysfunction and protein aggregation. PMID:23566333

  20. MRS in Mild Cognitive Impairment: Early Differentiation of Dementia with Lewy Bodies and Alzheimer's Disease

    PubMed Central

    Zhang, Bing; Ferman, Tanis J.; Boeve, Bradley F.; Smith, Glenn E.; Maroney-Smith, Mandie; Spychalla, Anthony J; Knopman, David S.; Jack, Clifford R.; Petersen, Ronald C.; Kantarci, Kejal

    2014-01-01

    Background and Purpose Mild cognitive impairment (MCI) precedes both Alzheimer's disease (AD) dementia and with Lewy bodies (DLB). We investigated proton magnetic resonance spectroscopy (MRS) characteristics of MCI patients who progressed to DLB compared to those who progressed to AD dementia or remained stable. Methods Consecutive MCI patients who underwent single voxel MRS at baseline and progressed to DLB (n=10) were identified during a median follow-up period of 18 months. From the same cohort, we identified age- and sex-matched MCI patients who progressed to AD dementia (n=27) or remained stable (n=20) during a similar follow-up period. This study was approved by the Institutional Review Board and informed consent was from every subject. Results MCI patients who progressed to AD dementia were characterized by lower N-acetylaspartate (NAA)/Cr ratio in the posterior cingulate voxel compared to those who progressed to DLB (p=0.001). Decreased NAA/Cr in the posterior cingulate voxel differentiated MCI patients who progressed to DLB from those who progressed to AD with an area under the receiver operating characteristic curve of 0.85 (p<0.001) on logistic regression analysis. Conclusions MRS may be useful in differentiating MCI patients with prodromal AD dementia from those with prodromal DLB for early disease-specific interventions. PMID:25039916

  1. Clinical and Neuropsychological Differences between Mild Parkinson's Disease Dementia and Dementia with Lewy Bodies

    PubMed Central

    Petrova, Mariya; Mehrabian-Spasova, Shima; Aarsland, Dag; Raycheva, Margarita; Traykov, Latchezar

    2015-01-01

    Background The specific profile of dementia in Parkinson's disease (PDD) and dementia with Lewy bodies (DLB) in the earliest stages of dementia is still unclear and subject of considerable controversy. Methods We investigated 27 PDD patients and 24 DLB patients with parkinsonism in the early stage of dementia, i.e. with a Mini-Mental State Examination score of ≥24. Results Compared to PDD, patients with DLB demonstrated significantly lower scores when testing attention and executive functions [modified card sorting test (p < 0.001) and digit span backward (p < 0.02)], as well as when testing constructive abilities [copy of complex designs (p = 0.001) and pentagon (p < 0.001)]. Using logistic regression analysis, diagnosis was predicted from the cognitive profile, with an overall accuracy of 88.2%. In addition, PDD patients showed a significantly higher Unified Parkinson's Disease Rating Scale (UPDRS) motor subscore (p < 0.001) as well as higher UPDRS motor item scores [tremor at rest (p = 0.01) and bradykinesia (p = 0.001)]. Conclusions The cognitive profile in PDD differs from that in DLB in the early stage of dementia, with worse performance on tests of attention and executive functions and constructive abilities in DLB compared to PDD patients. In contrast, motor symptoms are more severe in PDD than in DLB. PMID:26195977

  2. 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

  3. Clinical correlates of pathology in the claustrum in Parkinson's disease and dementia with Lewy bodies.

    PubMed

    Kalaitzakis, M E; Pearce, R K B; Gentleman, S M

    2009-09-11

    Dementia and visual hallucinations are common complications of Parkinson's disease (PD), yet their patho-anatomical bases are poorly defined. We studied alpha-synuclein (alphaSyn), tau and amyloid-beta (Abeta) pathology in the claustrum of 20 PD cases without dementia, 12 PD cases with dementia (PDD) and 7 cases with dementia with Lewy bodies (DLB). alphaSyn positivity was observed in 75% of PD cases without dementia and in 100% of PDD and DLB cases. Abeta was observed in the claustrum in 25% of PD, 58% of PDD and 100% of DLB cases. Tau was negligible in all cases restricting further analysis. Compared to PD cases without dementia, PDD cases demonstrated a significantly greater alphaSyn burden in the claustrum (p=0.0003). In addition, DLB cases showed a significantly increased alphaSyn deposition when compared to PDD (p=0.02) and PD without dementia (p=0.0002). A similar hierarchy, PDdisease and DLB. PMID:19523504

  4. Prodromal dementia with Lewy bodies.

    PubMed

    Fujishiro, Hiroshige; Nakamura, Shinichiro; Sato, Kiyoshi; Iseki, Eizo

    2015-07-01

    Dementia with Lewy bodies (DLB) is the second most common neurodegenerative dementing disorder after Alzheimer's disease (AD), but there is limited information regarding the prodromal DLB state compared with that of AD. Parkinson's disease (PD) and DLB share common prodromal symptoms with Lewy body disease (LBD), allowing us to use a common strategy for identifying the individuals with an underlying pathophysiology of LBD. Dysautonomia, olfactory dysfunction, rapid eye movement sleep behavior disorder (RBD) and psychiatric symptoms antedate the onset of dementia by years or even decades in patients with DLB. Although RBD is the most potentially accurate prodromal predictor of DLB, disease progression before the onset of dementia could differ between the prodromal DLB state with and without RBD. Experts who specialize in idiopathic RBD and DLB might need communication in order to clarify the clinical relevance of RBD with the disease progression of DLB. The presence of prodromal LBD symptoms or findings of occipital hypoperfusion/hypometabolism helps us to predict the possible pathophysiological process of LBD in non-demented patients. This approach might provide the opportunity for additional neuroimaging, including cardiac (123) I-metaiodobenzylguanidine scintigraphy and dopamine transporter imaging. Although limited radiological findings in patients with prodromal DLB states have been reported, there is now a need for larger clinical multisite studies with pathological verification. The long prodromal phase of DLB provides a critical opportunity for potential intervention with disease-modifying therapy, but only if we are able to clearly identify the diversity in the clinical courses of DLB. In the present article, we reviewed the limited literature regarding the clinical profiles of prodromal DLB. PMID:25690399

  5. 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

  6. 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

  7. 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

  8. Gene expression profiling of Lewy body-bearing neurons in Parkinson's disease.

    PubMed

    Lu, Lixia; Neff, Frauke; Alvarez-Fischer, Daniel; Henze, Carmen; Xie, Yanhui; Oertel, Wolfgang H; Schlegel, Jürgen; Hartmann, Andreas

    2005-09-01

    Lewy bodies (LB) are a pathological hallmark of Parkinson's disease (PD). Whether LBs are neuroprotective, cytotoxic, or an age-related epiphenomenon is still debated. In the present study, the genetic fingerprints of mesencephalic dopaminergic (DA) neurons containing LBs versus mesencephalic DA neurons not containing LBs were compared in five PD patients. Total RNA from single neurons of both neuronal subpopulations was obtained by immuno-laser capture microdissection. Subsequently, RNA arbitrarily primed PCR was employed to generate expression profiles from the extracted RNA. Differentially displayed polymorphic fragments were dissected from silver-stained polyacrylamide gels. Most of these expressed sequence tags (ESTs) were homologous to known human sequences (56/64, 87.5%). Based on the potential significance of individual ESTs in neurodegenerative disorders, 5 ESTs of interest were selected for further quantitative expression analysis by real-time quantitative reverse transcription PCR (rtq RT-PCR). DA neurons without LBs preferentially expressed molecules beneficial for cell survival, whereas genes preferentially expressed in DA neurons containing LBs may support a cytotoxic role of LBs. Thus, we favor the view that LB-positive DA neurons are sicker than their LB-negative counterparts, and that inhibition of LB formation may indeed represent a therapeutic strategy in PD. PMID:15944136

  9. The effect of MAPT haplotype on neocortical Lewy body pathology in Parkinson disease.

    PubMed

    Robakis, Daphne; Cortes, Etty; Clark, Lorraine N; Vonsattel, Jean Paul G; Virmani, Tuhin; Alcalay, Roy N; Crary, John F; Levy, Oren A

    2016-06-01

    The H1 haplotype of the microtubule-associated protein tau gene (MAPT) is associated with an increased risk of Parkinson disease (PD) compared with the H2 haplotype, but its effect on Lewy body (LB) formation is unclear. In this study, we compared the MAPT haplotype frequency between pathologically confirmed PD patients (n = 71) and controls (n = 52). We analyzed Braak LB stage, Braak neurofibrillary tangle (NFT) stage, and CERAD amyloid score by haplotype. We further tested the association between MAPT haplotype and semi-quantitative counts of LBs, NFTs, and neuritic plaques (NPs) in multiple neocortical regions. Consistent with previous reports, PD cases had an increased likelihood of carrying an H1/H1 genotype compared to controls (OR = 5.72, 95 % CI 1.80-18.21, p = 0.003). Braak LB, Braak NFT and CERAD scores did not differ by haplotype. However, H1/H1 carriers had higher LB counts in parietal cortex (p = 0.02) and in overall neocortical LBs (p = 0.03) compared to non-H1/H1 cases. Our analyses suggest that PD patients homozygous for the H1 haplotype have a higher burden of neocortical LB pathology. PMID:27098667

  10. Structural Connectivity is Differently Altered in Dementia with Lewy Body and Alzheimer’s Disease

    PubMed Central

    Delli Pizzi, Stefano; Franciotti, Raffaella; Taylor, John-Paul; Esposito, Roberto; Tartaro, Armando; Thomas, Astrid; Onofrj, Marco; Bonanni, Laura

    2015-01-01

    The structural connectivity within cortical areas and between cortical and subcortical structures was investigated in dementia with Lewy bodies (DLB) and Alzheimer’s disease (AD). We hypothesized that white matter (WM) tracts, which are linked to visual, attentional, and mnemonic functions, would be differentially and selectively affected in DLB as compared to AD and age-matched control subjects. Structural tensor imaging and diffusion tensor imaging (DTI) were performed on 14 DLB patients, 14 AD patients, and 15 controls. DTI metrics related to WM damage were assessed within tracts reconstructed by FreeSurfer’s TRActs Constrained by UnderLying Anatomy pipeline. Correlation analysis between WM and gray matter (GM) metrics was performed to assess whether the structural connectivity alteration in AD and DLB could be secondary to GM neuronal loss or a consequence of direct WM injury. Anterior thalamic radiation (ATR) and cingulum-cingulate gyrus were altered in DLB, whereas cingulum-angular bundle (CAB) was disrupted in AD. In DLB patients, secondary axonal degeneration within ATR was found in relation to microstructural damage within medio-dorsal thalamus, whereas axonal degeneration within CAB was related to precuneus thinning. WM alteration within the uncinate fasciculus was present in both groups of patients and was related to frontal and to temporal thinning in DLB and AD, respectively. We found structural connectivity alterations within fronto-thalamic and fronto-parietal (precuneus) network in DLB whereas, in contrast, disruption of structural connectivity of mnemonic pathways was present in AD. Furthermore, the high correlation between GM and WM metrics suggests that the structural connectivity alteration in DLB could be linked to GM neuronal loss rather than by direct WM injury. Thus, this finding supports the key role of cortical and subcortical atrophy in DLB. PMID:26578952

  11. 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

  12. Comparison of cognitive decline between dementia with Lewy bodies and Alzheimer's disease: a cohort study

    PubMed Central

    McKeith, Ian; Rodda, Joanne; Qassem, Tarik; Tatsch, Klaus; Booij, Jan; Darcourt, Jacques; O'Brien, John

    2012-01-01

    Objectives Dementia with Lewy bodies (DLB) accounts for 10%–15% of dementia cases at autopsy and has distinct clinical features associated with earlier institutionalisation and a higher level of carer distress than are seen in Alzheimer's disease (AD). At present, there is on-going debate as to whether DLB is associated with a more rapid cognitive decline than AD. An understanding of the rate of decline of cognitive and non-cognitive symptoms in DLB may help patients and carers to plan for the future. Design In this cohort study, the authors compared 100 AD and 58 DLB subjects at baseline and at 12-month follow-up on cognitive and neuropsychiatric measures. Setting Patients were recruited from 40 European centres. Participants Subjects with mild–moderate dementia. Diagnosis of DLB or AD required agreement between consensus panel clinical diagnosis and visual rating of 123I-FP-CIT (dopamine transporter) single photon emission computed tomography neuroimaging. Outcome measures The Cambridge Cognitive Examination including Mini-Mental State Examination and Neuropsychiatric Inventory (NPI). Results The AD and DLB groups did not differ at baseline in terms of age, gender, Clinical Dementia Rating score and use of cholinesterase inhibitors or memantine. NPI and NPI carer distress scores were statistically significantly higher for DLB subjects at baseline and at follow-up, and there were no differences between AD and DLB in cognitive scores at baseline or at follow-up. There was no significant difference in rate of progression of any of the variables analysed. Conclusions DLB subjects had more neuropsychiatric features at baseline and at follow-up than AD, but the authors did not find any statistically significant difference in rate of progression between the mild–moderate AD and DLB groups on cognitive or neuropsychiatric measures over a 12-month follow-up period. PMID:22318660

  13. Recognition Memory Span in Autopsy-Confirmed Dementia with Lewy Bodies and Alzheimer’s Disease

    PubMed Central

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

    2016-01-01

    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. PMID:26184443

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

    PubMed

    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

    2016-07-01

    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: χ(2) = 22.1, df = 2, p < 0.001, Nagelkerke R(2) = 0.47, classification = 77% (AD 87%, DLB 62%)). For MRI, MTA also predicted AD and DLB (model: χ(2) = 6.5, df = 1, p = 0.01, Nagelkerke R(2) = 0.16, classification = 67% (77% AD, 52% DLB). However, a combined EEG-MRI model showed greater prediction in AD and DLB (model: χ(2) = 31.1, df = 3, p < 0.001, Nagelkerke R(2) = 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

  15. In dementia with Lewy bodies, Braak stage determines phenotype, not Lewy body distribution.

    PubMed

    Weisman, D; Cho, M; Taylor, C; Adame, A; Thal, L J; Hansen, L A

    2007-07-24

    We used an autopsy series to determine whether the newest dementia with Lewy bodies (DLB) consensus pathologic classification correlates with premortem diagnosis of DLB. Neocortical sections from a total of 95 cases with Lewy bodies were stained with alpha-synuclein antibodies. We assigned cases according to the DLB consensus' categories and found a significant association with the premortem clinical diagnosis of DLB. Clinical diagnosis of DLB, however, depended on the presence of low Alzheimer disease pathology (by Braak staging) rather than on Lewy body distribution. PMID:17646627

  16. Dementia with Lewy Bodies

    MedlinePlus

    ... DLB and Parkinson’s disease, and between DLB and Alzheimer’s disease, can often make it difficult for a ... in the brains of people with Parkinson's and Alzheimer’s diseases. These findings suggest that either DLB is ...

  17. UPDATE ON DEMENTIA WITH LEWY BODIES

    PubMed Central

    Karantzoulis, Stella; Galvin, James E.

    2014-01-01

    Dementia with Lewy bodies (DLB) is the second most common form of dementia after Alzheimer disease (AD). DLB is characterized pathologically by Lewy body and Lewy neuritic pathology, often with variable levels of Alzheimer-type pathology. Core clinical features include fluctuating cognition, visual hallucinations, and parkinsonism resulting in greater impairments of quality of life, more caregiver burden, and higher health-related costs compared with AD. These issues, together with a high sensitivity to adverse events with treatment with antipsychotic agents, make the need for an early and accurate diagnosis of DLB essential. Unfortunately, current consensus criteria are highly specific but lack sufficient sensitivity. Use of composite risk scores may improve accuracy of clinical diagnosis. Imaging findings, particularly targeting dopaminergic systems have shown promise as potential markers to differentiate DLB from AD. A combination of non-pharmacologic treatments and pharmacotherapy interventions may maximize cognitive function and overall quality of life in DLB patients. PMID:25379359

  18. 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…

  19. 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

  20. 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). PMID:27446628

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

    PubMed Central

    Roberts, Julie; Lloyd-Williams, Huw; 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). PMID:27446628

  2. Age-associated changes of brain copper, iron, and zinc in Alzheimer's disease and dementia with Lewy bodies.

    PubMed

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

    2014-01-01

    Disease-, age-, and gender-associated changes in brain copper, iron, and zinc were assessed in postmortem neocortical tissue (Brodmann area 7) from patients with moderate Alzheimer's disease (AD) (n = 14), severe AD (n = 28), dementia with Lewy bodies (n = 15), and normal age-matched control subjects (n = 26). Copper was lower (20%; p < 0.001) and iron higher (10-16%; p < 0.001) in severe AD compared with controls. Intriguingly significant Group*Age interactions were observed for both copper and iron, suggesting gradual age-associated decline of these metals in healthy non-cognitively impaired individuals. Zinc was unaffected in any disease pathologies and no age-associated changes were apparent. Age-associated changes in brain elements warrant further investigation. PMID:25024342

  3. [Magnetic resonance imaging with 21.1 T and pathological correlations--diffuse Lewy body disease].

    PubMed

    Fujioka, Shinsuke; Murray, Melissa E; Foroutan, Parastou; Schweitzer, Katherine J; Dickson, Dennis W; Grant, Samuel C; Wszolek, Zbigniew K

    2011-08-01

    We investigated fixed basal ganglia specimens, including globus pallidus and putamen, with 21.1-Tesla MRI allowing us to achieve a microscopic level resolution from a patient with pathologically confirmed dementia with Lewy bodies (DLB) and a neurologically normal control case. We acquired T2 and T2 * weighted images that demonstrated diffuse and patchy lower intensities in the basal ganglia compared to control. There are several paramagnetic substances in brain tissue that could potentially reduce both T2 and T2 * relaxation times, including ferritin, iron (Fe3+), manganese, copper and others. Because iron is most abundant, low intensities on T2 and T2 * weighted images most likely reflect iron deposition. Iron, especially Fe3+, deposition was visible in the pathological specimens stained with Prussian blue after images were obtained. Although radiological-pathological comparisons are not straightforward with respect to either the MRI signal or relaxation quantification, there appears to be a correlation between the relative increase in iron as assessed by Prussian blue staining and the decrease in T2 * value between the DLB and control specimens. As such, this exceptionally high field MRI technique may provide details about the role that iron deposition plays either directly or indirectly as a biomarker in neurodegenerative processes. PMID:21878728

  4. 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…

  5. 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…

  6. 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

  7. Gene-Wise Association of Variants in Four Lysosomal Storage Disorder Genes in Neuropathologically Confirmed Lewy Body Disease

    PubMed Central

    Clark, Lorraine N.; Chan, Robin; Cheng, Rong; Liu, Xinmin; Park, Naeun; Parmalee, Nancy; Kisselev, Sergey; Cortes, Etty; Torres, Paola A.; Pastores, Gregory M.; Vonsattel, Jean P.; Alcalay, Roy; Marder, Karen; Honig, Lawrence L.; Fahn, Stanley; Mayeux, Richard; Shelanski, Michael; Di Paolo, Gilbert; Lee, Joseph H.

    2015-01-01

    Objective Variants in GBA are associated with Lewy Body (LB) pathology. We investigated whether variants in other lysosomal storage disorder (LSD) genes also contribute to disease pathogenesis. Methods We performed a genetic analysis of four LSD genes including GBA, HEXA, SMPD1, and MCOLN1 in 231 brain autopsies. Brain autopsies included neuropathologically defined LBD without Alzheimer Disease (AD) changes (n = 59), AD without significant LB pathology (n = 71), Alzheimer disease and lewy body variant (ADLBV) (n = 68), and control brains without LB or AD neuropathology (n = 33). Sequencing of HEXA, SMPD1, MCOLN1 and GBA followed by ‘gene wise’ genetic association analysis was performed. To determine the functional effect, a biochemical analysis of GBA in a subset of brains was also performed. GCase activity was measured in a subset of brain samples (n = 64) that included LBD brains, with or without GBA mutations, and control brains. A lipidomic analysis was also performed in brain autopsies (n = 67) which included LBD (n = 34), ADLBV (n = 3), AD (n = 4), PD (n = 9) and control brains (n = 17), comparing GBA mutation carriers to non-carriers. Results In a ‘gene-wise’ analysis, variants in GBA, SMPD1 and MCOLN1 were significantly associated with LB pathology (p range: 0.03–4.14 x10-5). Overall, the mean levels of GCase activity were significantly lower in GBA mutation carriers compared to non-carriers (p<0.001). A significant increase and accumulation of several species for the lipid classes, ceramides and sphingolipids, was observed in LBD brains carrying GBA mutations compared to controls (p range: p<0.05-p<0.01). Interpretation Our study indicates that variants in GBA, SMPD1 and MCOLN1 are associated with LB pathology. Biochemical data comparing GBA mutation carrier to non-carriers support these findings, which have important implications for biomarker development and therapeutic strategies. PMID:25933391

  8. Role of Donepezil in the Management of Neuropsychiatric Symptoms in Alzheimer's Disease and Dementia with Lewy Bodies.

    PubMed

    Cummings, Jeffrey; Lai, Te-Jen; Hemrungrojn, Solaphat; Mohandas, E; Yun Kim, Sang; Nair, Girish; Dash, Amitabh

    2016-03-01

    Alzheimer's disease (AD) is a progressive condition that affects cognition, function, and behavior. Approximately 60-90% of patients with AD develop neuropsychiatric symptoms (NPS) such as hallucinations, delusions, agitation/aggression, dysphoria/depression, anxiety, irritability, disinhibition, euphoria, apathy, aberrant motor behavior, sleep disturbances, appetite and eating changes, or altered sexual behavior. These noncognitive behavior changes are thought to result from anatomical and biochemical changes within the brain, and have been linked, in part, to cholinergic deficiency. Cholinesterase inhibitors may reduce the emergence of NPS and have a role in their treatment. These agents may delay initiation of, or reduce the need for, other drugs such as antipsychotics. This article summarizes the effects of donepezil, a cholinesterase inhibitor, on the NPS of dementia with emphasis on AD and dementia with Lewy bodies. PMID:26778658

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

    PubMed Central

    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

    2015-01-01

    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. PMID:26621077

  10. 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.

  11. On the Utility of MIBG SPECT/CT in Evaluating Cardiac Sympathetic Dysfunction in Lewy Body Diseases

    PubMed Central

    Odagiri, Hayato; Baba, Toru; Nishio, Yoshiyuki; Iizuka, Osamu; Matsuda, Minoru; Inoue, Kentaro; Kikuchi, Akio; Hasegawa, Takafumi; Aoki, Masashi; Takeda, Atsushi; Taki, Yasuyuki; Mori, Etsuro

    2016-01-01

    Background Abnormal cardiac uptake of 123I-metaiodobenzylguanidine (123I-MIBG) is a diagnostic marker of Lewy body diseases (LBDs), e.g., Parkinson’s disease (PD) and dementia with Lewy bodies (DLB). Planar imaging is generally used to assess cardiac sympathetic dysfunction in 123I-MIBG scintigraphy; however, its clinical utility requires further improvement. We hypothesized that the co-registration of single-photon emission tomography (SPECT) and computed tomography (CT) images would improve the diagnostic accuracy of 123I-MIBG cardiac scintigraphy for LBDs. This study sought to evaluate the effects of SPECT/CT imaging on 123I-MIBG cardiac scintigraphy for diagnosing LBDs. Methods We retrospectively investigated data of 54 patients (consecutive 18 patients in each PD, DLB, and idiopathic normal pressure hydrocephalus [iNPH] groups) who underwent 123I-MIBG cardiac scintigraphy (planar and SPECT/CT) because of suspected LBDs at the Tohoku University hospital from June 2012 to June 2015. We compared the diagnostic accuracies of the conventional planar 123I-MIBG method and SPECT/CT methods (manual and semi-automatic). Results In the conventional planar analysis, 123I-MIBG uptake decreased only in the DLB group compared with the iNPH group. In contrast, the SPECT/CT analysis revealed significantly lower 123I-MIBG uptake in both the PD and DLB groups compared with the iNPH group. Furthermore, a receiver operating characteristic analysis revealed that both the manual and semi-automatic SPECT/CT methods were superior to the conventional planar method in differentiating the 3 disorders. Conclusions SPECT/CT 123I-MIBG cardiac scintigraphy can detect mild cardiac sympathetic dysfunction in LDBs. Our results suggest that the SPECT/CT technique improves diagnostic accuracy for LBDs. PMID:27055151

  12. 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

  13. 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. PMID:26740557

  14. Hippocampal sclerosis in Lewy body disease is a TDP-43 proteinopathy similar to FTLD-TDP Type A.

    PubMed

    Aoki, Naoya; Murray, Melissa E; Ogaki, Kotaro; Fujioka, Shinsuke; Rutherford, Nicola J; Rademakers, Rosa; Ross, Owen A; Dickson, Dennis W

    2015-01-01

    Hippocampal sclerosis (HpScl) is frequent in frontotemporal lobar degeneration with TDP-43 pathology (FTLD-TDP), but it also occurs in dementia of the elderly with or without accompanying Alzheimer type pathology. HpScl has been hypothesized to be a neurodegenerative process given its association with TDP-43 pathology, but this is still controversial. TDP-43 pathology is found in Lewy body disease (LBD), but no study has focused on the pathologic and genetic characteristics of HpScl in LBD. We found HpScl in 5.2% of 669 LBD cases (289 transitional and 380 diffuse). Older age, higher Braak neurofibrillary tangle (NFT) stage, and presence of TDP-43 pathology were associated with HpScl. There was no difference in the frequency of HpScl between transitional and diffuse LBD, suggesting that Lewy-related pathology appears to have no direct association with HpScl. All HpScl cases had TDP-43 pathology consistent with Type A pattern. HpScl cases harbored genetic variation in TMEM106B that has been previously associated with FTLD-TDP. Interestingly, the severity of TDP-43-positive fine neurites in CA1 sector, a possible pathologic precursor of HpScl, was associated with the TMEM106B variant. These results demonstrate HpScl in LBD is a TDP-43 proteinopathy and is similar to FTLD-TDP Type A. Furthermore, a subset of LBD cases without HpScl ("pre-HpScl") had similar pathologic and genetic characteristics to typical HpScl, suggesting that the spectrum of HpScl pathology may be wider than previously thought. Some cases with many extracellular NFTs also had a similar profile. We suggest that HpScl is "masked" in these cases. PMID:25367383

  15. Hippocampal sclerosis in Lewy body disease is a TDP-43 proteinopathy similar to FTLD-TDP Type A

    PubMed Central

    Aoki, Naoya; Murray, Melissa E.; Ogaki, Kotaro; Fujioka, Shinsuke; Rutherford, Nicola J.; Rademakers, Rosa; Ross, Owen A.; Dickson, Dennis W.

    2014-01-01

    Hippocampal sclerosis (HpScl) is frequent in frontotemporal lobar degeneration with TDP-43 pathology (FTLD-TDP), but it also occurs in dementia of the elderly with or without accompanying Alzheimer type pathology. HpScl has been hypothesized to be a neurodegenerative process given its association with TDP-43 pathology, but this is still controversial. TDP-43 pathology is found in Lewy body disease (LBD), but no study has focused on the pathologic and genetic characteristics of HpScl in LBD. We found HpScl in 5.2% of 669 LBD cases (289 transitional and 380 diffuse). Older age, higher Braak neurofibrillary tangle (NFT) stage, and presence of TDP-43 pathology were associated with HpScl. There was no difference in the frequency of HpScl between transitional and diffuse LBD, suggesting that Lewy related pathology appears to have no direct association with HpScl. All HpScl cases had TDP-43 pathology consistent with Type A pattern. HpScl cases harbored genetic variation in TMEM106B that has been previously associated with FTLD-TDP. Interestingly, the severity of TDP-43-positive fine neurites in CA1 sector, a possible pathologic precursor of HpScl, was associated with the TMEM106B variant. These results demonstrate HpScl in LBD is a TDP-43 proteinopathy and is similar to FTLD-TDP Type A. Furthermore, a subset of LBD cases without HpScl (“pre-HpScl”) had similar pathologic and genetic characteristics to typical HpScl, suggesting that the spectrum of HpScl pathology may be wider than previously thought. Some cases with many extracellular NFTs also had a similar profile. We suggest that HpScl is “masked” in these cases. PMID:25367383

  16. Relationship between Dementia Severity and Behavioral and Psychological Symptoms of Dementia in Dementia with Lewy Bodies and Alzheimer's Disease Patients

    PubMed Central

    Hashimoto, Mamoru; Yatabe, Yusuke; Ishikawa, Tomohisa; Fukuhara, Ryuji; Kaneda, Keiichiro; Honda, Kazuki; Yuki, Seiji; Ogawa, Yusuke; Imamura, Toru; Kazui, Hiroaki; Kamimura, Naoto; Shinagawa, Syunichiro; Mizukami, Katsuyoshi; Mori, Etsuro; Ikeda, Manabu

    2015-01-01

    Background/Aims Behavioral and psychological symptoms of dementia (BPSD) are common in the clinical manifestation of dementia. Although most patients with dementia exhibit some BPSD during the course of the illness, the association of BPSD with the stage of dementia remains unclear. It was the aim of this study to evaluate the impact of severity of dementia on the expression of BPSD in patients with dementia with Lewy bodies (DLB) and Alzheimer's disease (AD). Methods Ninety-seven patients with DLB and 393 patients with AD were recruited from 8 dementia clinics across Japan. BPSD were assessed by the Neuropsychiatric Inventory (NPI). A relationship between BPSD and dementia stage classified by the Clinical Dementia Rating (CDR) in each type of dementia was assessed. Results No significant difference was seen in NPI total score across CDR staging in the DLB group. On the other hand, the NPI total score significantly increased with dementia stage in the AD group. Conclusion The relationship of dementia stage with the expression of BPSD was different according to the type of dementia. BPSD and dementia stage were correlated in AD subjects, in whom psychiatric symptoms increase as the disease progresses, but not in DLB subjects. PMID:26195980

  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. PMID:23909972

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

    PubMed Central

    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. PMID:26137443

  20. Kynurenic Acid Levels in Cerebrospinal Fluid from Patients with Alzheimer’s Disease or Dementia with Lewy Bodies

    PubMed Central

    Wennström, Malin; Nielsen, Henrietta M; Orhan, Funda; Londos, Elisabet; Minthon, Lennart; Erhardt, Sophie

    2014-01-01

    Kynurenic acid (KYNA) is implicated in cognitive functions. Altered concentrations of the compound are found in serum and cerebrospinal fluid (CSF) of patients with Alzheimer’s disease (AD). Further studies to determine whether KYNA serves as a biomarker for cognitive decline and dementia progression are required. In this study, we measured CSF KYNA levels in AD patients (n = 19), patients with dementia with Lewy bodies (DLB) (n = 18), and healthy age-matched controls (Ctrls)) (n = 20) to further explore possible correlations between KYNA levels, cognitive decline, and well-established AD and inflammatory markers. Neither DLB patients nor AD patients showed significantly altered CSF KYNA levels compared to Ctrls. However, female AD patients displayed significantly higher KYNA levels compared to male AD patients, a gender difference not seen in the Ctrl or DLB group. Levels of KYNA significantly correlated with the AD-biomarker P-tau and the inflammation marker soluble intercellular adhesion molecule-1 (sICAM-1) in the AD patient group. No associations between KYNA and cognitive functions were found. Our study shows that, although KYNA was not associated with cognitive decline in AD or DLB patients, it may be implicated in AD-related hyperphosphorylation of tau and inflammation. Further studies on larger patient cohorts are required to understand the potential role of KYNA in AD and DLB. PMID:24855376

  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. PMID:26137443

  2. Visuoperceptual assessments for differentiating dementia with Lewy bodies and Alzheimer's disease: illusory contours and other neuropsychological examinations.

    PubMed

    Ota, Kazumi; Murayama, Norio; Kasanuki, Koji; Kondo, Daizo; Fujishiro, Hiroshige; Arai, Heii; Sato, Kiyoshi; Iseki, Eizo

    2015-05-01

    We examined the utility of illusory contours (ICs) for the differentiation of dementia with Lewy bodies (DLB) from Alzheimer's disease (AD). Thirty-five probable DLB patients, 35 probable AD patients controlled by age, years of education, and Mini-Mental State Examination (MMSE) score, and 30 cognitively normal subjects controlled by age and years of education underwent visuoperceptual examinations including ICs, pentagon copying in MMSE, overlapping figures, clock drawing test, cube copying, and line orientation. Four items in ICs (ICs-4) were found to be significantly impaired in DLB compared with AD, and a sensitivity and a specificity of total score of ICs-4 were 88.6% and 37.1%, respectively. When a score of ICs-4 is combined with a 10-point scaled score of pentagon copying in MMSE, a sensitivity and a specificity were 77.1% and 82.9%, respectively. The present study suggests that ICs-4 can be included in neuropsychological examinations to assess visuoperceptual impairment in DLB. PMID:25908613

  3. Passive Immunization Reduces Behavioral and Neuropathological Deficits in an Alpha-Synuclein Transgenic Model of Lewy Body Disease

    PubMed Central

    Masliah, Eliezer; Rockenstein, Edward; Mante, Michael; Crews, Leslie; Spencer, Brian; Adame, Anthony; Patrick, Christina; Trejo, Margarita; Ubhi, Kiren; Rohn, Troy T.; Mueller-Steiner, Sarah; Seubert, Peter; Barbour, Robin; McConlogue, Lisa; Buttini, Manuel; Games, Dora; Schenk, Dale

    2011-01-01

    Dementia with Lewy bodies (DLB) and Parkinson's Disease (PD) are common causes of motor and cognitive deficits and are associated with the abnormal accumulation of alpha-synuclein (α-syn). This study investigated whether passive immunization with a novel monoclonal α-syn antibody (9E4) against the C-terminus (CT) of α-syn was able to cross into the CNS and ameliorate the deficits associated with α-syn accumulation. In this study we demonstrate that 9E4 was effective at reducing behavioral deficits in the water maze, moreover, immunization with 9E4 reduced the accumulation of calpain-cleaved α-syn in axons and synapses and the associated neurodegenerative deficits. In vivo studies demonstrated that 9E4 traffics into the CNS, binds to cells that display α-syn accumulation and promotes α-syn clearance via the lysosomal pathway. These results suggest that passive immunization with monoclonal antibodies against the CT of α-syn may be of therapeutic relevance in patients with PD and DLB. PMID:21559417

  4. Cortical Lewy body dementia: clinical features and classification.

    PubMed Central

    Gibb, W R; Luthert, P J; Janota, I; Lantos, P L

    1989-01-01

    Seven patients, aged 65-72 years, are described with dementia and cortical Lewy bodies. In one patient a Parkinsonian syndrome was followed by dementia and motor neuron disease. In the remaining six patients dementia was accompanied by dysphasia, dyspraxia and agnosia. One developed a Parkinsonian syndrome before the dementia, in three cases a Parkinsonian syndrome occurred later, and in two cases not at all. All patients showed Lewy bodies and cell loss in the substantia nigra, locus coeruleus and dorsal vagal nucleus, as in Parkinson's disease. The severity of cell loss in the nucleus basalis varied from mild to severe. Lewy bodies were also present in the parahippocampus and cerebral cortex, but Alzheimer-type pathology was mild or absent, and insufficient for a diagnosis of Alzheimer's disease. Patients with moderate or severe dementia, some with temporal or parietal features, may have cortical Lewy body disease, Alzheimer's disease, or a combination of the two. Cortical Lewy body disease may be associated with dementia in Parkinson's disease more often than realised, but is not necessarily associated with extensive Alzheimer pathology. Images PMID:2467966

  5. Microglia in dementia with Lewy bodies.

    PubMed

    Streit, Wolfgang J; Xue, Qing-Shan

    2016-07-01

    Microglial activation (neuroinflammation) is often cited as a pathogenic factor in the development of neurodegenerative diseases. However, there are significant caveats associated with the idea that inflammation directly causes either α-synuclein pathology or neurofibrillary degeneration (NFD). We have performed immunohistochemical studies on microglial cells in five cases of dementia with Lewy bodies (DLB), median age 87, and nine cases of non-demented (ND) controls, median age 74, using tissue samples from the temporal lobe and the superior frontal gyrus. Three different antibodies known to label microglia and macrophages were employed: iba1, anti-CD68, and anti-ferritin. All DLB cases showed both α-synuclein pathology (Lewy bodies and neurites) and NFD ranging from Braak stage II to IV. In contrast, all controls were devoid of α-synuclein pathology but did show NFD ranging from Braak stage I to III. Using iba1 labeling, our current results show a notable absence of activated microglia in all cases with the exception of two controls that showed small focal areas of microglial activation and macrophage formation. Both iba1 and ferritin antibodies revealed a mixture of ramified and dystrophic microglial cells throughout the regions examined, and there were no measurable differences in the prevalence of dystrophic microglial cells between DLB and controls. Double-labeling for α-synuclein and iba1-positive microglia showed that cortical Lewy bodies were surrounded by both ramified and dystrophic microglial cells. We found an increase in CD68 expression in DLB cases relative to controls. Since microglial dystrophy has been linked to NFD and since it did not appear to be worse in DLB cases over controls, our findings support the idea that the additional Lewy body pathology in DLB is not the result of intensified microglial dystrophy. CD68 is likely associated with lipofuscin deposits in microglial cells which may be increased in DLB cases because of impaired

  6. Alteration of Upstream Autophagy-Related Proteins (ULK1, ULK2, Beclin1, VPS34 and AMBRA1) in Lewy Body Disease.

    PubMed

    Miki, Yasuo; Tanji, Kunikazu; Mori, Fumiaki; Utsumi, Jun; Sasaki, Hidenao; Kakita, Akiyoshi; Takahashi, Hitoshi; Wakabayashi, Koichi

    2016-05-01

    Autophagy is associated with the pathogenesis of Lewy body disease, including Parkinson's disease (PD) and dementia with Lewy bodies (DLB). It is known that several downstream autophagosomal proteins are incorporated into Lewy bodies (LBs). We performed immunostaining and Western blot analysis using a cellular model of PD and human brain samples to investigate the involvement of upstream autophagosomal proteins (ULK1, ULK2, Beclin1, VPS34 and AMBRA1), which initiate autophagy and form autophagosomes. Time course analysis of cultured cells transfected with flag-α-synuclein and synphilin-1 revealed upregulation of these upstream proteins with accumulation of LB-like inclusions. In human specimens, only mature LBs were positive for upstream autophagosomal proteins. Western blotting of fractionated brain lysates showed that upstream autophagosomal proteins were detected in the soluble and insoluble fraction in DLB, corresponding to the bands of phosphorylated α-synuclein. However, Western blot analysis of total brain lysates in PD and DLB showed that the increase of upstream autophagosomal proteins was only partial. The quantitative, qualitative and locational alteration of upstream autophagosomal proteins in the present study indicates their involvement in the pathogenesis of LB disease. Our data also suggest that misinduction or impairment of upstream autophagy might occur in the disease process of LB disease. PMID:26260450

  7. 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

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

    PubMed

    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

  9. Exome sequencing in dementia with Lewy bodies.

    PubMed

    Keogh, M J; Kurzawa-Akanbi, M; Griffin, H; Douroudis, K; Ayers, K L; Hussein, R I; Hudson, G; Pyle, A; Cordell, H J; Attems, J; McKeith, I G; O'Brien, J T; Burn, D J; Morris, C M; Thomas, A J; Chinnery, P F

    2016-01-01

    Dementia with Lewy bodies (DLB) is the second most common form of degenerative dementia. Siblings of affected individuals are at greater risk of developing DLB, but little is known about the underlying genetic basis of the disease. We set out to determine whether mutations in known highly penetrant neurodegenerative disease genes are found in patients with DLB. Whole-exome sequencing was performed on 91 neuropathologically confirmed cases of DLB, supplemented by independent APOE genotyping. Genetic variants were classified using established criteria, and additional neuropathological examination was performed for putative mutation carriers. Likely pathogenic variants previously described as causing monogenic forms of neurodegenerative disease were found in 4.4% of patients with DLB. The APOE ɛ4 allele increased the risk of disease (P=0.0001), conferred a shorter disease duration (P=0.043) and earlier age of death (P=0.0015). In conclusion, although known pathogenic mutations in neurodegenerative disease genes are uncommon in DLB, known genetic risk factors are present in >60% of cases. APOE ɛ4 not only modifies disease risk, but also modulates the rate of disease progression. The reduced penetrance of reported pathogenic alleles explains the lack of a family history in most patients, and the presence of variants previously described as causing frontotemporal dementia suggests a mechanistic overlap between DLB and other neurodegenerative diseases. PMID:26836416

  10. Exome sequencing in dementia with Lewy bodies

    PubMed Central

    Keogh, M J; Kurzawa-Akanbi, M; Griffin, H; Douroudis, K; Ayers, K L; Hussein, R I; Hudson, G; Pyle, A; Cordell, H J; Attems, J; McKeith, I G; O'Brien, J T; Burn, D J; Morris, C M; Thomas, A J; Chinnery, P F

    2016-01-01

    Dementia with Lewy bodies (DLB) is the second most common form of degenerative dementia. Siblings of affected individuals are at greater risk of developing DLB, but little is known about the underlying genetic basis of the disease. We set out to determine whether mutations in known highly penetrant neurodegenerative disease genes are found in patients with DLB. Whole-exome sequencing was performed on 91 neuropathologically confirmed cases of DLB, supplemented by independent APOE genotyping. Genetic variants were classified using established criteria, and additional neuropathological examination was performed for putative mutation carriers. Likely pathogenic variants previously described as causing monogenic forms of neurodegenerative disease were found in 4.4% of patients with DLB. The APOE ɛ4 allele increased the risk of disease (P=0.0001), conferred a shorter disease duration (P=0.043) and earlier age of death (P=0.0015). In conclusion, although known pathogenic mutations in neurodegenerative disease genes are uncommon in DLB, known genetic risk factors are present in >60% of cases. APOE ɛ4 not only modifies disease risk, but also modulates the rate of disease progression. The reduced penetrance of reported pathogenic alleles explains the lack of a family history in most patients, and the presence of variants previously described as causing frontotemporal dementia suggests a mechanistic overlap between DLB and other neurodegenerative diseases. PMID:26836416

  11. 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

  12. 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

  13. Comparison of Costs of Care between Patients with Alzheimer’s Disease and Dementia with Lewy Bodies

    PubMed Central

    Zhu, Carolyn W.; Scarmeas, Nikolaos; Stavitsky, Karina; Albert, Marilyn; Brandt, Jason; Blacker, Deborah; Sano, Mary; Stern, Yaakov

    2008-01-01

    Objectives To compare total costs of care and its major components for community-living patients with Alzheimer’s disease (AD) or dementia with Lewy bodies (DLB). Design Cross-sectional analysis of baseline data from the Predictors II Study. Setting Three university-based AD centers in the US. Participants Community-living patients clinically-diagnosed with probable AD (n=170) or DLB (n=25) with a modified Mini-Mental State examination (mMMS) score≥30, equivalent to a score of approximately≥16 on the Folstein Mini-Mental State Examination (MMSE). Measurements Patient and informant reported on patients’ use of direct medical care, direct non-medical care, and informal care. Patients’ clinical and demographic characteristics included global cognitive status (measured by MMSE), functional capacity (measured by Blessed Dementia Rating Scale, BDRS), psychotic symptoms, behavioral problems, depressive symptoms, extrapyramidal signs, comorbidities, age, and sex. Costs were compared using covariate matching methods. Results Unadjusted total costs and direct medical costs were not significantly different between AD and DLB patients. Compared to AD patients, unadjusted indirect costs were significantly higher and unadjusted direct non-medical costs were significantly lower among DLB patients. After adjusting for age, sex, cognitive and functional status, differences in all cost components between DLB and AD patients were no longer statistically significant. Conclusions Apparent cost differences were largely attributed to differences in patients’ cognitive and functional status. However, the small sample size for DLB patients may have limited power to detect statistically significant differences in costs of care between these groups. PMID:18631979

  14. 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

  15. [Differential diagnosis of dementia with lewy bodies].

    PubMed

    Orimo, Satoshi

    2015-04-01

    Kosaka and colleagues first reported dementia with Lewy bodies (DLB) in 1976. They have also established the concept of DLB. It is important to differentiate DLB from other dementia, especially Alzheimer disease (AD), because the medical treatment, management, and prognosis of DLB and AD are different. We have used several clinical features and imaging tools to differentiate between DLB and AD. With regard to clinical features, patients with DLB have relatively mild memory disturbances and fluctuating cognition. However, compared to patients with AD they have more severe disturbances of attention and executive, visuospatial functions, visual hallucination, depression, autonomic symptoms. In addition, they show the presence of REM sleep behavior disorder and idiopathic parkinsonism. On performing imaging analysis, patients with DLB showed milder atrophy in the medial temporal lobe on brain MRI, reduced occipital activity on SPECT or PET, reduced MIBG uptake on MIBG cardiac scintigraphy, and low dopamine transporter activity in the basal ganglia on SPECT or PET. PMID:25846590

  16. Limbic and nigral Lewy bodies and Alzheimer's disease pathology mimicking progressive supranuclear palsy in a 75-year-old man with preserved cardiac uptake of MIBG.

    PubMed

    Kasahata, Naoki; Uchihara, Toshiki; Orimo, Satoshi; Nakamura, Ayako; Makita, Yoshihisa

    2012-01-01

    A 75-year-old man developed l-dopa non-responsive parkinsonism, supranuclear ophthalmoplegia, neck dorsiflexion, and dementia. Atrophy of the midbrain tegmentum on MRI and normal myocardial uptake of MIBG led to the clinical diagnosis of progressive supranuclear palsy (PSP). Autopsy revealed depigmentation of the substantia nigra and locus ceruleus. Alzheimer's disease pathology was advanced with PSP-like neurofibrillary tangles distribution, and Lewy bodies were abundant in limbic lobe, while scarce in lower brainstem nuclei. Tuft-shaped astrocytes were not apparent. Although decreased myocardial uptake of MIBG is a rule in patients harboring Lewy bodies, its normal uptake may be related to their absence in lower brainstem nuclei. PMID:22886008

  17. Lewy Body Disease Treatment

    MedlinePlus

    ... a medication like melatonin and/or clonazepam. Neuroleptic Sensitivity Severe sensitivity to neuroleptics is common in LBD. Neuroleptics, also ... with any antipsychotic medication may experience severe neuroleptic sensitivity, such as worsening cognition, heavy sedation, increased or ...

  18. Mitochondrial quality, dynamics and functional capacity in Parkinson’s disease cybrid cell lines selected for Lewy body expression

    PubMed Central

    2013-01-01

    Background Lewy bodies (LB) are a neuropathological hallmark of Parkinson’s disease (PD) and other synucleinopathies. The role their formation plays in disease pathogenesis is not well understood, in part because studies of LB have been limited to examination of post-mortem tissue. LB formation may be detrimental to neuronal survival or merely an adaptive response to other ongoing pathological processes. In a human cytoplasmic hybrid (cybrid) neural cell model that expresses mitochondrial DNA from PD patients, we observed spontaneous formation of intracellular protein aggregates (“cybrid LB” or CLB) that replicate morphological and biochemical properties of native, cortical LB. We studied mitochondrial morphology, bioenergetics and biogenesis signaling by creating stable sub-clones of three PD cybrid cell lines derived from cells expressing CLB. Results Cloning based on CLB expression had a differential effect on mitochondrial morphology, movement and oxygen utilization in each of three sub-cloned lines, but no long-term change in CLB expression. In one line (PD63CLB), mitochondrial function declined compared to the original PD cybrid line (PD63Orig) due to low levels of mtDNA in nucleoids. In another cell line (PD61Orig), the reverse was true, and cellular and mitochondrial function improved after sub-cloning for CLB expression (PD61CLB). In the third cell line (PD67Orig), there was no change in function after selection for CLB expression (PD67CLB). Conclusions Expression of mitochondrial DNA derived from PD patients in cybrid cell lines induced the spontaneous formation of CLB. The creation of three sub-cloned cybrid lines from cells expressing CLB resulted in differential phenotypic changes in mitochondrial and cellular function. These changes were driven by the expression of patient derived mitochondrial DNA in nucleoids, rather than by the presence of CLB. Our studies suggest that mitochondrial DNA plays an important role in cellular and mitochondrial

  19. Lewy Body Dementia: Information for Patients, Families, and Professionals

    MedlinePlus

    ... About ADEAR Lewy Body Dementia: Information for Patients, Families, and Professionals Introduction Lewy body dementia mostly affects ... find a cure—people with LBD and their families struggle day to day to get an accurate ...

  20. Lewy body pathology in fetal grafts.

    PubMed

    Chu, Yaping; Kordower, Jeffrey H

    2010-01-01

    Although fetal nigral transplants have been shown to survive grafting into the striatum, increased [(18)F]6-fluroro-L-3,4-dihydroxyphenylalanine ((18)F-DOPA) uptake and improved motor function in open-label assessments have failed to establish any clinical benefits in double-blind, sham-controlled studies. To understand morphological and neurochemical alterations of grafted neurons, we performed postmortem analyses on six Parkinson's disease (PD) patients who had received fetal tissue transplantation 18-19 months, 4 years, and 14 years previously. These studies revealed robust neuronal survival with normal dopaminergic phenotypes in 18-month-old grafts and decreased dopamine transporter and increased cytoplasmic alpha-synuclein in 4-year-old grafts. We also found a decline of both dopamine transporter and tyrosine hydroxylase and the formation of Lewy body-like inclusions in 14-year-old grafts, which stained positive for alpha-synuclein and ubiquitin proteins. These pathological changes suggest that PD is an ongoing process that affects grafted cells in the striatum in a manner similar to how resident dopamine neurons are affected in the substantia nigra. PMID:20146690

  1. 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

  2. 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

  3. Cerebrospinal Fluid Levels of sAPPα and sAPPβ in Lewy Body and Alzheimer's Disease: Clinical and Neurochemical Correlates.

    PubMed

    Mulugeta, Ezra; Londos, Elisabet; Hansson, Oskar; Ballard, Clive; Skogseth, Ragnhild; Minthon, Lennart; Blennow, Kaj; Zetterberg, Henrik; Aarsland, Dag

    2011-01-01

    We measured cerebrospinal fluid (CSF) levels of the soluble isoforms of amyloid precursor protein (APP; sAPPα sAPPβ) and other CSF biomarkers in 107 patients with Alzheimer's disease (AD), dementia with Lewy body dementia (DLB), Parkinson's disease dementia (PDD), and normal controls (NC) using commercial kits. DLB and PDD were combined in a Lewy body dementia group (LBD). No differences were observed in sAPPα and sAPPβ levels between the groups. Significant correlations were observed between sAPPα and sAPPβ and between sAPPβ and Mini-Mental State Examination scores in the total group analysis as well as when LBD and AD groups were analyzed separately. sAPPα and sAPPβ levels correlated with Aβ38, Aβ40, Aβ42, and Tau in the LBD group. In AD, sAPPα correlated with p-Tau and sAPPβ with Aβ40. The differential association between sAPPα and sAPPβ with Aβ and Tau species between LBD and AD groups suggests a possible relationship with the underlying pathologies in LBD and AD. PMID:21966597

  4. 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. PMID:23566691

  5. Neuropsychiatric Symptoms in Parkinson’s Disease Dementia Are More Similar to Alzheimer’s Disease than Dementia with Lewy Bodies: A Case-Control Study

    PubMed Central

    Chiu, Pai-Yi; Tsai, Chun-Tang; Chen, Ping-Kun; Chen, Whe-Jen; Lai, Te-Jen

    2016-01-01

    Background and purpose Previous studies on the clinical and pathological manifestations of Parkinson’s disease dementia (PDD) have reported findings more similar to dementia with Lewy bodies (DLB) than to Alzheimer’s disease (AD). The aim of this study was to investigate the neuropsychiatric symptoms of PDD compared to DLB and AD. Methods We conducted a retrospective case-control study on 125 newly diagnosed consecutive PDD patients and age- and dementia stage-matched controls with either DLB (N = 250) or AD (N = 500) who visited the same hospital over the same period. For each case and control, neuropsychiatric symptoms were assessed using the Neuropsychiatric Inventory (NPI). Results Overall, 513 (58.6%) patients were female and 362 (41.4%) were male. Comparisons of clinical data revealed that the PDD group, similar to the AD group, had a lower NPI total score, NPI caregiver burden score, and rate of antipsychotic use (all p < 0.001) than the DLB group. One or more psychiatric symptoms were reported in 95.2% of the PDD, 99.2% of the DLB, and 96.8% of the AD patients. The PDD group had lower subscores in the items of delusions, hallucinations, agitation, anxiety, irritation, aberrant motor behavior compared to the DLB group. Severe neuropsychiatric symptoms among all dementia patients were associated with younger age, more advanced stage, and a diagnosis of DLB. Conclusion Neuropsychiatric symptoms in PDD were more like those in AD than in DLB. Severe neuropsychiatric symptoms in degenerative dementia were associated with younger age, more advanced stage of dementia, and a diagnosis of DLB. PMID:27101140

  6. 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…

  7. Imaging and acetylcholinesterase inhibitor response in dementia with Lewy bodies.

    PubMed

    Graff-Radford, Jonathan; Boeve, Bradley F; Pedraza, Otto; Ferman, Tanis J; Przybelski, Scott; Lesnick, Timothy G; Vemuri, Prashanthi; Senjem, Matthew L; Smith, Glenn E; Knopman, David S; Lowe, Val; Jack, Clifford R; Petersen, Ronald C; Kantarci, Kejal

    2012-08-01

    Acetylcholinesterase inhibitors are commonly used to treat patients with dementia with Lewy bodies. Hippocampal atrophy on magnetic resonance imaging and amyloid-β load on positron emission tomography are associated with the Alzheimer's disease-related pathology in patients with dementia with Lewy bodies. To date, few studies have investigated imaging markers that predict treatment response in patients with dementia with Lewy bodies. Our objective was to determine whether imaging markers of Alzheimer's disease-related pathology such as hippocampal volume, brain amyloid-β load on (11)C Pittsburgh compound B positron emission tomography predict treatment response to acetylcholinesterase inhibitors in patients with dementia with Lewy bodies. We performed a retrospective analysis on consecutive treatment-naive patients with dementia with Lewy bodies (n = 54) from the Mayo Clinic Alzheimer's Disease Research Centre who subsequently received acetylcholinesterase inhibitors and underwent magnetic resonance imaging with hippocampal volumetry. Baseline and follow-up assessments were obtained with the Mattis Dementia Rating Scale. Subjects were divided into three groups (reliable improvement, stable or reliable decline) using Dementia Rating Scale reliable change indices determined previously. Associations between hippocampal volumes and treatment response were tested with analysis of covariance adjusting for baseline Dementia Rating Scale, age, gender, magnetic resonance field strength and Dementia Rating Scale interval. Seven subjects underwent (11)C Pittsburgh compound B imaging within 12 weeks of magnetic resonance imaging. Global cortical (11)C Pittsburgh compound B retention (scaled to cerebellar retention) was calculated in these patients. Using a conservative psychometric method of assessing treatment response, there were 12 patients with reliable decline, 29 stable cases and 13 patients with reliable improvement. The improvers had significantly larger

  8. The organization of narrative discourse in Lewy body spectrum disorder.

    PubMed

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

    2011-10-01

    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 patients with LBSD, and we related their narrative impairments to gray matter (GM) atrophy using voxel-based morphometry. We found that patients with PDD and DLB have significant difficulty organizing their narrative speech. This was correlated with deficits on measures of executive functioning and speech fluency. Regression analyses associated this deficit with reduced cortical volume in inferior frontal and anterior cingulate regions. These findings are consistent with a model of narrative discourse that includes executive as well as language components and with an impairment of the organizational component of narrative discourse in patients with PDD and DLB. PMID:21689852

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

    PubMed Central

    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 patients with LBSD, and we related their narrative impairments to gray matter (GM) atrophy using voxel-based morphometry. We found that patients with PDD and DLB have significant difficulty organizing their narrative speech. This was correlated with deficits on measures of executive functioning and speech fluency. Regression analyses associated this deficit with reduced cortical volume in inferior frontal and anterior cingulate regions. These findings are consistent with a model of narrative discourse that includes executive as well as language components and with an impairment of the organizational component of narrative discourse in patients with PDD and DLB. PMID:21689852

  10. 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

  11. 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

  12. Lewy Bodies: A Spectator or Salient Killer?

    PubMed

    Sian-Hulsmann, Jeswinder; Monoranu, Camelia; Strobel, S; Riederer, Peter

    2015-01-01

    Lewy bodies (LBs) are characteristic hallmarks of Parkinson's disease (PD). However, their role in the pathology of PD is not established yet. Are they primary events in the neurodegenerative process or only secondary phenomena? Are they signs of protecting neurons from toxicity or are they toxic per se? How are they are formed? Are LBs targets for therapeutic strategies? Addressing these questions may be of pivotal importance to unravel the basic mechanisms of neurodegeneration in PD. On the basis of current evidence, we intend to elucidate the possible role of LBs as triggers and/or markers of disease progression in PD. We present evidence for the morphogenesis of brain stem and cortical LBs, the role in neuronal cell death mechanisms, which seem to be correlated with the adhesion of LBs to and finally disruption of their inner neuronal membrane. Taken as such, LBs would be salient killers of nerve cells. However, they may also play a neuroprotective role in the early phases of neuronal pathology (LBs as a spectator), yet harmful to neuronal stability in later stages of LB development. Generation of LB pathology in the periphery (early subclinical Braak stage) might be due to reactive oxygen species (ROS) due to (chronic) bacteria-induced and/or otherwise intestinal inflammation, both leading to alpha-synuclein structural changes, oligomerization, seeding and propagation in a prion-like mechanism. If so, LB generation is a secondary process following ROS/inflammation pathology. Therapeutic implication based on LB pathology include drug development to inhibit protein misfolding, templating and transmission or vaccination against LBs, neuron regeneration strategies, anti-inflammatory and anti-biotic drugs as well as nutritional specialities to prevent intestine intoxications. In conclusion, evidence suggests LBs to be secondary hallmarks of PD pathology, induced by ROS/inflammation or other pathological triggers able to modify protein (alpha-synuclein) steric

  13. Risk factors for dementia with Lewy bodies

    PubMed Central

    Boot, Brendon P.; Orr, Carolyn F.; Ahlskog, J. Eric; Ferman, Tanis J.; Roberts, Rosebud; Pankratz, Vernon S.; Dickson, Dennis W.; Parisi, Joseph; Aakre, Jeremiah A.; Geda, Yonas E.; Knopman, David S.; Petersen, Ronald C.

    2013-01-01

    Objective: To determine the risk factors associated with dementia with Lewy bodies (DLB). Methods: We identified 147 subjects with DLB and sampled 2 sex- and age-matched cognitively normal control subjects for each case. We also identified an unmatched comparison group of 236 subjects with Alzheimer disease (AD). We evaluated 19 candidate risk factors in the study cohort. Results: Compared with controls, subjects with DLB were more likely to have a history of anxiety (odds ratio; 95% confidence interval) (7.4; 3.5–16; p < 0.0001), depression (6.0; 3.7–9.5; p < 0.0001), stroke (2.8; 1.3–6.3; p = 0.01), a family history of Parkinson disease (PD) (4.6; 2.5–8.6; p < 0.0001), and carry APOE ε4 alleles (2.2; 1.5–3.3; p < 0.0001), but less likely to have had cancer (0.44; 0.27–0.70; p = 0.0006) or use caffeine (0.29; 0.14–0.57; p < 0.0001) with a similar trend for alcohol (0.65; 0.42–1.0; p = 0.0501). Compared with subjects with AD, subjects with DLB were younger (72.5 vs 74.9 years, p = 0.021) and more likely to be male (odds ratio; 95% confidence interval) (5.3; 3.3–8.5; p < 0.0001), have a history of depression (4.3; 2.4–7.5; p < 0.0001), be more educated (2.5; 1.1–5.6; p = 0.031), have a positive family history of PD (5.0; 2.4–10; p < 0.0001), have no APOE ε4 alleles (0.61; 0.40–0.93; p = 0.02), and to have had an oophorectomy before age 45 years (7.6; 1.5–39; p = 0.015). Conclusion: DLB risk factors are an amalgam of those for AD and PD. Smoking and education, which have opposing risk effects on AD and PD, are not risk factors for DLB; however, depression and low caffeine intake, both risk factors for AD and PD, increase risk of DLB more strongly than in either. PMID:23892702

  14. Familial Dementia With Lewy Bodies With an Atypical Clinical Presentation

    PubMed Central

    Bonner, Lauren T.; Tsuang, Debby W.; Cherrier, Monique M.; Eugenio, Charisma J.; Du, Jennifer Q.; Steinbart, Ellen J.; Limprasert, Pornprot; La Spada, Albert R.; Seltzer, Benjamin; Bird, Thomas D.; Leverenz, James B.

    2006-01-01

    The authors report a case of a 64-year-old male with Alzheimer’s disease (AD) and dementia with Lewy bodies (DLB) pathology at autopsy who did not manifest the core symptoms of DLB until very late in his clinical course. His initial presentation of early executive and language dysfunction suggested a cortical dementia similar to frontotemporal lobar degeneration (FTLD). Core symptoms of DLB including dementia, hallucination, and parkinsonian symptoms were not apparent until late in the course of his illness. Autopsy revealed both brainstem and cortical Lewy bodies and AD pathology. Family history revealed 7 relatives with a history of dementia including 4 with possible or probable DLB. This case is unique because of the FTLD-like presentation, positive family history of dementia, and autopsy confirmation of DLB. PMID:12641375

  15. 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

  16. Compensatory changes in the noradrenergic nervous system in the locus ceruleus and hippocampus of postmortem subjects with Alzheimer's disease and dementia with Lewy bodies.

    PubMed

    Szot, Patricia; White, Sylvia S; Greenup, J Lynne; Leverenz, James B; Peskind, Elaine R; Raskind, Murray A

    2006-01-11

    In Alzheimer's disease (AD), there is a significant loss of locus ceruleus (LC) noradrenergic neurons. However, functional and anatomical evidence indicates that the remaining noradrenergic neurons may be compensating for the loss. Because the noradrenergic system plays an important role in learning and memory, it is important to determine whether compensation occurs in noradrenergic neurons in the LC and hippocampus of subjects with AD or a related dementing disorder, dementia with Lewy bodies (DLB). We observed profound neuronal loss in the LC in AD and DLB subjects with three major changes in the noradrenergic system consistent with compensation: (1) an increase in tyrosine hydroxylase (TH) mRNA expression in the remaining neurons; (2) sprouting of dendrites into peri-LC dendritic zone, as determined by alpha2-adrenoreceptors (ARs) and norepinephrine transporter binding sites; and (3) sprouting of axonal projections to the hippocampus as determined by alpha2-ARs. In AD and DLB subjects, the postsynaptic alpha1-ARs were normal to elevated. Expression of alpha1A- and alpha2A-AR mRNA in the hippocampus of AD and DLB subjects were not altered, but expression of alpha1D- and alpha2C-AR mRNA was significantly reduced in the hippocampus of AD and DLB subjects. Therefore, in AD and DLB subjects, there is compensation occurring in the remaining noradrenergic neurons, but there does appear to be a loss of specific AR in the hippocampus. Because changes in these noradrenergic markers in AD versus DLB subjects were similar (except neuronal loss and the increase in TH mRNA were somewhat greater in DLB subjects), the presence of Lewy bodies in addition to plaques and tangles in DLB subjects does not appear to further affect the noradrenergic compensatory changes. PMID:16407544

  17. 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…

  18. Striatal and extrastriatal dopamine transporter levels relate to cognition in Lewy body diseases: an 11C altropane positron emission tomography study

    PubMed Central

    2014-01-01

    Introduction The biological basis of cognitive impairment in parkinsonian diseases is believed to be multifactorial. We investigated the contribution of dopamine deficiency to cognition in Parkinson disease (PD) and dementia with Lewy bodies (DLB) with dopamine transporter (DAT) imaging. Methods We acquired 11C altropane PET, magnetic resonance imaging and cognitive testing in 19 nondemented subjects with PD, 10 DLB and 17 healthy control subjects (HCS). We analyzed DAT concentration in putamen, caudate, anterior cingulate (AC), orbitofrontal and prefrontal regions, using the Standardized Uptake Volume Ratio with partial volume correction, and we related DAT concentration and global cortical thickness to neuropsychological performance. Results DAT concentration in putamen and in caudate were similar in PD and DLB groups and significantly lower than in HCS. Reduced caudate DAT concentration was associated with worse Clinical Dementia Rating Scale–sum of boxes (CDR-SB) scores and visuospatial skills in DLB but not in PD or HCS groups. Adjusting for putamen DAT concentration, as a measure of severity of motor disease, caudate DAT concentration was lower in DLB than in PD. Higher AC DAT concentration was associated with lower putamen DAT concentration in DLB and with higher putamen DAT concentration in PD. Higher AC DAT concentration in DLB correlated with greater impairment in semantic memory and language. Conclusions Caudate and AC dopamine dysfunction contribute in opposing directions to cognitive impairment in DLB. PMID:25429309

  19. Influence of apolipoprotein E genotype on senile dementia of the Alzheimer and Lewy body types. Significance for etiological theories of Alzheimer's disease.

    PubMed Central

    Harrington, C. R.; Louwagie, J.; Rossau, R.; Vanmechelen, E.; Perry, R. H.; Perry, E. K.; Xuereb, J. H.; Roth, M.; Wischik, C. M.

    1994-01-01

    Alzheimer's disease (AD) is associated with an increased frequency of the apolipoprotein E type epsilon 4 allele. To address both the disease and the allele specificity of this association, we have examined the apolipoprotein E allele distribution in 255 elderly persons including those with autopsy-confirmed AD, senile dementia of the Lewy body type (SDLT), vascular dementia, Parkinson's disease (PD) or Huntington's disease and in nondemented controls either with or without coronary complications. The epsilon 4 allele frequency was increased in SDLT (0.365) and AD (0.328) as compared with controls (0.147), PD (0.098), or Huntington's chorea (0.171). Coronary disease and vascular dementia were associated with marginally higher epsilon 4 allele frequencies than in controls. In PD, amyloid beta-protein accumulated to a greater extent in those cases possessing an epsilon 4 allele than in those without. Those PD cases with dementia were not distinguished from either controls or PD cases without dementia, whether tested biochemically or by apolipoprotein E genotype. It is the comparison of the results in AD and SDLT that yielded the most significant findings. There was a 1.8-fold excess of amyloid beta-protein in AD as compared with controls, and the levels in SDLT were intermediate between those in AD and controls. In contrast, AD was discriminated from both controls and SDLT by the substantial accumulation of paired helical filament tau and phosphorylated tau (both increased more than 20-fold as compared with controls). SDLT was nevertheless characterized by an increased epsilon 4 allele frequency in the absence of significant tau pathology (at least 10-fold less than that in AD). These findings indicate that tau processing is more specifically associated with AD than is amyloid beta-protein accumulation and that presence of the epsilon 4 allele is not an etiological factor that accounts for tau pathology. PMID:7992850

  20. Flow cytometry analysis of synaptosomes from post-mortem human brain reveals changes specific to Lewy Body and Alzheimer’s Disease

    PubMed Central

    Postupna, Nadia O.; Keene, C. Dirk; Latimer, Caitlin; Sherfield, Emily E.; Van Gelder, Rachel D.; Ojemann, Jeffrey G.; Montine, Thomas J.; Darvas, Martin

    2014-01-01

    Synaptic dysfunction is thought to play an important role in the pathophysiology of neurodegenerative diseases, such as Alzheimer’s disease (AD) and Lewy body disease (LBD). To improve our understanding of synaptic alterations in health and disease, we investigated synaptosomes prepared from post-mortem human cerebral cortex, putamen, and two regions of the caudate nucleus, dorso-lateral (DL) and ventro-medial (VM), regions commonly affected in AD and LBD. We observed that the fraction of synaptosomal particles with reactivity for dopamine transporter (DAT) was significantly reduced in the putamen and VM caudate of patients with neuropathological diagnosis of LBD. As expected, these differences also were reflected in direct measurements of dopamine (DA) and its metabolite, 3,4-dihydroxyphenylacetic acid (DOPAC), in caudate and putamen of LBD patients. The fraction of synaptosomal particles positive for amyloid β (Aβ) was significantly increased in frontal cortical samples of patients with the neuropathological diagnosis of severe AD, and was positively correlated with disease progression. We also prepared synaptosomes from the striatum of mice with severe loss of DA neurons (Slc6a3-DTR mice) and wild-type littermate controls. We observed dramatically reduced levels of DAT-positive synaptosomes in Slc6a3-DTR mice following exposure to diphtheria toxin (DT). Striatal levels of DA and DOPAC in Slc6a3-DTR mice also were reduced significantly following DT exposure. We conclude that flow cytometric analysis of synaptosomes prepared from human or mouse brain provides an opportunity to study expression of pathology-associated proteins and also the specific loss of dopaminergic nerve terminals. Hence, we believe it is a valid method to detect pathological changes at the level of the synapse in LBD as well as AD. PMID:25068655

  1. Polysomnographic Findings in Dementia With Lewy Bodies

    PubMed Central

    Pao, Winnie C.; Boeve, Bradley F.; Ferman, Tanis J.; Lin, Sioung-Chi; Smith, Glenn E.; Knopman, David S.; Graff-Radford, Neill R.; Petersen, Ronald C.; Parisi, Joseph E.; Dickson, Dennis W.; Silber, Michael H.

    2013-01-01

    Introduction The clinical features of dementia with Lewy bodies (DLB) during wakefulness are well known. Other than REM sleep behavior disorder (RBD), only limited data exists on other sleep disturbances and disorders in DLB. We sought to characterize the polysomnographic (PSG) findings in a series of DLB patients with sleep-related complaints. Methods Retrospective study of patients with DLB who underwent clinical PSG at Mayo Clinic Rochester or Mayo Clinic Jacksonville over an almost 11 year span for evaluation of dream enactment behavior, excessive nocturnal movements, sleep apnea, hypersomnolence, or insomnia. The following variables were analyzed: respiratory disturbance index (RDI) in disordered breathing events/hour, periodic limb movement arousal index (PLMAI), arousals for no apparent reason (AFNAR), total arousal index (TAI), presence of REM sleep without atonia (RSWA), and percent sleep efficiency (SE). Results Data on 78 patients (71M, 7F) were analyzed. The mean age was 71 ± 8 years. Seventy-five (96%) patients had histories of recurrent dream enactment during sleep with 83% showing confirmation of RSWA +/- dream enactment during PSG. Mean RDI = 11.9 ± 5.8, PLMAI = 5.9 ± 8.5, AFNARI = 10.7 ± 12.0, and TAI = 26.6 ± 17.4. SE was <80% in 72% of the sample, <70% in 49%, and <60% in 24%. In patients who did not show evidence of significant disordered breathing (23 with RDI<5), 62% of arousals were AFNARs. In those patients who had significant disordered breathing (55 with RDI ≥ 5), 36% of arousals were AFNARs. Six patients underwent evaluations with PSG plus MSLT. Two patients had mean initial sleep latencies less than five minutes, and both had RDI<5. No patient had any sleep onset rapid eye movement periods. Nineteen patients have undergone neuropathologic examination, and 18 have had limbic- or neocortical-predominant Lewy body pathology. One had progressive supranuclear palsy, but no REM sleep was recorded in prior PSG. Conclusions In patients

  2. Imaging in Dementia With Lewy Bodies: An Overview.

    PubMed

    Watson, Rosie; Colloby, Sean J

    2016-09-01

    Dementia with Lewy bodies (DLB) while common in older age can present a diagnostic challenge to clinicians and is often misdiagnosed as Alzheimer disease (AD). Imaging studies have improved our understanding of the neurobiological changes in DLB during life and how they differ from AD. This has led to significant advances in the development of new techniques, such as dopaminergic imaging, which can aid the clinical diagnosis. Other functional imaging methods also show promise in helping to assess the influence of differing pathologies in DLB, most notably, AD-related and vascular pathology during life. This article will provide an overview of the main imaging findings in DLB. PMID:27502300

  3. 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

  4. Longitudinal live imaging of retinal α-synuclein::GFP deposits in a transgenic mouse model of Parkinson's Disease/Dementia with Lewy Bodies.

    PubMed

    Price, Diana L; Rockenstein, Edward; Mante, Michael; Adame, Anthony; Overk, Cassia; Spencer, Brian; Duong-Polk, Karen X; Bonhaus, Douglas; Lindsey, James; Masliah, Eliezer

    2016-01-01

    Abnormal α-synuclein (α-syn) accumulation in the CNS may underlie neuronal cell and synaptic dysfunction leading to motor and cognitive deficits in synucleinopathies including Parkinson's disease (PD) and Dementia with Lewy Bodies (DLB). Multiple groups demonstrated α-syn accumulation in CNS accessory structures, including the eyes and olfactory terminals, as well as in peripheral organs of Parkinsonian patients. Retinal imaging studies of mice overexpressing fused α-syn::GFP were conducted to evaluate the presence and progression of retinal pathology in a PD/DLB transgenic mouse model. Bright-field image retinal maps and fluorescent images were acquired at 1-month intervals for 3 months. Retinal imaging revealed the accumulation of GFP-tagged α-syn in retinal ganglion cell layer and in the edges of arterial blood vessels in the transgenic mice. Double labeling studies confirmed that the α-syn::GFP-positive cells were retinal ganglion cells containing α-syn. Accumulation of α-syn persisted in the same cells and increased with age. Accumulation of α-syn::GFP was reduced by immunization with single chain antibodies against α-syn. In conclusion, longitudinal live imaging of the retina in the PDGF-α-syn::GFP mice might represent a useful, non-invasive tool to monitor the fate of α-syn accumulation in the CNS and to evaluate the therapeutic effects of compounds targeting α-syn. PMID:27389831

  5. Longitudinal live imaging of retinal α-synuclein::GFP deposits in a transgenic mouse model of Parkinson’s Disease/Dementia with Lewy Bodies

    PubMed Central

    Price, Diana L.; Rockenstein, Edward; Mante, Michael; Adame, Anthony; Overk, Cassia; Spencer, Brian; Duong-Polk, Karen X.; Bonhaus, Douglas; Lindsey, James; Masliah, Eliezer

    2016-01-01

    Abnormal α-synuclein (α-syn) accumulation in the CNS may underlie neuronal cell and synaptic dysfunction leading to motor and cognitive deficits in synucleinopathies including Parkinson’s disease (PD) and Dementia with Lewy Bodies (DLB). Multiple groups demonstrated α-syn accumulation in CNS accessory structures, including the eyes and olfactory terminals, as well as in peripheral organs of Parkinsonian patients. Retinal imaging studies of mice overexpressing fused α-syn::GFP were conducted to evaluate the presence and progression of retinal pathology in a PD/DLB transgenic mouse model. Bright-field image retinal maps and fluorescent images were acquired at 1-month intervals for 3 months. Retinal imaging revealed the accumulation of GFP-tagged α-syn in retinal ganglion cell layer and in the edges of arterial blood vessels in the transgenic mice. Double labeling studies confirmed that the α-syn::GFP-positive cells were retinal ganglion cells containing α-syn. Accumulation of α-syn persisted in the same cells and increased with age. Accumulation of α-syn::GFP was reduced by immunization with single chain antibodies against α-syn. In conclusion, longitudinal live imaging of the retina in the PDGF-α-syn::GFP mice might represent a useful, non-invasive tool to monitor the fate of α-syn accumulation in the CNS and to evaluate the therapeutic effects of compounds targeting α-syn. PMID:27389831

  6. EEG-directed connectivity from posterior brain regions is decreased in dementia with Lewy bodies: a comparison with Alzheimer's disease and controls.

    PubMed

    Dauwan, Meenakshi; van Dellen, Edwin; van Boxtel, Lotte; van Straaten, Elisabeth C W; de Waal, Hanneke; Lemstra, Afina W; Gouw, Alida A; van der Flier, Wiesje M; Scheltens, Philip; Sommer, Iris E; Stam, Cornelis J

    2016-05-01

    Directed information flow between brain regions might be disrupted in dementia with Lewy bodies (DLB) and relate to the clinical syndrome of DLB. To investigate this hypothesis, resting-state electroencephalography recordings were obtained in patients with probable DLB and Alzheimer's disease (AD), and controls (N = 66 per group, matched for age and gender). Phase transfer entropy was used to measure directed connectivity in the groups for the theta, alpha, and beta frequency band. A posterior-to-anterior phase transfer entropy gradient, with occipital channels driving the frontal channels, was found in controls in all frequency bands. This posterior-to-anterior gradient was largely lost in DLB in the alpha band (p < 0.05). In the beta band, posterior brain regions were less driving in information flow in AD than in DLB and controls. In conclusion, the common posterior-to-anterior pattern of directed connectivity in controls is disturbed in DLB patients in the alpha band, and in AD patients in the beta band. Disrupted alpha band-directed connectivity may underlie the clinical syndrome of DLB and differentiate between DLB and AD. PMID:27103525

  7. 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. PMID:25362038

  8. Comorbidity profile in dementia with Lewy bodies versus Alzheimer’s disease: a linkage study between the Swedish Dementia Registry and the Swedish National Patient Registry

    PubMed Central

    2014-01-01

    Introduction Compared to Alzheimer’s disease (AD), dementia with Lewy bodies (DLB) is usually associated with a more complex clinical picture and higher burden of care. Yet, few investigations have been performed on comorbidities and risk factors of DLB. Therefore, we aimed to compare clinical risk factors and comorbidity profile in DLB and AD patients using two nationwide registries. Methods This is a linkage study between the Swedish dementia registry (SveDem) and the Swedish National Patient Registry conducted on 634 subjects with DLB and 9161 individuals with AD registered during the years 2007–2012. Comorbidity profile has been coded according to the International Classification of Diseases version 10 (ICD 10) in addition to the date of each event. The main chapters of the ICD-10, the Charlson score of comorbidities and a selected number of neuropsychiatric diseases were compared between the DLB and AD groups. Comorbidity was registered before and after the dementia diagnosis. Results “Mental and behavioral disorders”, “diseases of the nervous system”, “diseases of the eye and adnexa”, diseases of the “circulatory”, “respiratory”, and “genitourinary” systems, “diseases of the skin and subcutaneous tissue” and “diseases of the musculoskeletal system and connective tissue” occurred more frequently in the DLB group after multivariate adjustment. Depression [adjusted OR = 2.12 (95%CI 1.49 to 3.03)] and migraine [adjusted OR = 3.65 (95%CI 1.48 to 9.0)] were more commonly recorded before the diagnosis of dementia in the DLB group. Following dementia diagnosis, ischemic stroke [adjusted OR = 1.89 (95%CI 1.21 to 2.96)] was more likely to happen among the DLB patients compared to the AD population. Conclusions Our study indicated a worse comorbidity profile in DLB patients with higher occurrence of depression, stroke and migraine compared with the AD group. Deeper knowledge about the underlying mechanisms of these

  9. Impairments of Speech Fluency in Lewy Body Spectrum Disorder

    PubMed Central

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

    2011-01-01

    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 narrative speech sample in order to characterize impairments of speech fluency and to determine the factors contributing to reduced speech fluency in these patients. Both demented and non-demented PD patients exhibited reduced speech fluency, characterized by reduced overall speech rate and long pauses between sentences. Reduced speech rate in LBSD correlated with measures of between-utterance pauses, executive functioning, and grammatical comprehension. Regression analyses related non-fluent speech, grammatical difficulty, and executive difficulty to atrophy in frontal brain regions. These findings indicate that multiple factors contribute to slowed speech in LBSD, and this is mediated in part by disease in frontal brain regions. PMID:22099969

  10. 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. PMID:25104558

  11. 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. PMID:25125459

  12. Brain (18)F-FDG, (18)F-Florbetaben PET/CT, (123)I-FP-CIT SPECT and Cardiac (123)I-MIBG Imaging for Diagnosis of a "Cerebral Type" of Lewy Body Disease.

    PubMed

    Van Der Gucht, Axel; Cleret de Langavant, Laurent; Bélissant, Ophélie; Rabu, Corentin; Cottereau, Anne-Ségolène; Evangelista, Eva; Chalaye, Julia; Bonnot-Lours, Sophie; Fénelon, Gilles; Itti, Emmanuel

    2016-09-01

    A 67-year-old man was referred for fluctuating neuropsychiatric symptoms, featuring depression, delirious episodes, recurrent visual hallucinations and catatonic syndrome associated with cognitive decline. No parkinsonism was found clinically even under neuroleptic treatment. (18)F-FDG PET/CT showed hypometabolism in the posterior associative cortex including the occipital cortex, suggesting Lewy body dementia, but (123)I-FP-CIT SPECT was normal and cardiac (123)I-MIBG imaging showed no signs of sympathetic denervation. Alzheimer's disease was excluded by a normal (18)F-florbetaben PET/CT. This report suggests a rare case of α-synucleinopathy without brainstem involvement, referred to as "cerebral type" of Lewy body disease. PMID:27540431

  13. Outcomes of Inpatient Treatment for Behavioral and Psychological Symptoms of Dementia in Alzheimer’s Disease Versus Dementia With Lewy Bodies

    PubMed Central

    Kitamura, Tatsuru; Tochimoto, Shinnichi; Madachi, Shuhei; Hino, Shoryoku

    2015-01-01

    Objective Most community-based studies have shown a more malignant clinical course for patients with dementia with Lewy bodies (DLB) than Alzheimer’s disease (AD). We examined differences in outcomes between patients with DLB and AD hospitalized for the treatment of behavioral and psychological symptoms of dementia. Method A chart review was conducted of patients with either AD or DLB hospitalized in the acute psychogeriatric ward between January 2008 and December 2011 in Kahoku-City, Ishikawa, Japan. Outcome measures were discharge destinations and time to death. A diagnosis of AD was made according to DSM-5 criteria, whereas a diagnosis of DLB was made according to the Consortium on DLB International Workshop criteria for probable DLB. Pharmacologic treatment was optimized under constant monitoring of patients. Cholinesterase inhibitors and yi-gan san were tried prior to antipsychotics in DLB patients. Results The study cohort consisted of 224 patients with AD and 106 with DLB. After matching for sociodemographic factors and cognitive and physical function, it was found that antipsychotics were less frequently used during hospitalization in patients with DLB than AD (63% vs 82%, respectively, P < .01), whereas cholinesterase inhibitors (88% vs 43%, P < .001) and yi-gan san (35% vs 20%, P < .05) were more frequently used in patients with DLB. There were no significant differences in discharge destinations between the 2 groups. The 5-year cumulative survival rates were similar in the AD and DLB groups (46.4% vs 45.7%, respectively, P = .6225). Conclusions Optimization of pharmacologic treatment during hospitalization could reduce the use of antipsychotics and improve the subsequent clinical course in DLB. PMID:26835172

  14. Neuropsychological correlates of behavioral symptoms in Alzheimer's disease, frontal variant of frontotemporal, subcortical vascular, and lewy body dementias: a comparative study.

    PubMed

    Perri, Roberta; Monaco, Marco; Fadda, Lucia; Caltagirone, Carlo; Carlesimo, Giovanni Augusto

    2014-01-01

    The aim of this study was to investigate the neuropsychological correlates of behavioral and psychological symptoms (BPSD) in patients affected by various forms of dementia, namely Alzheimer's disease (AD), frontal-variant frontotemporal dementia (fvFTD), Lewy body dementia (LBD), and subcortical ischemic vascular dementia (SIVD). 21 fvFTD, 21 LBD, 22 AD, and 22 SIVD patients matched for dementia severity received a battery of neuropsychological tests and the Neuropsychiatry Inventory (NPI). The possible association between performance on neuropsychological tests and severity of BPSD was assessed by correlational analysis and multivariate regression. BPSD were present in 99% of patients. Most behavioral symptoms were not related to a particular dementia group or to a specific cognitive deficit. Euphoria and disinhibition were predicted by fvFTD diagnosis. Hallucinations correlated with the severity of visuospatial deficits in the whole sample of patients and were predicted by LBD diagnosis. Apathy, which was found in all dementia groups, correlated with executive functions and was predicted by both reduced set-shifting aptitude and fvFTD diagnosis. The results confirm the high prevalence of BPSD in the mild to moderate stages of dementia and show that most BPSD are equally distributed across dementia groups. Most of the cognitive and behavioral symptoms are independent dimensions of the dementia syndromes. Nevertheless, hallucinations in LBD and euphoria and disinhibition in fvFTD are related to the structural brain alterations that are responsible for cognitive decline in these dementia groups. Finally, apathy arises from damage in the frontal cortical areas that are also involved in executive functions. PMID:24254701

  15. Axonopathy in an α-Synuclein Transgenic Model of Lewy Body Disease Is Associated with Extensive Accumulation of C-Terminal–Truncated α-Synuclein

    PubMed Central

    Games, Dora; Seubert, Peter; Rockenstein, Edward; Patrick, Christina; Trejo, Margarita; Ubhi, Kiren; Ettle, Benjamin; Ghassemiam, Majid; Barbour, Robin; Schenk, Dale; Nuber, Silke; Masliah, Eliezer

    2014-01-01

    Progressive accumulation of α-synuclein (α-syn) in limbic and striatonigral systems is associated with the neurodegenerative processes in dementia with Lewy bodies (DLB) and Parkinson’s disease (PD). The murine Thy-1 (mThy1)-α-syn transgenic (tg) model recapitulates aspects of degenerative processes associated with α-syn accumulation in these disorders. Given that axonal and synaptic pathologies are important features of DLB and PD, we sought to investigate the extent and characteristics of these alterations in mThy1-α-syn tg mice and to determine the contribution of α-syn c-terminally cleaved at amino acid 122 (CT α-syn) to these abnormalities. We generated a novel polyclonal antibody (SYN105) against the c-terminally truncated sequence (amino acids 121 to 123) of α-syn (CT α-syn) and performed immunocytochemical and ultrastructural analyses in mThy1-α-syn tg mice. We found abundant clusters of dystrophic neurites in layers 2 to 3 of the neocortex, the stratum lacunosum, the dentate gyrus, and cornu ammonis 3 of the hippocampus, striatum, thalamus, midbrain, and pons. Dystrophic neurites displayed intense immunoreactivity detected with the SYN105 antibody. Double-labeling studies with antibodies to phosphorylated neurofilaments confirmed the axonal location of full-length and CT α-syn. α-Syn immunoreactive dystrophic neurites contained numerous electrodense laminated structures. These results show that neuritic dystrophy is a prominent pathologic feature of the mThy1-α-syn tg model and suggest that CT α-syn might play an important role in the process of axonal damage in these mice as well as in DLB and PD. PMID:23313024

  16. Axonopathy in an α-synuclein transgenic model of Lewy body disease is associated with extensive accumulation of C-terminal-truncated α-synuclein.

    PubMed

    Games, Dora; Seubert, Peter; Rockenstein, Edward; Patrick, Christina; Trejo, Margarita; Ubhi, Kiren; Ettle, Benjamin; Ghassemiam, Majid; Barbour, Robin; Schenk, Dale; Nuber, Silke; Masliah, Eliezer

    2013-03-01

    Progressive accumulation of α-synuclein (α-syn) in limbic and striatonigral systems is associated with the neurodegenerative processes in dementia with Lewy bodies (DLB) and Parkinson's disease (PD). The murine Thy-1 (mThy1)-α-syn transgenic (tg) model recapitulates aspects of degenerative processes associated with α-syn accumulation in these disorders. Given that axonal and synaptic pathologies are important features of DLB and PD, we sought to investigate the extent and characteristics of these alterations in mThy1-α-syn tg mice and to determine the contribution of α-syn c-terminally cleaved at amino acid 122 (CT α-syn) to these abnormalities. We generated a novel polyclonal antibody (SYN105) against the c-terminally truncated sequence (amino acids 121 to 123) of α-syn (CT α-syn) and performed immunocytochemical and ultrastructural analyses in mThy1-α-syn tg mice. We found abundant clusters of dystrophic neurites in layers 2 to 3 of the neocortex, the stratum lacunosum, the dentate gyrus, and cornu ammonis 3 of the hippocampus, striatum, thalamus, midbrain, and pons. Dystrophic neurites displayed intense immunoreactivity detected with the SYN105 antibody. Double-labeling studies with antibodies to phosphorylated neurofilaments confirmed the axonal location of full-length and CT α-syn. α-Syn immunoreactive dystrophic neurites contained numerous electrodense laminated structures. These results show that neuritic dystrophy is a prominent pathologic feature of the mThy1-α-syn tg model and suggest that CT α-syn might play an important role in the process of axonal damage in these mice as well as in DLB and PD. PMID:23313024

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

    PubMed Central

    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. PMID:25031635

  18. 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

  19. Can we clinically diagnose dementia with Lewy bodies yet?

    PubMed Central

    2013-01-01

    Dementia with Lewy Bodies (DLB) was initially identified and confirmed primarily by pathology, but is soon to be incorporated into the Diagnostic and Statistical Manual criteria as a clinical disease entity. Despite these advances over more than 20 years, current data suggest that the sensitivity of accurate clinical diagnosis of DLB is still very low, although there is mounting evidence that supportive features may increase diagnostic accuracy. Although DLB remains easy to identify pathologically with different cellular pathologies differentiating it from other dementia syndromes, pathological identification using only Lewy body pathology has been shown to be inaccurate due to overlap with patients without dementia symptoms. A number of studies now suggest that a combination of cellular pathologies, which include α-synuclein and β-amyloid deposition as well as dopamine denervation, assist with differentiating this dementia syndrome from others. The clinical and pathological overlap with the tauopathy of Alzheimer’s disease still remains to be clarified. To determine more robust and independent clinicopathological correlates from Alzheimer’s disease, longitudinal prospective studies, using specific clinical batteries on dementia patients reaching the proposed criteria for DLB, with post-mortem assessment of the multiple pathologies associated with dementia, are required. Identifying genetic causes for DLB is another approach to investigate the pathogenesis of DLB. However this approach has been hindered to date by difficulties with identifying DLB clinically. The use of novel techniques is likely to advance knowledge on the pathogenesis of DLB and assist with redefining clinical and pathologic diagnostic criteria. To achieve the goal of more accurate clinical diagnosis of DLB, breakthroughs are necessary on the pathogenesis of DLB. PMID:23398715

  20. Cholinesterase inhibitor use does not significantly influence the ability of 123I‐FP‐CIT imaging to distinguish Alzheimer's disease from dementia with Lewy bodies

    PubMed Central

    Taylor, John‐Paul; Colloby, Sean J; McKeith, Ian G; Burn, David J; Williams, David; Patterson, Jim; O'Brien, John T

    2007-01-01

    Background 123I‐labelled 2β‐carbomethoxy‐3β‐(4‐iodophenyl)‐N‐(3‐fluoropropyl) nortropane (123I‐FP‐CIT) imaging is a diagnostic tool to help differentiate dementia with Lewy bodies (DLB) from Alzheimer's disease (AD). However, in animals, cholinesterase inhibitors (ChEi) have been reported to reduce radioligand binding to the striatal dopamine transporter. As ChEi are frequently used in people with dementia, it is important to determine whether their use affects 123I‐FP‐CIT uptake in the striatum. Objective To clarify whether chronic ChEi therapy modulates striatal dopamine transporter binding measured by 123I‐FP‐CIT in patients with AD, DLB and Parkinson's disease with dementia (PDD). Design Cross sectional study in 99 patients with AD (nine on ChEi, 25 not on ChEi), DLB (nine on ChEi, 19 not on ChEi) and PDD (six on ChEi, 31 not on ChEi) comparing 123I‐FP‐CIT striatal binding (caudate, anterior and posterior putamen) in patients receiving compared with those not receiving ChEi, correcting for key clinical variables including diagnosis, age, sex, Mini‐Mental State Examination score, severity of parkinsonism and concurrent antidepressant use. Results As previously described, 123I‐FP‐CIT striatal uptake was lower in DLB and PDD subjects compared with those with AD. Median duration of ChEi use was 180 days. 123I‐FP‐CIT uptake was not significantly reduced in subjects receiving ChEi compared those not receiving ChEi (mean percentage reduction: AD 4.3%; DLB 0.7%; PDD 6.1%; p = 0.40). ChEi use did not differentially affect striatal 123FP‐CIT uptake between patient groups (p = 0.83). Conclusions Use of ChEi does not significantly influence the ability of 123I‐FP‐CIT imaging to distinguish AD from DLB. PMID:17299017

  1. Identification of biomarkers in Lewy-body disorders.

    PubMed

    Warr, L; Walker, Z

    2012-02-01

    Dementia with Lewy bodies (DLB) may account for up to 30% of all dementia cases. The symptoms of DLB can be difficult to disentangle from other dementia subtypes, particularly Alzheimer's disease (AD). AD and DLB pathologies often overlap within individuals. Like DLB, Parkinson's disease dementia (PDD) also shares common features with DLB. Currently, whether an individual is diagnosed with PDD or DLB depends solely on the timing of symptom onset. Early, accurate diagnosis is needed for optimal management and treatment. It is hoped that the development of existing and new Lewy body disorders biomarkers will facilitate more accurate diagnosis. Reduced dopamine transporter levels in DLB as shown with [123I]FP-CIT-SPECT currently appears to be the most reliable and valid biomarker, although other (predominantly imaging-based) methods also appear to have the high sensitivity and specificity required for a good biomarker. This includes (in DLB compared to AD) reduced cardiac 123I-MIBG uptake, occipital hypometabolism on FDG-PET and preservation of medial temporal lobe structures on CT/MRI. Perfusion SPECT, cerebrospinal fluid protein levels (amyloid, tau and α-synuclein), electroencephalography, saccadic eye movement tracking and 11C-PiB amyloid imaging also hold promise as biomarkers in terms of differentiating DLB, AD, PDD and other neurodegenerative disorders, although findings are less consistent. Studies utilising a combination approach in which two or more potential biomarkers are compared seem to provide very good sensitivity and specificity. In general, longitudinal studies, pathological confirmation of diagnosis and the combined approach may hold the most promise for the identification of biomarkers. PMID:22460159

  2. 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

  3. Sudden Death: An Uncommon Occurrence in Dementia with Lewy Bodies.

    PubMed

    Molenaar, Joery P; Wilbers, Joyce; Aerts, Marjolein B; Leijten, Quinten H; van Dijk, Jan G; Esselink, Rianne A; Bloem, Bastiaan R

    2016-01-01

    We present a 75-year-old woman with dementia and parkinsonism who developed severe orthostatic hypotension and eventually died. Autopsy revealed extensive Lewy body formation in the midbrain, limbic system, intermediate spinal cord, and medulla oblongata. Furthermore, a vast amount of Lewy bodies was seen in the paravertebral sympathetic ganglia which likely explained the severe autonomic failure. We speculate that this autonomic failure caused sudden death through dysregulation of respiration or heart rhythm, reminiscent of sudden death in multiple system atrophy (MSA). Clinicians should be aware of this complication in patients presenting with parkinsonism and autonomic dysfunction, and that sudden death may occur in dementia with Lewy bodies (DLB) as it does in MSA. PMID:26891177

  4. Multi-organ distribution of phosphorylated alpha-synuclein histopathology in subjects with Lewy body disorders.

    PubMed

    Beach, Thomas G; Adler, Charles H; Sue, Lucia I; Vedders, Linda; Lue, Lihfen; White Iii, Charles L; Akiyama, Haru; Caviness, John N; Shill, Holly A; Sabbagh, Marwan N; Walker, Douglas G

    2010-06-01

    A sensitive immunohistochemical method for phosphorylated alpha-synuclein was used to stain sets of sections of spinal cord and tissue from 41 different sites in the bodies of 92 subjects, including 23 normal elderly, 7 with incidental Lewy body disease (ILBD), 17 with Parkinson's disease (PD), 9 with dementia with Lewy bodies (DLB), 19 with Alzheimer's disease with Lewy bodies (ADLB) and 17 with Alzheimer's disease with no Lewy bodies (ADNLB). The relative densities and frequencies of occurrence of phosphorylated alpha-synuclein histopathology (PASH) were tabulated and correlated with diagnostic category. The greatest densities and frequencies of PASH occurred in the spinal cord, followed by the paraspinal sympathetic ganglia, the vagus nerve, the gastrointestinal tract and endocrine organs. The frequency of PASH within other organs and tissue types was much lower. Spinal cord and peripheral PASH was most common in subjects with PD and DLB, where it appears likely that it is universally widespread. Subjects with ILBD had lesser densities of PASH within all regions, but had frequent involvement of the spinal cord and paraspinal sympathetic ganglia, with less-frequent involvement of end-organs. Subjects with ADLB had infrequent involvement of the spinal cord and paraspinal sympathetic ganglia with rare involvement of end-organs. Within the gastrointestinal tract, there was a rostrocaudal gradient of decreasing PASH frequency and density, with the lower esophagus and submandibular gland having the greatest involvement and the colon and rectum the lowest. PMID:20306269

  5. Clinicians' ability to diagnose dementia with Lewy bodies is not affected by β-amyloid load

    PubMed Central

    Attems, Johannes; Thomas, Alan; Brown, Andrew; Jaros, Evelyn; Lett, Debbie J.; Ossola, Maria; Perry, Robert H.; Ramsay, Lynne; Walker, Lauren; McKeith, Ian G.

    2015-01-01

    Objective: To investigate whether an increasing load of β-amyloid and/or neuritic plaques influences the phenotype, and thus the clinical diagnostic accuracy, of dementia with Lewy bodies (DLB). Methods: A series of 64 subjects with autopsy-proven DLB was studied. Last diagnosis before death was used to determine the clinical diagnostic accuracy of DLB in relation to Lewy body distribution and extent of Alzheimer β-amyloid and/or neuritic pathology. DLB pathologic diagnosis was made according to consensus criteria, using α-synuclein immunostaining for Lewy body identification. β-Amyloid immunostaining was used for quantifying β-amyloid deposits. The Consortium to Establish a Registry for Alzheimer's Disease criteria and Braak stage were applied for semiquantitative grading of neuritic plaque and neurofibrillary tangle pathology. Results: Overall clinical diagnostic accuracy for the entire DLB cohort was high (80%), reflecting the high prevalence of core clinical features (fluctuations [81%], parkinsonism [77%], visual hallucinations [70%]). Lower frequencies of core clinical features of DLB, resulting in lower accuracy of its clinical diagnosis, were associated with decreasing Lewy body distribution (p < 0.0001) and with increasing neuritic plaque pathology (p = 0.035), but not with the number of β-amyloid plaque deposits. Conclusions: The likelihood of occurrence of the DLB clinical syndrome is positively related to the extent of Lewy body pathology and negatively related to the severity of Alzheimer neuritic pathology, while β-amyloid load has no effect. PMID:25552579

  6. The possible involvement of mitochondrial dysfunctions in Lewy body dementia: a systematic review

    PubMed Central

    Spano, Mariangela; Signorelli, Maria; Vitaliani, Roberta; Aguglia, Eugenio; Giometto, Bruno

    2015-01-01

    Summary The hallmark of dementia with Lewy bodies (DLB) is the “Lewy body”, an abnormal aggregation of alpha-synuclein found in some areas of the brain. The brain is the organ/system that is most vulnerable to this oxidative damage, and reactive oxygen species can cause neurodegenerative diseases. Different models of mitochondrial deregulation have been compared in DLB. The results are consistent with the hypothesis that alpha-synuclein affects the mitochondria themselves, increasing their sensitivity or leading to cell death through protective (neurosin) and accelerating (cytochrome c) factors. This systematic review suggests that mitochondria play an important role in neurodegeneration and a crucial role in the formation of Lewy bodies. DLB is a disease characterized by abnormal accumulation of alpha-synuclein that could result in the release of cytochrome c and subsequent activation of the apoptotic cascade. PMID:26346695

  7. Lewy Body Digest eNewsletter

    MedlinePlus

    ... Body Dementia Association, Inc. Connect With Us LinkedIn facebook twitter google youtube lbda.org Home Learn About LBD Find Support Resources Research Ways to Give About Us Contact Us Join LBDA ...

  8. Regional Multiple Pathology Scores Are Associated with Cognitive Decline in Lewy Body Dementias.

    PubMed

    Howlett, David R; Whitfield, David; Johnson, Mary; Attems, Johannes; O'Brien, John T; Aarsland, Dag; Lai, Mitchell K P; Lee, Jasinda H; Chen, Christopher; Ballard, Clive; Hortobágyi, Tibor; Francis, Paul T

    2015-07-01

    Dementia with Lewy bodies (DLB) and Parkinson's disease dementia (PDD) are characterized by the presence of α-synuclein-containing Lewy bodies and Lewy neurites. However, both dementias also show variable degrees of Alzheimer's disease (AD) pathology (senile plaques and neurofibrillary tangles), particularly in areas of the cortex associated with higher cognitive functions. This study investigates the contribution of the individual and combined pathologies in determining the rate of cognitive decline. Cortical α-synuclein, phosphorylated tau (phosphotau) and Aβ plaque pathology in 34 PDD and 55 DLB patients was assessed semi-quantitatively in four regions of the neocortex. The decline in cognition, assessed by Mini Mental State Examination, correlated positively with the cortical α-synuclein load. Patients also had varying degrees of senile Aβ plaque and phosphotau pathology. Regression analyses pointed to a combined pathology (Aβ plaque plus phosphotau plus α-synuclein-positive features), particularly in the prefrontal cortex (BA9) and temporal lobe neocortex with the superior and middle temporal gyrus (BA21, 22), being a major determining factor in the development of dementia. Thus, cognitive decline in Lewy body dementias is not a consequence of α-synuclein-induced neurodegeneration alone but senile plaque and phosphorylated tau pathology also contribute to the overall deficits. PMID:25103200

  9. Apoptotic-like changes in Lewy-body-associated disorders and normal aging in substantia nigral neurons.

    PubMed Central

    Tompkins, M. M.; Basgall, E. J.; Zamrini, E.; Hill, W. D.

    1997-01-01

    In Parkinson's disease and other Lewy-body-associated disorders, the substantia nigra pars compacta undergoes degeneration, but the mechanism of cell death has not been previously described. The substantia nigra of normal and Alzheimer's disease cases were compared with substantia nigra from patients with Lewy-body-associated disorders (Parkinson's disease, concomitant Alzheimer's/Parkinson's disease, and diffuse Lewy body disease) using in situ end labeling to detect fragmented DNA. In situ end-labeled neurons demonstrated changes resembling apoptosis: nuclear condensation, chromatin fragmentation, and formation of apoptotic-like bodies. Ultrastructural analysis confirmed nuclear condensation and formation of apoptotic-like bodies. Apoptotic-like changes were seen in the substantia nigra of both normal and diseased cases; concomitant Alzheimer's/Parkinson's disease and diffuse Lewy body disease cases had significantly higher amounts of apoptotic-like changes than normal controls or Alzheimer patients. The finding of neuronal death by apoptosis may have relevance for the development of new treatment strategies for Parkinson's disease and related disorders. Images Figure 1 Figure 2 Figure 5 PMID:9006329

  10. TREM2 p.R47H substitution is not associated with dementia with Lewy bodies.

    PubMed

    Walton, Ronald L; Soto-Ortolaza, Alexandra I; Murray, Melissa E; Lorenzo-Betancor, Oswaldo; Ogaki, Kotaro; Heckman, Michael G; Rayaprolu, Sruti; Rademakers, Rosa; Ertekin-Taner, Nilüfer; Uitti, Ryan J; van Gerpen, Jay A; Wszolek, Zbigniew K; Smith, Glenn E; Kantarci, Kejal; Lowe, Val J; Parisi, Joseph E; Jones, David T; Savica, Rodolfo; Graff-Radford, Jonathan; Knopman, David S; Petersen, Ronald C; Graff-Radford, Neill R; Ferman, Tanis J; Dickson, Dennis W; Boeve, Bradley F; Ross, Owen A; Labbé, Catherine

    2016-08-01

    Dementia with Lewy bodies (DLB) is the second leading cause of neurodegenerative dementia in the elderly and is clinically characterized by the presence of cognitive decline, parkinsonism, REM sleep behavior disorder, and visual hallucinations.(1,2) At autopsy, α-synuclein-positive Lewy-related pathology is observed throughout the brain. Concomitant Alzheimer disease-related pathology including amyloid plaques and, to a lesser degree, neurofibrillary tangles are often present.(2) The clinical characteristics of DLB share overlapping features with Alzheimer disease dementia (AD) and Parkinson disease (PD). A recent genetic association study examining known hits from PD and AD identified variants at both the α-synuclein (SNCA) and APOE loci as influencing the individual risk to DLB.(3) These findings would suggest that DLB may be a distinct disease with shared genetic risk factors with PD and AD. PMID:27458607

  11. Visual cortical excitability in dementia with Lewy bodies.

    PubMed

    Taylor, John-Paul; Firbank, Michael; O'Brien, John T

    2016-05-01

    Alterations in the visual system may underlie visual hallucinations in dementia with Lewy bodies (DLB). However, cortical excitability as measured by transcranial magnetic stimulation (TMS) and functional magnetic resonance imaging (fMRI) activation of lower visual areas (V1-3) to visual stimuli appear normal in DLB. We explored the relationship between TMS-determined phosphene threshold and fMRI-related visual activation and found a positive relationship between the two in controls but a negative one in DLB. This double dissociation suggests a loss of inhibition in the visual system in DLB, which may predispose individuals to visual dysfunction and visual hallucinations. PMID:26541688

  12. Visual cortical excitability in dementia with Lewy bodies

    PubMed Central

    Taylor, John-Paul; Firbank, Michael; O'Brien, John T.

    2016-01-01

    Alterations in the visual system may underlie visual hallucinations in dementia with Lewy bodies (DLB). However, cortical excitability as measured by transcranial magnetic stimulation (TMS) and functional magnetic resonance imaging (fMRI) activation of lower visual areas (V1–3) to visual stimuli appear normal in DLB. We explored the relationship between TMS-determined phosphene threshold and fMRI-related visual activation and found a positive relationship between the two in controls but a negative one in DLB. This double dissociation suggests a loss of inhibition in the visual system in DLB, which may predispose individuals to visual dysfunction and visual hallucinations. PMID:26541688

  13. 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.

  14. Visual hallucinations in dementia with Lewy bodies: transcranial magnetic stimulation study

    PubMed Central

    Taylor, John-Paul; Firbank, Michael; Barnett, Nicola; Pearce, Sarah; Livingstone, Anthea; Mosimann, Urs; Eyre, Janet; McKeith, Ian G.; O’Brien, John T.

    2011-01-01

    Background The aetiology of visual hallucinations is poorly understood in dementia with Lewy bodies. Pathological alterations in visual cortical excitability may be one contributory mechanism. Aims To determine visual cortical excitability in people with dementia with Lewy bodies compared with aged-matched controls and also the relationship between visual cortical excitability and visual hallucinations in dementia with Lewy bodies. Method Visual cortical excitability was determined by using transcranial magnetic stimulation (TMS) applied to the occiput to elicit phosphenes (transient subjective visual responses) in 21 patients with dementia with Lewy bodies and 19 age-matched controls. Results Phosphene parameters were similar between both groups. However, in the patients with dementia with Lewy bodies, TMS measures of visual cortical excitability correlated strongly with the severity of visual hallucinations (P = 0.005). Six patients with dementia with Lewy bodies experienced visual hallucination-like phosphenes (for example, seeing people or figures on stimulation) compared with none of the controls (P = 0.02). Conclusions Increased visual cortical excitability in dementia with Lewy bodies does not appear to explain visual hallucinations but it may be a marker for their severity. PMID:22016436

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

    PubMed Central

    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. PMID:25671083

  16. Altered neurofilament expression does not contribute to Lewy body formation.

    PubMed Central

    Bergeron, C.; Petrunka, C.; Weyer, L.; Pollanen, M. S.

    1996-01-01

    Lewy bodies (LBs) are cytoskeletal alterations found in several neurodegenerative disorders. Although neurofilaments are the main constituent of the LB, the precise mechanisms that underlie their formation remain speculative. To examine the pathogenesis of this inclusion, we measured the mRNA level of the low molecular weight neurofilament subunit in the nigral dopaminergic neurons of patients with LB disorders and neurologically normal controls. We found a small but significant decrease in the mean mRNA values in the LB group as compared with controls. However, a comparison of LB-bearing and non-LB-bearing neurons on the same section showed no significant difference between these two neuronal populations. We conclude that altered neurofilament expression is not a major contributory event in the pathogenesis of the LB. The decrease in neurofilament mRNA expression observed in the overall nigral dopaminergic neuronal population of LB disorders probably represents a nonspecific response to neuronal injury independent of LB formation. Images Figure 1 PMID:8546215

  17. Cerebrospinal Fluid Biomarkers for Dementia with Lewy Bodies

    PubMed Central

    Mukaetova-Ladinska, Elizabeta B.; Monteith, Rachael; Perry, Elaine K.

    2010-01-01

    More than 750,000 of the UK population suffer from some form of cognitive impairment and dementia. Of these, 5–20% will have Dementia with Lewy Bodies (DLB). Clinico-pathological studies have shown that it is the low frequency of DLB clinical core features that makes the DLB diagnosis hardly recognisable during life, and easily misdiagnosed for other forms of dementia. This has an impact on the treatment and long-term care of the affected subjects. Having a biochemical test, based on quantification of a specific DLB biomarker within Cerebrospinal Fluid (CSF) could be an effective diagnostic method to improve the differential diagnosis. Although some of the investigated DLB CSF biomarkers are well within the clinical criteria for sensitivity and specificity (>90%), they all seem to be confounded by the contradictory data for each of the major groups of biomarkers (α-synuclein, tau and amyloid proteins). However, a combination of CSF measures appear to emerge, that may well be able to differentiate DLB from other dementias: α-synuclein reduction in early DLB, a correlation between CSF α-synuclein and Aβ42 measures (characteristic for DLB only), and t-tau and p-tau181 profile (differentiating AD from DLB). PMID:21048932

  18. Regional differences in the severity of Lewy body pathology across the olfactory cortex.

    PubMed

    Silveira-Moriyama, Laura; Holton, Janice L; Kingsbury, Ann; Ayling, Hilary; Petrie, Aviva; Sterlacci, William; Poewe, Werner; Maier, Hans; Lees, Andrew J; Revesz, Tamas

    2009-04-01

    We studied alpha-synuclein pathology in the rhinencephalon of ten cases of Parkinson's disease (PD) and twelve neurologically normal controls, of which seven had incidental Lewy bodies in the substantia nigra at autopsy and five had no pathological evidence of neurological disease. In all PD and incidental Lewy bodies cases, alpha-synuclein pathology was found in all five subregions of the primary olfactory cortex that were sampled, and amongst them the pathology was significantly more severe in the temporal division of the piriform cortex than in the frontal division of the piriform cortex, olfactory tubercle or anterior portions of the entorhinal cortex. The orbitofrontal cortex, which is an area of projection from the primary olfactory cortex, was affected in some cases but overall the alpha-synuclein pathology was less severe in this area than in the primary olfactory cortex. Because different areas of the rhinencephalon are likely to play different roles in olfaction and our data indicate a differential involvement by alpha-synuclein deposition of structures implicated in smell, future prospective studies investigating the pathophysiological basis of hyposmia in PD should consider to examine the areas of primary olfactory cortex separately. PMID:19356597

  19. DJ-1 linked parkinsonism (PARK7) is associated with Lewy body pathology.

    PubMed

    Taipa, Ricardo; Pereira, Conceição; Reis, Inês; Alonso, Isabel; Bastos-Lima, António; Melo-Pires, Manuel; Magalhães, Marina

    2016-06-01

    Mutations in DJ-1 (encoded by PARK7) are a very rare cause of early-onset recessive Parkinson's disease. We describe a patient with early-onset parkinsonism, starting at the age of 22, with poor response to levodopa and additional features in progression (dystonia, pyramidal signs and dementia), who died when he was 49 years old. The neuropathological study showed severe substantia nigra and locus coeruleus neuronal loss, with diffuse Lewy body pathology (Lewy bodies, aberrant neurites, grain-like structures, spheroids and scattered glial pathology). Genetic analysis revealed a novel c.515T > A; p.L172Q mutation in the PARK7 gene. To evaluate the pathogenicity of this new mutation we explored DJ-1 expression levels in vitro showing a massive reduction in DJ-1 protein levels due to a highly unstable and rapidly degraded L172Q mutant. DJ-1 immunohistochemistry of brain tissue revealed no staining in our case. This is the first neuropathological report of a brain from DJ-1-linked parkinsonism that, although based on a single case study, suggests that DJ-1 mutations are causative of α-synucleinopathy. These results can help in the understanding of Parkinson's disease pathophysiology, promote research studies to increase the knowledge on the pathways involved in the neurodegeneration process, and pave the way for new therapeutic interventions. PMID:27085187

  20. p62/SQSTM1-Dependent Autophagy of Lewy Body-Like α-Synuclein Inclusions

    PubMed Central

    Watanabe, Yoshihisa; Tatebe, Harutsugu; Taguchi, Katsutoshi; Endo, Yasuhisa; Tokuda, Takahiko; Mizuno, Toshiki; Nakagawa, Masanori; Tanaka, Masaki

    2012-01-01

    α-Synuclein is the main component of Lewy bodies, the intraneuronal inclusion bodies characteristic of Parkinson’s disease. Although α-synuclein accumulation is caused by inhibition of proteasome and autophagy-lysosome, the degradation of α-synuclein inclusions is still unknown. Formation of Lewy body-like inclusions can be replicated in cultured cells by introducing α-synuclein fibrils generated in vitro. We used this cell culture model to investigate the autophagy of α-synuclein inclusions and impaired mitochondria. The intracellular α-synuclein inclusions immediately underwent phosphorylation and ubiquitination. Simultaneously they were encircled by an adaptor protein p62/SQSTM1 and directed to the autophagy-lysosome pathway in HEK293 cell line. Most phospho-α-synuclein-positive inclusions were degraded in 24 h, however, lysosomal dysfunction with bafilomycin A1 significantly affected their clearance. Moreover, inhibition of autophagy by Atg-5 siRNA treatment reduced the incorporation of α-synuclein inclusions into LC3-positive autophagosomes. Knockdown experiments demonstrated the requirement of p62 for α-synuclein autophagy. These results demonstrate that α-synuclein inclusions are preferred targets for p62-dependent autophagy. Next, we investigated the autophagic clearance of impaired mitochondria in α-synuclein inclusion-containing cells. Impaired mitochondria were almost completely eliminated after mitochondrial uncoupling even in the presence of α-synuclein inclusions, suggesting that mitochondrial clearance is not prevented by α-synuclein inclusions in HEK293 cells. PMID:23300799

  1. Multiple organ involvement by alpha-synuclein pathology in Lewy body disorders.

    PubMed

    Gelpi, Ellen; Navarro-Otano, Judith; Tolosa, Eduardo; Gaig, Carles; Compta, Yaroslau; Rey, María Jesús; Martí, Maria José; Hernández, Isabel; Valldeoriola, Francesc; Reñé, Ramon; Ribalta, Teresa

    2014-07-01

    Lewy body (LB) diseases are characterized by alpha-synuclein (AS) aggregates in the central nervous system (CNS). Involvement of the peripheral autonomic nervous system (pANS) is increasingly recognized, although less studied. The aim of this study was to systematically analyze the distribution and severity of AS pathology in the CNS and pANS. Detailed postmortem histopathological study of brain and peripheral tissues from 28 brain bank donors (10 with Parkinson's disease [PD], 5 with dementia with LB [DLB], and 13 with non-LB diseases including atypical parkinsonism and non-LB dementia). AS aggregates were found in the pANS of all 15 LB disease cases (PD, DLB) in stellate and sympathetic ganglia (100%), vagus nerve (86.7%), gastrointestinal tract (86.7%), adrenal gland and/or surrounding fat (53.3%), heart (100%), and genitourinary tract (13.3%), as well as in 1 case of incidental Lewy body disease (iLBD). A craniocaudal gradient of AS burden in sympathetic chain and gastrointestinal tract was observed. DLB cases showed higher amounts of CNS AS aggregates than PD cases, but this was not the case in the pANS. No pANS AS aggregates were detected in Alzheimer's disease (AD) cases with or without CNS AS aggregates. All pathologically confirmed LB disease cases including 1 case of iLBD had AS aggregates in the pANS with a craniocaudal gradient of pathology burden in sympathetic chain and gastrointestinal tract. AS was not detected in the pANS of any AD case. These findings may help in the search of peripheral AS aggregates in vivo for the early diagnosis of PD. PMID:24395122

  2. Advocacy, education, and the role of not-for-profit organizations in Lewy body dementias

    PubMed Central

    2014-01-01

    Lewy body dementias (LBDs) represent a spectrum of dementias that are associated with the presence of Lewy bodies in the brain and that dramatically impact both the person diagnosed and the family caregiver. LBD charities provide education of the public and health-care professionals, emotional support to families, and advocacy to policy-makers on the needs of LBD families and advance research. The US-based Lewy Body Dementia Association and the Lewy Body Society in the UK play an important role in reducing the burden that LBD places on families and society and provide leadership on issues affecting LBD families. Health-care providers are encouraged to refer families upon diagnosis to LBD charities as an additional resource to clinical care. PMID:26082807

  3. Advocacy, education, and the role of not-for-profit organizations in Lewy body dementias.

    PubMed

    Taylor, Angela; Yardley, Cecilia

    2014-01-01

    Lewy body dementias (LBDs) represent a spectrum of dementias that are associated with the presence of Lewy bodies in the brain and that dramatically impact both the person diagnosed and the family caregiver. LBD charities provide education of the public and health-care professionals, emotional support to families, and advocacy to policy-makers on the needs of LBD families and advance research. The US-based Lewy Body Dementia Association and the Lewy Body Society in the UK play an important role in reducing the burden that LBD places on families and society and provide leadership on issues affecting LBD families. Health-care providers are encouraged to refer families upon diagnosis to LBD charities as an additional resource to clinical care. PMID:26082807

  4. Validation of the Neuropathologic Criteria of the Third Consortium for Dementia with Lewy Bodies for Prospectively Diagnosed Cases

    PubMed Central

    Fujishiro, Hiroshige; Ferman, Tanis J.; Boeve, Bradley F.; Smith, Glenn E.; Graff-Radford, Neill R.; Uitti, Ryan J.; Wszolek, Zbigniew K.; Knopman, David S.; Petersen, Ronald C.; Parisi, Joseph E.; Dickson, Dennis W.

    2009-01-01

    There is limited information on the validity of the pathological criteria of the Third Consortium on Dementia with Lewy bodies (CDLB) and none based upon prospectively diagnosed cases. In this study the core clinical features of dementia with Lewy bodies (DLB) and the suggestive clinical feature of rapid eye movement sleep behavior disorder were assessed using a battery of standardized clinical instruments in 76 patients with the clinical diagnosis of either DLB or Alzheimer disease. At autopsy, 29 patients had high-likelihood, 17 had intermediate-likelihood and 6 had low-likelihood DLB pathology. The frequency of core clinical features and the accuracy of the clinical diagnosis of probable DLB were significantly greater in high-likelihood than in low-likelihood cases. This is consistent with the concept that the DLB clinical syndrome is directly related to Lewy body pathology and inversely related to Alzheimer pathology. Thus, the Third CDLB neuropathological criteria scheme performed reasonably well and is useful for estimating the likelihood of the premortem DLB syndrome based upon postmortem findings. In view of differences in the frequency of clinically probable DLB in cases with Braak NFT stages V (90%) and VI (20%) and diffuse cortical Lewy bodies, a possible modification of the scheme considering cases with NFT stage VI to be low-likelihood DLB is suggested. PMID:18596548

  5. Next-generation sequencing reveals substantial genetic contribution to dementia with Lewy bodies.

    PubMed

    Geiger, Joshua T; Ding, Jinhui; Crain, Barbara; Pletnikova, Olga; Letson, Christopher; Dawson, Ted M; Rosenthal, Liana S; Pantelyat, Alexander; Gibbs, J Raphael; Albert, Marilyn S; Hernandez, Dena G; Hillis, Argye E; Stone, David J; Singleton, Andrew B; Hardy, John A; Troncoso, Juan C; Scholz, Sonja W

    2016-10-01

    Dementia with Lewy bodies (DLB) is the second most common neurodegenerative dementia after Alzheimer's disease. Although an increasing number of genetic factors have been connected to this debilitating condition, the proportion of cases that can be attributed to distinct genetic defects is unknown. To provide a comprehensive analysis of the frequency and spectrum of pathogenic missense mutations and coding risk variants in nine genes previously implicated in DLB, we performed exome sequencing in 111 pathologically confirmed DLB patients. All patients were Caucasian individuals from North America. Allele frequencies of identified missense mutations were compared to 222 control exomes. Remarkably, ~25% of cases were found to carry a pathogenic mutation or risk variant in APP, GBA or PSEN1, highlighting that genetic defects play a central role in the pathogenesis of this common neurodegenerative disorder. In total, 13% of our cohort carried a pathogenic mutation in GBA, 10% of cases carried a risk variant or mutation in PSEN1, and 2% were found to carry an APP mutation. The APOE ε4 risk allele was significantly overrepresented in DLB patients (p-value <0.001). Our results conclusively show that mutations in GBA, PSEN1, and APP are common in DLB and consideration should be given to offer genetic testing to patients diagnosed with Lewy body dementia. PMID:27312774

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

    PubMed

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

    2016-03-01

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

  7. Selective loss of dopamine D2 receptors in temporal cortex in dementia with Lewy bodies, association with cognitive decline.

    PubMed

    Piggott, Margaret A; Ballard, Clive G; Rowan, Elise; Holmes, Clive; McKeith, Ian G; Jaros, Evelyn; Perry, Robert H; Perry, Elaine K

    2007-11-01

    Dementia with Lewy bodies (DLB) is a progressive dementia frequently accompanied by psychotic symptoms. Similar symptoms can occur in Alzheimer's disease (AD) to a lesser extent. The use of neuroleptic medication to treat psychosis in both diseases is of modest efficacy and can induce severe adverse reactions in DLB. Dopamine D2 receptors in the cerebral cortex are the putative target for the antipsychotic action of these drugs, but the status of these receptors in DLB is unknown. Autoradiography was used to examine the density D2 receptors in postmortem temporal cortex tissue from prospectively assessed patients with neuropathologically confirmed DLB and AD. D2 receptors were substantially (over 40%) and significantly (P < 0.001) reduced in temporal cortex in DLB, and in DLB with concomitant Alzheimer pathology, but was not significantly changed in AD. This reduction correlated with greater cognitive decline (P < 0.01), but was not significantly related to visual or auditory hallucinations or delusions. D2 receptor density was inversely correlated with cortical Lewy body pathology in the neocortex (P < 0.001). The specific loss of D2 receptors associated with Lewy body pathology, in conjunction with our previous finding of low D2 receptors in striatum in DLB, provides a possible explanation for neuroleptic intolerance. That the reduction of D2 receptors correlated with cognitive decline suggests that neuroleptics, as dopamine D2 receptor antagonists, may have a deleterious effect on cognition in DLB. PMID:17663455

  8. 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…

  9. Effects of gabapentin enacarbil on restless legs syndrome and leg pain in dementia with Lewy bodies.

    PubMed

    Fujishiro, Hiroshige

    2014-06-01

    Restless legs syndrome (RLS) is a common neurological disorder. Dementia with Lewy bodies (DLB) is the second most common form of neurodegenerative dementia after Alzheimer's disease. Both RLS and DLB can be effectively treated by dopaminergic medications, suggesting the role of dopamine dysfunction in the pathogenesis of both diseases. Here, I report on a Japanese woman with probable DLB and RLS who was treated with gabapentin enacarbil, a non-dopaminergic agent. Because a dopamine agonist, a first-line therapy for moderate to severe RLS, caused the occurrence of metamorphopsia, an alternative treatment of gabapentin enacarbil was used; this treatment improved the patient's RLS without worsening her psychiatric symptoms. An alternative treatment is desirable for DLB patients with RLS because they often experience intolerable side-effects with a dopamine agonist, especially visual hallucinations. Administering gabapentin enacarbil also improved the continuous leg pain that occurred in conjunction with the development of RLS. Although the neurobiological mechanism in the development of pain remains unclear, a range of non-dopaminergic structures likely mediated pain processing in DLB in the present case based on neuropharmacological results. This is the first report reporting the effects of gabapentin enacarbil for RLS and leg pain in a DLB patient with psychiatric symptoms. PMID:24528871

  10. In vivo imaging of neurodegeneration in dementia with Lewy bodies (DLB).

    PubMed

    Onyike, Chiadi U; Smith, Gwenn S

    2016-04-01

    For almost two decades, O'Brien and colleagues have investigated virtually every facet of dementia with Lewy bodies (DLB), phenomenology, treatment, and neurobiology, ranging from genetics to post-mortem and in vivo imaging studies. The latest study from this group, reported here, describes differences in regional grey matter volumes using magnetic resonance (MR) imaging and an automated segmentation analysis method in a well-characterized sample of patients with Alzheimer disease (AD), DLB, and a healthy control group (Watson et al., 2015). The study incorporated detailed psychometric assessments of cognitive and motor functions for correlation with the grey matter volumes, and age, gender and dementia severity were included as covariates in the statistical analysis. The key observations are relatively greater hippocampal volumes and lower subcortical volumes in DLB compared to AD, but it is to be noted that most of these differences in subcortical volume were demonstrated indirectly through comparisons of the disease groups with age-matched healthy control subjects. Thus, replication in studies that make direct comparisons between DLB and AD subjects, perhaps in a larger sample size, is necessary. Still, these results highlight the potential for MR imaging to provide indicators of the extent of the neurodegenerative process in DLB. Furthermore, the results underscore the importance of correcting molecular imaging data for the effects of cerebral atrophy (partial volume correction) that may further enhance the ability of these methods to reveal pathophysiological processes. PMID:27009322

  11. "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…

  12. Apolipoprotein E ε2 genotype delays onset of dementia with Lewy bodies in a Norwegian cohort

    PubMed Central

    Berge, Guro; Sando, Sigrid B; Rongve, Arvid; Aarsland, Dag; White, Linda R

    2014-01-01

    Background Results conflict concerning the relevance of APOE alleles on the development of dementia with Lewy bodies (DLB), though they are well established in connection with Alzheimer's disease (AD). The role of APOE alleles in a Norwegian cohort of patients with DLB was therefore examined compared with patients with AD and healthy control individuals. Methods The study included 156 patients with DLB diagnosed according to the consensus criteria guidelines, 519 patients diagnosed with AD according to the National Institute of Neurological and Communicative Diseases and Stroke/Alzheimer's Disease and Related Disorders Association (NINCDS/ARDRA) criteria and 643 healthy elderly volunteers. Patients were recruited through hospitals, outpatient clinics, nursing homes or from local care authorities in central and south-western parts of Norway. Healthy individuals were recruited from caregivers and societies for retired people. Results Subjects carrying an APOE ε2 allele had a reduced risk for developing DLB (OR 0.4, CI 0.3 to 0.8, p=0.004), and the onset of disease was delayed by 4 years (p=0.01, Mann–Whitney U test). Conversely, the APOE ε4 allele increased the risk for development of DLB (OR 5.9, CI 2.7 to 13.0, p<0.0005 for homozygotes). Similar results were found for patients with AD regarding the effect of APOE ε2, though the protective effect appeared to be slightly less pronounced than in DLB. This study is one of the largest regarding DLB and APOE to date. Conclusion The results indicate that APOE ε2, a protective factor in AD, has a clear beneficial effect on the development of DLB also. PMID:24639435

  13. 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. PMID:24491313

  14. Pattern of Brain Atrophy Rates in Autopsy-Confirmed Dementia with Lewy Bodies

    PubMed Central

    Nedelska, Zuzana; Ferman, Tanis J.; Boeve, Bradley F.; Przybelski, Scott A.; Lesnick, Timothy L.; Murray, Melissa E.; Gunter, Jeffrey L.; Senjem, Matthew L.; Vemuri, Prashanti; Smith, Glenn E.; Geda, Yonas E.; Graff-Radford, Jonathan; Knopman, David S.; Petersen, Ronald C.; Parisi, Joseph E.; Dickson, Dennis W.; Jack, Clifford R.; Kantarci, Kejal

    2014-01-01

    Dementia with Lewy bodies (DLB) is characterized by preserved whole brain and medial temporal lobe volumes compared to Alzheimer’s disease dementia (AD) on MRI. However, frequently coexistent AD-type pathology may influence the pattern of regional brain atrophy rates in DLB patients. We investigated the pattern and magnitude of the atrophy rates from two serial MRIs in autopsy-confirmed DLB (n=20) and mixed DLB/AD patients (n=22), compared to AD (n=30) and elderly non-demented controls (n=15), followed antemortem. DLB patients without significant AD-type pathology were characterized by lower global and regional rates of atrophy, similar to controls. The mixed DLB/AD patients displayed greater rates in the whole brain, temporo-parietal cortices, hippocampus and amygdala, and ventricle expansion, similar to AD patients. In the DLB and DLB/AD patients, the atrophy rates correlated with Braak neurofibrillary tangle stage, cognitive decline and progression of motor symptoms. Global and regional atrophy rates are associated with AD-type pathology in DLB, and can be used as biomarkers of AD progression in patients with LB pathology. PMID:25128280

  15. Driving Competence in Mild Dementia with Lewy Bodies: In Search of Cognitive Predictors Using Driving Simulation

    PubMed Central

    Yamin, Stephanie; Stinchcombe, Arne; Gagnon, Sylvain

    2015-01-01

    Driving is a multifactorial behaviour drawing on multiple cognitive, sensory, and physical systems. Dementia is a progressive and degenerative neurological condition that impacts the cognitive processes necessary for safe driving. While a number of studies have examined driving among individuals with Alzheimer's disease, less is known about the impact of Dementia with Lewy Bodies (DLB) on driving safety. The present study compared simulated driving performance of 15 older drivers with mild DLB with that of 21 neurologically healthy control drivers. DLB drivers showed poorer performance on all indicators of simulated driving including an increased number of collisions in the simulator and poorer composite indicators of overall driving performance. A measure of global cognitive function (i.e., the Mini Mental State Exam) was found to be related to the overall driving performance. In addition, measures of attention (i.e., Useful Field of View, UFOV) and space processing (Visual Object and Space Perception, VOSP, Test) correlated significantly with a rater's assessment of driving performance. PMID:26713169

  16. Protein Clearance Mechanisms of Alpha-Synuclein and Amyloid-Beta in Lewy Body Disorders

    PubMed Central

    Deleidi, Michela; Maetzler, Walter

    2012-01-01

    Protein clearance is critical for the maintenance of the integrity of neuronal cells, and there is accumulating evidence that in most—if not all—neurodegenerative disorders, impaired protein clearance fundamentally contributes to functional and structural alterations eventually leading to clinical symptoms. Dysfunction of protein clearance leads to intra- and extraneuronal accumulation of misfolded proteins and aggregates. The pathological hallmark of Lewy body disorders (LBDs) is the abnormal accumulation of misfolded proteins such as alpha-synuclein (Asyn) and amyloid-beta (Abeta) in a specific subset of neurons, which in turn has been related to deficits in protein clearance. In this paper we will highlight common intraneuronal (including autophagy and unfolded protein stress response) and extraneuronal (including interaction of neurons with astrocytes and microglia, phagocytic clearance, autoimmunity, cerebrospinal fluid transport, and transport across the blood-brain barrier) protein clearance mechanisms, which may be altered across the spectrum of LBDs. A better understanding of the pathways underlying protein clearance—in particular of Asyn and Abeta—in LBDs may result in the identification of novel biomarkers for disease onset and progression and of new therapeutic targets. PMID:23133788

  17. Regional Proton Magnetic Resonance Spectroscopy Patterns in Dementia with Lewy Bodies

    PubMed Central

    Graff-Radford, Jonathan; Boeve, Bradley F.; Murray, Melissa; Ferman, Tanis J.; Tosakulwong, Nirubol; Lesnick, Timothy G.; Maroney-Smith, Mandie; Senjem, Matthew L.; Gunter, Jeffrey; Smith, Glenn E.; Knopman, David S.; Jack, Clifford R.; Dickson, Dennis W.; Petersen, Ronald C.; Kantarci, Kejal

    2014-01-01

    Magnetic resonance spectroscopy (MRS) characteristics of dementia with Lewy bodies (DLB) Alzheimer’s disease (AD) and cognitively normal controls (CN) were compared. DLB (n=34), AD (n=35) and CN (n=148) participated in a MRS study from frontal, posterior cingulate and occipital voxels. We investigated DLB patients with preserved hippocampal volumes to determine the MRS changes in DLB with low probability of overlapping AD pathology. DLB patients were characterized by decreased NAA/Cr in the occipital voxel. AD patients were characterized by lower NAA/Cr in the frontal and posterior cingulate voxels. Normal NAA/Cr levels in the frontal voxel differentiated DLB patients with preserved hippocampal volumes from AD patients. DLB and AD patients had elevated Cho/Cr and mI/Cr in the posterior cingulate. MRS abnormalities associated with loss of neuronal integrity localized to the occipital lobes in DLB, and the posterior cingulate gyri and frontal lobes in AD. This pattern of MRS abnormalities may have a role in differential diagnosis of DLB and in distinguishing DLB patients with overlapping AD pathology. PMID:24468473

  18. 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

  19. 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. PMID:20451446

  20. Clinical and Cognitive Phenotype of Mild Cognitive Impairment Evolving to Dementia with Lewy Bodies

    PubMed Central

    Cagnin, Annachiara; Bussè, Cinzia; Gardini, Simona; Jelcic, Nela; Guzzo, Caterina; Gnoato, Francesca; Mitolo, Micaela; Ermani, Mario; Caffarra, Paolo

    2015-01-01

    Objective The aim of this study was to determine which characteristics could better distinguish dementia with Lewy bodies (DLB) from Alzheimer's disease (AD) at the mild cognitive impairment (MCI) stage, with particular emphasis on visual space and object perception abilities. Methods Fifty-three patients with mild cognitive deficits that were eventually diagnosed with probable DLB (MCI-DLB: n = 25) and AD (MCI-AD: n = 28) at a 3-year follow-up were retrospectively studied. At the first visit, the patients underwent cognitive assessment including the Qualitative Scoring Mini Mental State Examination Pentagon Test and the Visual Object and Space Perception Battery. The Neuropsychiatric Inventory Questionnaire, Unified Parkinson's Disease Rating Scale (UPDRS) and questionnaires for cognitive fluctuations and sleep disorders were also administered. Results The best clinical predictor of DLB was the presence of soft extrapyramidal signs (mean UPDRS score: 4.04 ± 5.9) detected in 72% of patients, followed by REM sleep behavior disorder (60%) and fluctuations (60%). Wrong performances in the pentagon's number of angles were obtained in 44% of DLB and 3.7% of AD patients and correlated with speed of visual attention. Executive functions, visual attention and visuospatial abilities were worse in DLB, while verbal episodic memory impairment was greater in AD. Deficits in the visual-perceptual domain were present in both MCI-DLB and AD. Conclusions Poor performance in the pentagon's number of angles is specific of DLB and correlates with speed of visual attention. The dorsal visual stream seems specifically more impaired in MCI-DLB with respect to the ventral visual stream, the latter being involved in both DLB and AD. These cognitive features, associated with subtle extrapyramidal signs, should alert clinicians to a diagnostic hypothesis of DLB. PMID:26674638

  1. Multicatalytic proteinase is associated with characteristic oval structures in cortical Lewy bodies: an immunocytochemical study with light and electron microscopy.

    PubMed

    Masaki, T; Ishiura, S; Sugita, H; Kwak, S

    1994-04-01

    The ATP-ubiquitin-dependent proteolytic pathway (ubiquitin pathway) is believed to be involved in the formation of various neuronal inclusion bodies including Lewy bodies (LBs), a pathological hallmark of Parkinson disease and diffuse Lewy body disease (DLBD). Since multicatalytic proteinase (MCP) is involved in the ubiquitin pathway, an investigation of whether MCP is involved in neuronal inclusion bodies would provide a clue to the mechanism underlying the formation of neuronal inclusion bodies as well as to the pathogenesis of degenerative neurological disorders. In this study, we investigated detailed immunolocalization of MCP in LBs in DLBD brains using light and electron microscopy. We raised three different monoclonal antibodies against purified human MCP. Each of them recognized different sets of MCP subunits on Western blotting. Immunohistochemically, anti-MCP antibodies recognized all ubiquitin-positive cortical LBs in situ as well as those isolated from frozen DLBD cortices, suggesting that MCP is present in LBs as a whole molecule exhibiting protease activity. In electron microscopy, MCP immunoreactivity (MCP-IR) was exclusively localized on a characteristic oval structure with an approximate diameter of 100 nm. This structure was distributed throughout the LBs and was devoid of ubiquitin immunoreactivity. Treatment of isolated LBs with 2% SDS, but not with 0.5% Triton X-100, removed this structure from LBs in which fibrous materials predominated. Ubiquitin immunoreactivity was also decreased in isolated LBs treated with 2% SDS, suggesting that the fibrous structures in LBs were not ubiquitinated in situ. Thus, it is suggested that LBs are subjected to a proteolytic process in which MCP plays a role via processing of specific components of LBs. PMID:8021694

  2. Clinical features of dementia with lewy bodies in 35 Chinese patients

    PubMed Central

    2014-01-01

    Objective To investigate the clinical features of dementia with Lewy bodies (DLB) in a Chinese population. Methods Computer-based online searches through China Biology Medicine disc and China National Knowledge Infrastructure were performed to collect case reports of DLB published between 1980 and 2012. Clinical characteristics were analyzed. Results A total of 18 studies comprising 35 patients (26 males and 9 females) were included. The mean age at onset was 67.2 ± 9.8 years. Onset was characterized by memory impairment and accounted for 58.8% of all cases, followed by parkinsonism (11.8%), visual hallucinations (8.8%), and compulsive personality disorder (2.9%). The other patients (17.6%) presented two of the three core features of DLB at onset. With disease progression, parkinsonism was reported in 100% of cases, followed by visual hallucinations (97.1%), psychiatric symptoms (85.7%), severe neuroleptic sensitivity (81.8%), fluctuating cognition (68.6%), repeated falls (40.0%), sleep disorders (22.9%), and transient loss of consciousness (17.1%). 26 patients who were subjected to Mini-Mental State Examination scored ≤ 24. 10 patients presented relative preservation of hippocampus and medial temporal lobe structures on CT/MRI scan. Occipital hypometabolism occurred in 2 of 3 patients who underwent SPECT/PET perfusion scan. 12 patients showed an increasing of slow frequency activity on EEG, prominently in frontal and temporal lobes. Conclusions DLB often strikes elderly individuals. Its clinical core features are dementia, fluctuating cognition, recurrent visual hallucinations and spontaneous features of parkinsonism. Neuropsychological, neuroimaging and EEG examinations may improve the diagnostic accuracy and discriminate DLB from other dementias. PMID:24398160

  3. Cognitive decline in dementia with Lewy bodies: a 5-year prospective cohort study

    PubMed Central

    Rongve, A; Soennesyn, H; Skogseth, Ragnhild; Oesterhus, Ragnhild; Hortobágyi, T; Ballard, Clive; Auestad, B H; Aarsland, D

    2016-01-01

    Objectives We report the cognitive decline in persons diagnosed with mild dementia with Lewy bodies (DLB) and mild Alzheimer's disease (AD) during 5 years of annual follow-ups. Methods Patients were recruited into the study from geriatric, psychiatric and neurology clinics in Western Norway during 2005–2013. They were diagnosed according to clinical consensus criteria, based on standardised clinical rating scales. Autopsy-based diagnoses were available for 20 cases. Cognitive decline for up to 5 years was assessed using the Clinical Dementia Rating (CDR) scale and the Mini-Mental State Examination (MMSE). Survival analysis including Cox regression (time to reach severe dementia) and linear mixed-effects (lme) modelling were used to model the decline on MMSE. Results At least one follow-up assessment was available for 67 patients with DLB and 107 patients with AD, with a median follow-up time of 4.3 years. The time to reach severe dementia was significantly shorter in DLB (median 1793 days) compared with AD (1947 days; p=0.033), and the difference remained significant in the multiple Cox regression analysis (HR=2.0, p<0.02). In the adjusted lme model, MMSE decline was faster in DLB (annual decline 4.4 points) compared with AD (3.2 points; p<0.008). Conclusions Our findings show that from the mild dementia stage, patients with DLB have a more rapid cognitive decline than in AD. Such prognostic information is vital for patients and families and crucial for planning clinical trials and enabling health economic modelling. PMID:26928028

  4. The relationship between hallucinations and FDG-PET in dementia with Lewy bodies.

    PubMed

    Firbank, Michael J; Lloyd, Jim; O'Brien, John T

    2016-09-01

    Visual hallucinations are common in dementia with Lewy bodies (DLB), although their etiology is unclear. This study aimed to investigate the relationship between severity and frequency of hallucinations and regional brain glucose metabolism. We performed brain FDG-PET scanning on 28 subjects with DLB (mean age 76). The neuropsychiatric index (NPI) was used to assess frequency and severity of hallucinations. We used the SPM package to investigate voxelwise correlations between NPI hallucination score (severity x frequency) and FDG uptake relative to the cerebellum. There was a bilateral medial occipital region where reduced FDG was associated with increased hallucination severity and frequency. We conclude that the reduced occipital metabolism frequently seen in DLB is associated with frequency and severity of visual hallucinations. Further studies are required to investigate whether this is the result of deficits in top-down or bottom-up visual processing pathways. PMID:26239998

  5. Hallucinations predict attentional improvements with rivastigmine in dementia with lewy bodies.

    PubMed

    McKeith, Ian G; Wesnes, Keith A; Perry, Elaine; Ferrara, Roberto

    2004-01-01

    The aim of this analysis of the effects of cholinergic therapy in dementia with Lewy bodies was to determine whether rivastigmine-induced benefits in attention and memory could be predicted by the presence of visual hallucinations. At study entry, 74% of patients were hallucinators and 26% were non-hallucinators. The population was analyzed for two-factor scores: power of attention (PoA) and quality of memory (QoM). A significant effect over placebo on PoA was observed in hallucinators at weeks 12 (p = 0.023) and 20 (p = 0.0019), while no treatment effects were seen in non-hallucinators. Significant treatment effects on QoM were not observed in either subgroup. Visual hallucinations predicted greater improvements in PoA, but not QoM. This may reflect the greater cholinergic deficits in areas of the brain responsible for visual hallucinations, offering greater potential for attentional improvement. PMID:15087584

  6. 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. PMID:24973356

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

    PubMed Central

    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

    2014-01-01

    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. PMID:24973356

  8. White matter integrity in dementia with Lewy bodies: a voxel-based analysis of diffusion tensor imaging.

    PubMed

    Nedelska, Zuzana; Schwarz, Christopher G; Boeve, Bradley F; Lowe, Val J; Reid, Robert I; Przybelski, Scott A; Lesnick, Timothy G; Gunter, Jeffrey L; Senjem, Matthew L; Ferman, Tanis J; Smith, Glenn E; Geda, Yonas E; Knopman, David S; Petersen, Ronald C; Jack, Clifford R; Kantarci, Kejal

    2015-06-01

    Many patients with dementia with Lewy bodies (DLB) have overlapping Alzheimer's disease (AD)-related pathology, which may contribute to white matter (WM) diffusivity alterations on diffusion tensor imaging (DTI). Consecutive patients with DLB (n = 30), age- and sex-matched AD patients (n = 30), and cognitively normal controls (n = 60) were recruited. All subjects underwent DTI, 18F 2-fluoro-deoxy-d-glucose, and (11)C Pittsburgh compound B positron emission tomography scans. DLB patients had reduced fractional anisotropy (FA) in the parietooccipital WM but not elsewhere compared with cognitively normal controls, and elevated FA in parahippocampal WM compared with AD patients, which persisted after controlling for β-amyloid load in DLB. The pattern of WM FA alterations on DTI was consistent with the more diffuse posterior parietal and occipital glucose hypometabolism of 2-fluoro-deoxy-d-glucose positron emission tomography in the cortex. DLB is characterized by a loss of parietooccipital WM integrity, independent of concomitant AD-related β-amyloid load. Cortical glucose hypometabolism accompanies WM FA alterations with a concordant pattern of gray and WM involvement in the parietooccipital lobes in DLB. PMID:25863527

  9. White matter integrity in dementia with Lewy bodies: A Voxel-Based Analysis of Diffusion Tensor Imaging

    PubMed Central

    Nedelska, Zuzana; Schwarz, Christopher G.; Boeve, Bradley F.; Lowe, Val; Reid, Robert I.; Przybelski, Scott A.; Lesnick, Timothy G.; Gunter, Jeffrey L.; Senjem, Matthew L.; Ferman, Tanis J.; Smith, Glenn E.; Geda, Yonas E.; Knopman, David S.; Petersen, Ronald C.; Jack, Clifford R.; Kantarci, Kejal

    2015-01-01

    Many patients with dementia with Lewy bodies have overlapping Alzheimer's disease (AD)–related pathology, which may contribute to white matter (WM) diffusivity alterations on diffusion tensor imaging (DTI). Consecutive patients with DLB (n=30), age and sex matched AD patients (n=30), and cognitively normal controls (CN; n=60) were recruited. All subjects underwent DTI, 18F 2-fluoro-deoxy-d-glucose (FDG) and 11C Pittsburgh compound B (PiB) PET scans. DLB patients had reduced fractional anisotropy (FA) in the parieto-occipital WM but not elsewhere compared to CN, and elevated FA in parahippocampal WM compared to AD patients, which persisted after controlling for Aβ load in DLB. The pattern of WM FA alterations on DTI was consistent with the more diffuse posterior parietal and occipital glucose hypometabolism of FDG PET in the cortex. DLB is characterized by a loss of parieto-occipital WM integrity, independent of concomitant AD-related Aβ load. Cortical glucose hypometabolism accompanies WM FA alterations with a concordant pattern of gray and white matter involvement in the parieto-occipital lobes in DLB. PMID:25863527

  10. Reduced vascular endothelial growth factor and capillary density in the occipital cortex in dementia with Lewy bodies.

    PubMed

    Miners, Scott; Moulding, Hayley; de Silva, Rohan; Love, Seth

    2014-07-01

    In dementia with Lewy bodies (DLB), blood flow tends to be reduced in the occipital cortex. We previously showed elevated activity of the endothelin and angiotensin pathways in Alzheimer's disease (AD). We have measured endothelin-1 (ET-1) level and angiotensin-converting enzyme (ACE) activity in the occipital cortex in DLB and control brains. We also measured vascular endothelial growth factor (VEGF); factor VIII-related antigen (FVIIIRA) to indicate microvessel density; myelin-associated glycoprotein (MAG), a marker of ante-mortem hypoperfusion; total α-synuclein (α-syn) and α-synuclein phosphorylated at Ser129 (α-syn-p129). In contrast to findings in AD, ACE activity and ET-1 level were unchanged in DLB compared with controls. VEGF and FVIIIRA levels were, however, significantly lower in DLB. VEGF correlated positively with MAG concentration (in keeping with a relationship between reduction in VEGF and hypoperfusion), and negatively with α-syn and α-syn-p129 levels. Both α-syn and α-syn-p129 levels increased in human SH-SY5Y neuroblastoma cells after oxygen-glucose deprivation (OGD), and VEGF level was reduced in SH-SY5Y cells overexpressing α-syn. Taken together, our findings suggest that reduced microvessel density rather than vasoconstriction is responsible for lower occipital blood flow in DLB, and that the loss of microvessels may result from VEGF deficiency, possible secondary to the accumulation of α-syn. PMID:24521289

  11. 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

  12. Delirium and dementia with Lewy bodies: distinct diagnoses or part of the same spectrum?

    PubMed

    Gore, Rachel L; Vardy, Emma R L C; O'Brien, John T

    2015-01-01

    Dementia with Lewy bodies (DLB) is recognised as the second most common form of dementia in older people. Delirium is a condition of acute brain dysfunction for which a pre-existing diagnosis of dementia is a risk factor. Conversely delirium is associated with an increased risk of developing dementia. The reasons for this bidirectional relationship are not well understood. Our aim was to review possible similarities in the clinical presentation and pathophysiology between delirium and DLB, and explore possible links between these diagnoses. A systematic search using Medline, Embase and Psychinfo was performed. References were scanned for relevant articles, supplemented by articles identified from reference lists and those known to the authors. 94 articles were selected for inclusion in the review. Delirium and DLB share a number of clinical similarities, including global impairment of cognition, fluctuations in attention and perceptual abnormalities. Delirium is a frequent presenting feature of DLB. In terms of pathophysiological mechanisms, cholinergic dysfunction and genetics may provide a common link. Neuroimaging studies suggest a brain vulnerability in delirium which may also occur in dementia. The basal ganglia, which play a key role in DLB, have also been implicated in delirium. The role of Cerebrospinal fluid (CSF) and serum biomarkers for both diagnoses is an interesting area although some results are conflicting and further work in this area is needed. Delirium and DLB share a number of features and we hypothesise that delirium may, in some cases, represent early or 'prodromal' DLB. Further research is needed to test the novel hypothesis that delirium may be an early marker for future DLB, which would aid early diagnosis of DLB and identify those at high risk. PMID:24860139

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

    PubMed

    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

  14. 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

  15. 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

  16. 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. PMID:23782134

  17. Constitutive renal Rel/nuclear factor-κB expression in Lewis polycystic kidney disease rats

    PubMed Central

    Ta, Michelle H T; Schwensen, Kristina G; Liuwantara, David; Huso, David L; Watnick, Terry; Rangan, Gopala K

    2016-01-01

    AIM: To determine the temporal expression and pattern of Rel/nuclear factor (NF)-κB proteins in renal tissue in polycystic kidney disease (PKD). METHODS: The renal expression of Rel/NF-κB proteins was determined by immunohistochemistry, immunofluorescence and immunoblot analysis in Lewis polycystic kidney rats (LPK, a genetic ortholog of human nephronopthsis-9) from postnatal weeks 3 to 20. At each timepoint, renal disease progression and the mRNA expression of NF-κB-dependent genes (TNFα and CCL2) were determined. NF-κB was also histologically assessed in human PKD tissue. RESULTS: Progressive kidney enlargement in LPK rats was accompanied by increased renal cell proliferation and interstitial monocyte accumulation (peaking at weeks 3 and 10 respectively), and progressive interstitial fibrosis (with α smooth muscle actin and Sirius Red deposition significantly increased compared to Lewis kidneys from weeks 3 to 6 onwards). Rel/NF-κB proteins (phosphorylated-p105, p65, p50, c-Rel and RelB) were expressed in cystic epithelial cells (CECs) of LPK kidneys as early as postnatal week 3 and sustained until late-stage disease at week 20. From weeks 10 to 20, nuclear p65, p50, RelB and cytoplasmic IκBα protein levels, and TNFα and CCL2 expression, were upregulated in LPK compared to Lewis kidneys. NF-κB proteins were consistently expressed in CECs of human PKD. The DNA damage marker γ-H2AX was also identified in the CECs of LPK and human polycystic kidneys. CONCLUSION: Several NF-κB proteins are consistently expressed in CECs in human and experimental PKD. These data suggest that the upregulation of both the canonical and non-canonical pathways of NF-κB signaling may be a constitutive and early pathological feature of cystic renal diseases. PMID:27458563

  18. Diagnostic Accuracy of 123I-Meta-Iodobenzylguanidine Myocardial Scintigraphy in Dementia with Lewy Bodies: A Multicenter Study

    PubMed Central

    Yoshita, Mitsuhiro; Arai, Heii; Arai, Hiroyuki; Arai, Tetsuaki; Asada, Takashi; Fujishiro, Hiroshige; Hanyu, Haruo; Iizuka, Osamu; Iseki, Eizo; Kashihara, Kenichi; Kosaka, Kenji; Maruno, Hirotaka; Mizukami, Katsuyoshi; Mizuno, Yoshikuni; Mori, Etsuro; Nakajima, Kenichi; Nakamura, Hiroyuki; Nakano, Seigo; Nakashima, Kenji; Nishio, Yoshiyuki; Orimo, Satoshi; Samuraki, Miharu; Takahashi, Akira; Taki, Junichi; Tokuda, Takahiko; Urakami, Katsuya; Utsumi, Kumiko; Wada, Kenji; Washimi, Yukihiko; Yamasaki, Junichi; Yamashina, Shouhei; Yamada, Masahito

    2015-01-01

    Background and Purpose Dementia with Lewy bodies (DLB) needs to be distinguished from Alzheimer’s disease (AD) because of important differences in patient management and outcome. Severe cardiac sympathetic degeneration occurs in DLB, but not in AD, offering a potential system for a biological diagnostic marker. The primary aim of this study was to investigate the diagnostic accuracy, in the ante-mortem differentiation of probable DLB from probable AD, of cardiac imaging with the ligand 123I-meta-iodobenzylguanidine (MIBG) which binds to the noradrenaline reuptake site, in the first multicenter study. Methods We performed a multicenter study in which we used 123I-MIBG scans to assess 133 patients with clinical diagnoses of probable (n = 61) or possible (n = 26) DLB or probable AD (n = 46) established by a consensus panel. Three readers, unaware of the clinical diagnosis, classified the images as either normal or abnormal by visual inspection. The heart-to-mediastinum ratios of 123I-MIBG uptake were also calculated using an automated region-of-interest based system. Results Using the heart-to-mediastinum ratio calculated with the automated system, the sensitivity was 68.9% and the specificity was 89.1% to differentiate probable DLB from probable AD in both early and delayed images. By visual assessment, the sensitivity and specificity were 68.9% and 87.0%, respectively. In a subpopulation of patients with mild dementia (MMSE ≥ 22, n = 47), the sensitivity and specificity were 77.4% and 93.8%, respectively, with the delayed heart-to-mediastinum ratio. Conclusions Our first multicenter study confirmed the high correlation between abnormal cardiac sympathetic activity evaluated with 123I-MIBG myocardial scintigraphy and a clinical diagnosis of probable DLB. The diagnostic accuracy is sufficiently high for this technique to be clinically useful in distinguishing DLB from AD, especially in patients with mild dementia. PMID:25793585

  19. 100 years of Lewy pathology.

    PubMed

    Goedert, Michel; Spillantini, Maria Grazia; Del Tredici, Kelly; Braak, Heiko

    2013-01-01

    In 1817, James Parkinson described the symptoms of the shaking palsy, a disease that was subsequently defined in greater detail, and named after Parkinson, by Jean-Martin Charcot. Parkinson expected that the publication of his monograph would lead to a rapid elucidation of the anatomical substrate of the shaking palsy; in the event, this process took almost a century. In 1912, Fritz Heinrich Lewy identified the protein aggregates that define Parkinson disease (PD) in some brain regions outside the substantia nigra. In 1919, Konstantin Nikolaevich Tretiakoff found similar aggregates in the substantia nigra and named them after Lewy. In the 1990s, α-synuclein was identified as the main constituent of the Lewy pathology, and its aggregation was shown to be central to PD, dementia with Lewy bodies, and multiple system atrophy. In 2003, a staging scheme for idiopathic PD was introduced, according to which α-synuclein pathology originates in the dorsal motor nucleus of the vagal nerve and progresses from there to other brain regions, including the substantia nigra. In this article, we review the relevance of Lewy's discovery 100 years ago for the current understanding of PD and related disorders. PMID:23183883

  20. The ABO, Lewis or P blood group phenotypes are not associated with recurrent pelvic inflammatory disease.

    PubMed

    Lurie, S; Sigler, E; Fenakel, K

    1991-01-01

    An assumption that ABO, Lewis, or P blood group phenotypes are associated with recurrent pelvic inflammatory disease (PID) in a similar way as with recurrent urinary tract infection has been tried to establish. Of 20 patients with PID 9 (45%) had blood type A, 6 (30%) type B, 1 (5%) type AB and 4 (20%) type O; 14 (70%) had Le(a-b+), 5 (25%) had Le(a+b-), and 1 (5%) had Le(a-b-). Of the 20 controls 10 (50%) had blood type A, 3 (15%) type B, 1 (5%) type AB and 6 (30%) type O; 12 (60%) had Le(a-b+), 4 (20%) had Le(a+b-), and 4 (20%) had Le(a-b-). The difference in the proportions of the A, B, AB, and O phenotypes as well as the proportion of combined recessive and nonsecretor phenotype Le(a+/-b-) between patients with recurrent PID and controls were not statistically significant. The distribution was consistent with that in the general population. 2 of the patient group (10%) and 6 (30%) of the controls had positive blood type P1 (Fisher's exact probability = 0.0958). The distribution of P1 between the patients and controls was opposite to that in the general population. We could not demonstrate association of ABO, Lewis or P blood group phenotypes with recurrent PID. PMID:2071054

  1. 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

    2016-01-01

    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. PMID:27609071

  2. Proteomic analysis of mitral valve in Lewis rat with acute rheumatic heart disease

    PubMed Central

    Li, Wenting; Zeng, Zhiyu; Gui, Chun; Zheng, Huilei; Huang, Weiqiang; Wei, Heng; Gong, Danping

    2015-01-01

    Rheumatic heart disease (RHD) makes a heavy burden in human lives and economy. The proteomic analysis of acute rheumatic heart disease (ARHD) can provide precious data to study RHD at the early stages, but no one has looked into. So based on our early research we applied the method of continuous GAS stimulation on Lewis rats to duplicate the animal model of ARHD. And the mitral valves of rats in control group (n=10) and ARHD group (n=10) were selected for proteomic analysis of ARHD with the iTRAQ labeling based 2D LC-ESI-MS/MS quantitative technology. We identified 3931 proteins in valve tissue out of which we obtained 395 differentially expressed proteins containing 176 up-regulated proteins and 119 down-regulated proteins. Changes in levels of GAPDH (6.793 times higher than the control group) and CD9 (2.63 times higher than the control group) were confirmed by Western blot or immunohistochemistry. The differentially expressed proteins such as GAPDH, CD9, myosin, collagen and RAC1 may be potential biomarkers for ARHD. Moreover, the mitral valve protein profile shed light on further understanding and investigating ARHD. PMID:26823728

  3. [A Patient with Probable Dementia with Lewy Bodies and Positive Autoantibodies against the Anti-NH2-terminal of α-Enolase].

    PubMed

    Ikura, Takahiro; Fujishiro, Hiroshige; Takahashi, Yukitoshi; Yoneda, Makoto; Saito, Tomoyuki; Chiba, Yuhei; Kamada, Ayuko; Katsuse, Omi; Hirayasu, Yoshio

    2015-07-01

    Dementia with Lewy bodies (DLB) is clinically characterized by progressive dementia that is frequently accompanied by neurological and psychiatric manifestations. Hashimoto's encephalopathy (HE) is a rare autoimmune disease with neurological and psychiatric manifestations that is not well understood. However, this disease has attracted growing attention as a treatable dementia. Although autoimmune mechanisms are thought to play a pathogenic role in HE, the etiology of the disease remains unclear. Recently, it was reported that the serum in patients with HE is frequency positive for autoantibodies against the anti-NH2-terminal of α-enolase (anti-NAE), indicating a useful serological diagnostic marker for HE. We report the case of an 81-year-old Japanese woman with probable DLB and hypothyroidism. In her serum, elevated anti-thyroid antibodies and positive autoantibodies against anti-NAE were observed. Elevated levels of anti-glutamate receptor ε2 subunit (GluRε2) antibodies were also detected in her cerebrospinal fluid. Because her clinical condition became stable after treatment with cholinesterase inhibitor, levodopa, and levothyroxine, immunotherapy was not performed. Although the relationship between autoimmunity and cognitive decline in this patient was unclear, the present observations suggest the coexistence of neurodegeneration and autoimmunity as the underlying pathogenic mechanism. PMID:26160824

  4. Dementia with Lewy bodies presenting marked tongue protrusion and bite due to lingual dystonia: A case report.

    PubMed

    Shiga, Yuji; Kanaya, Yuhei; Kono, Ryuhei; Takeshima, Shinichi; Shimoe, Yutaka; Kuriyama, Masaru

    2016-06-22

    We report the patient of a 53-year-old woman who developed subacute-onset marked tonge protrusion and bite. She was diagnosed as dementia with Lewy bodies (DLB) from the clinical features including progressive cognitive decline, visual hallucinations, parkinsonism, and severe insomnia and depression, and the radiological finding of low dopamine transported uptake in basal ganglia by Dat SCAN and low blood circulation in occipital lobe of cerebrum. The patient received 600 mg doses of levodopa for over a year, followed by rotigotine and ropinirole with a rapid increase of dosage. It is believed that these treatments stimulated and sensitized dopamine D1 receptors, thereby inducing lingual dystonia. Furthermore, the patient demonstrated dyspnea and attacks of apnea caused by the closure of bilateral vocal cords due to laryngeal dyskinesia. After initiation of the neuroleptic, olanzapine, for a short duration, the high dose of levodopa overlapped with neuroleptic sensitivity, suggesting DOPA-induced dystonia and dyskinesia. This interaction can sometimes lead to lethal adverse events, and must be considered very important when treating patients with DLB. PMID:27212676

  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

    2016-01-01

    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. PMID:27357212

  6. Neural Stem Cells Rescue Cognitive and Motor Dysfunction in a Transgenic Model of Dementia with Lewy Bodies through a BDNF-Dependent Mechanism

    PubMed Central

    Goldberg, Natalie R.S.; Caesar, Jacqueline; Park, Ashley; Sedgh, Shawn; Finogenov, Gilana; Masliah, Eliezer; Davis, Joy; Blurton-Jones, Mathew

    2015-01-01

    Summary Accumulation of α-synuclein (α-syn) into insoluble aggregates occurs in several related disorders collectively referred to as synucleinopathies. To date, studies have used neural stem cells (NSCs) to examine questions about α-syn propagation, but have overlooked the therapeutic potential of NSC transplantation to modulate cognition in disorders such as dementia with Lewy bodies or Parkinson’s disease dementia. Here, we show that striatal transplantation of NSCs into aged α-syn transgenic mice significantly improves performance in multiple cognitive and motor domains. This recovery is associated with NSC expression of brain-derived neurotrophic factor (BDNF), which restores depleted levels and modulates dopaminergic and glutamatergic systems. Most importantly, transplantation of BDNF-depleted NSCs fails to improve behavior, whereas AAV-mediated BDNF delivery mimics the benefits of NSC transplantation, supporting a critical role for this neurotrophin in functional improvement. Thus, NSC transplantation could offer a promising approach to treat the understudied yet devastating cognitive components of many synucleinopathies. PMID:26489892

  7. Lewy Body Dementia Glossary

    MedlinePlus

    ... most often involve visual disturbances, such as the perception of lights, lines, shimmering, distortions in the appearance ... for complex processes such as problem solving, attention, perception, advanced motor function, language, and memory. cerebrospinal fluid ( ...

  8. Lewy Body Dementia Association

    MedlinePlus

    ... Related Organizations LBD stories submit a caregiver story forums Research Research Articles Research Abstracts Clinical Trials Resources ... support Patients and Caregiver Services LBD Stories Discussion Forums Local LBD Support Groups Virtual Groups We are ...

  9. 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

  10. Small intestine perforation due to accidental press-through package ingestion in an elderly patient with Lewy body dementia and recurrent cardiopulmonary arrest.

    PubMed

    Hashizume, Tsuyoshi; Tokumaru, Aya M; Harada, Kazumasa

    2015-01-01

    An octogenarian with Lewy body dementia presented to our hospital in cardiac arrest and was successfully resuscitated. Although he had abdominal pain the previous day, small bowel wall oedema and ascites were the only abnormalities noted on abdominal CT. Despite treatment with catecholamines and antimicrobials, he died of recurrent cardiopulmonary arrest later the same day. An autopsy showed that the patient's death was the result of a small bowel perforation caused by accidental ingestion of a press-through package (PTP). Precautions regarding PTP use and improved packaging design are necessary to prevent PTP ingestion, especially in elderly patients with dementia. PMID:26678691

  11. alpha 4 Integrins and sialyl Lewis x modulation in chronic Chagas disease: further evidence of persistent immune activation.

    PubMed

    Laucella, S A; Riarte, A; Prado, N; Zapata, J; Segura, E L

    2001-05-01

    We have previously shown that titers of soluble platelet selectin (s-P-selectin) and soluble vascular cell adhesion molecule-1 (s-VCAM-1) were increased in sera of patients with chronic Trypanosoma cruzi infection. In this study, we analyzed the expression of CD49d-integrins, that bind to VCAM-1, and sialyl Lewis x (SLe(x)), which binds selectins, in peripheral blood lymphocytes of 27 patients with Chagas' disease at different levels of disease severity. Patients with a mild form of Chagas' disease showed a lower number of CD49d(+) cells, in comparison with those with severe chronic cardiopathy. Decreased levels of CD49d(+) cells were detected in CD3(-) cell populations. Conversely, SLe(x) expression was found to be decreased in patients with severe Chagas' disease. Levels of soluble platelet endothelial cell adhesion molecule-1 (s-PECAM-1) were significantly increased in the plasma of patients with severe Chagas' disease while unaltered levels of MCP-1 were recorded. These data show that VCAM-1 and P-Selectin ligands are differentially expressed during the chronic phase of the Trypanosoma cruzi infection. These findings also reinforce a role of the P-selectin/SLe(x) adhesion pathway rather than very late antigen-4 (VLA-4)/VCAM-1, in the pathogenesis of Chagas' disease. PMID:11309161

  12. Multisensory body representation in autoimmune diseases.

    PubMed

    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

  13. 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

  14. 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.

  15. Body fluid biomarkers in Alzheimer's disease.

    PubMed

    Lu, Huan; Zhu, Xi-Chen; Jiang, Teng; Yu, Jin-Tai; Tan, Lan

    2015-04-01

    A heterogeneous and slowly progressive disease with extracellular amyloid-β (Aβ) deposits and intracellular hyperphosphorylated tau protein aggregates, Alzheimer's disease (AD) is already a hard nut to crack, featured with cognitive decline and memory lapse. Body fluid biomarkers are proved to be useful in exploring further study of AD, might benefit for a full comprehension of the etiopathogenesis, an improved precision of the prognosis and diagnosis, and a positive response of treatments. The cerebrospinal fluid biomarkers Aβ, total tau, and hyperphosphorylated tau reflect the main pathologic changes of AD. We also review data from several novel biomarkers, such as, β-site APP cleaving enzyme 1, soluble amyloid precursor proteins α and β, soluble Aβ oligomers and so on, which are associated with the occurrence and deterioration of this disease and couldn't be ignored. The rationale for the clinical use of those biomarkers, the challenges faced with and the properties of the most appropriate biomarkers are also summarized in the paper. We aim to find several ideal biomarkers to improve the diagnosis and optimize the treatment respectively. PMID:25992369

  16. Parkinson's Disease Dementia

    MedlinePlus

    ... Is Dementia Types of Dementia Chronic Traumatic Encephalopathy (CTE) Creutzfeldt-Jakob Disease Dementia with Lewy Bodies Down ... Research Traumatic Brain Injury and Chronic Traumatic Encephalopathy (CTE) Awardees Year Researcher Study Name 2015 Jesse Mez ...

  17. Petrology and geochemistry of Patuxent Range 91501, a clast-poor impact-melt from the L chondrite parent body, and Lewis Cliff 88663, an L7 chondrite

    NASA Astrophysics Data System (ADS)

    Mittlefehldt, David W.; Lindstrom, Marilyn M.

    2001-03-01

    We have performed petrologic and geochemical studies of Patuxent Range 91501 and Lewis Cliff 88663. PAT 91501, originally classified as an L7 chondrite, is rather a unique, near total impact-melt from the L chondrite parent body. Lewis Cliff 88663 was originally classified as an "achondrite (?)," but we find that it is a very weakly shocked L7 chondrite. PAT 91501 is an unshocked, homogeneous, igneous-textured ultramafic rock composed of euhedral to subhedral olivine, low-Ca pyroxene, augite and chrome-rich spinels with interstitial albitic plagioclase and minor silica-alumina-alkali-rich glass. Only ~10% relict chondritic material is present. Olivine grains are homogeneous (Fa25.2-26.8). Low-Ca pyroxene (Wo1.9-7.2En71.9-78.2Fs19.9-20.9) and augite (Wo29.8-39.0En49.2-55.3Fs11.8-14.9) display a strong linear TiO2-Al2O3 correlations resulting from igneous fractionation. Plagioclase is variable in composition; Or3.0-7.7Ab79.8-84.1An8.2-17.2. Chrome-rich spinels are variable in composition and zoned from Cr-rich cores to Ti-Al-rich rims. Some have evolved compositions with up to 7.9 wt% TiO2. PAT 91501 bulk silicate has an L chondrite lithophile element composition except for depletions in Zn and Br. Siderophile and chalcophile elements are highly depleted due to sequestration in cm-size metal-troilite nodules. The minerals in LEW 88663 are more uniform in composition than those in PAT 91501. Olivine grains have low CaO and Cr2O3 contents similar to those in L5-6 chondrites. Pyroxenes have high TiO2 contents with only a diffuse TiO2-Al2O3 correlations. Low-Ca pyroxenes are less calcic (Wo1.6-3.1En76.5-77.0Fs20.4-21.4), while augites (Wo39.5-45.6En46.8-51.1Fs7.6-9.4) and plagioclases (Or2.6-5.7Ab74.1-83.1An11.2-23.3) are more calcic. Spinels are homogeneous and compositionally similar to those in L6 chondrites. LEW 88663 has an L chondrite bulk composition for lithophile elements, and only slight depletions in siderophile and chalcophile elements that are plausibly due

  18. Treating the whole body in Huntington's disease.

    PubMed

    Carroll, Jeffrey B; Bates, Gillian P; Steffan, Joan; Saft, Carsten; Tabrizi, Sarah J

    2015-11-01

    Huntington's disease is a genetic neurodegenerative disorder with symptoms that are linked to the progressive dysfunction and neuronal death in corticostriatal circuits. The causative gene (mutated HTT) is widely expressed outside the CNS and several peripheral signs of disease, including weight loss and increased proinflammatory signalling, are often seen; however, their importance in the pathophysiology of Huntington's disease is not clear. Studies in animals have shown that features of the disease involving the CNS, including synapse loss and behavioural alterations, are susceptible to modulation by treatments that target tissues and organs outside the CNS. Links between peripheral biology and neurodegeneration have also been shown in other chronic neurodegenerative diseases, suggesting that modulation of these peripheral targets can offer new approaches to therapeutic development. Treatments targeted to tissues and organs outside the CNS might therefore substantially improve the quality of life of patients with Huntington's disease, even in the absence of disease-modifying effects. PMID:26466780

  19. 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

  20. Association between Human Body Composition and Periodontal Disease.

    PubMed

    Salekzamani, Yagoub; Shirmohammadi, Adileh; Rahbar, Mohammad; Shakouri, Seyed-Kazem; Nayebi, Farough

    2011-01-01

    Obesity in humans might increase the risk of periodontitis. The aim of the present study was to examine the relationship between body composition of males and their periodontal status. AS total of 150 males (aged 30-60) were selected: 31 were periodontally healthy, 45 had gingivitis, 39 had initial periodontitis, and 35 suffered from established periodontitis. BMI (body mass index), WC (waist circumference), and body composition parameters (consisting of body water, body fat, and skeletal muscle and bone mass) were measured. After adjusting for age, history of diabetes, smoking, physical activity status, and socioeconomic status, statistically significant correlations were found between periodontitis and BMI, WC, and body composition. There was only a statistically significant difference between the periodontal health and established periodontitis; that is, periodontal disease in mild forms (gingivitis) and initial periodontitis do not influence these variables (BMI, WC, and body composition parameters) and only the severe form of the disease influences the variables. These data suggest that there is a considerable association between severe forms of periodontal disease in males and their body composition, but this preliminary finding needs to be confirmed in more extensive studies. PMID:22111011

  1. 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…

  2. 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

  3. Carotid body tumor imitator: An interesting case of Castleman's disease

    PubMed Central

    Shakir, Hakeem J.; Diletti, Sara M.; Hart, Alexandra M.; Meyers, Joshua E.; Dumont, Travis M.; Siddiqui, Adnan H.

    2015-01-01

    Background: There are very few reports in the literature of Castleman's disease affecting the carotid artery and a single previous report of a case of Castleman's disease of the neck originally mistaken as a carotid body tumor. Case Description: We describe a rare case of Castleman's disease, manifesting with classic radiographic hallmarks of a carotid body tumor. The postoperative pathologic examination identified the resected mass as Castleman's lymphadenopathy. The management of this particular case is discussed, and the findings are highlighted. Conclusions: We present a unique case of a tumor initially and incorrectly diagnosed as a carotid body tumor. However, after comprehensive treatment with endovascular and surgical modalities and subsequent pathologic examination, the diagnosis of this rare entity was made. PMID:26677415

  4. Inclusion body disease (herpesvirus infection) of falcons (IBDF).

    PubMed

    Graham, D L; Mare, C J; Ward, F P; Peckham, M C

    1975-01-01

    Inclusion body disease of falcons (IBDF) is caused by a herpesvirus. The clinical course is short, 24 to 72 hours in duration, and is characterized by mild to severe depression and weakness often accompanied by anorexia. The disease is invariably fatal. The virus has a marked affinity for the reticuloendothelial system and hepatocytes,producing focal to diffuse necrosis of infected tissues accompanied by the formation of intranuclear inclusion bodies. The virus is pathogenic for American kestrels (Falco sparverius) and great horned owls (Bubo virginianus) in which typical lesions of IBDF are reproduced. The lesions of IBDF are similar to those produced by some herpesvirus infections in other avian species. PMID:163383

  5. Mind body therapies in rehabilitation of patients with rheumatic diseases.

    PubMed

    Del Rosso, Angela; Maddali-Bongi, Susanna

    2016-02-01

    Mind body therapies (MBT) share a global approach involving both mental and physical dimensions, and focus on relationship between brain, mind, body and behavior and their effects on health and disease. MBT include concentration based therapies and movement based therapies, comprising traditional Oriental practices and somatic techniques. The greatest part of rheumatic diseases have a chronic course, leading to progressive damages at musculoskeletal system and causing physical problems, psychological and social concerns. Thus, rheumatic patients need to be treated with a multidisciplinary approach integrating pharmacological therapies and rehabilitation techniques, that not should only aim to reduce the progression of damages at musculoskeletal system. Thus, MBT, using an overall approach, could be useful in taking care of the overall health of the patients with chronic rheumatic diseases. This review will deal with different MBT and with their effects in the most common chronic rheumatic diseases (Rheumatoid Arthritis, Ankylosing Spondylitis, Fibromyalgia Syndrome). PMID:26850811

  6. 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. PMID:27526187

  7. [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. PMID:20961842

  8. Carotid body chemoreceptors, sympathetic neural activation, and cardiometabolic disease.

    PubMed

    Iturriaga, Rodrigo; Del Rio, Rodrigo; Idiaquez, Juan; Somers, Virend K

    2016-01-01

    The carotid body (CB) is the main peripheral chemoreceptor that senses the arterial PO2, PCO2 and pH. In response to hypoxemia, hypercapnia and acidosis, carotid chemosensory discharge elicits reflex respiratory, autonomic and cardiovascular adjustments. The classical construct considers the CB as the main peripheral oxygen sensor, triggering reflex physiological responses to acute hypoxemia and facilitating the ventilatory acclimation to chronic hypoxemia at high altitude. However, a growing body of experimental evidence supports the novel concept that an abnormally enhanced CB chemosensory input to the brainstem contributes to overactivation of the sympathetic nervous system, and consequent pathology. Indeed, the CB has been implicated in several diseases associated with increases in central sympathetic outflow. These include hypertension, heart failure, sleep apnea, chronic obstructive pulmonary disease and metabolic syndrome. Indeed, ablation of the CB has been proposed for the treatment of severe and resistant hypertension in humans. In this review, we will analyze and discuss new evidence supporting an important role for the CB chemoreceptor in the progression of autonomic and cardiorespiratory alterations induced by heart failure, obstructive sleep apnea, chronic obstructive pulmonary disease and metabolic syndrome. PMID:26920146

  9. Adult polyglucosan body disease in a patient originally diagnosed with Fabry's disease.

    PubMed

    Sagnelli, A; Savoiardo, M; Marchesi, C; Morandi, L; Mora, M; Morbin, M; Farina, L; Mazzeo, A; Toscano, A; Pagliarani, S; Lucchiari, S; Comi, G P; Salsano, E; Pareyson, D

    2014-03-01

    Adult polyglucosan body disease is a rare autosomal recessive disease, caused by glycogen branching enzyme gene mutations, characterised by urinary dysfunction, spastic paraplegia with vibration sense loss, peripheral neuropathy, and cognitive impairment. Fabry's disease is an X-linked lysosomal storage disorder caused by α-galactosidase A gene mutations; neurological manifestations include cerebrovascular accidents, small-fibre neuropathy and autonomic dysfunction. Here, we report the case of a 44-year-old Sicilian male with stroke-like episodes, hypohidrosis and mild proteinuria, which led to the diagnosis of Fabry's disease after a hemizygous mutation (p.Ala143Thr) in α-galactosidase A gene was detected. Subsequently, he developed progressive walking difficulties and dementia, which were considered atypical for Fabry's disease. Therefore, we performed additional investigations that eventually led to the diagnosis of adult polyglucosan body disease caused by two novel missense mutations (p.Asp413His and p.Gly534Val) in the glycogen branching enzyme gene. Recently, the pathogenic role of the p.Ala143Thr mutation in causing Fabry's disease has been questioned. This case underlines the importance of performing further investigations when facing with atypical features even in the presence of a genetic diagnosis of a rare disease. PMID:24380807

  10. Frustrated Lewis Pairs.

    PubMed

    Stephan, Douglas W

    2015-08-19

    The articulation of the notion of "frustrated Lewis pairs" (FLPs), which emerged from the discovery that H2 can be reversibly activated by combinations of sterically encumbered Lewis acids and bases, has prompted a great deal of recent activity. Perhaps the most remarkable consequence has been the development of FLP catalysts for the hydrogenation of a range of organic substrates. In the past 9 years, the substrate scope has evolved from bulky polar species to include a wide range of unsaturated organic molecules. In addition, effective stereoselective metal-free hydrogenation catalysts have begun to emerge. The mechanism of this activation of H2 has been explored, and the nature and range of Lewis acid/base combinations capable of effecting such activation have also expanded to include a variety of non-metal species. The reactivity of FLPs with a variety of other small molecules, including olefins, alkynes, and a range of element oxides, has also been developed. Although much of this latter chemistry has uncovered unique stoichiometric transformations, metal-free catalytic hydroamination, CO2 reduction chemistry, and applications in polymerization have also been achieved. The concept is also beginning to find applications in bioinorganic and materials chemistry as well as heterogeneous catalysis. This Perspective highlights many of these developments and discusses the relationship between FLPs and established chemistry. Some of the directions and developments that are likely to emerge from FLP chemistry in the future are also presented. PMID:26214241

  11. Body fluid biomarkers in Alzheimer’s disease

    PubMed Central

    Lu, Huan; Zhu, Xi-Chen; Jiang, Teng

    2015-01-01

    A heterogeneous and slowly progressive disease with extracellular amyloid-β (Aβ) deposits and intracellular hyperphosphorylated tau protein aggregates, Alzheimer’s disease (AD) is already a hard nut to crack, featured with cognitive decline and memory lapse. Body fluid biomarkers are proved to be useful in exploring further study of AD, might benefit for a full comprehension of the etiopathogenesis, an improved precision of the prognosis and diagnosis, and a positive response of treatments. The cerebrospinal fluid biomarkers Aβ, total tau, and hyperphosphorylated tau reflect the main pathologic changes of AD. We also review data from several novel biomarkers, such as, β-site APP cleaving enzyme 1, soluble amyloid precursor proteins α and β, soluble Aβ oligomers and so on, which are associated with the occurrence and deterioration of this disease and couldn’t be ignored. The rationale for the clinical use of those biomarkers, the challenges faced with and the properties of the most appropriate biomarkers are also summarized in the paper. We aim to find several ideal biomarkers to improve the diagnosis and optimize the treatment respectively. PMID:25992369

  12. Gender Associated High Body Mass Index in Allergic Diseases

    PubMed Central

    Lokaj-Berisha, Violeta; Gacaferri-Lumezi, Besa; Minci–Bejtullahu, Ganimete; Latifi-Pupovci, Hatixhe; Karahoda–Gjurgjeala, Natyra; Berisha, Naser; Morina, Teuta

    2014-01-01

    BACKGROUND: The increasing prevalence of allergic diseases and atopy is affected by sex, age and lifestyle factors. Obesity and excess weight are reported to be potential risk factors for atopy and specifically for asthma symptoms in children and adults. OBJECTIVE: To assess the relation between body mass index (BMI) and allergic diseases in patients of both genders, as well as association of BMI with atopy in healthy subjects. METHODS: BMI (kg/m2), skin-prick test and total serum immunoglobulin E levels were assessed in 139 subjects: 109 were patients with allergic diseases (M to F ratio was 51:58) and 30 were healthy controls (M to F ratio was 6:24). RESULTS: The study population was grouped into asthma, asthmarhinitis, rhinitis, Urticaria oreczema and controls by BMI and sex. Females with the highest BMI were in asthma and urticaria/eczema group. Males with the highest BMI were in asthmarhinitis and urticariaeczema group. High BMI was associated with atopy in both genders of healthy controls. High levels of total IgE were in male allergic patients. CONCLUSION: High BMI was associated with asthma in females, urticaria/eczema in both genders and atopy in both genders of healthy controls. Higher levels of total IgE were concluded in male patients.

  13. 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.

  14. A novel GBE1 mutation and features of polyglucosan bodies autophagy in adult polyglucosan body disease.

    PubMed

    Sampaolo, Simone; Esposito, Teresa; Gianfrancesco, Fernando; Napolitano, Filomena; Lombardi, Luca; Lucà, Roberta; Roperto, Franco; Di Iorio, Giuseppe

    2015-03-01

    We report the clinical, neuro-imaging, pathological and biochemical features of an Italian family in which two siblings have the Adult Polyglucosan Body Disease (APBD). APBD is a rare autosomal recessive disorder characterized by a gradually progressive involvement of both the central and peripheral nervous systems caused by the deficiency of the glycogen branching enzyme (GBE1). The two affected siblings, a 64-year-old man and his 67-year-old sister who had complained of urinary urgency and sporadic incontinence and also progressive gait difficulty for 6 and 7 years respectively, had severely impaired deep sensations on direct examination and a moderately severe symmetrical, axonal sensory-motor neuropathy on electrophysiological testing. GBE1 activity was below 25% of the normal rate in leukocytes and sural nerves. The siblings were homozygous for the novel GBE1 mutation p.N541D. All other members of the pedigree are heterozygous and manifest no symptoms, even in the very elderly. The affected siblings showed polyglucosan bodies (PBs) included within non-myelinating Schwann cells and within lymphocyte vesicles, which were positive for the autophagy markers P62 and LC3-II at immunofluorescence microscopy. PMID:25544507

  15. Schaumann bodies in Crohn's disease: a case report and review of the literature.

    PubMed

    Lorenzi, Luisa; Bisoffi, Zeno; Bortesi, Laura; Zamboni, Giuseppe; Liut, Francesca; Villanacci, Vincenzo

    2012-08-01

    Schaumann bodies are inclusion bodies, first described by Schaumann in 1941, typically seen in granulomatous diseases such as tuberculosis, sarcoidosis and chronic beryllium diseases. Williams WJ, in 1964, reported Schaumann bodies to occur in 10% of Crohn's disease (CD). We report a case of Crohn's disease, initially misdiagnosed as a schistosoma-related colitis for the presence of numerous calcified bodies resembling calcified ova and scattered granulomas. Subsequent biopsies showed more typical histological features and, in combination with a more complete clinical history, diagnosis of Crohn's disease was made. PMID:22503169

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

    PubMed

    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

  17. 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

  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. A Biographical Sketch of Lewis Dexter

    PubMed Central

    Mukhopadhyay, Madhuri

    2001-01-01

    Dr. Lewis Dexter was an outstanding cardiovascular physiologist and clinician, a respected teacher and scientist, and, most importantly, a fine human being. During his life, he brought the cardiac catheter from the laboratory to the patient and trained several generations of cardiologists. Dexter's laboratory was the first to elucidate the pathophysiologic alterations present in many forms of congenital heart disease, including atrial septal defects, patent ductus arteriosus, tetralogy of Fallot, ventricular septal defects, and pulmonic stenosis. Subsequent work in Dexter's laboratory led to the 1st measurements of pulmonary capillary wedge pressure and to the precise calculation of stenotic valve areas from hemodynamic parameters measured during cardiac catheterization. During a teaching exercise, Dexter demonstrated that exercise with a cardiac catheter in the heart was safe and produced clinically important data, by having a cardiac catheter inserted in himself. Over the years, many significant pathophysiologic studies that explored pulmonary embolism, valvular heart disease, right and left ventricular function, and pulmonary hypertension were published from Dexter's laboratory. But Lewis Dexter was more than a brilliant researcher. “Lew” was very close to his fellows and students, whom he considered extensions of his family. Dexter was a remarkable teacher, a compassionate physician, and a scrupulously honest investigator. Dr. Lewis Dexter had a major impact on modern medicine and was one of the great cardiologists of the 20th century. PMID:11453126

  20. Body mass index and mortality in chronic obstructive pulmonary disease

    PubMed Central

    Guo, Yibin; Zhang, Tianyi; Wang, Zhiyong; Yu, Feifei; Xu, Qin; Guo, Wei; Wu, Cheng; He, Jia

    2016-01-01

    Abstract The aim of this study is to summarize the evidence on the dose–response relationship between body mass index (BMI) and mortality in patients with chronic obstructive pulmonary disease (COPD). We performed a systemic literature search in PubMed, Embase, and Web of Science for relevant studies that were published until June 2015. A random effects meta-analysis was used to estimate the pooled relative risks (RRs) of all-cause mortality in COPD patients with normal weight compared with those who were underweight, overweight, or obese. In addition, a dose–response meta-analysis was conducted to explore the dose–response relationship between BMI and all-cause mortality in COPD patients. A total of 17 observational studies involving 30,182 COPD patients among 285,960 participants were included. Compared with the reference category, the RRs of underweight, overweight, and obese individuals were 1.40 (95% confidence interval (CI), 1.20–1.63), 0.80 (95% CI, 0.67–0.96), and 0.77 (95% CI, 0.62–0.95), respectively. A significant nonlinear relationship between BMI and mortality of COPD patients was found by using a random effects model. COPD patients with BMI of <21.75 kg/m2 had a higher risk of death. Moreover, an increase in the BMI resulted in a decrease in the risk of death. The risk of death was lowest when BMI was 30 kg/m2 (RR = 0.69; 95% CI, 0.53–0.89). The BMI was not associated with all-cause mortality when BMI was >32 kg/m2. Our findings indicate that overweight is associated with a lower risk of all-cause mortality among patients with COPD whereas underweight is associated with a higher risk of all-cause mortality in these patients. However, there is limited evidence to support the association between obesity and the risk of all-cause mortality in patients with COPD. PMID:27428228

  1. 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. PMID:26243866

  2. Significance of Lewis phenotyping using saliva and gastric tissue: comparison with the Lewis phenotype inferred from Lewis and secretor genotypes.

    PubMed

    Hong, Yun Ji; Hwang, Sang Mee; Kim, Taek Soo; Song, Eun Young; Park, Kyoung Un; Song, Junghan; Han, Kyou-Sup

    2014-01-01

    Lewis phenotypes using various types of specimen were compared with the Lewis phenotype predicted from Lewis and Secretor genotypes. This is the first logical step in explaining the association between the Lewis expression and Helicobacter pylori. We performed a study of the followings on 209 patients who underwent routine gastroscopy: erythrocyte and saliva Lewis phenotyping, gastric Lewis phenotyping by the tissue array, and the Lewis and Secretor genes genotyping. The results of phenotyping were as follows [Le(a-b-), Le(a+b-), Le(a-b+), and Le(a+b+), respectively, in order]: erythrocyte (12.4%, 25.8%, 61.2%, and 0.5%); saliva (2.4%, 27.3%, 70.3%, and 0.0%); gastric mucosa (8.1%, 6.7%, 45.5%, and 39.7%). The frequency of Le, le (59/508) , le (59/1067) , and le (59) alleles was 74.6%, 21.3%, 3.1%, and 1.0%, respectively, among 418 alleles. The saliva Lewis phenotype was completely consistent with the Lewis phenotype inferred from Lewis and Secretor genotypes, but that of gastric mucosa could not be predicted from genotypes. Lewis phenotyping using erythrocytes is only adequate for transfusion needs. Saliva testing for the Lewis phenotype is a more reliable method for determining the peripheral Lewis phenotype of an individual and the gastric Lewis phenotype must be used for the study on the association between Helicobacter pylori and the Lewis phenotype. PMID:24783214

  3. A revision of Megalocraerus Lewis, 1902 (Coleoptera, Histeridae: Exosternini)

    PubMed Central

    Caterino, Michael S.; Tishechkin, Alexey K.

    2016-01-01

    Abstract The formely monotypic Neotropical genus Megalocraerus Lewis is revised to include five species, known from southeastern Brazil to Costa Rica: Megalocraerus rubricatus Lewis, Megalocraerus mandibularis sp. n., Megalocraerus chico sp. n., Megalocraerus madrededios sp. n., and Megalocraerus tiputini sp. n. We describe the species, map their distributions, and provide a key for their identification. Their subcylindrical body form and emarginate mesosternum have previously hindered placement to tribe, although their curent assignment to Exosternini now appears well supported by morphological evidence. Nothing is known of the natural history of the species. PMID:26877699

  4. 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.

  5. Inclusion body disease in a great horned owl.

    PubMed

    Sileo, L; Carlson, H C; Crumley, S C

    1975-01-01

    The carcass of a great horned owl (Bubo virginianus), which had been found moribund in southern Ontario, was presented for necropsy. Throughout the liver and spleen were numerous white foci 1-2 mm in diameter; also noted were white plaques in the mucosae of the pharyngeal papillae and intestine. Results of light and electron microscopic studies and experimental transmission to two captive great horned owls suggested that this was a herpvirus disease similar and possibly indentical to the owl disease reported by other workers in Wiconsin and Australia. PMID:163384

  6. 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…

  7. Gaucher Disease and the Synucleinopathies

    PubMed Central

    Hruska, Kathleen S.; Goker-Alpan, Ozlem; Sidransky, Ellen

    2006-01-01

    Several recent observations suggest a connection between Gaucher disease, the inherited deficiency of glucocerebrosidase, and the synucleinopathies. Rare patients have been observed who develop both Gaucher disease and parkinsonism. Autopsy studies on these subjects reveal synuclein-positive Lewy bodies and inclusions. An increased incidence of synucleinopathies also has been noted in relatives of Gaucher probands. In complementary studies, screening of patients with parkinsonism has identified a greater than expected frequency of glucocerebrosidase mutations. These glucocerebrosidase mutation carriers have a wide spectrum of associated parkinsonian phenotypes, ranging from classic L-dopa-responsive Parkinson disease to a phenotype more characteristic of Lewy body dementia. Despite this association, the vast majority of Gaucher carriers and patients with Gaucher disease never develop parkinsonism. However, mutations in this gene are likely to be a contributing risk factor in subjects otherwise prone to developing synucleinopathies. PMID:17047314

  8. 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.

  9. 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,…

  10. 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…

  11. About Body Water

    MedlinePlus

    ... Thoughts As Traffic Piles Up, So Does Air Pollution Heart Docs: Never Expose Kids to Cigarette Smoke ... Insulin Delivery Additional Content Medical News About Body Water By James L. Lewis, III, MD NOTE: This ...

  12. Dr. Lewis' 10-Year Audit.

    PubMed

    Berlin, Joey

    2015-11-01

    Kaufman pediatrician Charles Turner Lewis, MD, battled fraud allegations levied against him by the Office of Inspector General (OIG) from 2005 to 2008 and emerged victorious. To his dismay, he is once again on the receiving end of an OIG letter alleging Medicaid overpayment. The 2015 Texas Legislature responded to TMA's call for improvements in OIG Medicaid fraud investigations of physicians with passage of Senate Bill 207. Organized medicine hopes the law's safeguards will afford due process to doctors under investigation. PMID:26536514

  13. 5/6th Nephrectomy in Combination with High Salt Diet and Nitric Oxide Synthase Inhibition to Induce Chronic Kidney Disease in the Lewis Rat

    PubMed Central

    van Koppen, Arianne; Verhaar, Marianne C.; Bongartz, Lennart G.; Joles, Jaap A.

    2013-01-01

    Chronic kidney disease (CKD) is a global problem. Slowing CKD progression is a major health priority. Since CKD is characterized by complex derangements of homeostasis, integrative animal models are necessary to study development and progression of CKD. To study development of CKD and novel therapeutic interventions in CKD, we use the 5/6th nephrectomy ablation model, a well known experimental model of progressive renal disease, resembling several aspects of human CKD. The gross reduction in renal mass causes progressive glomerular and tubulo-interstitial injury, loss of remnant nephrons and development of systemic and glomerular hypertension. It is also associated with progressive intrarenal capillary loss, inflammation and glomerulosclerosis. Risk factors for CKD invariably impact on endothelial function. To mimic this, we combine removal of 5/6th of renal mass with nitric oxide (NO) depletion and a high salt diet. After arrival and acclimatization, animals receive a NO synthase inhibitor (NG-nitro-L-Arginine) (L-NNA) supplemented to drinking water (20 mg/L) for a period of 4 weeks, followed by right sided uninephrectomy. One week later, a subtotal nephrectomy (SNX) is performed on the left side. After SNX, animals are allowed to recover for two days followed by LNNA in drinking water (20 mg/L) for a further period of 4 weeks. A high salt diet (6%), supplemented in ground chow (see time line Figure 1), is continued throughout the experiment. Progression of renal failure is followed over time by measuring plasma urea, systolic blood pressure and proteinuria. By six weeks after SNX, renal failure has developed. Renal function is measured using 'gold standard' inulin and para-amino hippuric acid (PAH) clearance technology. This model of CKD is characterized by a reduction in glomerular filtration rate (GFR) and effective renal plasma flow (ERPF), hypertension (systolic blood pressure>150 mmHg), proteinuria (> 50 mg/24 hr) and mild uremia (>10 mM). Histological

  14. 5/6th nephrectomy in combination with high salt diet and nitric oxide synthase inhibition to induce chronic kidney disease in the Lewis rat.

    PubMed

    van Koppen, Arianne; Verhaar, Marianne C; Bongartz, Lennart G; Joles, Jaap A

    2013-01-01

    Chronic kidney disease (CKD) is a global problem. Slowing CKD progression is a major health priority. Since CKD is characterized by complex derangements of homeostasis, integrative animal models are necessary to study development and progression of CKD. To study development of CKD and novel therapeutic interventions in CKD, we use the 5/6th nephrectomy ablation model, a well known experimental model of progressive renal disease, resembling several aspects of human CKD. The gross reduction in renal mass causes progressive glomerular and tubulo-interstitial injury, loss of remnant nephrons and development of systemic and glomerular hypertension. It is also associated with progressive intrarenal capillary loss, inflammation and glomerulosclerosis. Risk factors for CKD invariably impact on endothelial function. To mimic this, we combine removal of 5/6th of renal mass with nitric oxide (NO) depletion and a high salt diet. After arrival and acclimatization, animals receive a NO synthase inhibitor (NG-nitro-L-Arginine) (L-NNA) supplemented to drinking water (20 mg/L) for a period of 4 weeks, followed by right sided uninephrectomy. One week later, a subtotal nephrectomy (SNX) is performed on the left side. After SNX, animals are allowed to recover for two days followed by LNNA in drinking water (20 mg/L) for a further period of 4 weeks. A high salt diet (6%), supplemented in ground chow (see time line Figure 1), is continued throughout the experiment. Progression of renal failure is followed over time by measuring plasma urea, systolic blood pressure and proteinuria. By six weeks after SNX, renal failure has developed. Renal function is measured using 'gold standard' inulin and para-amino hippuric acid (PAH) clearance technology. This model of CKD is characterized by a reduction in glomerular filtration rate (GFR) and effective renal plasma flow (ERPF), hypertension (systolic blood pressure>150 mmHg), proteinuria (> 50 mg/24 hr) and mild uremia (>10 mM). Histological

  15. 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

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

    PubMed

    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

  17. ‘Crohn'z meanz Heinz’: foreign body inflammatory mass mimicking Crohn’s disease

    PubMed Central

    Visagan, R; Grossman, R; Dimitriadis, P A; Desai, A

    2013-01-01

    The authors present a patient with a presumed diagnosis of Crohn's disease for 6 years turning out to be an unusual inflammatory mass caused by ileal perforation due to a foreign body. When surgical intervention became necessary for admissions with recurrent obstruction, laparoscopy revealed an inflammatory mass in the terminal ileum, exposing two pieces of plastic bearing the word ‘Heinz’. Resection of the inflammatory mass led to the complete resolution of symptoms. Histology from the operative specimen showed no features of Crohn's disease. There were no granulomas and no fissuring ulcers. This case highlights that an inflammatory mass in the small intestine caused by the perforation of ingested foreign body can mimic Crohn's disease. To our knowledge, this is the first report of a synthetic plastic packaging causing ileo-caecal junctional perforation mimicking Crohn’s disease. PMID:23749825

  18. Adolescent Overweight, Obesity and Chronic Disease-Related Health Practices: Mediation by Body Image

    PubMed Central

    Farhat, Tilda; Iannotti, Ronald J.; Caccavale, Laura J.

    2014-01-01

    Background/Aims To examine whether body image mediates the association between overweight/obesity and chronic disease-related health practices (CDRHP), including lack of physical activity (PA), infrequent breakfast consumption (IBC), screen-based media use (SBM), and smoking. Methods The 2006 Health Behaviors in School-Age Children survey was administered to a nationally representative sample of US students (n = 8,028) in grades 6 to10 (mean age=14.3). Outcome variables included self-reported measures of PA, SBM, IBC and smoking. Body image was assessed with 5 items from the Body Investment Scale (α = .87) asking for agreement/disagreement with statements about one’s body. Stratifying on gender, an initial regression model estimated the association between overweight/obesity and CDRHP. Mediation models that included body image were then compared to the initial model to determine the role of body image in the relationship between overweight/obesity and CDRHP. Results Among boys, body image mediated the relationships of overweight/obesity with SBM, and of obesity with IBC. Among girls, it mediated the relationships of obesity with PA, IBC and smoking, and of overweight with SBM. Conclusion As the prevalence of overweight/obesity among adolescent boys and girls remains high, efforts to improve their body image could result in less frequent engagement in CDRHP. PMID:24356530

  19. Curvilinear bodies in hydroxychloroquine-induced renal phospholipidosis resembling Fabry disease

    PubMed Central

    Costa, Rui M.; Martul, Eduardo V.; Reboredo, Juan M.; Cigarrán, Secundino

    2013-01-01

    Inherited and acquired metabolic disorders are responsible for renal intracellular accumulation of phospholipids. Ultrastructural analysis revealing typical myeloid or zebra bodies was previously thought to be exclusive to Fabry disease. However, chloroquine/hydroxychloroquine toxicity can cause similar abnormalities. Recent studies have mentioned curvilinear bodies (CLB) in renal cells in such cases, never described in Fabry nephropathy. We report a 31-year-old patient with systemic lupus erythematosus who was on long-term hydroxychloroquine treatment. The presence of zebra bodies on electron microscopy lead to initial interpretation of Fabry disease, but subsequent genetic analysis did not show a relevant mutation. Further evaluation revealed CLB in renal cells, supporting the diagnosis of hydroxycholoroquine-induced renal phospholipidosis. PMID:26120446

  20. Dietary intakes, resting metabolic rates, and body composition in benign and malignant gastrointestinal disease.

    PubMed Central

    Burke, M; Bryson, E I; Kark, A E

    1980-01-01

    Dietary protein and energy intakes were assessed in 42 patients with cancer and 24 with benign conditions of the gastrointestinal tract. The relations of dietary intake to body composition was examined. Resulting metabolic rate was measured in 51 patients. No significant differences in dietary intake or metabolic rate were found between patients with cancer and those with benign disease. There were significant positive correlations between protein and energy intakes and the ratio of total body potassium to total body water in patients with benign disease but not in those with cancer. Weight loss was probably due to inadequate food intake, the main defect being energy deficiency, since protein intake was usually well maintained. Supplementing with energy the voluntary ingested diet of patients with cancer would probably prevent weight loss in most cases. PMID:7427083

  1. Biomagnetism: Measuring and Imaging the Natural and Disease Fields from the Human Body

    SciTech Connect

    Flynn, Edward

    2001-01-17

    Biomagnetism involves the measurement of the magnetic fields emanating from biological tissue with emphasis on human beings. The fields are small, ranging from femto- to pico-Tesla and are measured with sensitive instruments; typically SQUIDs with sensitivities of several fT. An example of natural field measurements is magnetoencephalography where large SQUID arrays are being used to image magnetic sources in normal and abnormal human brain behavior arising from neuronal currents. A new area of biomagnetism involves the use of targeted magnetic nanoparticles in the early detection of disease. These superparamagnetic particles offer unique characteristics for localizing disease sites ranging from various types of cancer to neurological diseases. By using small pulsed magnetic polarizing fields, SQUID sensors detect small numbers of cells in the body targeted by antibody-labeled nanoparticles through their decaying remanence fields. Localization of these biomagnetic sources in the body involves theoretical modeling of the inverse electromagnetic problem.

  2. Body composition assessment and coronary heart disease risk factors among college students of three ethnic groups.

    PubMed Central

    Koutoubi, Samer; Huffman, Fatma G.

    2005-01-01

    OBJECTIVES: This study identified and compared anthropometric measurements, body composition and coronary heart disease (CHD) risk factors among college students of three ethnic groups. METHODS: Subjects were assessed for cardiovascular risk. Body composition analysis was performed using the Bioelectrical Impedance Analysis (BIA). RESULTS: Black non-Hispanic females (30%) were significantly (p < 0.017) more in the "overweight" category compared to white non-Hispanic females (6.7%). Black non-Hispanic females had significantly (p < 0.044) higher percentages of body fat and lower percentages of body lean, and significantly (p < 0.040) lower percentages of body water than white non-Hispanic females. Significant positive correlations were found between CHD Risk Point Standard (CHDRPS) and percentages of body fat in white non-Hispanic males (p < 0.005), Hispanic males (p < 0.016) and Hispanic females (p < 0.001). Significant inverse correlations were found between CHDRPS and percentages of body water in white non-Hispanic males (p < 0.004), Hispanic males (p < 0.013) and Hispanic females (p < 0.001): body lean in white non-Hispanic males (p < 0.005), Hispanic males (p < 0.016) and Hispanic females (p < 0.001); and lean/fat ratio in white non-Hispanic males (p < 0.008), Hispanic males (p < 0.030), black non-Hispanic males (p < 0.020) and Hispanic females (p < 0.008). CONCLUSIONS: The high prevalence of overweight justifies a high priority for weight control in young adults in an effort to prevent cardiovascular diseases (CVDs) later in life. PMID:16035576

  3. 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. PMID:26250623

  4. Identification of misfolded proteins in body fluids for the diagnosis of prion diseases.

    PubMed

    Properzi, Francesca; Pocchiari, Maurizio

    2013-01-01

    Transmissible spongiform encephalopathy (TSE) or prion diseases are fatal rare neurodegenerative disorders affecting man and animals and caused by a transmissible infectious agent. TSE diseases are characterized by spongiform brain lesions with neuronal loss and the abnormal deposition in the CNS, and to less extent in other tissues, of an insoluble and protease resistant form of the cellular prion protein (PrP(C)), named PrP(TSE). In man, TSE diseases affect usually people over 60 years of age with no evident disease-associated risk factors. In some cases, however, TSE diseases are unequivocally linked to infectious episodes related to the use of prion-contaminated medicines, medical devices, or meat products as in the variant Creutzfeldt-Jakob disease (CJD). Clinical signs occur months or years after infection, and during this silent period PrP(TSE), the only reliable marker of infection, is not easily measurable in blood or other accessible tissues or body fluids causing public health concerns. To overcome the limit of PrP(TSE) detection, several highly sensitive assays have been developed, but attempts to apply these techniques to blood of infected hosts have been unsuccessful or not yet validated. An update on the latest advances for the detection of misfolded prion protein in body fluids is provided. PMID:24027585

  5. Identification of Misfolded Proteins in Body Fluids for the Diagnosis of Prion Diseases

    PubMed Central

    Pocchiari, Maurizio

    2013-01-01

    Transmissible spongiform encephalopathy (TSE) or prion diseases are fatal rare neurodegenerative disorders affecting man and animals and caused by a transmissible infectious agent. TSE diseases are characterized by spongiform brain lesions with neuronal loss and the abnormal deposition in the CNS, and to less extent in other tissues, of an insoluble and protease resistant form of the cellular prion protein (PrPC), named PrPTSE. In man, TSE diseases affect usually people over 60 years of age with no evident disease-associated risk factors. In some cases, however, TSE diseases are unequivocally linked to infectious episodes related to the use of prion-contaminated medicines, medical devices, or meat products as in the variant Creutzfeldt-Jakob disease (CJD). Clinical signs occur months or years after infection, and during this silent period PrPTSE, the only reliable marker of infection, is not easily measurable in blood or other accessible tissues or body fluids causing public health concerns. To overcome the limit of PrPTSE detection, several highly sensitive assays have been developed, but attempts to apply these techniques to blood of infected hosts have been unsuccessful or not yet validated. An update on the latest advances for the detection of misfolded prion protein in body fluids is provided. PMID:24027585

  6. 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

  7. PTG Depletion Removes Lafora Bodies and Rescues the Fatal Epilepsy of Lafora Disease

    PubMed Central

    Turnbull, Julie; DePaoli-Roach, Anna A.; Zhao, Xiaochu; Cortez, Miguel A.; Pencea, Nela; Tiberia, Erica; Piliguian, Mark; Roach, Peter J.; Wang, Peixiang; Ackerley, Cameron A.; Minassian, Berge A.

    2011-01-01

    Lafora disease is the most common teenage-onset neurodegenerative disease, the main teenage-onset form of progressive myoclonus epilepsy (PME), and one of the severest epilepsies. Pathologically, a starch-like compound, polyglucosan, accumulates in neuronal cell bodies and overtakes neuronal small processes, mainly dendrites. Polyglucosan formation is catalyzed by glycogen synthase, which is activated through dephosphorylation by glycogen-associated protein phosphatase-1 (PP1). Here we remove PTG, one of the proteins that target PP1 to glycogen, from mice with Lafora disease. This results in near-complete disappearance of polyglucosans and in resolution of neurodegeneration and myoclonic epilepsy. This work discloses an entryway to treating this fatal epilepsy and potentially other glycogen storage diseases. PMID:21552327

  8. 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.

  9. 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…

  10. Familial clustering of the ataxic form of Creutzfeldt-Jakob disease with Hirano bodies.

    PubMed Central

    Cartier, L; Gálvez, S; Gajdusek, D C

    1985-01-01

    A family cluster of the ataxic form of Creutzfeldt-Jakob disease with one probable and two autopsy proven cases that occurred in a single generation between 1974 and 1982 is reported. The clinical characteristics of the cases are closely similar to those of kuru patients, with a fair correlation between the prominent truncal ataxia and the intense devastation of the cerebellar cortex most marked in the vermis. Pathologically, the marked hippocampal involvement rarely seen in typical transmissible Creutzfeldt-Jakob disease and the finding of Hirano bodies in the Ammon's horn without specific Alzheimer's senile changes are noteworthy features. Images PMID:2984334

  11. Inclusion body disease in two captive Australian pythons (Morelia spilota variegata and Morelia spilota spilota).

    PubMed

    Carlisle-Nowak, M S; Sullivan, N; Carrigan, M; Knight, C; Ryan, C; Jacobson, E R

    1998-02-01

    Two captive Australian pythons, one carpet and one diamond python, presented with signs of central nervous system dysfunction. The carpet python was agitated. Its head was tilting and it was incoordinated and had convulsions. It was treated with antibiotics and anthelmintics but was eventually euthanased after failing to respond to therapy. The diamond python had flaccid paralysis of the caudal half. It was not treated and became disoriented and died. Hepatocytes from both pythons contained irregular 2 to 10 micron eosinophilic intracytoplasmic inclusion bodies. The brain of the diamond python was not available for examination. Occasional neurones in the carpet python brain contained similar inclusion bodies and other changes suggestive of viral infection. The clinical signs and histopathological findings in both pythons were consistent with boid inclusion body disease. PMID:9578777

  12. An autopsy case of frontotemporal lobar degeneration with the appearance of fused in sarcoma inclusions (basophilic inclusion body disease) clinically presenting corticobasal syndrome.

    PubMed

    Matsumoto, Arifumi; Suzuki, Hiroyoshi; Fukatsu, Reiko; Shimizu, Hiroshi; Suzuki, Yasushi; Hisanaga, Kinya

    2016-02-01

    We describe an autopsy case of basophilic inclusion body disease (BIBD), a subtype of frontotemporal lobar degeneration (FTLD) with the appearance of fused in sarcoma (FUS) inclusions (FTLD-FUS), clinically presenting corticobasal syndrome (CBS). A 54-year-old man initially developed worsening of stuttering and right hand clumsiness. Neurological examinations revealed rigidity in the right upper and lower extremities, buccofacial apraxia, and right-side dominant limb-kinetic and ideomotor apraxia. Neuroimaging showed asymmetric left-dominant brain atrophy and a cerebral blood flow reduction in the ipsilateral frontal region. At 56 years, his apraxia had advanced, and ideational apraxia was observed. Furthermore, the asymmetry in the limb-kinetic and ideomotor apraxia had disappeared, and both conditions had become bilateral. He had a new onset of aphasia. His symptoms progressed and he died 9 years after the initial symptoms. The brain weighed 955 g. Diffuse brain atrophy was most obvious in the bilateral frontotemporal regions. The atrophy of the left superior frontal and precentral gyri and bilateral basal ganglia was remarkable. Histologically, there was a marked loss of neurons with gliosis in the affected areas, where basophilic neuronal cytoplasmic inclusions were observed. The inclusions were immunoreactive for FUS, p62, and TATA-binding protein-associated factor 15 (TAF15), but not for phosphorylated tau, transactive response DNA-binding protein of 43 kDa (TDP-43), neurofilament protein, or Ewing sarcoma (EWS). From these pathological findings, this case was diagnosed as having BIBD as an FTLD-FUS variant. Spinal cord lower motor neurons were spared in number, similar to primary lateral sclerosis. Mutations in FUS were undetectable. Common background pathologies for CBS include corticobasal degeneration, Alzheimer's disease, PSP, FTLD with phosphorylated TDP-43 inclusions (FTLD-TDP), Pick's disease, Lewy body disease and CJD. However, FTLD-FUS (BIBD

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

    PubMed

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

    2015-08-01

    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

  14. 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

  15. 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.

  16. [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. PMID:23045804

  17. Deletion of antigens of the Lewis a/b blood group family in human prostatic carcinoma.

    PubMed Central

    Young, W. W.; Mills, S. E.; Lippert, M. C.; Ahmed, P.; Lau, S. K.

    1988-01-01

    The expression of antigens of the blood group Lewis a/b family were studied in a series of 42 prostatectomy specimens from patients with adenocarcinoma clinically confined to the prostate; 19 of these were later reclassified as pathologic Stage C. Staining of normal or hyperplastic versus neoplastic epithelium was assessed in routinely processed, paraffin-embedded tissue using murine monoclonal antibodies and an avidin-biotin immunoperoxidase technique. Antigens screened and the antibodies used to recognize them were Lewis a (CF4C4), Lewis b and Type 1 H (NS10), monosialosyl Lewis a I (19.9), and disialosyl Lewis a and monosialosyl Lewis a II (FH7). FH7 strongly stained the benign epithelium of all 39 Lewis positive cases, suggesting that the sialyltransferase responsible for synthesis of FH7-reactive determinants is highly active in benign prostatic tissue. When compared to the reactivity of benign epithelium in Lewis positive cases, the staining of the carcinomas was markedly reduced in 18 cases (46%) and absent in 16 cases (41%). This reduction or loss of staining of the malignant epithelium was observed for all antibodies that stained the corresponding benign epithelium of each case. In only five of the cases (13%) was the intensity of staining in the carcinoma equal to that of the surrounding benign epithelium. No cases in this latter group had recurrence of disease, whereas in the other staining groups 25-33% of the cases had recurrences; median follow-up for the entire group was 78 months. No correlation was apparent between Gleason score and the staining pattern with these antigens. In summary, antigens of the Lewis a/b family are deleted in a high percentage of cases of prostatic adenocarcinoma. Images Figure 2 Figure 3 Figure 4 Figure 5 Figure 6 PMID:2454582

  18. Parkinson Disease and Dementia.

    PubMed

    Garcia-Ptacek, Sara; Kramberger, Milica G

    2016-09-01

    Dementia is a frequent complication of Parkinson disease (PD) with a yearly incidence of around 10% of patients with PD. Lewy body pathology is the most important factor in the development of Parkinson disease dementia (PDD) and there is evidence for a synergistic effect with β-amyloid. The clinical phenotype in PDD extends beyond the dysexecutive syndrome that is often present in early PD and encompasses deficits in recognition memory, attention, and visual perception. Sleep disturbances, hallucinations, neuroleptic sensitivity, and fluctuations are often present. This review provides an update on current knowledge of PDD including aspects of epidemiology, pathology, clinical presentation, management, and prognosis. PMID:27502301

  19. 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

  20. 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. PMID:27282783

  1. Is Cell Death Primary or Secondary in the Pathophysiology of Idiopathic Parkinson’s Disease?

    PubMed Central

    Schulz-Schaeffer, Walter J.

    2015-01-01

    Currently, the pathophysiology of idiopathic Parkinson’s disease is explained by a loss of mainly dopaminergic nerve cells that causes a neurotransmitter deficiency. In the final stage of the disease, there is a marked loss of neurons in the substantia nigra. In addition, Lewy bodies can be found in some of the remaining neurons, which serve as the pathological hallmark of the disease. These Lewy bodies are composed mainly of aggregated α-synuclein, a physiological presynaptic protein. Lewy bodies were thought to be the pathophysiologically relevant form of α-synuclein because their appearance coincided with neuron loss in the substantia nigra. In consequence, neuron loss was thought to be the primary step in the neurodegeneration in Parkinson’s disease. On the other hand, the clinical syndrome suggests a synaptic disorder. If α-synuclein aggregation was causally linked to the pathophysiology of disease, α-synuclein pathology should be found at the synapse. As recently demonstrated, one to two orders of magnitude more α-synuclein aggregates are present in presynaptic terminals than in Lewy bodies or Lewy neurites. Degeneration of dendritic spines associated with synaptic α-synuclein aggregates has been shown to occur in human disease. In experiments, using transgenic mice or cell cultures, mild (two- to three-fold) overexpression of α-synuclein caused an altered vesicle turnover and led to a reduction in neurotransmitter release. Different approaches linked these alterations to presynaptic aggregation of α-synuclein. These findings may fundamentally change the pathophysiological concept of Parkinson’s disease: not nerve cell loss, but the synaptic dysfunction of still existing nerve cells should become the focus of attention. From recent findings, it is quite evident that the death of dopaminergic neurons is a secondary event in the pathophysiology of Parkinson’s disease. PMID:26193328

  2. 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

  3. 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. PMID:23926354

  4. Stereotactic Body Radiosurgery for Spinal Metastatic Disease: An Evidence-Based Review

    PubMed Central

    Hall, William A.; Stapleford, Liza J.; Hadjipanayis, Costas G.; Curran, Walter J.; Crocker, Ian; Shu, Hui-Kuo G.

    2011-01-01

    Spinal metastasis is a problem that afflicts many cancer patients. Traditionally, conventional fractionated radiation therapy and/or surgery have been the most common approaches for managing such patients. Through technical advances in radiotherapy, high dose radiation with extremely steep drop off can now be delivered to a limited target volume along the spine under image-guidance with very high precision. This procedure, known as stereotactic body radiosurgery, provides a technique to rapidly treat selected spinal metastasis patients with single- or limited-fraction treatments that have similar to superior efficacies compared with more established approaches. This review describes current treatment systems in use to deliver stereotactic body radiosurgery as well as results of some of the larger case series from a number of institutions that report outcomes of patients treated for spinal metastatic disease. These series include nearly 1400 patients and report a cumulative local control rate of 90% with myelopathy risk that is significantly less than 1%. Based on this comprehensive review of the literature, we believe that stereotactic body radiosurgery is an established treatment modality for patients with spinal metastatic disease that is both safe and highly effective. PMID:22312536

  5. 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.

  6. Higher Body Mass Index and Increased Prevalence of Paranasal Sinus Disease

    PubMed Central

    Kabeya, Yusuke; Kato, Kiyoe; Tomita, Masuomi; Katsuki, Takeshi; Oikawa, Yoichi; Shimada, Akira

    2016-01-01

    Background We hypothesized that higher body mass index (BMI) was associated with increased prevalence of paranasal sinus disease and examined the hypothesis in Japanese adults. Methods This was a cross-sectional study including 1350 Japanese adults aged 40 years or more who participated in a health check-up program focusing on brain diseases and metabolic syndrome. Participants were divided into quartiles of BMI levels. Paranasal sinus disease was confirmed by a head MRI scan. The association between BMI and paranasal sinus disease was examined using logistic regression analysis, which was adjusted for age, sex, waist:hip ratio, hemoglobin A1c, systolic blood pressure, smoking status, alcohol intake, and white blood cell count. Results Of the 1350 participants, 151 (11.2%) had paranasal sinus disease. In relation to those in the lowest quartile of BMI, the odds ratios of having the disease among those in the 2nd, 3rd, and 4th quartiles of BMI were 1.89 (95% confidence interval [CI], 1.03–3.48), 2.26 (95% CI, 1.20–4.23) and 2.26 (95% CI, 1.14–4.51), respectively. When BMI was analysed as a continuous variable, an increase of one unit in BMI was significantly associated with increased odds of having the disease, with an OR of 1.08 (95% CI, 1.01–1.16). Conclusions The present study suggests that patients with higher BMI are more likely to have paranasal sinus disease. PMID:26830349

  7. M. paratuberculosis and Parkinson's disease--is this a trigger.

    PubMed

    Dow, Coad Thomas

    2014-12-01

    Genetic linkage studies and genome wide analysis have provided insights into complex medical diseases. Mycobacterium avium ss. paratuberculosis (MAP) causes Johne's disease, an important enteric inflammatory disease mostly studied in ruminant animals. MAP is also the putative cause of Crohn's disease. Moreover, MAP has been linked to other inflammatory diseases: sarcoidosis, Blau syndrome, autoimmune diabetes, autoimmune thyroiditis and multiple sclerosis. Genetic studies reveal an association between Parkinson's disease (PD), leprosy and Crohn's disease and since discovered, these findings have been considered "surprising". Autophagy and ubiquitin-proteosome systems are cellular systems that both fight intracellular pathogens (xenophagy) and maintain cellular protein quality control. PD is a common neurodegenerative disease that manifests clinically as a profound movement disorder. The recognized genetic defects of PD create disruption of cellular homeostasis that result in protein folding abnormalities of PD called Lewy bodies. Those same genetic defects are associated with susceptibility to intracellular pathogens, including mycobacteria. It is now understood that PD Lewy body pathology starts in the enteric nervous system and "spreads" to the brain in a retrograde fashion via the vagus nerve. This is the same process by which prions affect the brain. Lewy body pathology of the enteric nervous system predates the Lewy body pathology of the central nervous system (CNS) by years or even decades. This article proposes that genetic defects associated with PD also result in a permissive environment for MAP infection--ineffective xenophagy. It postulates that beginning as an enteric infection, MAP--via the vagus nerve--initiates a pathologic process that results in a targeted neuroinvasion of the CNS. The article proposes that MAP infection and resultant PD pathology are due, in the genetically at-risk and age dependant, to the consumptive exhaustion of the protein

  8. Mammillary Bodies in Alzheimer's Disease: A Golgi and Electron Microscope Study.

    PubMed

    Baloyannis, Stavros J; Mavroudis, Ioannis; Baloyannis, Ioannis S; Costa, Vassiliki G

    2016-05-01

    Alzheimer's disease (AD) is a progressive neurodegenerative disorder, characterized by irreversible memory decline, concerning no rarely spatial memory and orientation, alterations of the mood and personality, gradual loss of motor skills, and substantial loss of capacities obtained by previous long education. We attempted to describe the morphological findings of the mammillary bodies in early cases of AD. Samples were processed for electron microscopy and silver impregnation techniques. The nuclei of the mammillary bodies demonstrated a substantial decrease in the neuronal population and marked abbreviation of dendritic arbors. Decrease in spine density and morphological abnormalities of dendritic spines was also seen. Synaptic alterations were prominent. Alzheimer's pathology, such as deposits of amyloid-β peptide and neurofibrillary degeneration, was minimal. Electron microscopy revealed mitochondrial alterations and fragmentation of Golgi apparatus, associated frequently with synaptic pathology. PMID:26399484

  9. 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 according to…

  10. 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,…

  11. 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. PMID:21270462

  12. Whole-Body In Vivo Monitoring of Inflammatory Diseases Exploiting Human Interleukin 6-Luciferase Transgenic Mice.

    PubMed

    Hayashi, Makiko; Takai, Jun; Yu, Lei; Motohashi, Hozumi; Moriguchi, Takashi; Yamamoto, Masayuki

    2015-10-01

    Chronic inflammation underlies the pathological progression of various diseases, and thus many efforts have been made to quantitatively evaluate the inflammatory status of the diseases. In this study, we generated a highly sensitive inflammation-monitoring mouse system using a bacterial artificial chromosome (BAC) clone containing extended flanking sequences of the human interleukin 6 gene (hIL6) locus, in which the luciferase (Luc) reporter gene is integrated (hIL6-BAC-Luc). We successfully monitored lipopolysaccharide-induced systemic inflammation in various tissues of the hIL6-BAC-Luc mice using an in vivo bioluminescence imaging system. When two chronic inflammatory disease models, i.e., a genetic model of atopic dermatitis and a model of experimental autoimmune encephalomyelitis (EAE), were applied to the hIL6-BAC-Luc mice, luciferase bioluminescence was specifically detected in the atopic skin lesion and central nervous system, respectively. Moreover, the Luc activities correlated well with the disease severity. Nrf2 is a master transcription factor that regulates antioxidative and detoxification enzyme genes. Upon EAE induction, the Nrf2-deficient mice crossed with the hIL6-BAC-Luc mice exhibited enhanced neurological symptoms concomitantly with robust luciferase luminescence in the neuronal tissue. Thus, whole-body in vivo monitoring using the hIL6-BAC-Luc transgenic system (WIM-6 system) provides a new and powerful diagnostic tool for real-time in vivo monitoring of inflammatory status in multiple different disease models. PMID:26283726

  13. A clinico-pathological study of subtypes in Parkinson's disease.

    PubMed

    Selikhova, M; Williams, D R; Kempster, P A; Holton, J L; Revesz, T; Lees, A J

    2009-11-01

    We have carried out a systematic review of the case files of 242 donors with pathologically verified Parkinson's disease at the Queen Square Brain Bank for Neurological Disorders in an attempt to corroborate the data-driven subtype classification proposed by Lewis and colleagues (Heterogeneity of Parkinson's disease in the early clinical stages using a data driven approach. J Neurol Neurosurg Psychiatry 2005; 76: 343-8). Cases were segregated into earlier disease onset (25%), tremor dominant (31%), non-tremor dominant (36%) and rapid disease progression without dementia (8%) subgroups. We found a strong association between a non-tremor dominant disease pattern and cognitive disability. The earlier disease onset group had the longest duration to death, and greatest delay to the onset of falls and cognitive decline. Patients with a tremor dominant disease pattern did not live significantly longer than non-tremor dominant patients and showed no difference in mean time to onset of falls and hallucinations. Rapid disease progression was associated with older age, early depression and early midline motor symptoms, and in 70% of the cases, tremulous onset. The non-tremor dominant subgroup had a significantly higher mean pathological grading of cortical Lewy bodies than all other groupings (P < 0.05) and more cortical amyloid-beta plaque load and cerebral amyloid angiopathy than early disease onset and tremor dominant groups (P = 0.047). An analysis of cases with pathologically defined neocortical Lewy body disease confirmed the link between bradykinetic onset, cognitive decline and Lewy body deposition in the neocortex. Although neuropathological examination failed to distinguish the other subtypes, the classification scheme was supported by an analysis of clinical data that were independent of the basic subgroup definitions. PMID:19759203

  14. Synergistic effects of pesticides and metals on the fibrillation of alpha-synuclein: implications for Parkinson's disease.

    PubMed

    Uversky, Vladimir N; Li, Jie; Bower, Kiowa; Fink, Anthony L

    2002-10-01

    Aggregation of alpha-synuclein has been implicated in the formation of proteinaceous inclusions in the brain (Lewy bodies, Lewy neurites) that are characteristic of neurodegenerative diseases, such as Parkinson's disease (PD) and dementia with Lewy bodies (DLBs). The etiology of PD is unknown, but recent work has shown that except in rare cases, there appears to be no direct genetic basis. However, several studies have implicated environmental factors, especially pesticides and metals. Here we show that certain pesticides and metals induce a conformational change in alpha-synuclein and directly accelerate the rate of formation of alpha-synuclein fibrils in vitro. In addition, the simultaneous presence of metal and pesticide led to synergistic effects on the rate of fibrillation. We propose a model in which environmentalfactors in conjunction with genetic susceptibility may form the underlying molecular basis for idiopathic PD. PMID:12428725

  15. Clinical relevance and contemporary methods for counting blood cells in body fluids suspected of inflammatory disease.

    PubMed

    Fleming, Chérina; Russcher, Henk; Lindemans, Jan; de Jonge, Robert

    2015-10-01

    In many inflammatory diseases, the cellular components in body fluids [cerebrospinal fluid (CSF), serous fluids] are increased, rendering essential diagnostic information. The diagnostic value of the total white blood cell count (WBC) and differential count has been evaluated extensively over the years, and a remarkable amount of knowledge has been gained; yet, there is a great deal of clinical uncertainty whether the diagnosis should be based solely on these variables. In some diseases, such as peritonitis, the total WBC and differential count has high sensitivity; whereas, in differentiating pleural effusions, it lacks the sensitivity required to be clinically useful. Nevertheless, many guidelines consider these tests as cornerstone parameters, and in combination with clinical variables, they can successfully guide clinical decision making in initiating or postponing a treatment course for infection and/or inflammatory diseases while awaiting culture results. Although other methods are available for detecting and differentiating WBCs in body fluids, manual microscopy is still considered the gold standard despite its many limitations. During the last decade, automated analyzers have become a popular method for first line screening. Continued progress in their design has led to major improvements including their speed, improved accuracy and lower variability compared with microscopy. Disadvantages of this method include high imprecision in low ranges (depending on the method) and interfering factors. In a time where automation is at the front line in clinical laboratories, it is essential the results obtained are precise, accurate and reproducible. This review provides an overview of the relevance for cell counting in a variety of diagnostic body fluids, and highlights the current technologies used. PMID:25879321

  16. 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)

  17. 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.

  18. 90 Seconds of Discovery: Frustrated Lewis Pairs

    ScienceCinema

    Kathmann, Shawn; Schenter, Greg; Autrey, Tom

    2014-07-21

    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.

  19. 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.

  20. 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)

  1. SSTI- Lewis Spacecraft Nickel-Hydrogen Battery

    NASA Technical Reports Server (NTRS)

    Tobias, R. F.

    1997-01-01

    Topics considered include: NASA-Small Spacecraft Technology Initiative (SSTI) objectives, SSTI-Lewis overview, battery requirement, two cells Common Pressure Vessel (CPV) design summary, CPV electric performance, battery design summary, battery functional description, battery performance.

  2. 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)

  3. Excerpts from the Books of Bernard Lewis.

    ERIC Educational Resources Information Center

    Lewis, Bernard

    1990-01-01

    Presents excerpts from the books of Bernard Lewis on Arab culture and history; Islamic religion, history, and politics; Orientalism; and slavery in the Middle East. Includes an excerpt on historiography and the problems of historical scholarship. (RW)

  4. 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.

    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

  5. 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

    2016-01-01

    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

  6. Stress and mind-body impact on the course of inflammatory bowel diseases.

    PubMed

    Anton, P A

    1999-01-01

    At present, the medical management of inflammatory bowel diseases (IBD) including Crohn's disease and ulcerative colitis, are focused on topical, locally active antiinflammatories and systemic immunosuppressives, which are thought to exert their targeted effects in the gastrointestinal mucosa. There is a paucity of controlled trials assessing the impact of mind, central nervous system (CNS), and neuromodulation on the overly active immune response in the intestinal mucosa. Patients and their physicians have long been aware of a strong association between attitude, stress, and flares of their IBD. Although reports to date remain mostly anecdotal, the degree to which mind-body influences and stress impact levels of local inflammation deserves closer attention with the aim of identifying contributing mechanisms, which may highlight new therapeutic interventions, as well as assist in identifying particular subsets of patients that may respond to novel forms of adjunctive treatments for IBD, including hypnosis, meditation, neuropeptide receptor modulation, and cortisol-releasing factor (CRF) modulation. PMID:10065768

  7. 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. PMID:25000715

  8. 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.

  9. Serum Albumin and Body Weight as Biomarkers for the Antemortem Identification of Bone and Gastrointestinal Disease in the Common Marmoset

    PubMed Central

    Baxter, Victoria K.; Shaw, Gillian C.; Sotuyo, Nathaniel P.; Carlson, Cathy S.; Olson, Erik J.; Zink, M. Christine; Mankowski, Joseph L.; Adams, Robert J.

    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. PMID:24324827

  10. 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

  11. 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. PMID:25380591

  12. The body politic: the relationship between stigma and obesity-associated disease

    PubMed Central

    Muennig, Peter

    2008-01-01

    Background It is commonly believed that the pathophysiology of obesity arises from adiposity. In this paper, I forward a complementary explanation; this pathophysiology arises not from adiposity alone, but also from the psychological stress induced by the social stigma associated with being obese. Methods In this study, I pursue novel lines of evidence to explore the possibility that obesity-associated stigma produces obesity-associated medical conditions. I also entertain alternative hypotheses that might explain the observed relationships. Results I forward four lines of evidence supporting the hypothesis that psychological stress plays a role in the adiposity-health association. First, body mass index (BMI) is a strong predictor of serological biomarkers of stress. Second, obesity and stress are linked to the same diseases. Third, body norms appear to be strong determinants of morbidity and mortality among obese persons; obese whites and women – the two groups most affected by weight-related stigma in surveys – disproportionately suffer from excess mortality. Finally, statistical models suggest that the desire to lose weight is an important driver of weight-related morbidity when BMI is held constant. Conclusion Obese persons experience a high degree of stress, and this stress plausibly explains a portion of the BMI-health association. Thus, the obesity epidemic may, in part, be driven by social constructs surrounding body image norms. PMID:18426601

  13. 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.

  14. 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

  15. Impaired intracellular trafficking defines early Parkinson's disease

    PubMed Central

    Hunn, Benjamin H.M.; Cragg, Stephanie J.; Bolam, J. Paul; Spillantini, Maria-Grazia; Wade-Martins, Richard

    2015-01-01

    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. PMID:25639775

  16. 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. PMID:26937324

  17. 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

  18. The effects of whole body vibration on mobility and balance in Parkinson disease: a systematic review.

    PubMed

    Sharififar, Sharareh; Coronado, Rogelio A; Romero, Sergio; Azari, Hassan; Thigpen, Mary

    2014-07-01

    Whole body vibration (WBV) is a contemporary treatment modality that holds promise as an exercise training method in health-compromised individuals. A growing number of studies on individuals with Parkinson Disease are examining whether WBV improves balance and functional mobility. However, interpreting WBV studies is challenging since there is variability in the manner in which WBV intervention is conducted. The primary goal of this systematic review was to investigate the effect of WBV on improving mobility and balance as measured by a battery of clinical tests, in patients with Parkinson disease. Studies based on WBV parameters were characterized and a systematic search of peer-reviewed literature in five major databases was conducted. Randomized-controlled trials investigating the effects of WBV in patients with a Parkinson diagnosis and no cognitive impairment were included. A total of six publications met the inclusion criteria. Overall, studies demonstrated mixed results in favor of WBV for improving balance or mobility. The majority of studies seem to suggest a favorable benefit following WBV for mobility and balance, but not when compared to other active intervention or placebo. There was variability in the manner in which WBV intervention was applied. Variations among the six studies included: duration of intervention and rest, follow-up period, type of control groups, frequency of vibration, number of treatment sessions and sex distribution of subjects. Future research is needed to investigate the effects of different types of equipment and treatment dosage in individuals with Parkinson disease. PMID:25031483

  19. The Effects of Whole Body Vibration on Mobility and Balance in Parkinson Disease: a Systematic Review

    PubMed Central

    Sharififar, Sharareh; Coronado, Rogelio A.; Romero, Sergio; Azari, Hassan; Thigpen, Mary

    2014-01-01

    Whole body vibration (WBV) is a contemporary treatment modality that holds promise as an exercise training method in health–compromised individuals. A growing number of studies on individuals with Parkinson Disease are examining whether WBV improves balance and functional mobility. However, interpreting WBV studies is challenging since there is variability in the manner in which WBV intervention is conducted. The primary goal of this systematic review was to investigate the effect of WBV on improving mobility and balance as measured by a battery of clinical tests, in patients with Parkinson disease. Studies based on WBV parameters were characterized and a systematic search of peer-reviewed literature in five major databases was conducted. Randomized-controlled trials investigating the effects of WBV in patients with a Parkinson diagnosis and no cognitive impairment were included. A total of six publications met the inclusion criteria. Overall, studies demonstrated mixed results in favor of WBV for improving balance or mobility. The majority of studies seem to suggest a favorable benefit following WBV for mobility and balance, but not when compared to other active intervention or placebo. There was variability in the manner in which WBV intervention was applied. Variations among the six studies included: duration of intervention and rest, follow-up period, type of control groups, frequency of vibration, number of treatment sessions and sex distribution of subjects. Future research is needed to investigate the effects of different types of equipment and treatment dosage in individuals with Parkinson disease. PMID:25031483

  20. Glycation in Parkinson's disease and Alzheimer's disease.

    PubMed

    Vicente Miranda, Hugo; El-Agnaf, Omar M A; Outeiro, Tiago Fleming

    2016-06-01

    Glycation is a spontaneous age-dependent posttranslational modification that can impact the structure and function of several proteins. Interestingly, glycation can be detected at the periphery of Lewy bodies in the brain in Parkinson's disease. Moreover, α-synuclein can be glycated, at least under experimental conditions. In Alzheimer's disease, glycation of amyloid β peptide exacerbates its toxicity and contributes to neurodegeneration. Recent studies establish diabetes mellitus as a risk factor for several neurodegenerative disorders, including Parkinson's and Alzheimer's diseases. However, the mechanisms underlying this connection remain unclear. We hypothesize that hyperglycemia might play an important role in the development of these disorders, possibly by also inducing protein glycation and thereby dysfunction, aggregation, and deposition. Here, we explore protein glycation as a common player in Parkinson's and Alzheimer's diseases and propose it may constitute a novel target for the development of strategies for neuroprotective therapeutic interventions. © 2016 International Parkinson and Movement Disorder Society. PMID:26946341

  1. Body mass index is not a reliable tool in predicting celiac disease in children

    PubMed Central

    2014-01-01

    Background Untreated celiac disease is traditionally believed to be associated with malabsorption and underweight. However, studies describing body mass index (BMI) in individuals at the time of diagnosis have shown contradictory results. We investigated the differences in weight, height, and BMI in 12- year-old children with screening-detected celiac disease compared to their healthy peers. Methods In a population-based screening study of 12,632 12-year-old children, blood samples were analyzed for markers of celiac disease. Children with elevated markers were referred for a small bowel biopsy. Weight and height were measured in 239 out of 242 children with screening-detected celiac disease (57.3% girls) and in 12,227 children without celiac disease (48.5% girls). BMI was categorized according to the International Obesity Task Force. Age- and sex-specific cut-off points for underweight, normal weight, and overweight were used. Results Children with celiac disease weighed less and were shorter than their peers (median weight 45.2 kg, interquartile range (IQR) 40.2–52.2 kg vs. 47.0 kg, IQR 41.1–54.4 kg, respectively, p = 0.01; median height 156.5 cm, IQR 151.0–162.0 cm vs. 157.5 cm, IQR 152.0–163.0 cm, respectively, p = 0.04). In comparing those with celiac disease to their healthy peers, 4.2% vs. 5.2% were underweight, 82.0% vs. 72.8% were normal weight, and 13.8% vs. 21.9% were overweight, respectively. There was no association between being underweight and the risk of having undiagnosed celiac disease (Odds ratio (OR) 1.3, 95% CI 0.7–2.4), but the risk was significantly lower among overweight children (OR 0.56, 95% CI 0.4–0.8). Median BMI was slightly lower among the children with screening-detected celiac disease compared to their healthy peers (18.6 kg/m2, IQR 17.1–19.8 kg/m2 vs. 18.8 kg/m2, IQR 17.2–21.1 kg/m2, respectively, p = 0.05), but most of the celiac disease cases had a normal BMI. Conclusions At a population level, children with celiac

  2. Surgical resection of epidural disease improves local control following postoperative spine stereotactic body radiotherapy

    PubMed Central

    Al-Omair, Ameen; Masucci, Laura; Masson-Cote, Laurence; Campbell, Mikki; Atenafu, Eshetu G.; Parent, Amy; Letourneau, Daniel; Yu, Eugene; Rampersaud, Raja; Massicotte, Eric; Lewis, Stephen; Yee, Albert; Thibault, Isabelle; Fehlings, Michael G.; Sahgal, Arjun

    2013-01-01

    Background Spine stereotactic body radiotherapy (SBRT) is increasingly being applied to the postoperative spine metastases patient. Our aim was to identify clinical and dosimetric predictors of local control (LC) and survival. Methods Eighty patients treated between October 2008 and February 2012 with postoperative SBRT were identified from our prospective database and retrospectively reviewed. Results The median follow-up was 8.3 months. Thirty-five patients (44%) were treated with 18–26 Gy in 1 or 2 fractions, and 45 patients (56%) with 18–40 Gy in 3–5 fractions. Twenty-one local failures (26%) were observed, and the 1-year LC and overall survival (OS) rates were 84% and 64%, respectively. The most common site of failure was within the epidural space (15/21, 71%). Multivariate proportional hazards analysis identified systemic therapy post-SBRT as the only significant predictor of OS (P = .02) and treatment with 18–26 Gy/1 or 2 fractions (P = .02) and a postoperative epidural disease grade of 0 or 1 (0, no epidural disease; 1, epidural disease that compresses dura only, P = .003) as significant predictors of LC. Subset analysis for only those patients (n = 48/80) with high-grade preoperative epidural disease (cord deformed) indicated significantly greater LC rates when surgically downgraded to 0/1 vs 2 (P = .0009). Conclusions Postoperative SBRT with high total doses ranging from 18 to 26 Gy delivered in 1–2 fractions predicted superior LC, as did postoperative epidural grade. PMID:24057886

  3. 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. PMID:25294650

  4. 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. PMID:21910268

  5. 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.

  6. 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.

  7. 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.

  8. Intramolecular cooperativity in frustrated Lewis pairs.

    PubMed

    Körte, Leif A; Blomeyer, Sebastian; Heidemeyer, Shari; Mix, Andreas; Neumann, Beate; Mitzel, Norbert W

    2016-08-01

    The doubly Lewis-acid functionalised aniline PhN[(CH2)3B(C6F5)2]2 features two competing boron functions in fast exchange for binding to the central Lewis base. It shows catalytic activity typical for FLPs in H/D-scrambling and catalytic hydrogenation experiments. By contrast, the singly acid-functionalised PhMeN(CH2)3B(C6F5)2 reveals a dramatically smaller catalytic activity in analogous experiments. PMID:27440500

  9. 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.

  10. Arachidonate 5-lipoxygenase (ALOX5) gene polymorphism is associated with Alzheimer's disease and body mass index.

    PubMed

    Šerý, Omar; Hlinecká, Lýdia; Povová, Jana; Bonczek, Ondřej; Zeman, Tomáš; Janout, Vladimír; Ambroz, Petr; Khan, Naim A; Balcar, Vladimir J

    2016-03-15

    Dementias of old age, in particular Alzheimer's disease (AD), pose a growing threat to the longevity and quality of life of individuals as well as whole societies world-wide. The risk factors are both genetic and environmental (life-style) and there is an overlap with similar factors predisposing to cardiovascular diseases (CVD). Using a case-control genetic approach, we have identified a SNP (rs10507391) in ALOX5 gene, previously associated with an increased risk of stroke, as a novel genetic risk factor for AD. ALOX5 gene encodes a 5'-lipoxygenase (5'-LO) activating protein (FLAP), a crucial component of the arachidonic acid/leukotriene inflammatory cascade. A-allele of rs4769874 polymorphism increases the risk of AD 1.41-fold (p<0.0001), while AA genotype does so 1.79-fold (p<0.0001). In addition, GG genotype of rs4769874 polymorphism is associated with a modest increase in body mass index (BMI). We discuss potential biochemical mechanisms linking the SNP to AD and suggest possible preventive pharmacotherapies some of which are based on commonly available natural products. Finally, we set the newly identified AD risk factors into a broader context of similar CVD risk factors to generate a more comprehensive picture of interacting genetics and life-style habits potentially leading to the deteriorating mental health in the old age. PMID:26944113

  11. Neuroprotective and reparative effects of carotid body grafts in a chronic MPTP model of Parkinson's disease.

    PubMed

    Muñoz-Manchado, Ana B; Villadiego, Javier; Suárez-Luna, Nela; Bermejo-Navas, Alfonso; Garrido-Gil, Pablo; Labandeira-García, José L; Echevarría, Miriam; López-Barneo, José; Toledo-Aral, Juan J

    2013-03-01

    Intrastriatal transplantation of dopaminergic carotid body (CB) cells ameliorates parkinsonism in animal models and, with less efficacy, in Parkinson's disease patients. CB-based cell therapy was initially proposed because of its high dopamine content. However, later studies suggested that its beneficial effect might be due to a trophic action exerted on nigrostriatal neurons. Compatible with this concept are the high levels of neurotrophic factors encountered in CB cells. To test experimentally this idea, unilateral striatal transplants were performed with a sham graft in the contralateral striatum, as a robust internal control. Thereafter, the dopaminergic neurotoxin 1-methyl-4-phenyl-1,2,3,6, -tetrahydropyridine was injected during 3 months. CB grafts protected from degeneration ipsilateral nigral dopaminergic neurons projecting to the transplant in a dose-dependent manner regarding size and glial cell line-derived neurotrophic factor expression. Grafts performed at different times after the onset of the neurotoxic treatment demonstrated with histological and behavioral methods protection and repair of the nigrostriatal pathway by CB transplants. This study provides a mechanistic explanation for the action of CB transplants on parkinsonian models. It should also help to improve cell therapy approaches to Parkinson's disease. PMID:22743091

  12. 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. PMID:26654593

  13. Cellular transfer of experimental allergic encephalomyelitis employing suckling and adult Lewis rats.

    PubMed

    Fujinami, R S; Paterson, P Y

    1981-07-01

    Experiments designed to assess the importance of age of donors and recipients in cellular transfer of experimental allergic encephalomyelitis (EAE) in inbred Lewis rats indicate: (a) that lymph node cells (LNC) of suckling rats sensitized to neuroantigen-adjuvant are just as effective in transfer of the disease to adult recipients as LNC from similarly sensitized adult donors, (b) that EAE can be transferred to suckling rats just as well as adults using lymphoid cells from either suckling or adult donors, and (c) while relatively low numbers of sensitized splenocytes from suckling or adult donors may transfer EAE, relatively large numbers of spleen cells do not. Based on additional EAE transfer experiments, in which recipients received combinations of sensitized LNC and normal splenocytes, no evidence could be secured that the spleen exerts a suppressive influence on cellular transfer of the disease in Lewis s may transfer EAE, relatively large numbers of spleen cells do not. Based on additional EAE transfer experiments, in which recipients received combinations of sensitized LNC and normal splenocytes, no evidence could be secured that the spleen exerts a suppressive influence on cellular transfer of the disease in Lewis s may transfer EAE, relatively large numbers of spleen cells do not. Based on additional EAE transfer experiments, in which recipients received combinations of sensitized LNC and normal splenocytes, no evidence could be secured that the spleen exerts a suppressive influence on cellular transfer of the disease in Lewis rats. PMID:6973635

  14. 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

  15. Molecular events linking cholesterol to Alzheimer's disease and inclusion body myositis in a rabbit model.

    PubMed

    Liu, Qing Yan; Koukiekolo, Roger; Zhang, Dong Ling; Smith, Brandon; Ly, Dao; Lei, Joy X; Ghribi, Othman

    2016-01-01

    Alzheimer's disease (AD) is the most common neurodegenerative disorder, characterized by cognitive impairment and dementia, resulting from progressive synaptic dysfunction, loss and neuronal cell death. Inclusion body myositis (IBM) is a skeletal muscle degenerative disease, displaying progressive proximal and distal muscle weakness, in association with muscle fiber atrophy, degeneration and death. Studies have shown that the late onset version of AD (LOAD) and sporadic IBM (sIBM) in muscle share many pathological features, including the presence of extracellular plaques of β-amyloid peptides and intracellular tangles of hyperphosphorylated tau proteins. High blood cholesterol is suggested to be a risk factor for LOAD. Many neuropathological changes of LOAD can be reproduced by feeding rabbits a 2% enriched cholesterol diet for 12 weeks. The cholesterol fed rabbit model also simultaneously develops sIBM like pathology, which makes it an ideal model to study the molecular mechanisms common to the development of both diseases. In the present study, we determined the changes of gene expression in rabbit brain and muscle during the progression of LOAD and sIBM pathology using a custom rabbit nucleotide microarray, followed by qRT-PCR analyses. Out of 869 unique transcripts screened, 47 genes showed differential expression between the control and the cholesterol-treated group during the 12 week period and 19 changed transcripts appeared to be common to LOAD and sIBM. The most notable changes are the upregulation of the hemoglobin gene family and the downregulation of the genes required for mitochondrial oxidative phosphorylation in both brain and muscle tissues throughout the time course. The significant overlap on the changes of gene expression in the brain and muscle of rabbits fed with cholesterol-enriched diet supports the notion that LOAD and sIBM may share a common etiology. PMID:27073745

  16. Glucocerebrosidase Involvement in Parkinson Disease and Other Synucleinopathies

    PubMed Central

    Almeida, Maria do Rosário

    2012-01-01

    Mutations in both copies (homozygous or compound heterozygous) of the gene encoding the lysosomal enzyme glucocerebrosidase, which cleaves the glycolipid glucocerebroside into glucose and ceramide cause Gaucher disease. However, multiple independent studies have also reported an association between GBA mutations and Parkinsonism with an increased frequency of heterozygous GBA mutations in various cohorts of patients with parkinsonism and other Lewy body disorders. Furthermore, GBA mutation carriers exhibit diverse parkinsonian phenotypes and present a diffuse pattern of Lewy body distribution in the cerebral cortex. This review provides an overview of the genetic basis for this association in various diseases with dysfunction of the central nervous system in which affected individuals developed Parkinsonian symptoms. The emerging clinical, pathological, and genetic studies in neuronal synucleinopathies suggest a common underlying mechanism in the etiology of these neurodegenerative disorders. PMID:22557990

  17. Alpha-Synuclein in Parkinson's Disease: From Pathogenetic Dysfunction to Potential Clinical Application

    PubMed Central

    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. PMID:27610264

  18. T-cell receptor (TCR) usage in Lewis rat experimental autoimmune encephalomyelitis: TCR beta-chain-variable-region V beta 8.2-positive T cells are not essential for induction and course of disease.

    PubMed Central

    Gold, R; Giegerich, G; Hartung, H P; Toyka, K V

    1995-01-01

    Predominant usage of V beta 8.2 gene segments, encoding a T-cell receptor (TCR) beta chain variable region, has been reported for pathogenic Lewis rat T cells reactive to myelin basic protein (MBP). However, up to 75% of the alpha/beta T cells in a panel of MBP-specific T-cell lines did not display TCR V beta 8.2, V beta 8.5, V beta 10, or V beta 16 elements. To further investigate TCR usage, we sorted the T-cell lines for V beta 8.2- and V beta 10-positive T cells or depleted the lines of cells with these TCRs. V beta 8.2-positive T cells and one of the depleted T-cell lines strongly reacted against the MBP peptide MBP-(68-88). The depleted T-cell line caused marked experimental autoimmune encephalomyelitis (EAE) even in Lewis rats in which endogenous V beta 8.2-positive T cells had been eliminated by neonatal treatment with anti-V beta 8.2 monoclonal antibodies. T-cell hybridomas generated from this line predominantly used V beta 3 TCR genes coexpressed with TCR V alpha 2 transcripts, which were also used by V beta 8.2-positive T cells. Furthermore, V beta 10-positive T cells reactive to MBP-(44-67) were encephalitogenic when injected immediately after positive selection. After induction of EAE by sorted V beta 8.2- or V beta 10-positive T-cell lines, immunocytochemical analysis of the spinal cord tissue showed a predominance of the injected TCR or of nontypable alpha/beta T cells after injection of the depleted line. Our results demonstrate heterogeneity of TCR beta-chain usage even for a single autoantigen in an inbred strain. Moreover, V beta 8.2-positive T cells are not essential for the induction and progression of adoptive-transfer EAE. Images Fig. 4 Fig. 5 PMID:7597040

  19. Is It Lewy Body Dementia or Something Else?

    MedlinePlus

    ... changes in walking or movement, visual hallucinations, a sleep disorder called REM sleep behavior disorder, in which people ... to medications for hallucinations. In some cases, the sleep disorder can precede the dementia and other symptoms of ...

  20. Lewis Carroll's Formula for Calendar Calculating.

    ERIC Educational Resources Information Center

    Spitz, Herman H.

    1993-01-01

    This paper presents Lewis Carroll's formula for mentally calculating the day of the week of a given date. The paper concludes that such formulas are too complex for individuals of low intelligence to learn by themselves, and thus "idiots savants" who perform such calendar calculations must be using other systems. (JDD)

  1. 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…

  2. 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)

  3. 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…

  4. 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…

  5. 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.

  6. 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…

  7. 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…

  8. Getting the Weights of Lewis Structures out of Huckel Theory: Huckel-Lewis Configuration Interaction (HL-CI)

    ERIC Educational Resources Information Center

    Humbel, Stephane

    2007-01-01

    A simple method is proposed based on energies obtained with the Huckel theory to compute the weights of the structures. The Huckel-Lewis CI technique extends to the Huckel theory the field of the resonance between Lewis structures.

  9. Adult Polyglucosan Body Disease (APBD): Anaplerotic diet therapy (Triheptanoin) and demonstration of defective methylation pathways.

    PubMed

    Roe, Charles R; Bottiglieri, Teodoro; Wallace, Mary; Arning, Erland; Martin, Alan

    2010-01-01

    APBD is a rare disorder most often affecting adults of Ashkenazi Jewish origin due to partial deficiency of the glycogen brancher enzyme (GBE). It is characterized by progressive involvement of both the central and peripheral nervous systems and deposition of amylopectin-like polyglucosan bodies. There have been no metabolic derangements that might suggest effective therapy nor have there been any clinical improvements for control of its relentless progression. The APBD patients, in this study, experienced stabilization of disease progression, and limited functional improvement in most patients with dietary triheptanoin. Due to a plateau in clinical improvement, the reduced plasma creatinine and methionine levels prompted evaluation of other plasma methylation intermediates in this complex integrated pathway system: decreased S-adenosylmethionine (SAM) (p<0.002), increased S-adenosylhomocysteine (p<0.001), elevated creatine (p=0.001) and increased free choline (p<0.001). Plasma levels of homocysteine and guanidinoacetate were normal. Impaired metabolism of choline and creatine may relate to the progressive dysmyelination and progressive muscle weakness associated with APBD. The partial deficiency of GBE appears to produce a secondary energy deficit possibly related to inadequate reserves of normal glycogen for efficient degradation to free glucose. Dysfunctional regulation of glycogen synthase (GS) may result in continued synthesis and deposition of polyglucosan bodies. This investigation has demonstrated, for the first time, arrest of clinical deterioration with limited functional recovery with triheptanoin diet therapy and the existence of significant derangement of methylation pathways that, when corrected, may lead to even greater therapeutic benefits. PMID:20655781

  10. The relation between body iron store and ferritin, and coronary artery disease

    PubMed Central

    Pourmoghaddas, Ali; Sanei, Hamid; Garakyaraghi, Mohammad; Esteki-Ghashghaei, Fatemeh; Gharaati, Maryam

    2014-01-01

    BACKGROUND Iron is essential for many physiological processes; whereas, iron overload has been known as a risk factor in progression of atherosclerosis. The aim of this study was to investigate the importance of serum ferritin levels, which are known as an indicator of body iron stored in the incidence of coronary artery disease (CAD). METHODS In a case-control study, we evaluated 432 eligible men who underwent coronary angiography at Chamran Cardiology Hospital, Isfahan, Iran. They were separated into two groups of case (with CAD) and control (without CAD). All subjects had given written informed consents. Then, the blood samples were taken after 12-14 hours of fast by a biologist for measuring cardiovascular risk factors and body iron stores, including serum ferritin, serum iron, and total iron binding capacity (TIBC). For statistical analyses, chi-square test, Student’s t-test, one-way ANOVA, and the logistic regression were used. RESULTS In the present study, 212 participants with CAD in the case group and 220 participants free of CAD in the control group were included in the analysis. At baseline, there were significant differences in serum ferritin (P < 0.001) and other cardiovascular risk factors between the two groups. Moreover, when other risk factors of CVD were included in the model, serum ferritin [Odd Ratio (OR) = 1.006, 95% confidence interval of 95% (95% CI) 1.00-1.01, P = 0.045] and serum ferritin ≥ 200 (OR = 4.49, 95% CI 1.72-11.70, P < 0.001) were associated with CAD. CONCLUSION High iron store, as assessed by serum ferritin, was associated with the increased risk of CAD. Furthermore, it was a strong and independent risk factor in the incident of atherosclerosis in the Iranian male population. PMID:24963311

  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. 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

  13. Nontraditional risk factors for cardiovascular disease and visceral adiposity index among different body size phenotypes

    PubMed Central

    Du, T; Zhang, J; Yuan, G; Zhang, M; Zhou, X; Liu, Z; Sun, X; Yu, X

    2014-01-01

    Background and Aims Increased cardiovascular disease and mortality risk in metabolically healthy obese (MHO) individuals remain highly controversial. Several studies suggested risk while others do not. The traditional cardiovascular risk factors may be insufficient to demonstrate the complete range of metabolic abnormalities in MHO individuals. Hence, we aimed to compare the prevalence of elevated lipoprotein (a), apolipoprotein B, and uric acid (UA) levels, apolipoprotein B/apolipoprotein A1 ratio, and visceral adiposity index (VAI) scores, and low apolipoprotein A1 levels among 6 body size phenotypes (normal weight with and without metabolic abnormalities, overweight with and without metabolic abnormalities, and obese with or without metabolic abnormalities). Methods and Results We conducted a cross-sectional analysis of 7765 Chinese adults using data from the nationwide China Health and Nutrition Survey 2009. MHO persons had intermediate prevalence of elevated apolipoprotein B and UA levels, apolipoprotein B/apolipoprotein A1 ratio and VAI scores, and low apolipoprotein A1 levels between metabolically healthy normal-weight (MHNW) and metabolically abnormal obese individuals (P < 0.001 for all comparisons). Elevated apolipoprotein B and UA concentrations, apolipoprotein B/apolipoprotein A1 ratio, and VAI scores were all strongly associated with the MHO phenotype (all P < 0.01). Conclusions Prevalence of elevated apolipoprotein B and UA levels, apolipoprotein B/apolipoprotein A1 ratio and VAI scores, and low levels of apolipoprotein A1 was higher among MHO persons than among MHNW individuals. The elevated levels of the nontraditional risk factors and VAI scores in MHO persons could contribute to the increased cardiovascular disease risk observed in long-term studies. PMID:25159728

  14. Therapeutic perspectives for the treatment of Huntington’s disease: Treating the whole body

    PubMed Central

    Martin, Bronwen; Golden, Erin; Keselman, Alex; Stone, Matthew; Mattson, Mark P.; Egan, Josephine M.; Maudsley, Stuart

    2008-01-01

    Summary Huntington’s disease (HD) is a tremendously debilitating disorder that strikes relatively young individuals and progresses rapidly over the next ten to fifteen years inducing a loss of cognitive and motor skills and eventually death occurs. The primary locus of the disorder is a polyglutamine expansion of the protein product of the huntingtin (htt) gene. The htt protein appears to be a scaffolding protein that orchestrates the complex assembly of multiple intracellular proteins involved in multiple processes, including vesicular movement and cell metabolism. The htt protein is ubiquitously expressed in human tissues but the predominance of the interest in the pathology lies in its effects on the central nervous system (CNS). Most of the current therapeutics for HD thus have been targeted at preventing neuronal damage in the CNS, however, a considerable body of evidence has been accumulating to suggest that the maintenance of a healthy nervous system is tightly linked with peripheral physiological health. Therefore treatment of both the peripheral and central pathophysiologies of HD could form the basis of a more effective HD therapeutic strategy. PMID:17999380

  15. 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.

  16. A cardiod based technique to identify cardiovascular diseases using mobile phones and body sensors.

    PubMed

    Sufi, Fahim; Khalil, Ibrahim; Tari, Zahir

    2010-01-01

    To prevent the threat of Cardiovascular Disease (CVD) related deaths, the usage of mobile phone based computational platforms, body sensors and wireless communications is proliferating. Since mobile phones have limited computational resources, existing PC based complex CVD detection algorithms are often unsuitable for wireless telecardiology applications. Moreover, if the existing Electrocardiography (ECG) based CVD detection algorithms are adopted for mobile telecardiology applications, then there will be processing delays due to the computational complexities of the existing algorithms. However, for a CVD affected patient, seconds worth of delay could be fatal, since cardiovascular cell damage is a totally irrecoverable process. This paper proposes a fast and efficient mechanism of CVD detection from ECG signal. Unlike the existing ECG based CVD diagnosis systems that detect CVD anomalies from hundreds of sample points, the proposed mechanism identifies cardiac abnormality from only 5 sample points. Therefore, according to our experiments the proposed mechanism is up to 3 times faster than the existing techniques. Due to less computational burden, the proposed mechanism is ideal for wireless telecardiology applications running on mobile phones. PMID:21096293

  17. 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.

  18. Body Mass Index and Risk of Nonalcoholic Fatty Liver Disease: Two Electronic Health Record Prospective Studies

    PubMed Central

    Kabadi, Shaum; Preiss, David; Hyde, Craig; Bonato, Vinicius; St. Louis, Matthew; Desai, Jigar; Gill, Jason M. R.; Welsh, Paul; Waterworth, Dawn

    2016-01-01

    Context: The relationship between rising body mass index (BMI) and prospective risk of nonalcoholic fatty liver disease (NAFLD)/nonalcoholic steatohepatitis (NASH) is virtually absent. Objective: Determine the extent of the association between BMI and risk of future NAFLD diagnosis, stratifying by sex and diabetes. Design: Two prospective studies using Humedica and Health Improvement Network (THIN) with 1.54 and 4.96 years of follow-up, respectively. Setting: Electronic health record databases. Participants: Patients with a recorded BMI measurement between 15 and 60 kg/m2, and smoking status, and 1 year of active status before baseline BMI. Patients with a diagnosis or history of chronic diseases were excluded. Interventions: None. Main Outcome Measure: Recorded diagnosis of NAFLD/NASH during follow-up (Humedica International Classification of Diseases, Ninth Revision code 571.8, and read codes for NAFLD and NASH in THIN). Results: Hazard ratios (HRs) were calculated across BMI categories using BMI of 20–22.5 kg/m2 as the reference category, adjusting for age, sex, and smoking status. Risk of recorded NAFLD/NASH increased linearly with BMI and was approximately 5-fold higher in Humedica (HR = 4.78; 95% confidence interval, 4.17–5.47) and 9-fold higher in THIN (HR = 8.93; 7.11–11.23) at a BMI of 30–32.5 kg/m2 rising to around 10-fold higher in Humedica (HR = 9.80; 8.49–11.32) and 14-fold higher in THIN (HR = 14.32; 11.04–18.57) in the 37.5- to 40-kg/m2 BMI category. Risk of NAFLD/NASH was approximately 50% higher in men and approximately double in those with diabetes. Conclusions: These data quantify the consistent and strong relationships between BMI and prospectively recorded diagnoses of NAFLD/NASH and emphasize the importance of weight reduction strategies for prevention and management of NAFLD. PMID:26672639

  19. Dendritic Spine Pathology in Neurodegenerative Diseases.

    PubMed

    Herms, Jochen; Dorostkar, Mario M

    2016-05-23

    Substantial progress has been made toward understanding the neuropathology, genetic origins, and epidemiology of neurodegenerative diseases, including Alzheimer's disease; tauopathies, such as frontotemporal dementia; α-synucleinopathies, such as Parkinson's disease or dementia with Lewy bodies; Huntington's disease; and amyotrophic lateral sclerosis with dementia, as well as prion diseases. Recent evidence has implicated dendritic spine dysfunction as an important substrate of the pathogenesis of dementia in these disorders. Dendritic spines are specialized structures, extending from the neuronal processes, on which excitatory synaptic contacts are formed, and the loss of dendritic spines correlates with the loss of synaptic function. We review the literature that has implicated direct or indirect structural alterations at dendritic spines in the pathogenesis of major neurodegenerative diseases, focusing on those that lead to dementias such as Alzheimer's, Parkinson's, and Huntington's diseases, as well as frontotemporal dementia and prion diseases. We stress the importance of in vivo studies in animal models. PMID:26907528

  20. 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.

  1. Quantitative electroencephalogram utility in predicting conversion of mild cognitive impairment to dementia with Lewy bodies☆

    PubMed Central

    Bonanni, Laura; Perfetti, Bernardo; Bifolchetti, Stefania; Taylor, John-Paul; Franciotti, Raffaella; Parnetti, Lucilla; Thomas, Astrid; Onofrj, Marco

    2015-01-01

    Mild cognitive impairment (MCI) as a precursor of dementia with Lewy bodies (DLB) is the focus of recent research, trying to explore the early mechanisms and possible biomarkers of DLB. Quantitative electroencephalogram (QEEG) methods are able to differentiate early DLB from Alzheimer's disease (AD). The aim of the present study was to assess whether QEEG abnormalities, characterized by dominant frequency <8 Hz and dominant frequency variability >1.5 Hz, typical of early DLB, are already present at the stage of MCI and to evaluate whether EEG abnormalities can predict the development of DLB. Forty-seven MCI subjects were followed for 3 years. EEG recordings were obtained at admission and at the end of the study. At the end of follow-up, 20 subjects had developed probable DLB (MCI-DLB), 14 had probable AD (MCI-AD), 8 did not convert to dementia, 5 developed a non-AD/DLB dementia. One hundred percent of MCI-DLB showed EEG abnormalities at admission. Ninety three percent of MCI-AD maintained a normal EEG throughout the study. QEEG may represent a powerful tool to predict the progression from MCI to DLB with a sensitivity and specificity close to 100%. PMID:25129239

  2. Trace element profiles in murine Lewis lung carcinoma by radioisotope-induced X-ray fluorescence.

    PubMed Central

    Frank, A. S.; Schauble, M. K.; Preiss, I. L.

    1986-01-01

    Trace element profiles of various body tissues and tumor were established during growth of the Lewis lung tumor (LLT) with the use of radioisotope-induced X-ray fluorescence (RIXRF) analysis. The LLT, a highly malignant experimental murine tumor, resembles its human counterpart, has a well-defined life cycle, and kills its host in 30 days. When compared with normal controls, Zn, Br, and Rb levels in lung, liver, and skeletal muscle and Zn and Sr levels in bone from tumor-bearing mice exhibited large fluctuations at critical points in the tumor life cycle. In addition, the 24-day primary tumor trace element profile resembled that of its tissue of origin, normal lung, and was quite different from other normal tissues studied. These findings indicate that trace element profiles may help in the diagnosis, staging, and monitoring of disease. RIXRF is an excellent technique for this purpose because it is sensitive and relatively nondestructive of samples and has multielement capabilities. Images Figure 1 p423-a PMID:3953767

  3. Body Composition Indices and Single and Clustered Cardiovascular Disease Risk Factors in Adolescents: Providing Clinical-Based Cut-Points.

    PubMed

    Gracia-Marco, Luis; Moreno, Luis A; Ruiz, Jonatan R; Ortega, Francisco B; de Moraes, Augusto César Ferreira; Gottrand, Frederic; Roccaldo, Romana; Marcos, Ascensión; Gómez-Martínez, Sonia; Dallongeville, Jean; Kafatos, Anthony; Molnar, Denes; Bueno, Gloria; de Henauw, Stefaan; Widhalm, Kurt; Wells, Jonathan C

    2016-01-01

    The aims of the present study in adolescents were 1) to examine how various body composition-screening tests relate to single and clustered cardiovascular disease (CVD) risk factors, 2) to examine how lean mass and body fatness (independently of each other) relate to clustered CVD risk factors, and 3) to calculate specific thresholds for body composition indices associated with an unhealthier clustered CVD risk. We measured 1089 European adolescents (46.7% boys, 12.5-17.49years) in 2006-2007. CVD risk factors included: systolic blood pressure, maximum oxygen uptake, homeostasis model assessment, C-reactive protein (n=748), total cholesterol/high density lipoprotein cholesterol and triglycerides. Body composition indices included: height, body mass index (BMI), lean mass, the sum of four skinfolds, central/peripheral skinfolds, waist circumference (WC), waist-to-height ratio (WHtR) and waist-to-hip ratio (WHR). Most body composition indices are associated with single CVD risk factors. The sum of four skinfolds, WHtR, BMI, WC and lean mass are strong and positively associated with clustered CVD risk. Interestingly, lean mass is positively associated with clustered CVD risk independently of body fatness in girls. Moderate and highly accurate thresholds for the sum of four skinfolds, WHtR, BMI, WC and lean mass are associated with an unhealthier clustered CVD risk (all AUC>0.773). In conclusion, our results support an association between most of the assessed body composition indices and single and clustered CVD risk factors. In addition, lean mass (independent of body fatness) is positively associated with clustered CVD risk in girls, which is a novel finding that helps to understand why an index such as BMI is a good index of CVD risk but a bad index of adiposity. Moderate to highly accurate thresholds for body composition indices associated with a healthier clustered CVD risk were found. Further studies with a longitudinal design are needed to confirm these findings

  4. 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

  5. Cognitive impairment in Parkinson's disease.

    PubMed

    Ransmayr, Gerhard

    2015-12-01

    Parkinson's disease is the second most frequent neurodegenerative disorder. There is significantly elevated risk of cognitive decline and associated neuropsychiatric symptoms. Dementia may develop insidiously several years after manifestation of Parkinson motor symptoms (dementia associated with Parkinson's disease; Parkinson's disease dementia) or in close temporal relationship (within one year) after onset of motor symptoms (Dementia with Lewy bodies). There are clinical, pathophysiological and therapeutic similarities between these two conditions. Men are more frequently affected than women. Risk factor or indicators are advanced age at disease onset, disease duration, rigidity, akinesia and posture and gait impairment and falls as opposed to tremor dominance, and associated neuropsychiatric symptoms (depression, apathy, hallucinosis, delirium). Dementia is treatable with cholinesterase inhibitors (rivastigmine, donepezil), memantine, and adjustment of the pharmacological regimen of parkinsonian motor symptoms. Concomitant autonomic nervous system symptoms and neuropsychiatric complications warrant early clinical awareness and are accessible to pharmacological therapy. PMID:26609664

  6. 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

  7. 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. PMID:24340066

  8. 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.

  9. Fuels research studies at NASA Lewis

    NASA Technical Reports Server (NTRS)

    Antoine, A. C.

    1982-01-01

    Fuels research studies carried out in a variety of areas related to aviation propulsion, ground transportation, and stationary power generation systems are discussed. The major efforts are directed to studies on fuels for jet aircraft. These studies involve fuels preparation, fuels analysis, and fuel quality evaluations. The scope and direction of research activities in these areas is discussed, descriptions of Lewis capabilities and facilities given, and results of recent research efforts reported.

  10. The NASA-Lewis terrestrial photovoltaics program

    NASA Technical Reports Server (NTRS)

    Bernatowicz, D. T.

    1974-01-01

    Those parts of the present NASA-Lewis research and technology effort on solar cells and arrays having relevance to terrestrial uses are outlined. These include raising cell efficiency, developing the FEP-covered module concept, and exploring low-cost cell concepts. Solar cell-battery power systems for remote weather stations have been built to demonstrate the capabilities of solar cells for terrestrial applications.

  11. Lewis Research Center earth resources program

    NASA Technical Reports Server (NTRS)

    Mark, H.

    1972-01-01

    The Lewis Research Center earth resources program efforts are in the areas of: (1) monitoring and rapid evaluation of water quality; (2) determining ice-type and ice coverage distribution to aid operations in a possible extension of the Great Lakes ice navigation and shipping season; (3) monitoring spread of crop viruses; and (4) extent of damage to strip mined areas as well as success of efforts to rehabilitate such areas for agriculture.

  12. Body Mass Index and the Risk of Incident Non-Communicable Diseases after Starting Antiretroviral Therapy

    PubMed Central

    Koethe, J. R.; Jenkins, C. A.; Turner, M.; Bebawy, S.; Shepherd, B. E.; Wester, C. W.; Sterling, T. R.

    2014-01-01

    Objective Obesity and HIV-infection are associated with an increased incidence of non-infectious co-morbid medical conditions, but the relationship between body mass index (BMI) and the development of non-communicable diseases (NCDs) among individuals on antiretroviral therapy (ART) has not been well-characterized. Methods A cohort study of adults initiating ART between 1998 and 2010 at an academic center with systematic laboratory and clinical data collection, including AIDS and NCD diagnoses. The relationship between BMI at ART initiation and the risk of incident cardiovascular, hepatic, renal or oncologic NCDs was assessed using Cox proportional hazard models. BMI was fit using restricted cubic splines and models adjusted for age, sex, race, CD4+ count, protease inhibitor use, year of initiation, and prior AIDS-defining illness. Results Among 1089 patients in the analysis cohort, 54% had normal BMI, 28% were overweight, and 18% were obese. Baseline BMI was associated with developing an incident NCD (p=<0.01) but the relationship was non-linear. Compared to a BMI of 25 kg/m2, a BMI of 30 kg/m2 conferred a lower risk of an incident NCD diagnosis (HR 0.59; 95% CI: 0.40, 0.87). This protective effect was attenuated at a BMI of 35 kg/m2 (HR 0.78; 95% CI: 0.49, 1.23). Results were similar in sensitivity analyses incorporating tobacco, alcohol and drug use, statin and antihypertensive exposure, and virologic suppression. Conclusions Overweight individuals starting ART have a lower risk of developing NCDs compared to normal BMI individuals, which may reflect a biological effect of adipose tissue versus differences in patient or provider behaviors. PMID:25230709

  13. Long-term whole-body vibration training in two late-onset Pompe disease patients.

    PubMed

    Montagnese, Federica; Thiele, Simone; Wenninger, Stephan; Schoser, Benedikt

    2016-08-01

    The treatment of late-onset Pompe disease (LOPD) relies on enzyme replacement therapy (ERT) and physiotherapy but the most appropriate exercise program is not yet established. Whole-body vibration training (WBVT) has showed promising results, improving motor performances in various populations. Our aim is to assess the effects of WBVT performed by two LOPD patients in addition to ERT and physiotherapy. A side-alternating WBVT lasting 2 years; clinical assessments included: manual muscle testing (MRC sumscore), knee extension and arm flection isometric strength (multi-muscle tester M3diagnos), timed function tests (10 m walking, standing-up from chair, ascending 4-steps), 6 min walking (6 MWT), motor disability (Walton Gardner-Medwin scale), pulmonary function. Follow-up evaluations performed for 9 years since ERT start (pre-WBVT and post-WBVT) are reported for comparison. MRC sumscore improved in both patients (Pt.1:41 → 48, Pt.2:42 → 47) as isometric strength of knee extension (Pt.1: + 62 %, Pt.2: + 26 %) and arm flection (Pt.1: + 88 %, Pt.2: + 66 %), 6 MWT improved in Pt.1 (+75 m). Timed function tests did not greatly change. Patients reported no significant CK elevation or WBVT-related complaints. WBVT may be safely used in LOPD and seems to moderately boost muscle strength in patients receiving ERT and physiotherapy for more than 3 years. Larger cohorts should be studied to better assess WBVT potential as adjunctive exercise tool in LOPD. PMID:27193587

  14. 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

    2016-03-01

    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. PMID:26592522

  15. 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.

  16. 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.

  17. Effects of ketone bodies in Alzheimer's disease in relation to neural hypometabolism, β-amyloid toxicity, and astrocyte function.

    PubMed

    Hertz, Leif; Chen, Ye; Waagepetersen, Helle S

    2015-07-01

    Diet supplementation with ketone bodies (acetoacetate and β-hydroxybuturate) or medium-length fatty acids generating ketone bodies has consistently been found to cause modest improvement of mental function in Alzheimer's patients. It was suggested that the therapeutic effect might be more pronounced if treatment was begun at a pre-clinical stage of the disease instead of well after its manifestation. The pre-clinical stage is characterized by decade-long glucose hypometabolism in brain, but ketone body metabolism is intact even initially after disease manifestation. One reason for the impaired glucose metabolism may be early destruction of the noradrenergic brain stem nucleus, locus coeruleus, which stimulates glucose metabolism, at least in astrocytes. These glial cells are essential in Alzheimer pathogenesis. The β-amyloid peptide Aβ interferes with their cholinergic innervation, which impairs synaptic function because of diminished astrocytic glutamate release. Aβ also reduces glucose metabolism and causes hyperexcitability. Ketone bodies are similarly used against seizures, but the effectively used concentrations are so high that they must interfere with glucose metabolism and de novo synthesis of neurotransmitter glutamate, reducing neuronal glutamatergic signaling. The lower ketone body concentrations used in Alzheimer's disease may owe their effect to support of energy metabolism, but might also inhibit release of gliotransmitter glutamate. Alzheimer's disease is a panglial-neuronal disorder with long-standing brain hypometabolism, aberrations in both neuronal and astrocytic glucose metabolism, inflammation, hyperexcitability, and dementia. Relatively low doses of β-hydroxybutyrate can have an ameliorating effect on cognitive function. This could be because of metabolic supplementation or inhibition of Aβ-induced release of glutamate as gliotransmitter, which is likely to reduce hyperexcitability and inflammation. The therapeutic

  18. [Morphological magnetic resonance imaging: its value for the diagnosis of neurodegenerative diseases].

    PubMed

    Hahn, U; Schwarz, J; Gratz, S; Kaiser, J W; Jarnig, M; Förstl, H

    2008-05-01

    Magnetic resonance imaging (MRI) plays an important role in differentiating idiopathic Parkinson's disease (PD) from its atypical forms. Causes like chronic vascular disease and normal-pressure hydrocephalus are easily visualized. Furthermore, specific atrophy patterns can be found with multi-system atrophies, corticobasal degeneration and progressive supranuclear palsy. In addition the review also deals with specific imaging criteria of other neurodegenerative disorders, such as Wilson's disease, neurodegeneration with iron accumulation in the brain and Huntington's chorea. MRI is of minor importance for differentiating Alzheimer's disease from frontotemporal dementia or dementia with Lewy bodies. However, specific patterns are found in cerebral amyloid angiopathy and prion diseases.. PMID:18437637

  19. Pertussis toxin promotes relapsing-remitting experimental autoimmune encephalomyelitis in Lewis rats.

    PubMed

    Mohajeri, Maryam; Sadeghizadeh, Majid; Javan, Mohammad

    2015-12-15

    Animal models simulate different aspects of human diseases and are essential to get a better understanding of the disease, studying treatments and producing new drugs. Experimental autoimmune encephalomyelitis (EAE) is a preferred model in multiple sclerosis research. Common EAE model in Lewis rats is induced using MBP peptide as a myelin antigen which results in a monophasic disease course. In the present study, EAE was induced in Lewis rats by homogenized guinea pig spinal cord along with or without pertussis toxin (PT). When PT was used, EAE turned into remitting-relapsing form and worsen the clinical symptoms. Higher inflammation and oxidative stress marker gene expression was observed when PT was administrated. PMID:26616879

  20. Artificial neural networks in the recognition of the presence of thyroid disease in patients with atrophic body gastritis

    PubMed Central

    Lahner, Edith; Intraligi, Marco; Buscema, Massimo; Centanni, Marco; Vannella, Lucy; Grossi, Enzo; Annibale, Bruno

    2008-01-01

    AIM: To investigate the role of artificial neural networks in predicting the presence of thyroid disease in atrophic body gastritis patients. METHODS: A dataset of 29 input variables of 253 atrophic body gastritis patients was applied to artificial neural networks (ANNs) using a data optimisation procedure (standard ANNs, T&T-IS protocol, TWIST protocol). The target variable was the presence of thyroid disease. RESULTS: Standard ANNs obtained a mean accuracy of 64.4% with a sensitivity of 69% and a specificity of 59.8% in recognizing atrophic body gastritis patients with thyroid disease. The optimization procedures (T&T-IS and TWIST protocol) improved the performance of the recognition task yielding a mean accuracy, sensitivity and specificity of 74.7% and 75.8%, 78.8% and 81.8%, and 70.5% and 69.9%, respectively. The increase of sensitivity of the TWIST protocol was statistically significant compared to T&T-IS. CONCLUSION: This study suggests that artificial neural networks may be taken into consideration as a potential clinical decision-support tool for identifying ABG patients at risk for harbouring an unknown thyroid disease and thus requiring diagnostic work-up of their thyroid status. PMID:18203288

  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. PMID:25453591

  2. 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

  3. Transition-Metal Oxos as the Lewis Basic Component of Frustrated Lewis Pairs.

    PubMed

    Lambic, Nikola S; Sommer, Roger D; Ison, Elon A

    2016-04-13

    The reaction of oxorhenium complexes that incorporate diamidopyridine (DAP) ligands with B(C6F5)3 results in the formation of classical Lewis acid-base adducts. The adducts effectively catalyze the hydrogenation of a variety of unactivated olefins at 100 °C. Control reactions with these complexes or B(C6F5)3 alone did not yield any hydrogenated products under these conditions. Mechanistic studies suggest a frustrated Lewis pair is generated between the oxorhenium DAP complexes and B(C6F5)3, which is effective at olefin hydrogenation. Thus, we demonstrate for the first time that the incorporation of a transition-metal oxo in a frustrated Lewis pair can have a synergistic effect and results in enhanced catalytic activity. PMID:27002927

  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. PMID:22069795

  5. "We don't wear it on our sleeve": Sickle cell disease and the (in)visible body in parts.

    PubMed

    Ciribassi, Rebekah M; Patil, Crystal L

    2016-01-01

    This paper approaches the lived experiences of patients with a genetically inherited chronic disease, sickle cell disease (SCD), through the lens of (in)visibility. SCD has been referred to as an "invisible" disease for a variety of interrelated reasons, including the difficulty of objectively measuring its characteristic symptoms, the lack of popular or specialist attention, and its characterization as a "black" disease. By mobilizing "invisibility" as a way of probing the day-to-day reinforcements of marginality, this article delves into how structural forces are experienced, interpreted, and negotiated by individual actors. To this end, we present ethnographic data collected from November 2009 until November 2013 with SCD patients and healthcare workers in Chicago. These data emphasize that rendering (in)visible is not a totalizing act, but rather meaningfully breaks the body into differentially visible and ideology-laden parts. More broadly, this indicates the need to rigorously question sources and effects of authority in biomedicine. PMID:26692094

  6. 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

  7. 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 ...

  8. 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. PMID:21217051

  9. 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

  10. 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. PMID:25776548

  11. An enzymatic ruler modulates Lewis antigen glycosylation of Helicobacter pylori LPS during persistent infection

    PubMed Central

    Nilsson, Christina; Skoglund, Anna; Moran, Anthony P.; Annuk, Heidi; Engstrand, Lars; Normark, Staffan

    2006-01-01

    Helicobacter pylori persistently colonizes about half the human population and contributes to the development of peptic ulcer disease and gastric cancer. This organism has evolved means to structurally alter its surface characteristics to evade innate and adaptive immune responses. H. pylori produces LPS O-antigen units that can be posttranslationally fucosylated to generate Lewis antigens, structures also found on human epithelial cells. We demonstrate an extensive diversity of Lewis x and Lewis y expression in LPS O-antigen units, occurring over time and in different regions of the human stomach. Lewis expression patterns were correlated with the on/off status of the three fucosyltransferases (FucT), FutA, FutB, and FutC, which are regulated via slipped-strand mispairing in intragenic polyC tract regions of the corresponding genes. The α1,3-FucT, FutA and FutB, each contain a C-terminal heptad repeat region, consisting of a variable number of DD/NLRV/INY tandem repeats. Variations in the number of heptad repeats correlated to the sizes of O-antigen polymers to become decorated by fucose residues. Our data support a molecular ruler mechanism for how H. pylori varies its LPS fucosylation pattern, where one heptad repeat in the enzyme corresponds to one N-acetyl-β-lactosamine unit in the O-antigen polysaccharide. PMID:16477004

  12. [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. PMID:25577484

  13. Replication of Boid Inclusion Body Disease-Associated Arenaviruses Is Temperature Sensitive in both Boid and Mammalian Cells

    PubMed Central

    Kipar, Anja; Korzyukov, Yegor; Bell-Sakyi, Lesley; Vapalahti, Olli; Hetzel, Udo

    2014-01-01

    ABSTRACT Boid inclusion body disease (BIDB) is a fatal disease of boid snakes, the etiology of which has only recently been revealed following the identification of several novel arenaviruses in diseased snakes. BIBD-associated arenaviruses (BIBDAV) are genetically divergent from the classical Old and New World arenaviruses and also differ substantially from each other. Even though there is convincing evidence that BIBDAV are indeed the etiological agent of BIBD, the BIBDAV reservoir hosts—if any exist besides boid snakes themselves—are not yet known. In this report, we use University of Helsinki virus (UHV; a virus that we isolated from a Boa constrictor with BIBD) to show that BIBDAV can also replicate effectively in mammalian cells, including human cells, provided they are cultured at 30°C. The infection induces the formation of cytoplasmic inclusion bodies (IB), comprised mainly of viral nucleoprotein (NP), similar to those observed in BIBD and in boid cell cultures. Transferring infected cells from 30°C to 37°C ambient temperature resulted in progressive declines in IB formation and in the amounts of viral NP and RNA, suggesting that BIBDAV growth is limited at 37°C. These observations indirectly indicate that IB formation is linked to viral replication. In addition to mammalian and reptilian cells, UHV infected arthropod (tick) cells when grown at 30°C. Even though our findings suggest that BIBDAV have a high potential to cross the species barrier, their inefficient growth at mammalian body temperatures indicates that the reservoir hosts of BIBDAV are likely species with a lower body temperature, such as snakes. IMPORTANCE The newly discovered boid inclusion body disease-associated arenaviruses (BIBDAV) of reptiles have drastically altered the phylogeny of the family Arenavirus. Prior to their discovery, known arenaviruses were considered mainly rodent-borne viruses, with each arenavirus species having its own reservoir host. BIBDAV have so far been

  14. Lewis Carroll's formula for calendar calculating.

    PubMed

    Spitz, H H

    1994-03-01

    One of the extraordinary skills occasionally displayed by individuals of low intelligence (so-called idiots savants) is the ability to name, within seconds, the day of the week for any given date, sometimes over a range of centuries. A number of scholarly papers contain references to formulas that can be used in making this calculation, but none cites one of the earliest published methods, that of Lewis Carroll. However, formulas such as Carroll's are too complex to be self-taught by idiots savants and, consequently, cannot account for their remarkable performance. Alternative explanatory hypotheses were briefly discussed. PMID:8192906

  15. 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.

  16. NASA Lewis Research Center photovoltaic application experiments

    NASA Technical Reports Server (NTRS)

    Ratajczak, A.; Bifano, W.; Martz, J.; Odonnell, P.

    1978-01-01

    The NASA Lewis Research Center has installed 16 geographically dispersed terrestrial photovoltaic systems as part of the DOE National Photovoltaic Program. Four additional experiments are in progress. Currently, operating systems are powering refrigerators, a highway warning sign, forest lookout towers, remote weather stations, a water chiller and insect survey traps. Experiments in progress include the world's first village power system, an air pollution monitor and seismic sensors. Under a separate activity, funded by the U.S. Agency for International Development, a PV-powered water pump and grain grinder is being prepared for an African village. System descriptions and status are included in this report.

  17. Ultrafast hydrolysis of a Lewis photoacid.

    PubMed

    Henrich, Joseph D; Suchyta, Scott; Kohler, Bern

    2015-02-12

    This study explores the concept that electronic excitation can dramatically enhance Lewis acidity. Specifically, it is shown that photoexcitation transforms an electron-deficient organic compound of negligible Lewis acidity in its electronic ground state into a potent excited-state Lewis acid that releases a proton from a nearby water molecule in 3.1 ps. It was shown previously (Peon et al. J. Phys. Chem. A 2001, 105, 5768) that the excited state of methyl viologen (MV(2+)) is quenched rapidly in aqueous solution with the formation of an unidentified photoproduct. In this study, the quenching mechanism and the identity of the photoproduct were investigated by the femtosecond transient absorption and fluorescence upconversion techniques. Transient absorption signals at UV probe wavelengths reveal a long-lived species with a pH-dependent lifetime due to reaction with hydronium ions at a bimolecular rate of 3.1 × 10(9) M(-1) s(-1). This species is revealed to be a charge-transfer complex consisting of a ground-state MV(2+) ion and a hydroxide ion formed when a water molecule transfers a proton to the bulk solvent. Formation of a contact ion pair between MV(2+) and hydroxide shifts the absorption spectrum of the former ion by a few nm to longer wavelengths, yielding a transient absorption spectrum with a distinctive triangle wave appearance. The slight shift of this spectrum, which is in excellent agreement with steady-state difference spectra recorded for MV(2+) at high pH, is consistent with an ion pair but not with a covalent adduct (pseudobase). The long lifetime of the ion pair at neutral pH indicates that dissociation occurs many orders of magnitude more slowly than predicted by the Smoluchowski-Debye equation. Remarkably, there is no evidence of geminate recombination, suggesting that the proton that is transferred to the solvent is conducted at least several water shells away. Although the hydrolysis mechanism has yet to be fully established, evidence suggests

  18. 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

  19. In a flurry of PINK, mitochondrial bioenergetics takes a leading role in Parkinson's disease.

    PubMed

    Murphy, Anne N

    2009-05-01

    For many years research in Parkinson's disease (PD) has linked mitochondrial dysfunction with the characteristic loss of dopaminergic neurons of the substantia nigra, accumulation of cytoplasmic inclusions termed Lewy bodies, and motor dysfunction (Henchcliffe & Beal, 2008). The most compelling connection is that Parkinsonism can be observed in both humans and animals following exposure to inhibitors of complex I of the electron transport chain (Betarbet et al, 2002). PMID:20049706

  20. 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

  1. Atypical sporadic CJD-MM phenotype with white matter kuru plaques associated with intranuclear inclusion body and argyrophilic grain disease.

    PubMed

    Berghoff, Anna S; Trummert, Anita; Unterberger, Ursula; Ströbel, Thomas; Hortobágyi, Tibor; Kovacs, Gabor G

    2015-08-01

    We describe an atypical neuropathological phenotype of sporadic Creutzfeldt-Jakob disease in a 76-year-old man. The clinical symptoms were characterized by progressive dementia, gait ataxia, rigidity and urinary incontinence. The disease duration was 6 weeks. MRI did not show prominent atrophy or hyperintensities in cortical areas, striatum or thalamus. Biomarker examination of the cerebrospinal fluid deviated from that seen in pure Alzheimer's disease. Triphasic waves in the EEG were detected only later in the disease course, while 14-3-3 assay was positive. PRNP genotyping revealed methionine homozygosity (MM) at codon 129. Neuropathology showed classical CJD changes corresponding to the MM type 1 cases. However, a striking feature was the presence of abundant kuru-type plaques in the white matter. This rare morphology was associated with neuropathological signs of intranuclear inclusion body disease and advanced stage of argyrophilic grain disease. These alterations did not show correlation with each other, thus seemed to develop independently. This case further highlights the complexity of neuropathological alterations in the ageing brain. PMID:25783686

  2. 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

  3. Assessing and managing body condition score for the prevention of metabolic disease in dairy cows.

    PubMed

    Roche, John R; Kay, Jane K; Friggens, Nic C; Loor, Juan J; Berry, Donagh P

    2013-07-01

    Body condition score (BCS) is an assessment of a cow's body fat (and muscle) reserves, with low values reflecting emaciation and high values equating to obesity. The intercalving profile of BCS is a mirror image of the milk lactation profile. The BCS at which a cow calves, her nadir BCS, and the amount of BCS lost after calving are associated with milk production, reproduction, and health. Genetics, peripartum nutrition, and management are factors that likely interact with BCS to determine the risk of health disorders. PMID:23809894

  4. Persistence of Ebola virus in various body fluids during convalescence: evidence and implications for disease transmission and control.

    PubMed

    Chughtai, A A; Barnes, M; Macintyre, C R

    2016-06-01

    The aim of this study was to review the current evidence regarding the persistence of Ebola virus (EBOV) in various body fluids during convalescence and discuss its implication on disease transmission and control. We conducted a systematic review and searched articles from Medline and EMBASE using key words. We included studies that examined the persistence of EBOV in various body fluids during the convalescent phase. Twelve studies examined the persistence of EBOV in body fluids, with around 800 specimens tested in total. Available evidence suggests that EBOV can persist in some body fluids after clinical recovery and clearance of virus from the blood. EBOV has been isolated from semen, aqueous humor, urine and breast milk 82, 63, 26 and 15 days after onset of illness, respectively. Viral RNA has been detectable in semen (day 272), aqueous humor (day 63), sweat (day 40), urine (day 30), vaginal secretions (day 33), conjunctival fluid (day 22), faeces (day 19) and breast milk (day 17). Given high case fatality and uncertainties around the transmission characteristics, patients should be considered potentially infectious for a period of time after immediate clinical recovery. Patients and their immediate contacts should be informed about these risks. Convalescent patients may need to abstain from sex for at least 9 months or should use condoms until their semen tests are negative. Breastfeeding should be avoided during the convalescent phase. There is a need for more research on persistence, and a uniform approach to infection control guidelines in convalescence. PMID:26808232

  5. 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.

  6. 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…

  7. Identification of TMEM230 mutations in familial Parkinson's disease.

    PubMed

    Deng, Han-Xiang; Shi, Yong; Yang, Yi; Ahmeti, Kreshnik B; Miller, Nimrod; Huang, Cao; Cheng, Lijun; Zhai, Hong; Deng, Sheng; Nuytemans, Karen; Corbett, Nicola J; Kim, Myung Jong; Deng, Hao; Tang, Beisha; Yang, Ziquang; Xu, Yanming; Chan, Piu; Huang, Bo; Gao, Xiao-Ping; Song, Zhi; Liu, Zhenhua; Fecto, Faisal; Siddique, Nailah; Foroud, Tatiana; Jankovic, Joseph; Ghetti, Bernardino; Nicholson, Daniel A; Krainc, Dimitri; Melen, Onur; Vance, Jeffery M; Pericak-Vance, Margaret A; Ma, Yong-Chao; Rajput, Ali H; Siddique, Teepu

    2016-07-01

    Parkinson's disease is the second most common neurodegenerative disorder without effective treatment. It is generally sporadic with unknown etiology. However, genetic studies of rare familial forms have led to the identification of mutations in several genes, which are linked to typical Parkinson's disease or parkinsonian disorders. The pathogenesis of Parkinson's disease remains largely elusive. Here we report a locus for autosomal dominant, clinically typical and Lewy body-confirmed Parkinson's disease on the short arm of chromosome 20 (20pter-p12) and identify TMEM230 as the disease-causing gene. We show that TMEM230 encodes a transmembrane protein of secretory/recycling vesicles, including synaptic vesicles in neurons. Disease-linked TMEM230 mutants impair synaptic vesicle trafficking. Our data provide genetic evidence that a mutant transmembrane protein of synaptic vesicles in neurons is etiologically linked to Parkinson's disease, with implications for understanding the pathogenic mechanism of Parkinson's disease and for developing rational therapies. PMID:27270108

  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. The utility of α-synuclein as biofluid marker in neurodegenerative diseases: a systematic review of the literature.

    PubMed

    Simonsen, Anja Hviid; Kuiperij, Bea; El-Agnaf, Omar Mukhtar Ali; Engelborghs, Sebastian; Herukka, Sanna-Kaisa; Parnetti, Lucilla; Rektorova, Irena; Vanmechelen, Eugeen; Kapaki, Elisabeth; Verbeek, Marcel; Mollenhauer, Brit

    2016-01-01

    The discovery of α-synuclein (α-syn) as a major component of Lewy bodies, neuropathological hallmark of Parkinson's disease (PD), dementia with Lewy bodies and of glial inclusions in multiple system atrophy initiated the investigation of α-syn as a biomarker in cerebrospinal fluid (CSF). Due to the involvement of the periphery in PD the quantification of α-syn in peripheral fluids such as serum, plasma and saliva has been investigated as well. We review how the development of multiple assays for the quantification of α-syn has yielded novel insights into the variety of α-syn species present in the different fluids; the optimal preanalytical conditions required for robust quantification and the potential clinical value of α-syn as biomarker. We also suggest future approaches to use of CSF α-syn in neurodegenerative diseases. PMID:26314196

  10. Stress, allostatic load, catecholamines, and other neurotransmitters in neurodegenerative diseases.

    PubMed

    Goldstein, David S

    2012-07-01

    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 catecholaminesin 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

  11. Stress, allostatic load, catecholamines, and other neurotransmitters in neurodegenerative diseases.

    PubMed

    Goldstein, D S

    2011-04-01

    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 catecholamines in the neuronal cytoplasm are autotoxic and that catecholamines from storage visicles leak into the cytoplasm continuously during life. 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

  12. 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

  13. 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. PMID:23195421

  14. Objective characterization of daily living transitions in patients with Parkinson's disease using a single body-fixed sensor.

    PubMed

    Bernad-Elazari, Hagar; Herman, Talia; Mirelman, Anat; Gazit, Eran; Giladi, Nir; Hausdorff, Jeffrey M

    2016-08-01

    Body-fixed sensors (BFS), e.g., accelerometers worn for several days, can be used to augment the traditional clinical assessment. Long-term recordings obtained with BFS have been applied to study tremor, postural control, freezing of gait, turning abilities, motor response fluctuations and fall risk among older adults and patients with Parkinson's disease (PD). We aimed to test whether BFS-derived measures of transitions differ between patients with PD and healthy controls, and to evaluate whether there are differences among patients with mild PD, compared to more severe patients, and to controls. We also explored the added value of the metrics extracted from the sensor as compared to traditional testing in the lab. Ninety-nine patients with PD and 38 healthy older adults (HOA) participated in this study and wore a body-fixed sensor for 3 days. Walk-to-sit (n = 3286) and Sit-to-walk (n = 2858) transitions were analyzed and a machine learning algorithm was applied to distinguish between the groups. Significant differences in transitions were observed between PD patients and HOA, between mild and severe PD, and between mild PD and HOA, both in temporal and distribution features. The machine learning algorithm discriminated patients from HOA (accuracy = 92.3 %), mild from severe patients (accuracy = 89.8 %), and mild patients from HOA (accuracy = 85.9 %). These initial results suggest that body-fixed sensor-derived metrics of everyday transitions can characterize disease severity and differentiate mild PD patients from healthy older adults. Perhaps this approach can help with the integration of BFS into clinical care and the tracking of disease progression and the response to therapy. PMID:27216626

  15. Case report: inclusion body disease of cranes: a serological follow-up to the 1978 die-off

    USGS Publications Warehouse

    Docherty, D.E.; Romaine, Renee I.

    1983-01-01

    A herpesvirus was isolated from captive cranes involved in a 1978 die-off. Neutralizing antibody to this virus was detected in this captive population as early as 1975 and consistently thereafter through 1979. Exposure to the virus evidently occurred at least 2 1/2 years before the die-off, without causing any mortality diagnosed as being caused by inclusion body disease of cranes (IBDC). Overcrowding and environmental conditions in 1978 may have contributed to the deaths of certain species of cranes in one area and not in another. Mortality ratios and serological data suggest that crane species vary in their response to IBDC virus.

  16. Hydatid Disease Involving Some Rare Locations in the Body: a Pictorial Essay

    PubMed Central

    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. PMID:18071284

  17. The alternative role of 14-3-3 zeta as a sweeper of misfolded proteins in disease conditions.

    PubMed

    Kaneko, Kiyotoshi; Hachiya, Naomi S

    2006-01-01

    Here, we propose a novel hypothesis that 14-3-3 zeta might act as a sweeper of misfolded proteins by facilitating the formation of aggregates, which are referred to as inclusion bodies. Studies on the localization of the 14-3-3 proteins in different types of inclusion bodies in the brain including neurofibrillary tangle in Alzheimer's disease, pick bodies in Pick's disease, Lewy body-like hyaline inclusions in sporadic amyotrophic lateral sclerosis, prion/florid plaques in sporadic/variant Creutzfeldt-Jakob disease, nuclear inclusions in spinocerebellar ataxia-1, and possibly Lewy bodies in Parkinson's disease suggest a close association of these diseases with 14-3-3 zeta. The highly conserved hydrophobic surface of the amphipathic groove in 14-3-3 zeta represents a general mechanism with diverse cellular proteins, and it may also allow for the molecular recognition of misfolded proteins by hydrophobic interaction in disease conditions. When the abnormal processing of misfolded proteins overwhelms the quality control systems of the cell, it is likely that 14-3-3 zeta is recruited to form deposits of protein aggregates with nonnative, misfolded proteins in order to protect the cell against toxicity. Hence, 14-3-3 zeta may be considered as an auxiliary therapeutic tool in the protein aggregation disorders. PMID:16516399

  18. Aluminium Diphosphamethanides: Hidden Frustrated Lewis Pairs.

    PubMed

    Styra, Steffen; Radius, Michael; Moos, Eric; Bihlmeier, Angela; Breher, Frank

    2016-07-01

    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. PMID:27271936

  19. NASA Lewis Meshed VSAT Workshop meeting summary

    NASA Technical Reports Server (NTRS)

    Ivancic, William

    1993-01-01

    NASA Lewis Research Center's Space Electronics Division (SED) hosted a workshop to address specific topics related to future meshed very small-aperture terminal (VSAT) satellite communications networks. The ideas generated by this workshop will help to identify potential markets and focus technology development within the commercial satellite communications industry and NASA. The workshop resulted in recommendations concerning these principal points of interest: the window of opportunity for a meshed VSAT system; system availability; ground terminal antenna sizes; recommended multifrequency for time division multiple access (TDMA) uplink; a packet switch design concept for narrowband; and fault tolerance design concepts. This report presents a summary of group presentations and discussion associated with the technological, economic, and operational issues of meshed VSAT architectures that utilize processing satellites.

  20. Formylborane formation with frustrated Lewis pair templates.

    PubMed

    Sajid, Muhammad; Kehr, Gerald; Daniliuc, Constantin G; Erker, Gerhard

    2014-01-20

    Boranes R2 BH react with carbon monoxide by forming the respective borane carbonyl compounds R2 BH(CO). The formation of (C6 F5 )2 BH(CO) derived from the Piers borane, HB(C6 F5 )2 , is a typical example. Subsequent CO-hydroboration does not take place, since the formation of the formylborane is usually endothermic. However, an "η(2) -formylborane" was formed by CO-hydroboration with the Piers borane at vicinal phosphane/borane frustrated Lewis pair (FLP) templates. Subsequent treatment with pyridine liberated the intact formylborane from the FLP framework, and (pyridine)(C6 F5 )2 BCHO was then isolated as a stable compound. This product underwent typical reactions of carbonyl compounds, such as Wittig olefination. PMID:24338931

  1. 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.

  2. The Fate of Mrs Robinson: Criteria for Recognition of Whole-Body Vibration Injury as AN Occupational Disease

    NASA Astrophysics Data System (ADS)

    HULSHOF, C. T. J.; VAN DER LAAN, G.; BRAAM, I. T. J.; VERBEEK, J. H. A. M.

    2002-05-01

    Several recently published critical reviews conclude that there is strong epidemiological evidence for a relationship between occupational exposure to whole-body vibration (WBV), low back pain (LBP) and back disorders. Whether this exposure is only a modest or a substantial risk factor for the onset and recurrence of LBP is still a matter of debate. In spite of this controversy, four European Union countries have decided to recognize and compensate LBP and certain spinal disorders as an occupational disease. In this paper, we review the criteria currently in use for the recognition of this occupational disease. A search of the literature was performed; additional information was obtained in work visits to national occupational disease institutes in Germany, France and Belgium, in annual reports and national statistics on occupational diseases. Belgium was the first country to add WBV injury to the official list of occupational diseases (1978), followed by Germany (1993), the Netherlands (1997), and France (1999). The incidence of newly recognized cases in 1999 varied considerably: 763 in Belgium, 269 in France, 16 in Germany, and 10 reported cases in the Netherlands. The findings of this review indicate that significant differences exist in the established and applied diagnostic and exposure criteria in the four EU countries. This is illustrated by the case of Mrs Robinson, a 41-year-old forklift driver with LBP, who would probably get recognition and compensation in the Netherlands and Belgium but would be rejected in France and Germany. The development of uniform internationally accepted criteria is recommended, also from an epidemiological point of view, as many data are collected in the process of recognition of this occupational disease.

  3. Paradoxes of body fluid volume regulation in health and disease. A unifying hypothesis.

    PubMed Central

    Schrier, R W; Niederberger, M

    1994-01-01

    The body's normal homeostasis is maintained by the integrity of the excretory capacity of the kidneys. In advanced cardiac failure, however, the avidity of the renal sodium and water retention contributes to the occurrence of pulmonary congestion and peripheral edema. In patients with advanced cirrhosis, the kidneys again fail to excrete the amounts of sodium and water ingested, thus leading to ascites and peripheral edema. The signals for this renal retention of sodium and water in a patient with cirrhosis must be extrarenal because when the same kidneys are transplanted into persons with normal liver function, renal sodium and water retention no longer occurs; rather, the kidneys maintain normal fluid and electrolyte balance. Excessive sodium and water retention by the kidneys also occurs during pregnancy despite a 30% to 50% increase in plasma volume, cardiac output, and glomerular filtration rate. What are the afferent and efferent signals whereby normal kidneys retain sodium and water so that total extracellular, interstitial, and intravascular volumes expand far beyond those limits observed in normal subjects? These dilemmas are the subject of this review, in which a "unifying hypothesis of body fluid volume regulation" is presented. PMID:7817551

  4. Neuropathology of Autosomal Dominant Alzheimer Disease in the National Alzheimer Coordinating Center Database.

    PubMed

    Ringman, John M; Monsell, Sarah; Ng, Denise W; Zhou, Yan; Nguyen, Andy; Coppola, Giovanni; Van Berlo, Victoria; Mendez, Mario F; Tung, Spencer; Weintraub, Sandra; Mesulam, Marek-Marsel; Bigio, Eileen H; Gitelman, Darren R; Fisher-Hubbard, Amanda O; Albin, Roger L; Vinters, Harry V

    2016-03-01

    Alzheimer disease (AD) represents a genetically heterogeneous entity. To elucidate neuropathologic features of autosomal dominant AD ([ADAD] due to PSEN1, APP, or PSEN2 mutations), we compared hallmark AD pathologic findings in 60 cases of ADAD and 120 cases of sporadic AD matched for sex, race, ethnicity, and disease duration. Greater degrees of neuritic plaque and neurofibrillary tangle formation and cerebral amyloid angiopathy (CAA) were found in ADAD (p values < 0.01). Moderate to severe CAA was more prevalent in ADAD (63.3% vs. 39.2%, p = 0.003), and persons with PSEN1 mutations beyond codon 200 had higher average Braak scores and severity and prevalence of CAA than those with mutations before codon 200. Lewy body pathology was less extensive in ADAD but was present in 27.1% of cases. We also describe a novel pathogenic PSEN1 mutation (P267A). The finding of more severe neurofibrillary pathology and CAA in ADAD, particularly in carriers of PSEN1 mutations beyond codon 200, warrants consideration when designing trials to treat or prevent ADAD. The finding of Lewy body pathology in a substantial minority of ADAD cases supports the assertion that development of Lewy bodies may be in part driven by abnormal β-amyloid protein precursor processing. PMID:26888304

  5. Neuropathology of Autosomal Dominant Alzheimer Disease in the National Alzheimer Coordinating Center Database

    PubMed Central

    Ringman, John M.; Monsell, Sarah; Ng, Denise W.; Zhou, Yan; Nguyen, Andy; Coppola, Giovanni; Van Berlo, Victoria; Mendez, Mario F.; Tung, Spencer; Weintraub, Sandra; Mesulam, Marek-Marsel; Bigio, Eileen H.; Gitelman, Darren R.; Fisher-Hubbard, Amanda O.; Albin, Roger L.; Vinters, Harry V.

    2016-01-01

    Alzheimer disease (AD) represents a genetically heterogeneous entity. To elucidate neuropathologic features of autosomal dominant AD ([ADAD] due to PSEN1, APP, or PSEN2 mutations), we compared hallmark AD pathologic findings in 60 cases of ADAD and 120 cases of sporadic AD matched for sex, race, ethnicity, and disease duration. Greater degrees of neuritic plaque and neurofibrillary tangle formation and cerebral amyloid angiopathy (CAA) were found in ADAD (p values < 0.01). Moderate to severe CAA was more prevalent in ADAD (63.3% vs. 39.2%, p = 0.003), and persons with PSEN1 mutations beyond codon 200 had higher average Braak scores and severity and prevalence of CAA than those with mutations before codon 200. Lewy body pathology was less extensive in ADAD but was present in 27.1% of cases. We also describe a novel pathogenic PSEN1 mutation (P267A). The finding of more severe neurofibrillary pathology and CAA in ADAD, particularly in carriers of PSEN1 mutations beyond codon 200, warrants consideration when designing trials to treat or prevent ADAD. The finding of Lewy body pathology in a substantial minority of ADAD cases supports the assertion that development of Lewy bodies may be in part driven by abnormal β-amyloid protein precursor processing. PMID:26888304

  6. Fragmentation of Lewis-type trisaccharides in the gas phase

    NASA Astrophysics Data System (ADS)

    Suzuki, Hiroaki; Yamagaki, Tohru; Tachibana, Kazuo; Fukui, Kazuhiko

    2008-11-01

    The mechanisms of fragmentation of the chlorinated Lewis-type trisaccharides Lewis a and Lewis X were studied by using experimental and theoretical methods. In the fragment ion spectra obtained by ESI-CID-MS, C- and Z-type fragmentations corresponding to 4- and 3-linked glycosyl bond cleavages of the N-acetylglucosamine moiety were observed. The relationships of the relative ion intensities of C- and Z-type fragmentations were Z > C in Lewis a and C > Z in Lewis X, suggesting that the relationships of the activation energies were C > Z in Lewis a and Z > C in Lewis X. Anomeric and acetoamide groups were assumed to be included in the mechanisms of C- and Z-type fragmentation; we therefore analyzed 3-fucosyllactose and methylated Lewis-type trisaccharides, which are the derivatives of Lewis-type trisaccharides. These analyses revealed that C-type fragmentation was little influenced by anomeric group and that Z-type fragmentation was influenced by both the anomeric and the acetoamide groups. Fragmentation mechanisms were proposed on the basis of the experimental results and were calculated at the HF/3-21G(d), HF/6-31G(d) levels. From the calculations, C-type fragmentation of the 4-linkage was considered to take place by electron transfer from the acetoamide group, and Z-type fragmentation at the 3-linkage was considered to take place in two steps: (i) elimination of the 3-linked saccharide moiety, and (ii) deprotonation of an anomeric proton by a chloride anion. The activation energies for C- and Z-type fragmentations, as determined by HF calculations, were consistent with the experimentally assumed trends.

  7. Whole-Body Lifetime Occupational Lead Exposure and Risk of Parkinson’s Disease

    SciTech Connect

    Coon , Steven; Stark, Azadeh; Peterson, Edward; Gloi, Aime; Kortsha, Gene; Pounds, Joel G.; Chettle, D. R.; Gorell, Jay M.

    2006-12-01

    We enrolled 121 PD patients and 414 age-, sex-, and race-, frequency-matched controls in a case–control study. As an indicator of chronic Pb exposure, we measured concentrations of tibial and calcaneal bone Pb stores using 109Cadmium excited K-series X-ray fluorescence. As an indicator of recent exposure, we measured blood Pb concentration. We collected occupational data on participants from 18 years of age until the age at enrollment, and an industrial hygienist determined the duration and intensity of environmental Pb exposure. We employed physiologically based pharmacokinetic modeling to combine these data, and we estimated whole-body lifetime Pb exposures for each individual. Logistic regression analysis produced estimates of PD risk by quartile of lifetime Pb exposure.

  8. The influence of body mass index, age and sex on inflammatory disease risk in semi-captive Chimpanzees.

    PubMed

    Obanda, Vincent; Omondi, George Paul; Chiyo, Patrick Ilukol

    2014-01-01

    Obesity and ageing are emerging issues in the management of captive primates, including Chimpanzees, Pan troglodytes. Studies on humans show that obesity and old age can independently increase the risk of inflammatory-associated diseases indicated by elevated levels of pro-inflammatory cells and proteins in the blood of older or obese compared to levels in younger or non-obese individuals. In humans, sex can influence the outcomes of these risks. Health management of these problems in chimpanzee populations requires an understanding of similarities and differences of factors influencing inflammatory disease risks in humans and in chimpanzees. We examined the relationship between age, sex and Body Mass Index (BMI) with hematological biomarkers of inflammatory disease risk established for humans which include the neutrophil to lymphocyte ratio (NLR), and neutrophil, white blood cell (WBC), platelet microparticle and platelet counts. We found that higher values of NLR, neutrophil count and platelet microparticle count were associated with higher BMI values and older age indicating increased inflammation risk in these groups; a similar pattern to humans. There was a strong sex by age interaction on inflammation risk, with older males more at risk than older females. In contrast to human studies, total WBC count was not influenced by BMI, but like humans, WBC and platelet counts were lower in older individuals compared to younger individuals. Our findings are similar to those of humans and suggest that further insight on managing chimpanzees can be gained from extensive studies of ageing and obesity in humans. We suggest that managing BMI should be an integral part of health management in captive chimpanzee populations in order to partially reduce the risk of diseases associated with inflammation. These results also highlight parallels in inflammation risk between humans and chimpanzees and have implications for understanding the evolution of inflammation related

  9. The association of body mass index with disease activity and clinical response to combination therapy in patients with rheumatoid arthritis

    PubMed Central

    Mirpourian, Maryam; Salesi, Mansour; Abdolahi, Hadi; Farajzadegan, Ziba; Karimzadeh, Hadi

    2014-01-01

    Background: The role of obesity in clinical curse of rheumatoid arthritis (RA) is not clear. We investigated the association of obesity and adiposity with disease activity and clinical response to combination therapy in RA patients. Materials and Methods: Active RA patients with the disease activity score using 28 joint counts (DAS28) > 2.6 were studied. Height, weight, and waist and hip circumferences were measured and body mass index (BMI) and waist to hip ratio were calculated. Patients were treated with methotrexate (7.5 to 10 mg/week) plus hydroxychloroquine (200 to 400 mg/day) and prednisolone (2.5 to 10 mg/day) and were followed by DAS28 for up to 24 weeks. Results: One hundred and six patients were studied; age = 48.5 ± 13.8 years, 87.7% female, disease duration = 4.4 years [SE = 0.48]. DAS28 was decreased from 4.5 ± 1.6 to 2.9 ± 1.4 (P < 0.001) after 24 weeks of treatment. Only in patients with disease duration of ≤2 years, BMI (r = –0.415, P = 0.005) and waist circumference (r = –0.296, P = 0.05) were correlated with baseline DAS28. Although BMI (r = –0.337, P = 0.025) and waist circumference (r = –0.315, P = 0.038) were correlated with change in DAS28 after therapy, these correlations were disappeared after controlling for baseline DAS28. Conclusion: Obesity and adiposity are associated with less severe disease activity in early stage of RA, but are not associated with response to combination therapy with methotrexate plus hydroxychloroquine in RA patients. PMID:25197291

  10. The Influence of Body Mass Index, Age and Sex on Inflammatory Disease Risk in Semi-Captive Chimpanzees

    PubMed Central

    Obanda, Vincent; Omondi, George Paul; Chiyo, Patrick Ilukol

    2014-01-01

    Obesity and ageing are emerging issues in the management of captive primates, including Chimpanzees, Pan troglodytes. Studies on humans show that obesity and old age can independently increase the risk of inflammatory-associated diseases indicated by elevated levels of pro-inflammatory cells and proteins in the blood of older or obese compared to levels in younger or non-obese individuals. In humans, sex can influence the outcomes of these risks. Health management of these problems in chimpanzee populations requires an understanding of similarities and differences of factors influencing inflammatory disease risks in humans and in chimpanzees. We examined the relationship between age, sex and Body Mass Index (BMI) with hematological biomarkers of inflammatory disease risk established for humans which include the neutrophil to lymphocyte ratio (NLR), and neutrophil, white blood cell (WBC), platelet microparticle and platelet counts. We found that higher values of NLR, neutrophil count and platelet microparticle count were associated with higher BMI values and older age indicating increased inflammation risk in these groups; a similar pattern to humans. There was a strong sex by age interaction on inflammation risk, with older males more at risk than older females. In contrast to human studies, total WBC count was not influenced by BMI, but like humans, WBC and platelet counts were lower in older individuals compared to younger individuals. Our findings are similar to those of humans and suggest that further insight on managing chimpanzees can be gained from extensive studies of ageing and obesity in humans. We suggest that managing BMI should be an integral part of health management in captive chimpanzee populations in order to partially reduce the risk of diseases associated with inflammation. These results also highlight parallels in inflammation risk between humans and chimpanzees and have implications for understanding the evolution of inflammation related

  11. Sporadic inclusion body myositis: HLA-DRB1 allele interactions influence disease risk and clinical phenotype.

    PubMed

    Mastaglia, Frank L; Needham, Merrilee; Scott, Adrian; James, Ian; Zilko, Paul; Day, Timothy; Kiers, Lynette; Corbett, Alastair; Witt, Campbell S; Allcock, Richard; Laing, Nigel; Garlepp, Michael; Christiansen, Frank T

    2009-11-01

    Susceptibility to sIBM is strongly associated with the HLA-DRB1*03 allele and the 8.1 MHC ancestral haplotype (HLA-A1, B8, DRB1*03) but little is known about the effects of allelic interactions at the DRB1 locus or disease-modifying effects of HLA alleles. HLA-A, B and DRB1 genotyping was performed in 80 Australian sIBM cases and the frequencies of different alleles and allele combinations were compared with those in a group of 190 healthy controls. Genotype-phenotype correlations were also investigated. Amongst carriers of the HLA-DRB1*03 allele, DRB1*03/*01 heterozygotes were over-represented in the sIBM group (p<0.003) while. DRB1*03/*04 heterozygotes were under-represented (p<0.008). The mean age-at-onset (AAO) was 6.5 years earlier in DRB1*03/*01 heterozygotes who also had more severe quadriceps muscle weakness than the rest of the cohort. The findings indicate that interactions between the HLA-DRB1*03 allele and other alleles at the DRB1 locus can influence disease susceptibility and the clinical phenotype in sIBM. PMID:19720533

  12. 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.

  13. Physical Activity, Body Mass Index, and Brain Atrophy in Alzheimer's Disease

    PubMed Central

    Erickson, Kirk I.; Lopez, Oscar L.; Becker, James T.; Gach, H. Michael; Longstreth, W. T.; Teverovskiy, Leonid; Kuller, Lewis H.; Carmichael, Owen T.; Thompson, Paul M.

    2015-01-01

    The purpose of this study was to utilize a novel imaging biomarker to assess the associations between physical activity (PA), body mass index (BMI), and brain structure in normal aging, mild cognitive impairment (MCI) and Alzheimer's dementia (AD). We studied 963 participants (mean age: 74.1 ± 4.4) from the multi-site Cardiovascular Health Study including healthy controls (n=724), AD (n=104), and MCI (n=135). Volumetric brain images were processed using tensor-based morphometry for analyzing regional brain volumes. We regressed the local brain tissue volume on reported PA and computed BMI, and performed conjunction analyses using both variables. Covariates included age, sex and study site. PA was independently associated with greater whole brain and regional brain volumes, and reduced ventricular dilation. People with higher BMI had lower whole brain and regional brain volumes. A PA-BMI conjunction analysis showed brain preservation with PA and volume loss with increased BMI in overlapping brain regions. In one of the largest voxel-based cross-sectional studies to date, PA and lower BMI may be beneficial to the brain across the spectrum of aging and neurodegeneration. PMID:25248607

  14. Earthing (Grounding) the Human Body Reduces Blood Viscosity—a Major Factor in Cardiovascular Disease

    PubMed Central

    Chevalier, Gaétan; Sinatra, Stephen T.; Delany, Richard M.

    2013-01-01

    Abstract Objectives Emerging research is revealing that direct physical contact of the human body with the surface of the earth (grounding or earthing) has intriguing effects on human physiology and health, including beneficial effects on various cardiovascular risk factors. This study examined effects of 2 hours of grounding on the electrical charge (zeta potential) on red blood cells (RBCs) and the effects on the extent of RBC clumping. Design/interventions Subjects were grounded with conductive patches on the soles of their feet and palms of their hands. Wires connected the patches to a stainless-steel rod inserted in the earth outdoors. Small fingertip pinprick blood samples were placed on microscope slides and an electric field was applied to them. Electrophoretic mobility of the RBCs was determined by measuring terminal velocities of the cells in video recordings taken through a microscope. RBC aggregation was measured by counting the numbers of clustered cells in each sample. Settings/location Each subject sat in a comfortable reclining chair in a soundproof experiment room with the lights dimmed or off. Subjects Ten (10) healthy adult subjects were recruited by word-of-mouth. Results Earthing or grounding increased zeta potentials in all samples by an average of 2.70 and significantly reduced RBC aggregation. Conclusions Grounding increases the surface charge on RBCs and thereby reduces blood viscosity and clumping. Grounding appears to be one of the simplest and yet most profound interventions for helping reduce cardiovascular risk and cardiovascular events. PMID:22757749

  15. Use of acetylcholinesterase inhibitors in Alzheimer's disease.

    PubMed

    Moghul, S; Wilkinson, D

    2001-09-01

    Alzheimer's disease is a growing problem in an aging Western world, estimated to have cost the US economy USD 1.75 trillion. Until recently, the management of Alzheimer's disease largely comprised support for the family, nursing care and the use of unlicensed medication to control behavioral disturbances. The three new acetylcholinesterase inhibitors licensed to treat Alzheimer's disease (donepezil, rivastigmine and galantamine) have provided clinicians with a major impetus to their desire to diagnose and treat this lethal disease. Their effects on cognition are proven. More recent work on the effects of acetylcholinesterase inhibitors on behavioral symptoms, activities of daily living and caregiver burden have also been encouraging. Emerging work indicates their likely efficacy in other dementias (e.g., vascular dementia, dementia with Lewy bodies). This review summarizes the evidence concerning the impact of acetylcholinesterase inhibitors in dementia both currently and over the next 5 years. PMID:19811047

  16. Interventions that improve body and brain bioenergetics for Parkinson's disease risk reduction and therapy.

    PubMed

    Mattson, Mark P

    2014-01-01

    Studies of Parkinson's disease (PD) patients, animal models and pathogenic actions of genetic mutations that cause familial PD have established that neuronal bioenergetics are compromised with brainstem and midbrain monoaminergic neurons being particularly vulnerable. Peripheral insulin resistance and diabetes in midlife may increase the risk of PD, and diet and lifestyle changes that increase insulin sensitivity (exercise and intermittent energy restriction) can counteract neurodegenerative processes and improve functional outcome in animal models. Insulin sensitizing glucagon-like peptide 1 (GLP-1) analogs are beneficial in animal models of PD, and the results of an initial clinical trial in PD patients are promising. In addition to improving peripheral and brain energy metabolism, exercise, intermittent energy restriction and GLP-1 analogs may bolster neuronal adaptive stress response pathways that enhance neurotrophic signaling, DNA repair, proteostasis and mitochondrial biogenesis. PMID:24473219

  17. 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.

  18. 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

  19. 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

  20. Symptomatic carotid stenosis in the setting of bilateral disease and coexisting carotid body tumor: management with a carotid stent and staged excision.

    PubMed

    Smeds, Matthew; Jacobs, Donald

    2013-12-01

    The aim of the paper is to describe the management of a patient with bilateral carotid artery stenosis, symptomatic on the left, with coexisting left carotid body tumor with left carotid stenting followed by right carotid endarterectomy and excision of carotid body tumor. A 60-year-old man with significant bilateral carotid stenosis was referred to us with symptomatic left carotid disease and concomitant left carotid body tumor. A Precise nitinol carotid stent (Cordis Endovascular, Miami Lakes, FL, USA) was placed in his left carotid artery followed by interval carotid endarterectomy on the right. Excision of the carotid body tumor was then performed. Carotid stenting is a treatment option in patients with carotid stenosis and coexisting carotid body tumor. To our knowledge, this is the first reported carotid stent for symptomatic carotid stenosis in a patient with a concomitant carotid body tumor. PMID:23493283

  1. Whole body plethysmography reveals differential ventilatory responses to ozone in rat models of cardiovascular disease.

    PubMed

    Dye, Janice A; Ledbetter, Allen D; Schladweiler, Mette C; Costa, Daniel L; Kodavanti, Urmila P

    2015-01-01

    To elucidate key factors of host susceptibility to air pollution, healthy and cardiovascular (CV)-compromised rats were exposed to air or ozone (O3) at 0.25, 0.5, or 1.0 ppm for 4 h. We hypothesized that rat strains with the least cardiac reserve would be most prone to develop significant health effects. Using flow whole body plethysmography (FWBP), ventilatory responses in healthy 3-month-old male rats [i.e. Wistar-Kyoto (WKY), Wistar (WIS), and Sprague-Dawley (SD) strains] were compared with hypertensive [i.e. spontaneously hypertensive (SH), fawn-hooded-hypertensive (FHH), and SH-stroke-prone (SHSP)] strains and obese [i.e. SH-heart failure-prone (SHHF) and JCR:LA-cp, atherosclerosis-prone (JCR)] strains. SH were slower to acclimate to the FWBP chambers. At 0-h post-air-exposure, SHSP and SHHF exhibited hyperpnea, indicative of cardiopulmonary insufficiency. At 0-h-post-O3, all but one strain showed significant concentration-dependent decreases in minute volume [MV = tidal volume (TV) × breathing frequency]. Comparing air with 1.0 ppm responses, MV declined 20-27% in healthy, 21-42% in hypertensive, and 33% in JCR rats, but was unchanged in SHHF rats. Penh increased significantly in all strains, with disproportionate increases in "responder" WKY and FHH strains. By 20 h, most changes had resolved, although Penh remained elevated in WKY, SH, and SHSP. Based on the effective dose estimates (O3 ppm × h × MV), the most CV-compromised (SHSP and SHHF) strains received significantly greater O3 lung deposition (25% and 40%, respectively). Data support epidemiologic associations that individuals with cardiopulmonary insufficiency are at greater risk for urban pollutant exposure due, in part, to enhanced lung deposition and exacerbation of hypoxia and pathophysiologic processes of heart failure. PMID:26667328

  2. 1. 1943 Plan View of 'Fort Lewis Station Hospital, Section ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    1. 1943 Plan View of 'Fort Lewis Station Hospital, Section No. 5.' Drawn by V. Steinbrueck for J.C. Boespflug Construction Co. July 23, 1943. HABS 8x10' negative was made from an 8.5 x 11' copy on card stock in the collection of the Community Library, Madigan Army Medical Center, Fort Lewis, WA. - Madigan Hospital, Bounded by Wilson & McKinley Avenues & Garfield & Lincoln Streets, DuPont, Pierce County, WA

  3. 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.

  4. 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.

  5. 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.

  6. 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.

  7. 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.

  8. Intramolecular Tetrylene Lewis Adducts: Synthesis and Reactivity.

    PubMed

    Schneider, Julia; Krebs, Kilian M; Freitag, Sarah; Eichele, Klaus; Schubert, Hartmut; Wesemann, Lars

    2016-07-01

    A series of benzyl(diphenylphosphino) and o-phenyl(diphenlyphosphino) substituted germylenes and plumbylenes were synthesized by nucleophilic substitution between the respective lithium reagent and tetrylene halide. The Lewis pairs were characterized by X-ray crystallography and NMR spectroscopy. The reactivity of the tetrylenes was investigated with respect to azide addition. In the germylene case, the germaniumimide was formed as the kinetically controlled product, which rearranges upon heating to give the phosphinimide. The stannylene and plumbylene derivatives react with adamantylazide to give the azide adducts. 1-Pentene reacts diastereoselectively with the phosphagermirane to give a cyclic addition product. Trimethysilylacetylene shows an addition with the benzylphosphino-substituted germylene and plumbylene to give the cycloheteropentene molecules. The addition product between phenylacetylene and the four membered Ge-P adduct shows after addition at room temperature a 1,4-phenylmigration to give a cyclic phosphine. Alkylnitrene insertion into a Ge-C bond of the alkyne addition product of the phosphagermirane was found in reaction with adamantylazide. PMID:27273819

  9. Sexual behavior, body image, and partnership in chronic illness: a comparison of Huntington's disease and multiple sclerosis.

    PubMed

    Reininghaus, Eva; Reininghaus, Bernd; Fitz, Werner; Hecht, Karen; Bonelli, Raphael Maria

    2012-08-01

    Huntington's disease (HD) and multiple sclerosis (MS) are both chronic progressive illnesses posing a serious challenge to affected patients and families. Sexual dysfunction in HD as well as in MS is a very common problem, although it is unclear whether the dysfunction is caused by the chronic illness itself or by the sociopsychiatric burden related to the illness. Twenty-nine patients with HD and 27 patients with MS each participated in a semistructured interview and several standardized questionnaires concerning partnership, sexual function, and body image. The results display significant differences in both patient groups, displaying higher sexual desire and activity in HD patients, but MS patients also reported fewer sexual problems compared to the norming values. Conversely, the MS patients' relationships seemed to be stable despite subjectively perceived lower initiative on sexual activities. The results are discussed under the possible influences of the underlying organic changes and the psychosocial consequences of chronic progressive disorders. PMID:22850308

  10. Feasibility study of a wearable system based on a wireless body area network for gait assessment in Parkinson's disease patients.

    PubMed

    Cancela, Jorge; Pastorino, Matteo; Arredondo, Maria T; Nikita, Konstantina S; Villagra, Federico; Pastor, Maria A

    2014-01-01

    Parkinson's disease (PD) alters the motor performance of affected individuals. The dopaminergic denervation of the striatum, due to substantia nigra neuronal loss, compromises the speed, the automatism and smoothness of movements of PD patients. The development of a reliable tool for long-term monitoring of PD symptoms would allow the accurate assessment of the clinical status during the different PD stages and the evaluation of motor complications. Furthermore, it would be very useful both for routine clinical care as well as for testing novel therapies. Within this context we have validated the feasibility of using a Body Network Area (BAN) of wireless accelerometers to perform continuous at home gait monitoring of PD patients. The analysis addresses the assessment of the system performance working in real environments. PMID:24608005

  11. Feasibility Study of a Wearable System Based on a Wireless Body Area Network for Gait Assessment in Parkinson's Disease Patients

    PubMed Central

    Cancela, Jorge; Pastorino, Matteo; Arredondo, Maria T.; Konstantina, Nikita S.; Villagra, Federico; Pastor, Maria A.

    2014-01-01

    Parkinson's disease (PD) alters the motor performance of affected individuals. The dopaminergic denervation of the striatum, due to substantia nigra neuronal loss, compromises the speed, the automatism and smoothness of movements of PD patients. The development of a reliable tool for long-term monitoring of PD symptoms would allow the accurate assessment of the clinical status during the different PD stages and the evaluation of motor complications. Furthermore, it would be very useful both for routine clinical care as well as for testing novel therapies. Within this context we have validated the feasibility of using a Body Network Area (BAN) of wireless accelerometers to perform continuous at home gait monitoring of PD patients. The analysis addresses the assessment of the system performance working in real environments. PMID:24608005

  12. Effect of garlic powder consumption on body composition in patients with nonalcoholic fatty liver disease: A randomized, double-blind, placebo-controlled trial

    PubMed Central

    Soleimani, Davood; Paknahad, Zamzam; Askari, Gholamreza; Iraj, Bijan; Feizi, Awat

    2016-01-01

    Background: Nonalcoholic fatty liver disease (NAFLD) is the most common chronic liver disease that is becoming a public health problem in recent decades. Obesity and overweight play a key role in NAFLD pathogenesis. Thus, weight loss (especially body fat mass) is one component of therapeutic strategies in NAFLD. Results from experimental studies have shown that garlic (Allium sativum L.) can reduce body weight and body fat mass. However, the effect of garlic on body fat mass and weight in the human population, which is addressed in this study, is still obscure. Materials and Methods: In this clinical trial, 110 subjects with NAFLD were randomly assigned to the intervention or the control group. The intervention group received two garlic tablets (containing 400 mg of garlic powder) daily while the control group received placebo tablets. Dietary intake and physical activity of participants were obtained by a validated questionnaire. Body composition was measured by bioelectrical impedance analysis. Data were analyzed using SPSS software version 16. Results: In the intervention group, significant reductions were observed in body weight and body fat mass (P < 0.05). We also observed a significant reduction in body weight in the control group, but there were no significant changes in total body water and lean body mass in both groups (P > 0.05). In the intervention group, the percentage change in body weight was significantly greater than the control group (−2.6 vs. −0.7, P = 0.02). No serious side effects associated with the intervention were reported. Conclusion: Our trial suggests that garlic supplemfrom experimental studies have shown thatentation can reduce body weight and fat mass among subjects with NAFLD. PMID:26955623

  13. Effects of body position, hyperinflation, and blood gas tensions on maximal respiratory pressures in patients with chronic obstructive pulmonary disease.

    PubMed Central

    Heijdra, Y. F.; Dekhuijzen, P. N.; van Herwaarden, C. L.; Folgering, H. T.

    1994-01-01

    BACKGROUND--Inspiratory muscle strength in patients with chronic obstructive pulmonary disease (COPD) can be affected by mechanical factors which influence the length of the diaphragm, and by non-mechanical factors. The aim of the present study was to evaluate firstly the effects of body position on respiratory pressures and, secondly, to determine the relative contribution of age, body mass index (BMI), lung volumes, and arterial blood gas tensions to respiratory muscle strength. METHODS--Thirty male patients with stable COPD (mean FEV1 40.4% predicted) participated in the study. Maximal inspiratory and expiratory mouth pressures (PImax, PEmax) and maximal inspiratory transdiaphragmatic pressures (PDI) in the sitting and supine position, lung function, and arterial blood gas tensions were measured. RESULTS--Mean (SD) PImax in the sitting position was higher than in the supine position (7.1(2.3)kPa v 6.4(2.2)kPa respectively). In contrast, PDI in the sitting position was lower than in the supine position (10.0(3.5)kPa v 10.8(3.7)kPa respectively). PEmax was higher in the sitting position (9.3(3.0)kPa) than in the supine position (8.7(2.8)kPa). Significant correlations were found between inspiratory muscle strength on the one hand, and lung function parameters, BMI, and arterial blood gas tensions on the other. CONCLUSIONS--Inspiratory muscle strength in patients with COPD is influenced by mechanical factors (body position, lung volumes) and non-mechanical factors (BMI, FEV1, and blood gases). PImax and PEmax are lower in the supine position while, in contrast to healthy subjects, PDI is higher in the supine position than in the sitting position. PMID:8016765

  14. Early detection of metastatic disease in asymptomatic breast cancer patients with whole-body imaging and defined tumour marker increase

    PubMed Central

    Di Gioia, D; Stieber, P; Schmidt, G P; Nagel, D; Heinemann, V; Baur-Melnyk, A

    2015-01-01

    Background: Follow-up care in breast cancer is still an issue of debate. Diagnostic methods are more sensitive, and more effective therapeutic options are now available. The risk of recurrence is not only influenced by tumour stage but also by the different molecular subtypes. This study was performed to evaluate the use of whole-body imaging combined with tumour marker monitoring for the early detection of asymptomatic metastatic breast cancer (MBC). Methods: This analysis was performed as part of a follow-up study evaluating 813 patients with a median follow-up of 63 months. After primary therapy, all patients underwent tumour marker monitoring for CEA, CA 15-3 and CA 125 at 6-week intervals within an intensified diagnostic aftercare algorithm. A reproducible previously defined increase was considered as a strong indicator of MBC. From 2007 to 2010, 44 patients with tumour marker increase underwent whole-body magnetic resonance imaging and/or an FDG-PET/CT scan. Histological clarification and/or imaging follow-up were done. Results: Metastases were detected in 65.9% (29/44) of patients, 13.6% (6/44) had secondary malignancies besides breast cancer and 20.5% (9/44) had no detectable malignancy. Limited disease was found in 24.1% (7/29) of patients. Median progression-free survival of MBC was 9.2 months and median overall survival was 41.1 months. The 3- and 5-year survival rates were 64.2% and 40.0%, respectively. Conclusions: A reproducible tumour marker increase followed by whole-body imaging is highly effective for early detection. By consequence, patients might benefit from earlier detection and improved therapeutic options with a prolonged survival. PMID:25647014

  15. Childhood body weight in relation to morbidity from cardiovascular disease and cancer in older adulthood: 67-year follow-up of participants in the 1947 Scottish Mental Survey.

    PubMed

    Batty, G David; Calvin, Catherine M; Brett, Caroline E; Čukić, Iva; Deary, Ian J

    2015-11-01

    Although it has been well documented that elevated body weight in middle- and older-aged populations is associated with multiple morbidities, the influence of childhood body weight on health endpoints other than coronary heart disease is not well understood. Accordingly, using a subsample of 4,620 participants (2,288 women) from the Scottish Mental Survey of 1947, we examined the association between body mass index measured at 11 years of age and future risk of 9 independent health endpoints as ascertained from national hospital admissions and cancer registers until 2014 (up to age 77 years). Although there was some evidence of a relationship between elevated childhood body mass index and higher rates of peripheral vascular disease (per each 1-standard deviation increase in body mass index, hazard ratio = 1.21, 95% confidence interval: 1.07, 1.37) and smoking-related cancers (per each 1-standard deviation increase in body mass index, hazard ratio = 1.09, 95% confidence interval: 1.01, 1.17), there was no apparent association with coronary heart disease, stroke (including ischemic stroke), heart failure, or carcinomas of the colorectum, stomach, lung, prostate, or breast. In conclusion, a relationship between childhood body weight and later morbidity was largely lacking in the present study. PMID:26443418

  16. Parkinson's Disease-Related Impairments in Body Movement, Coordination and Postural Control Mechanisms When Performing 80° Lateral Gaze Shifts.

    PubMed

    Bonnet, Cédrick T; Delval, Arnaud; Defebvre, Luc

    2015-09-01

    We investigated early signs of Parkinson's disease-related impairment in mediolateral postural control. Thirty-six participants (18 Hoehn & Yahr stage 2 patients in the off-drug condition and 18 healthy controls) were studied in a stationary gaze condition and when performing 80° lateral gaze shifts at 0.125 and 0.25 Hz. Body sway, coordination and postural control mechanisms were analyzed. All participants performed the visual tasks adequately. The patients were not unstable in the stationary gaze condition. In both groups, mediolateral ankle- and hip-based postural control mechanisms were significantly more active under gaze shift conditions than under the stationary gaze condition. As expected, the patients exhibited significantly greater angular movements of the lower back and significantly lower angular movements of the head (relative to controls) when performing gaze shifts. When considering linear displacements (rather than angular movements), the patients exhibited significantly greater displacements of the lower back and lower, slower displacements of the head than controls under gaze shift conditions. Relative to controls, the patients performed "en block" body movements. Overall, our results show that the patients' ankle- and hip-based mediolateral postural control mechanisms did not adapt to the difficulty of the visual task being performed. PMID:25423653

  17. Wearability assessment of a wearable system for Parkinson's disease remote monitoring based on a body area network of sensors.

    PubMed

    Cancela, Jorge; Pastorino, Matteo; Tzallas, Alexandros T; Tsipouras, Markos G; Rigas, Giorgios; Arredondo, Maria T; Fotiadis, Dimitrios I

    2014-01-01

    Wearable technologies for health monitoring have become a reality in the last few years. So far, most research studies have focused on assessments of the technical performance of these systems, as well as the validation of the clinical outcomes. Nevertheless, the success in the acceptance of these solutions depends not only on the technical and clinical effectiveness, but on the final user acceptance. In this work the compliance of a telehealth system for the remote monitoring of Parkinson's disease (PD) patients is presented with testing in 32 PD patients. This system, called PERFORM, is based on a Body Area Network (BAN) of sensors which has already been validated both from the technical and clinical point for view. Diverse methodologies (REBA, Borg and CRS scales in combination with a body map) are employed to study the comfort, biomechanical and physiological effects of the system. The test results allow us to conclude that the acceptance of this system is satisfactory with all the levels of effect on each component scoring in the lowest ranges. This study also provided useful insights and guidelines to lead to redesign of the system to improve patient compliance. PMID:25230307

  18. Wearability Assessment of a Wearable System for Parkinson's Disease Remote Monitoring Based on a Body Area Network of Sensors

    PubMed Central

    Cancela, Jorge; Pastorino, Matteo; Tzallas, Alexandros T.; Tsipouras, Markos G.; Rigas, Giorgios; Arredondo, Maria T.; Fotiadis, Dimitrios I.

    2014-01-01

    Wearable technologies for health monitoring have become a reality in the last few years. So far, most research studies have focused on assessments of the technical performance of these systems, as well as the validation of the clinical outcomes. Nevertheless, the success in the acceptance of these solutions depends not only on the technical and clinical effectiveness, but on the final user acceptance. In this work the compliance of a telehealth system for the remote monitoring of Parkinson's disease (PD) patients is presented with testing in 32 PD patients. This system, called PERFORM, is based on a Body Area Network (BAN) of sensors which has already been validated both from the technical and clinical point for view. Diverse methodologies (REBA, Borg and CRS scales in combination with a body map) are employed to study the comfort, biomechanical and physiological effects of the system. The test results allow us to conclude that the acceptance of this system is satisfactory with all the levels of effect on each component scoring in the lowest ranges. This study also provided useful insights and guidelines to lead to redesign of the system to improve patient compliance. PMID:25230307

  19. Myeloma bone and extra-medullary disease: Role of PET/CT and other whole-body imaging techniques.

    PubMed

    Rubini, Giuseppe; Niccoli-Asabella, Artor; Ferrari, Cristina; Racanelli, Vito; Maggialetti, Nicola; Dammacco, Francesco

    2016-05-01

    Multiple myeloma (MM) is the second most common hematological malignancy. Although it can affect different organs, the bone compartment stands out both in terms of prevalence and clinical impact. Despite the striking advances in MM therapy, bone disease can remarkably affect the patient's quality of life. The occurrence and extension of bone marrow and extra-medullary involvement should be carefully assessed to confirm the diagnosis, to locate and whenever possible prevent dreadful complications such as pathological fractures and spinal cord compression, and to establish suitable therapeutic measures. Many imaging techniques have been proposed for the detection of MM skeletal involvement. With the development of more sophisticated imaging tools, it is time to use the right technique at the right time. Based on the review of the literature and our own experience, this article discusses advantages and disadvantages of the different imaging methods in the work-up of MM patients, with particular emphasis on the role that PET/CT can play. It is emphasized that whole body low-dose computed tomography should be the preferred imaging technique at baseline. However, bone marrow infiltration and extra-medullary manifestations are better detected by whole body magnetic resonance imaging. Positron emission tomography/computed tomography, on the other hand, combines the benefits of the two mentioned imaging procedures and is particularly useful not only for the detection of osteolytic lesions unrevealed by conventional X-ray, but also in the assessment of prognosis and therapeutic response. PMID:26997302

  20. Autonomous identification of freezing of gait in Parkinson's disease from lower-body segmental accelerometry

    PubMed Central

    2013-01-01

    Background We have previously published a technique for objective assessment of freezing of gait (FOG) in Parkinson's disease (PD) from a single shank-mounted accelerometer. Here we extend this approach to evaluate the optimal configuration of sensor placement and signal processing parameters using seven sensors attached to the lumbar back, thighs, shanks and feet. Methods Multi-segmental acceleration data was obtained from 25 PD patients performing 134 timed up and go tasks, and clinical assessment of FOG was performed by two experienced raters from video. Four metrics were used to compare objective and clinical measures; the intraclass correlation coefficient (ICC) for number of FOG episodes and the percent time frozen per trial; and the sensitivity and specificity of FOG detection. Results The seven-sensor configuration was the most robust, scoring highly on all measures of performance (ICC number of FOG 0.75; ICC percent time frozen 0.80; sensitivity 84.3%; specificity 78.4%). A simpler single-shank sensor approach provided similar ICC values and exhibited a high sensitivity to FOG events, but specificity was lower at 66.7%. Recordings from the lumbar sensor offered only moderate agreement with the clinical raters in terms of absolute number and duration of FOG events (likely due to musculoskeletal attenuation of lower-limb 'trembling' during FOG), but demonstrated a high sensitivity (86.2%) and specificity (82.4%) when considered as a binary test for the presence/absence of FOG within a single trial. Conclusions The seven-sensor approach was the most accurate method for quantifying FOG, and is best suited to demanding research applications. A single shank sensor provided measures comparable to the seven-sensor approach but is relatively straightforward in execution, facilitating clinical use. A single lumbar sensor may provide a simple means of objective FOG detection given the ubiquitous nature of accelerometers in mobile telephones and other belt

  1. Whole-Body Magnetic Resonance Angiography at 3 Tesla Using a Hybrid Protocol in Patients with Peripheral Arterial Disease

    SciTech Connect

    Nielsen, Yousef W.; Eiberg, Jonas P.; Logager, Vibeke B.; Schroeder, Torben V.; Just, Sven; Thomsen, Henrik S.

    2009-09-15

    The purpose of this study was to determine the diagnostic performance of 3T whole-body magnetic resonance angiography (WB-MRA) using a hybrid protocol in comparison with a standard protocol in patients with peripheral arterial disease (PAD). In 26 consecutive patients with PAD two different protocols were used for WB-MRA: a standard sequential protocol (n = 13) and a hybrid protocol (n = 13). WB-MRA was performed using a gradient echo sequence, body coil for signal reception, and gadoterate meglumine as contrast agent (0.3 mmol/kg body weight). Two blinded observers evaluated all WB-MRA examinations with regard to presence of stenoses, as well as diagnostic quality and degree of venous contamination in each of the four stations used in WB-MRA. Digital subtraction angiography served as the method of reference. Sensitivity for detecting significant arterial disease (luminal narrowing {>=} 50%) using standard-protocol WB-MRA for the two observers was 0.63 (95%CI: 0.51-0.73) and 0.66 (0.58-0.78). Specificities were 0.94 (0.91-0.97) and 0.96 (0.92-0.98), respectively. In the hybrid protocol WB-MRA sensitivities were 0.75 (0.64-0.84) and 0.70 (0.58-0.8), respectively. Specificities were 0.93 (0.88-0.96) and 0.95 (0.91-0.97). Interobserver agreement was good using both the standard and the hybrid protocol, with {kappa} = 0.62 (0.44-0.67) and {kappa} = 0.70 (0.59-0.79), respectively. WB-MRA quality scores were significantly higher in the lower leg using the hybrid protocol compared to standard protocol (p = 0.003 and p = 0.03, observers 1 and 2). Distal venous contamination scores were significantly lower with the hybrid protocol (p = 0.02 and p = 0.01, observers 1 and 2). In conclusion, hybrid-protocol WB-MRA shows a better diagnostic performance than standard protocol WB-MRA at 3 T in patients with PAD.

  2. Pathway analysis of body mass index genome-wide association study highlights risk pathways in cardiovascular disease

    PubMed Central

    Zhao, Xin; Gu, Jinxia; Li, Ming; Xi, Jie; Sun, Wenyu; Song, Guangmin; Liu, Guiyou

    2015-01-01

    Cardiovascular disease (CVD) is a class of diseases that involve the heart or blood vessels. It is reported that body mass index (BMI) is risk factor for CVD. Genome-wide association studies (GWAS) have recently provided rapid insights into genetics of CVD and its risk factors. However, the specific mechanisms how BMI influences CVD risk are largely unknown. We think that BMI may influences CVD risk by shared genetic pathways. In order to confirm this view, we conducted a pathway analysis of BMI GWAS, which examined approximately 329,091 single nucleotide polymorphisms from 4763 samples. We identified 31 significant KEGG pathways. There is literature evidence supporting the involvement of GnRH signaling, vascular smooth muscle contraction, dilated cardiomyopathy, Gap junction, Wnt signaling, Calcium signaling and Chemokine signaling in CVD. Collectively, our study supports the potential role of the CVD risk pathways in BMI. BMI may influence CVD risk by the shared genetic pathways. We believe that our results may advance our understanding of BMI mechanisms in CVD. PMID:26264282

  3. A Brazilian family with hereditary inclusion body myopathy associated with Paget disease of bone and frontotemporal dementia.

    PubMed

    Fanganiello, R D; Kimonis, V E; Côrte, C C; Nitrini, R; Passos-Bueno, M R

    2011-04-01

    Inclusion body myopathy associated with Paget disease and frontotemporal dementia (IBMPFD) is a progressive and usually misdiagnosed autosomal dominant disorder. It is clinically characterized by a triad of features: proximal and distal myopathy, early onset Paget disease of bone (PDB), and frontotemporal dementia (FTD). It is caused by missense mutations in the valosin-containing protein (VCP) gene. We describe here the clinical and molecular findings of the first Brazilian family identified with IBMPFD. Progressive myopathy affecting the limb girdles was detected by clinical examination followed by muscle biopsy and creatine kinase measurement. PDB was suggested after anatomopathological bone examination and FTD was diagnosed by clinical, neuropsychological and language evaluations. Brain magnetic resonance revealed severe atrophy of the anterior temporal lobes, including the hippocampi. A R93C mutation in VCP was detected by direct sequencing screening in subject W (age 62) and in his mother. Four more individuals diagnosed with "dementia" were reported in this family. We also present a comprehensive genotype-phenotype correlation analysis of mutations in VCP in 182 patients from 29 families described in the literature and show that while IBM is a conspicuously penetrant symptom, PDB has a lower penetrance when associated with mutations in the AAAD1 domain and FTD has a lower penetrance when associated with mutations in the Junction (L1-D1) domain. Furthermore, the R93C mutation is likely to be associated with the penetrance of all the clinical symptoms of the triad. PMID:21412659

  4. Lewis base activation of Lewis acids: catalytic, enantioselective vinylogous aldol addition reactions.

    PubMed

    Denmark, Scott E; Heemstra, John R

    2007-07-20

    The generality of Lewis base catalyzed, Lewis acid mediated, enantioselective vinylogous aldol addition reactions has been investigated. The combination of silicon tetrachloride and chiral phosphoramides is a competent catalyst for highly selective additions of a variety of alpha,beta-unsaturated ketone-, 1,3-diketone-, and alpha,beta-unsaturated amide-derived dienolates to aldehydes. These reactions provided high levels of gamma-site selectivity for a variety of substitution patterns on the dienyl unit. Both ketone- and morpholine amide-derived dienol ethers afforded high enantio- and diastereoselectivity in the addition to conjugated aldehydes. Although alpha,beta-unsaturated ketone-derived dienolate did not react with aliphatic aldehydes, alpha,beta-unsaturated amide-derived dienolates underwent addition at reasonable rates affording high yields of vinylogous aldol product. The enantioselectivities achieved with the morpholine derived-dienolate in the addition to aliphatic aldehydes was the highest afforded to date with the silicon tetrachloride-chiral phosphoramide system. Furthermore, the ability to cleanly convert the morpholine amide to a methyl ketone was demonstrated. PMID:17583959

  5. Molecular events linking cholesterol to Alzheimer’s disease and inclusion body myositis in a rabbit model

    PubMed Central

    Liu, Qing Yan; Koukiekolo, Roger; Zhang, Dong Ling; Smith, Brandon; Ly, Dao; Lei, Joy X; Ghribi, Othman

    2016-01-01

    Alzheimer’s disease (AD) is the most common neurodegenerative disorder, characterized by cognitive impairment and dementia, resulting from progressive synaptic dysfunction, loss and neuronal cell death. Inclusion body myositis (IBM) is a skeletal muscle degenerative disease, displaying progressive proximal and distal muscle weakness, in association with muscle fiber atrophy, degeneration and death. Studies have shown that the late onset version of AD (LOAD) and sporadic IBM (sIBM) in muscle share many pathological features, including the presence of extracellular plaques of β-amyloid peptides and intracellular tangles of hyperphosphorylated tau proteins. High blood cholesterol is suggested to be a risk factor for LOAD. Many neuropathological changes of LOAD can be reproduced by feeding rabbits a 2% enriched cholesterol diet for 12 weeks. The cholesterol fed rabbit model also simultaneously develops sIBM like pathology, which makes it an ideal model to study the molecular mechanisms common to the development of both diseases. In the present study, we determined the changes of gene expression in rabbit brain and muscle during the progression of LOAD and sIBM pathology using a custom rabbit nucleotide microarray, followed by qRT-PCR analyses. Out of 869 unique transcripts screened, 47 genes showed differential expression between the control and the cholesterol-treated group during the 12 week period and 19 changed transcripts appeared to be common to LOAD and sIBM. The most notable changes are the upregulation of the hemoglobin gene family and the downregulation of the genes required for mitochondrial oxidative phosphorylation in both brain and muscle tissues throughout the time course. The significant overlap on the changes of gene expression in the brain and muscle of rabbits fed with cholesterol-enriched diet supports the notion that LOAD and sIBM may share a common etiology. PMID:27073745

  6. Reduced risk of Parkinson's disease associated with lower body mass index and heavy leisure-time physical activity.

    PubMed

    Sääksjärvi, Katri; Knekt, Paul; Männistö, Satu; Lyytinen, Jukka; Jääskeläinen, Tuija; Kanerva, Noora; Heliövaara, Markku

    2014-04-01

    The risk factors for Parkinson's disease (PD) are not well established. We therefore examined the prediction of various lifestyle factors on the incidence of PD in a cohort drawn from the Finnish Mobile Clinic Health Examination Survey, conducted in 1973-1976. The study population comprised 6,715 men and women aged 50-79 years and free of PD at the baseline. All of the subjects completed a baseline health examination (including height and weight measurements) and a questionnaire providing information on leisure-time physical activity, smoking, and alcohol consumption. During a 22-year follow-up, 101 incident cases of PD occurred. The statistical analyses were based on Cox's model including age, sex, education, community density, occupation, coffee consumption, body mass index (BMI), leisure-time physical activity, smoking and alcohol consumption as independent variables. At first, BMI was not associated with PD risk, but after exclusion of the first 15 years of follow-up, an elevated risk appeared at higher BMI levels (P for trend 0.02). Furthermore, subjects with heavy leisure-time physical activity had a lower PD risk than those with no activity [relative risk (RR) 0.27, 95 % confidence interval (CI) 0.08-0.90]. In variance with findings for other chronic diseases, current smokers had a lower PD risk than those who had never smoked (RR 0.23, 95 % CI 0.08-0.67), and individuals with moderate alcohol intake (at the level of <5 g/day) had an elevated PD risk compared to non-drinkers. The results support the hypothesis that lifestyle factors predict the occurrence of Parkinson's disease, but more research is needed. PMID:24633681

  7. A phenotypic model recapitulating the neuropathology of Parkinson's disease

    PubMed Central

    Ferris, Craig F; Marella, Mathieu; Smerkers, Brian; Barchet, Thomas M; Gershman, Benjamin; Matsuno-Yagi, Akemi; Yagi, Takao

    2013-01-01

    This study was undertaken to develop a phenotypic model recapitulating the neuropathology of Parkinson's disease (PD). Such a model would show loss of dopamine in the basal ganglia, appearance of Lewy bodies, and the early stages of motor dysfunction. The model was developed by subcutaneously injecting biodegradable microspheres of rotenone, a complex I inhibitor in 8–9 month old, ovariectomized Long–Evans rats. Animals were observed for changes in body weight and motor activity. At the end of 11–12 weeks animals were euthanized and the brains examined for histopathological changes. Rotenone treated animals gain weight and appear normal and healthy as compared to controls but showed modest hypokinesia around 5–6 weeks posttreatment. Animals showed loss of dopaminergic (DA) neurons and the appearance of putative Lewy bodies in the substantia nigra. Neuroinflammation and oxidative stress were evidenced by the appearance of activated microglia, iron precipitates, and 8-oxo-2′-deoxyguanosine a major product of DNA oxidation. The dorsal striatum, the projection site of midbrain DA neurons, showed a significant reduction in tyrosine hydroxylase immunostaining, together with an increase in reactive astrocytes, an early sign of DA nerve terminal damage. Levels of vesicular monoamine transporter 2 (VMAT2) were significantly reduced in the dorsal striatum; however, there was an unexpected increase in dopamine transporter (DAT) levels. Old, ovariectomized females treated with rotenone microspheres present with normal weight gain and good health but a modest hypokinesia. Accompanying this behavioral phenotype are a constellation of neuropathologies characteristic of PD that include loss of DA neurons, microglia activation, oxidative damage to nuclear DNA, iron deposition, and appearance of putative Lewy bodies. This phenotypic model recapitulating the neuropathology of Parkinson's disease could provide insight into early mechanisms of pathogenesis and could aid in

  8. A phenotypic model recapitulating the neuropathology of Parkinson's disease.

    PubMed

    Ferris, Craig F; Marella, Mathieu; Smerkers, Brian; Barchet, Thomas M; Gershman, Benjamin; Matsuno-Yagi, Akemi; Yagi, Takao

    2013-07-01

    This study was undertaken to develop a phenotypic model recapitulating the neuropathology of Parkinson's disease (PD). Such a model would show loss of dopamine in the basal ganglia, appearance of Lewy bodies, and the early stages of motor dysfunction. The model was developed by subcutaneously injecting biodegradable microspheres of rotenone, a complex I inhibitor in 8-9 month old, ovariectomized Long-Evans rats. Animals were observed for changes in body weight and motor activity. At the end of 11-12 weeks animals were euthanized and the brains examined for histopathological changes. Rotenone treated animals gain weight and appear normal and healthy as compared to controls but showed modest hypokinesia around 5-6 weeks posttreatment. Animals showed loss of dopaminergic (DA) neurons and the appearance of putative Lewy bodies in the substantia nigra. Neuroinflammation and oxidative stress were evidenced by the appearance of activated microglia, iron precipitates, and 8-oxo-2'-deoxyguanosine a major product of DNA oxidation. The dorsal striatum, the projection site of midbrain DA neurons, showed a significant reduction in tyrosine hydroxylase immunostaining, together with an increase in reactive astrocytes, an early sign of DA nerve terminal damage. Levels of vesicular monoamine transporter 2 (VMAT2) were significantly reduced in the dorsal striatum; however, there was an unexpected increase in dopamine transporter (DAT) levels. Old, ovariectomized females treated with rotenone microspheres present with normal weight gain and good health but a modest hypokinesia. Accompanying this behavioral phenotype are a constellation of neuropathologies characteristic of PD that include loss of DA neurons, microglia activation, oxidative damage to nuclear DNA, iron deposition, and appearance of putative Lewy bodies. This phenotypic model recapitulating the neuropathology of Parkinson's disease could provide insight into early mechanisms of pathogenesis and could aid in the

  9. Revisiting DLB Diagnosis: A Consideration of Prodromal DLB and of the Diagnostic Overlap With Alzheimer Disease.

    PubMed

    McKeith, Ian; Taylor, John-Paul; Thomas, Alan; Donaghy, Paul; Kane, Joseph

    2016-09-01

    Efforts to clinically diagnose cases having dementia with Lewy bodies (DLB) identify those with a characteristic clinical syndrome (probable DLB) at the expense of missing an equal, if not greater, number of cases who have atypical presentations thought to be associated with coexisting Alzheimer pathologies. This article argues that further efforts should now be made to characterize this atypical group that constitutes cases previously identified postmortem as the Lewy body variant of Alzheimer disease (AD) or as AD with Lewy bodies. Since such fine distinction is unlikely to be achieved on clinical grounds alone, this new diagnostic category will require robust biomarker validation. Turning to a consideration of early/prodromal diagnosis of both typical and atypical DLB cases, it is suggested that there will be at least 3 prototypical forms-a mild cognitive impairment variant, associated with early visuoperceptual and attentional deficits; a delirium onset DLB with provoked or spontaneous delirium as the presenting features; and a psychiatric disorder DLB with its primary presentation as a late-onset affective disorder or psychosis. PMID:27502299

  10. Caspase-1 causes truncation and aggregation of the Parkinson's disease-associated protein α-synuclein.

    PubMed

    Wang, Wei; Nguyen, Linh T T; Burlak, Christopher; Chegini, Fariba; Guo, Feng; Chataway, Tim; Ju, Shulin; Fisher, Oriana S; Miller, David W; Datta, Debajyoti; Wu, Fang; Wu, Chun-Xiang; Landeru, Anuradha; Wells, James A; Cookson, Mark R; Boxer, Matthew B; Thomas, Craig J; Gai, Wei Ping; Ringe, Dagmar; Petsko, Gregory A; Hoang, Quyen Q

    2016-08-23

    The aggregation of α-synuclein (aSyn) leading to the formation of Lewy bodies is the defining pathological hallmark of Parkinson's disease (PD). Rare familial PD-associated mutations in aSyn render it aggregation-prone; however, PD patients carrying wild type (WT) aSyn also have aggregated aSyn in Lewy bodies. The mechanisms by which WT aSyn aggregates are unclear. Here, we report that inflammation can play a role in causing the aggregation of WT aSyn. We show that activation of the inflammasome with known stimuli results in the aggregation of aSyn in a neuronal cell model of PD. The insoluble aggregates are enriched with truncated aSyn as found in Lewy bodies of the PD brain. Inhibition of the inflammasome enzyme caspase-1 by chemical inhibition or genetic knockdown with shRNA abated aSyn truncation. In vitro characterization confirmed that caspase-1 directly cleaves aSyn, generating a highly aggregation-prone species. The truncation-induced aggregation of aSyn is toxic to neuronal culture, and inhibition of caspase-1 by shRNA or a specific chemical inhibitor improved the survival of a neuronal PD cell model. This study provides a molecular link for the role of inflammation in aSyn aggregation, and perhaps in the pathogenesis of sporadic PD as well. PMID:27482083

  11. Inflammatory Biomarkers Associated with Lethal Rift Valley Fever Encephalitis in the Lewis Rat Model

    PubMed Central

    Caroline, Amy L.; Kujawa, Michael R.; Oury, Tim D.; Reed, Douglas S.; Hartman, Amy L.

    2016-01-01

    Rift Valley fever (RVF) is an emerging viral disease that causes significant human and veterinary illness in Africa and the Arabian Peninsula. Encephalitis is one of the severe complications arising from RVF virus (RVFV) infection of people, and the pathogenesis of this form of RVF is completely unknown. We use a novel reproducible encephalitic disease model in rats to identify biomarkers of lethal infection. Lewis rats were infected with RVFV strain ZH501 by aerosol exposure, then sacrificed daily to determine the course of infection and evaluation of clinical, virological, and immunological parameters. Weight loss, fever, and clinical signs occurred during the last 1–2 days prior to death. Prior to onset of clinical indications of disease, rats displayed marked granulocytosis and thrombocytopenia. In addition, high levels of inflammatory chemokines (MCP-1, MCS-F, Gro/KC, RANTES, and IL-1β) were detected first in serum (3–5 dpi) followed by brain (5–7 dpi). The results of this study are consistent with clinical data from human RVF patients and validate Lewis rats as an appropriate small animal model for RVF encephalitis. The biomarkers we identified here will be useful in future studies evaluating the efficacy of novel vaccines and therapeutics. PMID:26779164

  12. Extracellular α-synuclein--a possible initiator of inflammation in Parkinson's disease.

    PubMed

    Ren, Wen-qing; Tian, Zeng-min; Yin, Feng; Sun, Jun-zhao; Zhang, Jian-ning

    2016-02-01

    Parkinson's disease (PD) is a progressive neurodegenerative disease involving the loss of dopamine-producing neurons of the substantia nigra and the presence of Lewy bodies which contain high levels of α-synuclein. Although the causative factors of PD remain unclear, the progression of PD is accompanied by a highly localized inflammatory response mediated by reactive microglia. Recently, attention has focused on the relationship between α-synuclein and microglial activation. This review examines the role of α-synuclein on microglia in PD pathogenesis and progression, we also discuss the way of α-synuclein induced microglial activation. PMID:27004367

  13. Lewis rats have greater response impulsivity than Fischer rats.

    PubMed

    Hamilton, Kristen R; Potenza, Marc N; Grunberg, Neil E

    2014-11-01

    Impulsivity, a tendency toward immediate action without consideration of future consequences, is associated with a wide array of problematic behaviors. Response impulsivity, a type of behaviorally-assessed impulsivity characterized by behavioral disinhibition, is also associated with health risk behaviors. Response impulsivity is distinct from choice impulsivity, which is characterized by intolerance for delay. Lewis rats have higher levels of choice impulsivity than Fischer rats (Anderson & Woolverton, 2005; Madden et al., 2008; Stein et al., 2012). However, no studies have examined whether Lewis and Fischer rats have different levels of response impulsivity. The present research examined response impulsivity in the two rat strains. Subjects were 16 male Lewis and Fischer rats. Rats' response impulsivity was measured using the Five Choice Serial Reaction Time Task (5-CSRTT). In addition, their locomotor activity was measured in locomotor activity chambers. Lewis rats had more premature responses than Fischer rats during the 5-CSRTT assessment [F(1, 14)=5.34, p<0.05], indicating higher levels of response impulsivity. Locomotor activity did not differ between rat strain groups [F(1, 14)=3.05, p=.10], suggesting that overall movement did not account for group differences in response impulsivity on the 5-CSRTT. It can be concluded from this research that Lewis rats have higher levels of response impulsivity than Fischer rats, and therefore provide a valid rat model of individual differences in impulsivity. PMID:24613059

  14. Direct simulations of premixed turbulent flames with nonunity Lewis numbers

    SciTech Connect

    Rutland, C.J.; Trouve, A. . Dept. of Mechanical Engineering Stanford Univ., Stanford, CA . Center for Turbulence Research)

    1993-07-01

    A principal effect of turbulence on premixed flames in the flamelet regime is to wrinkle the flame fronts. For nonunity Lewis numbers, Le [ne] 1, the local flame structure is altered in curved regions. This effect is examined using direct numerical simulations of three-dimensional isotropic turbulence with constant density, single-step Arrhenius kinetics chemistry. Simulations of Lewis numbers 0.8, 1.0, and 1.2 are compared. At the local level, curvature effects dominated changes to the flame structure while strain effects were insignificant. A strong Lewis-number-dependent correlation was found between surface curvature and the local flame speed. The correlation was positive for Le < 1 and negative for Le > 1. At the global level, strain-related effects were more significant than curvature effects. The turbulent flame speed changed significantly with Lewis number, increasing as Le decreased. This was found to be due to strain effect that have a nonzero mean over the flame surface, rather than to curvature effects that have a nearly zero mean. The mean product temperature was also found to vary with Lewis number, being higher for Le > 1 and lower for Le < 1.

  15. Direct simulations of premixed turbulent flames with nonunity Lewis numbers

    NASA Technical Reports Server (NTRS)

    Rutland, C. J.; Trouve, A.

    1993-01-01

    A principal effect of turbulence on premixed flames in the flamelet regime is to wrinkle the flame fronts. For nonunity Lewis numbers, Le is not equal to 1, the local flame structure is altered in curved regions. This effect is examined using direct numerical simulations of 3D isotropic turbulence with constant density, single-step Arrhenius kinetics chemistry. Simulations of Lewis numbers 0.8, 1.0, and 1.2 are compared. At the local level, curvature effects dominated changes to the flame structure while strain effects were insignificant. A strong Lewis-number-dependent correlation was found between surface curvature and the local flame speed. The correlation was positive for Le less than 1 and negative for Le greater than 1. At the global level, strain-related effects were more significant than curvature effects. The turbulent flame speed changed significantly with Lewis number, increasing as Le decreased. This was found to be due to strain effects that have a nonzero mean over the flame surface, rather than to curvature effects that have a nearly zero mean. The mean product temperature was also found to vary with Lewis number, being higher for Le greater than 1 and lower for Le less than 1.

  16. [The role of alpha-synuclein in Parkinson's disease].

    PubMed

    Miklya, Ildikó; Pencz, Noémi; Hafenscher, Florencia; Göltl, Patricia

    2014-06-01

    α-synuclein, a small protein (140 amino acids) encoded by the SNCA gene is the best known isoform of the synuclein protein family. Though its physiological role is still not fully clarified, there is growing experimental evidence for a causal role of α-synuclein in the so-called conformational-neurodegenerative diseases. Conformational changes in the structure of the native soluble protein form insoluble neurotoxic aggregates and finally contribute to the formation of inclusion Lewy-bodies and Lewy-neurites. Neurodegeneration first hits the olfactory system, the peripheral autonomic nervous system, the enteric nervous system and the dorsal vagal motoneurons. The middle stage of the disease hits the dopaminergic neurons of the substantia nigra; and the neocortex is affected only in the late stage of the disease. This precise order of neurodegeneration is not always valid, but increases the likelihood that Lewy-bodies and neurodegenaration spread to intact areas in a prion-like way. Prions are infectious proteins which do not contain nucleic acids and cause diseases because they form toxic aggregates and filaments by misfolding in a β-sheet-rich conformation. The misfolded protein behaves like a template inducing conformational change in the wild type proteins causing cross-reaction and leading to neurodegeneration. Later, the defective proteins may infect healthy nerve cells, thus neurodegeneration is extended. Growing experimental evidence shows that monomers and aggregates of α-synuclein are secreted via exocytosis from damaged nerve cells and taken up via endocytosis by healthy nerve cells furnishing evidence for the prion-like role of α-synuclein. PMID:24978050

  17. Direct visualization of alpha-synuclein oligomers reveals previously undetected pathology in Parkinson’s disease brain

    PubMed Central

    Roberts, Rosalind F.

    2015-01-01

    Oligomeric forms of alpha-synuclein are emerging as key mediators of pathogenesis in Parkinson’s disease. Our understanding of the exact contribution of alpha-synuclein oligomers to disease is limited by the lack of a technique for their specific detection. We describe a novel method, the alpha-synuclein proximity ligation assay, which specifically recognizes alpha-synuclein oligomers. In a blinded study with post-mortem brain tissue from patients with Parkinson’s disease (n = 8, age range 73–92 years, four males and four females) and age- and sex-matched controls (n = 8), we show that the alpha-synuclein proximity ligation assay reveals previously unrecognized pathology in the form of extensive diffuse deposition of alpha-synuclein oligomers. These oligomers are often localized, in the absence of Lewy bodies, to neuroanatomical regions mildly affected in Parkinson’s disease. Diffuse alpha-synuclein proximity ligation assay signal is significantly more abundant in patients compared to controls in regions including the cingulate cortex (1.6-fold increase) and the reticular formation of the medulla (6.5-fold increase). In addition, the alpha-synuclein proximity ligation assay labels very early perikaryal aggregates in morphologically intact neurons that may precede the development of classical Parkinson’s disease lesions, such as pale bodies or Lewy bodies. Furthermore, the alpha-synuclein proximity ligation assay preferentially detects early-stage, loosely compacted lesions such as pale bodies in patient tissue, whereas Lewy bodies, considered heavily compacted late lesions are only very exceptionally stained. The alpha-synuclein proximity ligation assay preferentially labels alpha-synuclein oligomers produced in vitro compared to monomers and fibrils, while stained oligomers in human brain display a distinct intermediate proteinase K resistance, suggesting the detection of a conformer that is different from both physiological, presynaptic alpha

  18. Body mass index before and after breast cancer diagnosis: Associations with all-cause, breast cancer, and cardiovascular disease mortality

    PubMed Central

    Nichols, Hazel B.; Trentham-Dietz, Amy; Egan, Kathleen M.; Titus-Ernstoff, Linda; Holmes, Michelle D.; Bersch, Andrew J.; Holick, Crystal N.; Hampton, John M.; Stampfer, Meir J.; Willett, Walter C.; Newcomb, Polly A.

    2009-01-01

    Background Factors related to improving outcomes in breast cancer survivors are of increasing public health significance. We examined post-diagnosis weight change in relation to mortality risk in a cohort of breast cancer survivors. Methods We analyzed data from a cohort of 3,993 women aged 20−79 living in New Hampshire, Massachusetts or Wisconsin with invasive, nonmetastatic breast cancers diagnosed in 1988−1999 identified through state registries. Participants completed a structured telephone interview 1−2 years after diagnosis and returned a mailed follow-up questionnaire in 1998−2001 that addressed post-diagnosis weight and other factors. Vital status information was obtained from the National Death Index through December 2005. Hazard ratios (HR) and 95% confidence intervals (CI) were estimated from Cox proportional hazards models and adjusted for pre-diagnosis weight, age, stage, smoking, physical activity and other important covariates. Results During an average 6.3 years of follow-up from the post-diagnosis questionnaire, we identified 421 total deaths, including 121 deaths from breast cancer and 95 deaths from cardiovascular disease. Increasing post-diagnosis weight gain and weight loss were each associated with greater all-cause mortality. Among women who gained weight after breast cancer diagnosis, each 5 kg gain was associated with a 12% increase in all-cause mortality (p=0.004), a 13% increase in breast cancer-specific mortality (p=0.01), and a 19% increase in cardiovascular disease mortality (p=0.04). Associations with breast cancer mortality were not modified by pre-diagnosis menopausal status, cigarette smoking, or body mass index. Conclusion These findings suggest that efforts to minimize weight gain after a breast cancer diagnosis may improve survival. PMID:19366908

  19. Impact of Body Mass Index on Vascular Calcification and Pericardial Fat Volume Among Patients with Suspected Coronary Artery Disease

    PubMed Central

    Nafakhi, Hussein; Al-Mosawi, Abdulameer; Elwali, Hayder; Al-Nafakh, Hasan; Tawfeq, Raad; Nafakhi, Ahmed

    2016-01-01

    Objectives: This study aimed to assess the effect of body mass index (BMI) on the relationship between pericardial fat volume (PFV), aortic root calcification (ARC) and coronary artery calcification (CAC) among patients with suspected coronary artery disease (CAD). Methods: This cross-sectional study took place between January and December 2014 at the Kufa University Teaching Hospital, Najaf, Iraq. A total of 130 consecutive patients with an intermediate pretest probability of ischaemic heart disease who underwent 64-slice multidetector computed tomography (CT) angiography during the study period were recruited. Of these, 111 were included in the study and divided into groups according to BMI. Imaging markers were measured on CT angiography. Results: A total of 28 patients were obese, while 42 and 41 were overweight and normal weight, respectively. The median PFV, CAC and ARC was 109 cm3 (interquartile range [IQR]: 52–176 cm3), 0 Agatston score (IQR: 0–52 Agatston score) and 0 Agatston score (IQR: 0–15 Agatston score), respectively, in the normal weight group in comparison to 79 cm3 (IQR: 43–138 cm3), 0 Agatston score (IQR: 0–54 Agatston score) and 0 Agatston score (IQR: 0–0 Agatston score), respectively, in the obese group. Significant correlations were observed between PFV and CAC (r2 = 0.22; P = 0.002) and ARC and CAC (r2 = 0.37; P <0.001) in the normal weight group. However, no significant correlations were observed for obese and overweight patients. Conclusion: These findings indicate that BMI may not be an accurate tool for measuring adiposity or assessing subclinical coronary atherosclerosis in patients with suspected CAD. PMID:27606110

  20. Association of body mass index with disease severity and prognosis in patients with non-cystic fibrosis bronchiectasis.

    PubMed

    Qi, Q; Li, T; Li, J C; Li, Y

    2015-08-01

    The objective of this observational, multicenter study was to evaluate the association of body mass index (BMI) with disease severity and prognosis in patients with non-cystic fibrosis bronchiectasis. A total of 339 patients (197 females, 142 males) diagnosed with non-cystic fibrosis bronchiectasis by high-resolution computed tomography were classified into four groups: underweight (BMI<18.5 kg/m2), normal weight (18.5≤BMI<25.0 kg/m2), overweight (25.0≤BMI<30.0 kg/m2), and obese (BMI≥30.0 kg/m2). Clinical variables expressing disease severity were recorded, and acute exacerbations, hospitalizations, and survival rates were estimated during the follow-up period. The mean BMI was 21.90 kg/m2. The underweight group comprised 28.61% of all patients. BMI was negatively correlated with acute exacerbations, C-reactive protein, erythrocyte sedimentation rate, radiographic extent of bronchiectasis, and chronic colonization by P. aeruginosa and positively correlated with pulmonary function indices. BMI was a significant predictor of hospitalization risk independent of relevant covariates. The 1-, 2-, 3-, and 4-year cumulative survival rates were 94%, 86%, 81%, and 73%, respectively. Survival rates decreased with decreasing BMI (χ2=35.16, P<0.001). The arterial carbon dioxide partial pressure, inspiratory capacity, age, BMI, and predicted percentage of forced expiratory volume in 1 s independently predicted survival in the Cox proportional hazard model. In conclusion, an underweight status was highly prevalent among patients with non-cystic fibrosis bronchiectasis. Patients with a lower BMI were prone to developing more acute exacerbations, worse pulmonary function, amplified systemic inflammation, and chronic colonization by P. aeruginosa. BMI was a major determinant of hospitalization and death risks. BMI should be considered in the routine assessment of patients with non-cystic fibrosis bronchiectasis. PMID:26176309

  1. Whole body diffusion for metastatic disease assessment in neuroendocrine carcinomas: comparison with OctreoScan® in two cases.

    PubMed

    Cossetti, Rachel Jorge D; Bezerra, Regis Otaviano França; Gumz, Brenda; Telles, Adriana; Costa, Frederico P

    2012-01-01

    Neuroendocrine tumor (NET) patients must be adequately staged in order to improve a multidisciplinary approach and optimal management for metastatic disease. Currently available imaging studies include somatostatin receptor scintigraphy, like OctreoScan®, computed tomography (CT), scans and magnetic resonance imaging (MRI), which analyze vascular concentration and intravenous contrast enhancement for anatomic tumor localization. However, these techniques require high degree of expertise for interpretation and are limited by their availability, cost, reproducibility, and follow-up imaging comparisons. NETs significantly reduce water diffusion as compared to normal tissue. Diffusion-weighted imaging (DWI) in MRI has an advantageous contrast difference: the tumor is represented with high signal over a black normal surrounding background. The whole-body diffusion (WBD) technique has been suggested to be a useful test for detecting metastasis from various anatomic sites. In this article we report the use of DWI in MRI and WBD in two cases of metastatic pulmonary NET staging in comparison with OctreoScan® in order to illustrate the potential advantage of DWI and WBD in staging NETs. PMID:22591909

  2. Whole body diffusion for metastatic disease assessment in neuroendocrine carcinomas: comparison with OctreoScan® in two cases

    PubMed Central

    2012-01-01

    Neuroendocrine tumor (NET) patients must be adequately staged in order to improve a multidisciplinary approach and optimal management for metastatic disease. Currently available imaging studies include somatostatin receptor scintigraphy, like OctreoScan®, computed tomography (CT), scans and magnetic resonance imaging (MRI), which analyze vascular concentration and intravenous contrast enhancement for anatomic tumor localization. However, these techniques require high degree of expertise for interpretation and are limited by their availability, cost, reproducibility, and follow-up imaging comparisons. NETs significantly reduce water diffusion as compared to normal tissue. Diffusion-weighted imaging (DWI) in MRI has an advantageous contrast difference: the tumor is represented with high signal over a black normal surrounding background. The whole-body diffusion (WBD) technique has been suggested to be a useful test for detecting metastasis from various anatomic sites. In this article we report the use of DWI in MRI and WBD in two cases of metastatic pulmonary NET staging in comparison with OctreoScan® in order to illustrate the potential advantage of DWI and WBD in staging NETs. PMID:22591909

  3. [Power of music that moves mind and body--music therapy in the Hansen's disease sanatorium in Japan].

    PubMed

    Fukamizu, Yuu; En, Junichiro; Kano, Tatsuo; Arikawa, Isao

    2009-02-01

    Average age of residents living in National sanatorium Hoshizuka-Keiaien where people have past history of Hansen disease is around 80 years old at present, and many of them spend their whole days in watching TV or sleeping almost alone in their rooms. Therefore music therapy was introduced in order to improve their daily activities in our sanatorium. Singing, listening to music, playing the musical instruments, and dancing were performed, either in a group or individually. Reactivation of their brain function such as recollection, sense of unity and relaxation were expected. Improvement of cardiopulmonary function was also expected. Solidarity and relaxed state were observed by being with the other participants in the group therapy. For example, when using musical instruments, some participants with hesitation tried to use their instruments, and had good performance. They seemed to be satisfied and became confident with the musical instruments. Then their confidence and satisfaction activated the group. After the sessions, mutual conversation increased. These processes obtained a synergy effect, which means that a group affects of individuals at first and next alteration of individual behavior influences the group. We could observe a better effect in their motivation and activity in their daily life in the individual therapy. The music therapy was applied to the senior participants by the music therapist in this study. The participants could easily reinforce their mind and body through this therapy. Music therapy will be continued for the improvement of quality of life of residents in the sanatorium. PMID:19227147

  4. Random Whole Body Vibration over 5 Weeks Leads to Effects Similar to Placebo: A Controlled Study in Parkinson's Disease

    PubMed Central

    Gaßner, Heiko; Janzen, Annette; Schwirtz, Ansgar; Jansen, Petra

    2014-01-01

    Background. Random whole body vibration (WBV) training leads to beneficial short-term effects in patients with Parkinson's disease (PD). However, the effect of WBV lasting several weeks is not clear. Objectives. The aim of this study was to assess a random WBV training over 5 weeks in PD. Methods. Twenty-one participants with PD were allocated to either an experimental or a placebo group matched by age, gender, and Hoehn&Yahr stage. The WBV training consisted of 5 series, 60 s each. In the placebo group, vibration was simulated. The primary outcome was the change of performance in Functional reach test (FRT), step-walk-turn task, biomechanical Gait Analysis, Timed up and go test (TUG), and one leg stance. Findings. In most of the parameters, there was no significant interaction of “time∗group.” Both groups improved significantly in Gait parameters, TUG, and one leg stance. Only in the FRT [F(1,15) = 8.397; P < 0.05] and in the TUG [F(1,15) = 4.971; P < 0.05] the experimental group performed significantly better than the placebo group. Conclusions. Random WBV training over 5 weeks seems to be less effective than reported in previous studies performing short-term training. The slight improvements in the FRT and TUG are not clinically relevant. PMID:25371843

  5. Genetically predicted body mass index and Alzheimer's disease-related phenotypes in three large samples: Mendelian randomization analyses.

    PubMed

    Mukherjee, Shubhabrata; Walter, Stefan; Kauwe, John S K; Saykin, Andrew J; Bennett, David A; Larson, Eric B; Crane, Paul K; Glymour, M Maria

    2015-12-01

    Observational research shows that higher body mass index (BMI) increases Alzheimer's disease (AD) risk, but it is unclear whether this association is causal. We applied genetic variants that predict BMI in Mendelian randomization analyses, an approach that is not biased by reverse causation or confounding, to evaluate whether higher BMI increases AD risk. We evaluated individual-level data from the AD Genetics Consortium (ADGC: 10,079 AD cases and 9613 controls), the Health and Retirement Study (HRS: 8403 participants with algorithm-predicted dementia status), and published associations from the Genetic and Environmental Risk for AD consortium (GERAD1: 3177 AD cases and 7277 controls). No evidence from individual single-nucleotide polymorphisms or polygenic scores indicated BMI increased AD risk. Mendelian randomization effect estimates per BMI point (95% confidence intervals) were as follows: ADGC, odds ratio (OR) = 0.95 (0.90-1.01); HRS, OR = 1.00 (0.75-1.32); GERAD1, OR = 0.96 (0.87-1.07). One subscore (cellular processes not otherwise specified) unexpectedly predicted lower AD risk. PMID:26079416

  6. Effects of non-unity Lewis numbers in diffusion flames

    NASA Technical Reports Server (NTRS)

    Linan, A.; Orlandi, P.; Verzicco, R.; Higuera, F. J.

    1994-01-01

    The purpose of this work is to carry out direct numerical simulations of diffusion controlled combustion with non-unity Lewis numbers for the reactants and products, thus accounting for the differential diffusion effects of the temperature and concentration fields. We use a formulation based on combining the conservation equations in a way to eliminate the reaction terms similar to the method used by Burke and Schumann (1928) for unity Lewis numbers. We present calculations for an axisymmetric fuel jet and for a planar, time evolving mixing layer, leaving out the effects of thermal expansion and variations of the transport coefficients due to the heat release. Our results show that the front of the flame shifts toward the fuel or oxygen sides owing to the effect of the differential diffusion and that the location of maximum temperature may not coincide with the flame. The dependence of the distribution of the reaction products on their Lewis number has been investigated.

  7. Helicopter transmission testing at NASA Lewis Research Center

    NASA Technical Reports Server (NTRS)

    Lewicki, David G.; Coy, John J.

    1987-01-01

    The helicopter has evolved into a highly valuable air mobile vehicle for both military and civilian needs. The helicopter transmission requires advanced studies to develop a technology base for future rotorcraft advances. A joint helicopter transmission research program between the NASA Lewis Research Center and the U.S. Army Aviation Systems Command has existed since 1970. Program goals are to reduce weight and noise and to increase life and reliability. The current experimental activities at Lewis consist of full-scale helicopter transmission testing, a base effort in gearing technology, and a future effort in noise reduction technology. The experimental facilities at Lewis for helicopter transmission testing are described. A description of each of the rigs is presented along with some significant results and near-term plans.

  8. Bodily illusions in health and disease: physiological and clinical perspectives and the concept of a cortical 'body matrix'.

    PubMed

    Moseley, G Lorimer; Gallace, Alberto; Spence, Charles

    2012-01-01

    Illusions that induce a feeling of ownership over an artificial body or body-part have been used to explore the complex relationships that exist between the brain's representation of the body and the integrity of the body itself. Here we discuss recent findings in both healthy volunteers and clinical populations that highlight the robust relationship that exists between a person's sense of ownership over a body part, cortical