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Sample records for striatal fdopa ki

  1. Ability of 18F-DOPA PET/CT and fused 18F-DOPA PET/MRI to assess striatal involvement in paediatric glioma

    International Nuclear Information System (INIS)

    Morana, Giovanni; Severino, Mariasavina; Tortora, Domenico; Rossi, Andrea; Puntoni, Matteo; Garre, Maria Luisa; Massollo, Michela; Naseri, Merhdad; Piccardo, Arnoldo; Lopci, Egesta

    2016-01-01

    To assess the diagnostic performance of 18 F-DOPA PET/CT and fused 18 F-DOPA PET/MRI in detecting striatal involvement in children with gliomas. This retrospective study included 28 paediatric patients referred to our institution for the presence of primary, residual or recurrent glioma (12 boys, 16 girls; mean age 10.7 years) and investigated with 18 F-DOPA PET/CT and brain MRI. Fused 18 F-DOPA PET/MR images were obtained and compared with PET/CT and MRI images. Accuracy, sensitivity, specificity, negative predictive value (NPV) and positive predictive value (PPV) for striatal involvement were calculated for each diagnostic tool. Univariate and multivariate logistic analyses were applied to evaluate the associations between 18 F-DOPA PET/CT and fused 18 F-DOPA PET/MRI diagnostic results and tumour uptake outside the striatum, grade, dimension and site of striatal involvement (ventral and/or dorsal). Accuracy, sensitivity, specificity, PPV, and NPV were 100 % for MRI, 93 %, 89 %, 100 %, 100 % and 82 % for 18 F-DOPA PET/MRI, and 75 %, 74 %, 78 %, 88 % and 58 % for 18 F-DOPA PET/CT, respectively. 18 F-DOPA PET/MRI showed a trend towards higher accuracy compared with 18 F-DOPA PET/CT (p = 0.06). MRI showed significantly higher accuracy compared with 18 F-DOPA PET/CT (p = 0.01), but there was no significant difference between MRI and 18 F-DOPA PET/MRI. Both univariate and multivariate logistic analyses showed a significant association (OR 8.0 and 7.7, respectively) between the tumour-to-normal striatal uptake (T/S) ratio and the diagnostic ability of 18 F-DOPA PET/CT (p = 0.03). A strong significant association was also found between involvement of the dorsal striatum and the 18 F-DOPA PET/CT results (p = 0.001), with a perfect prediction of involvement of the dorsal striatum by 18 F-DOPA PET/MRI. Physiological striatal 18 F-DOPA uptake does not appear to be a main limitation in the evaluation of basal ganglia involvement. 18 F-DOPA PET/CT correctly detected

  2. Automated striatal uptake analysis of 18F-FDOPA PET images applied to Parkinson's disease patients

    International Nuclear Information System (INIS)

    Chang Icheng; Lue Kunhan; Hsieh Hungjen; Liu Shuhsin; Kao, Chinhao K.

    2011-01-01

    6-[ 18 F]Fluoro-L-DOPA (FDOPA) is a radiopharmaceutical valuable for assessing the presynaptic dopaminergic function when used with positron emission tomography (PET). More specifically, the striatal-to-occipital ratio (SOR) of FDOPA uptake images has been extensively used as a quantitative parameter in these PET studies. Our aim was to develop an easy, automated method capable of performing objective analysis of SOR in FDOPA PET images of Parkinson's disease (PD) patients. Brain images from FDOPA PET studies of 21 patients with PD and 6 healthy subjects were included in our automated striatal analyses. Images of each individual were spatially normalized into an FDOPA template. Subsequently, the image slice with the highest level of basal ganglia activity was chosen among the series of normalized images. Also, the immediate preceding and following slices of the chosen image were then selected. Finally, the summation of these three images was used to quantify and calculate the SOR values. The results obtained by automated analysis were compared with manual analysis by a trained and experienced image processing technologist. The SOR values obtained from the automated analysis had a good agreement and high correlation with manual analysis. The differences in caudate, putamen, and striatum were -0.023, -0.029, and -0.025, respectively; correlation coefficients 0.961, 0.957, and 0.972, respectively. We have successfully developed a method for automated striatal uptake analysis of FDOPA PET images. There was no significant difference between the SOR values obtained from this method and using manual analysis. Yet it is an unbiased time-saving and cost-effective program and easy to implement on a personal computer. (author)

  3. Nature or Nurture? Determining the Heritability of Human Striatal Dopamine Function: an [18F]-DOPA PET Study

    Science.gov (United States)

    Stokes, Paul R A; Shotbolt, Paul; Mehta, Mitul A; Turkheimer, Eric; Benecke, Aaf; Copeland, Caroline; Turkheimer, Federico E; Lingford-Hughes, Anne R; Howes, Oliver D

    2013-01-01

    Striatal dopamine function is important for normal personality, cognitive processes and behavior, and abnormalities are linked to a number of neuropsychiatric disorders. However, no studies have examined the relative influence of genetic inheritance and environmental factors in determining striatal dopamine function. Using [18F]-DOPA positron emission tomography (PET), we sought to determine the heritability of presynaptic striatal dopamine function by comparing variability in uptake values in same sex monozygotic (MZ) twins to dizygotic (DZ) twins. Nine MZ and 10 DZ twin pairs underwent high-resolution [18F]-DOPA PET to assess presynaptic striatal dopamine function. Uptake values for the overall striatum and functional striatal subdivisions were determined by a Patlak analysis using a cerebellar reference region. Heritability, shared environmental effects and non-shared individual-specific effects were estimated using a region of interest (ROI) analysis and a confirmatory parametric analysis. Overall striatal heritability estimates from the ROI and parametric analyses were 0.44 and 0.33, respectively. We found a distinction between striatal heritability in the functional subdivisions, with the greatest heritability estimates occurring in the sensorimotor striatum and the greatest effect of individual-specific environmental factors in the limbic striatum. Our results indicate that variation in overall presynaptic striatal dopamine function is determined by a combination of genetic factors and individual-specific environmental factors, with familial environmental effects having no effect. These findings underline the importance of individual-specific environmental factors for striatal dopaminergic function, particularly in the limbic striatum, with implications for understanding neuropsychiatric disorders such as schizophrenia and addictions. PMID:23093224

  4. Characterization of dopaminergic dysfunction in familial progressive supranuclear palsy: an 18F-dopa PET study

    International Nuclear Information System (INIS)

    Tai, Y.F.; Ahsan, R.L.; Pavese, N.; Brooks, D.J.; Piccini, P.; Yebenes de, J.G.

    2007-01-01

    We analyzed 18 F-dopa PET data from 11 members of kindreds with familial progressive supranuclear palsy (PSP) to characterize their cerebral dopaminergic dysfunction. Three clinically-affected PSP patients showed reduced 18 F-dopa uptake in the striatum, orbitofrontal cortex and amygdala. One asymptomatic subject exhibited progressive putamen dopaminergic dysfunction. 60 % of subjects with abnormal 18 F-dopa scans developed PSP subsequently. This is the first in vivo documentation of cortical dopaminergic deficiency in PSP. Reduced striatal 18 F-dopa uptake in susceptible relatives may predict later clinical disease. (author)

  5. Single cocaine exposure does not alter striatal pre-synaptic dopamine function in mice: an [18 F]-FDOPA PET study.

    Science.gov (United States)

    Bonsall, David R; Kokkinou, Michelle; Veronese, Mattia; Coello, Christopher; Wells, Lisa A; Howes, Oliver D

    2017-12-01

    Cocaine is a recreational drug of abuse that binds to the dopamine transporter, preventing reuptake of dopamine into pre-synaptic terminals. The increased presence of synaptic dopamine results in stimulation of both pre- and post-synaptic dopamine receptors, considered an important mechanism by which cocaine elicits its reinforcing properties. However, the effects of acute cocaine administration on pre-synaptic dopamine function remain unclear. Non-invasive imaging techniques such as positron emission tomography have revealed impaired pre-synaptic dopamine function in chronic cocaine users. Similar impairments have been seen in animal studies, with microdialysis experiments indicating decreased basal dopamine release. Here we use micro positron emission tomography imaging techniques in mice to measure dopamine synthesis capacity and determine the effect of acute cocaine administration of pre-synaptic dopamine function. We show that a dose of 20 mg/kg cocaine is sufficient to elicit hyperlocomotor activity, peaking 15-20 min post treatment (p dopamine synthesis capacity in the striatum was not significantly altered by acute cocaine treatment (KiCer: 0.0097 per min vs. 0.0112 per min in vehicle controls, p > 0.05). Furthermore, expression levels of two key enzymes related to dopamine synthesis, tyrosine hydroxylase and aromatic l-amino acid decarboxylase, within the striatum of scanned mice were not significantly affected by acute cocaine pre-treatment (p > 0.05). Our findings suggest that while the regulation of dopamine synthesis and release in the striatum have been shown to change with chronic cocaine use, leading to a reduced basal tone, these adaptations to pre-synaptic dopaminergic neurons are not initiated following a single exposure to the drug. © 2017 International Society for Neurochemistry.

  6. Direct comparison of FP-CIT SPECT and F-DOPA PET in patients with Parkinson's disease and healthy controls

    International Nuclear Information System (INIS)

    Eshuis, S.A.; Maguire, R.P.; Leenders, K.L.; Jager, P.L.; Jonkman, S.; Dierckx, R.A.

    2009-01-01

    Diagnosing Parkinson's disease (PD) on clinical grounds may be difficult, especially in the early stages of the disease. F-DOPA PET and FP-CIT SPECT scans are able to determine presynaptic dopaminergic activity in different ways. The aim of this study was to determine and compare the sensitivity and specificity of the two methods in the detection of striatal dopaminergic deficits in the same cohort of PD patients and healthy controls. Movement disorder specialists recruited 11 patients with early-stage PD and 17 patients with advanced PD. The patients underwent both an FP-CIT SPECT scan and an F-DOPA PET scan. In addition, 10 FP-CIT SPECT scans or 10 F-DOPA PET scans were performed in 20 healthy controls. A template with regions of interest was used to sample tracer activity of the caudate, putamen and a reference region in the brain. The outcome parameter was the striatooccipital ratio (SOR). Normal SOR values were determined in the controls. The sensitivity and specificity of both scanning methods were calculated. FP-CIT SPECT and F-DOPA PET scans were both able to discriminate PD patients from healthy controls. For the early phases of the disease, sensitivity and specificity of the contralateral striatal and putaminal uptake of FP-CIT and F-DOPA was 100%. When only caudate uptake was considered, the specificities were 100% and 90% for FP-CIT and F-DOPA, respectively, while the sensitivity was 91% for both scanning techniques. FP-CIT SPECT and F-DOPA PET scans are both able to diagnose presynaptic dopaminergic deficits in early phases of PD with excellent sensitivity and specificity. (orig.)

  7. Automated image registration for FDOPA PET studies

    International Nuclear Information System (INIS)

    Kang-Ping Lin; Sung-Cheng Huang, Dan-Chu Yu; Melega, W.; Barrio, J.R.; Phelps, M.E.

    1996-01-01

    In this study, various image registration methods are investigated for their suitability for registration of L-6-[18F]-fluoro-DOPA (FDOPA) PET images. Five different optimization criteria including sum of absolute difference (SAD), mean square difference (MSD), cross-correlation coefficient (CC), standard deviation of pixel ratio (SDPR), and stochastic sign change (SSC) were implemented and Powell's algorithm was used to optimize the criteria. The optimization criteria were calculated either unidirectionally (i.e. only evaluating the criteria for comparing the resliced image 1 with the original image 2) or bidirectionally (i.e. averaging the criteria for comparing the resliced image 1 with the original image 2 and those for the sliced image 2 with the original image 1). Monkey FDOPA images taken at various known orientations were used to evaluate the accuracy of different methods. A set of human FDOPA dynamic images was used to investigate the ability of the methods for correcting subject movement. It was found that a large improvement in performance resulted when bidirectional rather than unidirectional criteria were used. Overall, the SAD, MSD and SDPR methods were found to be comparable in performance and were suitable for registering FDOPA images. The MSD method gave more adequate results for frame-to-frame image registration for correcting subject movement during a dynamic FDOPA study. The utility of the registration method is further demonstrated by registering FDOPA images in monkeys before and after amphetamine injection to reveal more clearly the changes in spatial distribution of FDOPA due to the drug intervention. (author)

  8. Measurement of striatal dopamine metabolism with 6-[18F]-fluoro-L-dopa and PET

    International Nuclear Information System (INIS)

    Kuwabara, Y.; Otsuka, M.; Ichiya, Y.; Yoshikai, T.; Fukumura, T.; Masuda, K.; Kato, M.; Taniwaki, T.

    1992-01-01

    Striatal dopamine metabolism was studied with 6-[ 18 F]-fluoro-L-dopa ( 18 F-DOPA) and PET. The subjects were normal controls, and patients with Parkinson's disease (PD), parkinsonism, multiple system atrophy (MSA), progressive supranuclear palsy (PSP), Alzheimer's disease (AD), Huntington's disease (HD) and other cerebral disorders. Cerebral glucose metabolism (CMRGlc) was also measured in these patients. Striatal dopamine metabolism was evaluated by the relative striatal uptake of 18 F-DOPA referring cerebellum (S/C ratio). In normal controls, the S/C ratio was 2.82 ± 0.32 (n = 6, mean ± SD) at 120 min after injection of 18 F-DOPA. The S/C ratio was low in patients with PD, parkinsonism, MSA and PSP compared to the normal controls and thus coincident with the symptoms of parkinsonism due to decrease in striatal dopamine concentration. The decrease in the striatal CMRGlc was also observed in patients with parkinsonism and PSP, and it was preserved in patients with PD, thus representing that more neurons were damaged in patients with parkinsonism and PSP than in patients with PD. A patient with AD having symptoms of parkinsonism also showed a decrease in S/C ratio. In a patient with HD, the striatal CMRGlc sharply decreased, but the S/C ratio was normal. The measurements of striatal dopamine and glucose metabolism with PET may be useful for studying the pathophysiological mechanism in patients with cerebral disorders. (author)

  9. Common Variation in the DOPA Decarboxylase (DDC) Gene and Human Striatal DDC Activity In Vivo.

    Science.gov (United States)

    Eisenberg, Daniel P; Kohn, Philip D; Hegarty, Catherine E; Ianni, Angela M; Kolachana, Bhaskar; Gregory, Michael D; Masdeu, Joseph C; Berman, Karen F

    2016-08-01

    The synthesis of multiple amine neurotransmitters, such as dopamine, norepinephrine, serotonin, and trace amines, relies in part on DOPA decarboxylase (DDC, AADC), an enzyme that is required for normative neural operations. Because rare, loss-of-function mutations in the DDC gene result in severe enzymatic deficiency and devastating autonomic, motor, and cognitive impairment, DDC common genetic polymorphisms have been proposed as a source of more moderate, but clinically important, alterations in DDC function that may contribute to risk, course, or treatment response in complex, heritable neuropsychiatric illnesses. However, a direct link between common genetic variation in DDC and DDC activity in the living human brain has never been established. We therefore tested for this association by conducting extensive genotyping across the DDC gene in a large cohort of 120 healthy individuals, for whom DDC activity was then quantified with [(18)F]-FDOPA positron emission tomography (PET). The specific uptake constant, Ki, a measure of DDC activity, was estimated for striatal regions of interest and found to be predicted by one of five tested haplotypes, particularly in the ventral striatum. These data provide evidence for cis-acting, functional common polymorphisms in the DDC gene and support future work to determine whether such variation might meaningfully contribute to DDC-mediated neural processes relevant to neuropsychiatric illness and treatment.

  10. Complementary PET studies of striatal neuronal function in the differential diagnosis between multiple system atrophy and Parkinson's disease

    NARCIS (Netherlands)

    Antonini, A; Leenders, KL; Vontobel, P; Maguire, RP; Missimer, J; Psylla, M; Gunther, [No Value

    1997-01-01

    We used PET with the tracers [F-18]fluorodeoxyglucose (FDG), [F-18]fluorodopa (FDOPA) and [C-11]raclopride (RACLO) to study striatal glucose and dopa metabolism, and dopamine D-2 receptor binding, respectively, in nine patients with multiple system atrophy. Ten patients with classical Parkinson's

  11. Synthetic improvement and animal experiment of 6-18F-DOPA

    International Nuclear Information System (INIS)

    Tang Ganghua; Tang Xiaolan; Wang Mingfang; Luo Lei; Li Zhi; Huang Zuhan; Zhang Lan; Wang Yongxian

    2002-01-01

    Objective: To study synthetic improvement and biodistribution of 6- 18 F-DOPA in normal rats and hemi-Parkinsonism rats. Methods: 6- 18 F-DOPA was synthesized from the starting material 6-nitropiperonal via multi-step reaction including the nucleophilic fluorination, reductive iodination with diiodosilane on Sep-Pak column, chiral catalytic phase-transfer alkylation, and hydrolysis reaction. Biodistribution of 6- 18 F-DOPA in normal rats and the brain of hemi-Parkinsonism rats was determined. Results: The total time of synthesis was less than 110 min, the total uncorrected radiochemical yield from potassium 6- 18 F-DOPA was 5%-18%, and the enantiomeric purity and radiochemical purity were above 97% and 98%, respectively. High uptake in the kidney, blood, striatum, and hippocampus, rapid blood clearance in the kidney and blood, long retaining time and high striatum/cerebellum and striatum/cortex 6- 18 F-DOPA uptake ratio were found in normal rats. Compared with the intact side of hemi-Parkinsonism rats and pseudo-operated group, 6- 18 F-DOPA uptake and striatum/cerebellum and striatum/cortex 6- 18 F-DOPA uptake ratio reduced significantly in the lesioned side of hemi-Parkinsonism rats (P 18 F-DOPA. The synthetic 6- 18 F-DOPA is allowed to be used to study the animal and Parkinson's disease with PET imaging

  12. Increasing feasibility and utility of 18F-FDOPA PET for the management of glioma

    International Nuclear Information System (INIS)

    Bell, Christopher; Dowson, Nicholas; Puttick, Simon; Gal, Yaniv; Thomas, Paul; Fay, Mike; Smith, Jye; Rose, Stephen

    2015-01-01

    Introduction: Despite radical treatment therapies, glioma continues to carry with it a uniformly poor prognosis. Patients diagnosed with WHO Grade IV glioma (glioblastomas; GBM) generally succumb within two years, even those with WHO Grade III anaplastic gliomas and WHO Grade II gliomas carry prognoses of 2–5 and 2 years, respectively. PET imaging with 18 F-FDOPA allows in vivo assessment of the metabolism of glioma relative to surrounding tissues. The high sensitivity of 18 F-DOPA imaging grants utility for a number of clinical applications. Methods: A collection of published work about 18 F-FDOPA PET was made and a critical review was discussed and written. Results: A number of research papers have been published demonstrating that in conjunction with MRI, 18 F-FDOPA PET provides greater sensitivity and specificity than these modalities in detection, grading, prognosis and validation of treatment success in both primary and recurrent gliomas. In further comparisons with 11 C-MET, 18 F-FLT, 18 F-FET and MRI, 18 F-FDOPA has shown similar or better efficacy. Recently synthesis cassettes have become available, making 18 F-FDOPA more accessible. Conclusions: According to the available data, 18 F-FDOPA PET is a viable radiotracer for imaging and treatment planning of gliomas. Advances in knowledge and implication for patient care: 18 F-FDOPA PET appears to be a viable radiopharmaceutical for the diagnosis and treatment planning of gliomas cases, improving on that of MRI and 18 F-FDG PET

  13. FDOPA-PET as a paradigm of molecular imaging in oncology

    International Nuclear Information System (INIS)

    Brink, I.; Hentschel, M.; Neumann, H.P.H.; Schaefer, O.; Moser, E.

    2007-01-01

    In recent years, positron emission tomography with 6-[18F]fluoro-L-3,4-dihydroxyphenylalanine (FDOPA) has become a wide-spread method in the diagnostics of Parkinson's disease. The amino acid is an important component in protein metabolism. As a precursor in the synthesis of catecholamines it is also of use in metabolic imaging of a variety, mostly neuroendocrine, tumors. The specific uptake mechanisms make FDOPA a paradigm of metabolic imaging. The current review assesses the value of the tracer in the diagnostics of different oncological diseases. It summarizes own experiences and the published results of oncological FDOPA PET-studies. Above all, there is a very high impact of FDOPA in the staging of pheochromocytomas and paragangliomas as well as serotonin-positive neuroendocrine tumors of the gastroentero-pancreatic system (NET-GEPs). Additionally, FDOPA extends the diagnostic possibilities in recurrent medullary thyroid cancer. In the imaging of tumors of the central nervous system, FDOPA represents an alternative to 11 C-labelled PET-tracers. First reports show a high accuracy in the differentiation of radiation induced necrosis and recurrent disease in both high and low grade brain tumors. Furthermore, there is a correlation between the uptake of FDOPA and the expression of proliferation markers. Today, the noninvasive differentiation of focal and diffuse congenital hyperinsulinism has therapeutic consequences. In cases of focal disease, the extent of pancreas resection can be limited resulting in better prognosis without diabetes mellitus. (orig.)

  14. Loss of metabolites from monkey striatum during PET with FDOPA

    DEFF Research Database (Denmark)

    Cumming, P; Munk, O L; Doudet, D

    2001-01-01

    constants using data recorded during 240 min of FDOPA circulation in normal monkeys and in monkeys with unilateral 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) lesions. Use of the extended models increased the magnitudes of K(D)(i) and k(D)(3) in striatum; in the case of k(D)(3), variance...... of the estimate was substantially improved upon correction for metabolite loss. The rate constants for metabolite loss were higher in MPTP-lesioned monkey striatum than in normal striatum. The high correlation between individual estimates of k(Lin)(cl) and k(DA)(9) suggests that both rate constants reveal loss...

  15. 18F-DOPA PET/CT Physiological Distribution and Pitfalls: Experience in 215 Patients.

    Science.gov (United States)

    Calabria, Ferdinando F; Chiaravalloti, Agostino; Jaffrain-Rea, Marielise L; Zinzi, Maddalena; Sannino, Pasqualina; Minniti, Giuseppe; Rubello, Domenico; Schillaci, Orazio

    2016-10-01

    F-DOPA PET/CT is potentially helpful in the management of patients with low-grade brain tumors, movement disorders, and somatic neuroendocrine tumors. We describe the whole-body physiological distribution of F-DOPA uptake. We examined 215 patients with F-DOPA PET/CT. Among these, 161 had brain scans and 54 had whole-body scans. Physiological distribution was negligible in the brain, with the exception of basal ganglia, whereas greatest activity was noted in the liver, pancreas, other exocrine glands, and the urinary system. Incidental tracer uptake sites were identified in 5.5% of patients. Some of these findings were due to inflammation, whereas in most cases, uptake was seen in benign tumors of the brain or in the endocrine or exocrine glands. F-DOPA uptake may be seen in inflammatory tissue or benign tumors. Correlations with history, physical examination, laboratory examination, CT, MRI, and histology are necessary for optimal diagnosis.

  16. 18F-FDOPA PET/MRI fusion in patients with primary/recurrent gliomas: Initial experience

    International Nuclear Information System (INIS)

    Ledezma, Carlos J.; Chen, Wei; Sai, Victor; Freitas, Bonnie; Cloughesy, Tim; Czernin, Johannes; Pope, Whitney

    2009-01-01

    Background and purpose: 18 F-FDOPA PET demonstrates higher sensitivity and specificity for gliomas than traditional [ 18 F] FDG PET imaging. However, PET provides limited anatomic localization. The purpose of this study was to determine whether 18 F-FDOPA PET/MRI fusion can provide precise anatomic localization of abnormal tracer uptake and how this activity corresponds to MR signal abnormality. Methods: Two groups of patients were analyzed. Group I consisted of 21 patients who underwent 18 F-FDOPA PET and MRI followed by craniotomy for tumor resection. Group II consisted of 70 patients with a pathological diagnosis of glioma that had 18 F-FDOPA PET and MRI but lacked additional pathologic follow-up. Fused 18 F-FDOPA PET and MRI images were analyzed for concordance and correlated with histopathologic data. Results: Fusion technology facilitated precise anatomical localization of 18 F-FDOPA activity. In group I, all 21 cases showed pathology-confirmed tumor. Of these, 18 F-FDOPA scans were positive in 9/10 (90%) previously unresected tumors, and 11/11 (100%) of recurrent tumors. Of the 70 patients in group II, concordance between MRI and 18 F-FDOPA was found in 49/54 (90.1%) of patients with sufficient follow-up; in the remaining 16 patients concordance could not be determined due to lack of follow-up. 18 F-FDOPA labeling was comparable in both high- and low-grade gliomas and identified both enhancing and non-enhancing tumor equally well. In some cases, 18 F-FDOPA activity preceded tumor detection on MRI. Conclusion: 18 F-FDOPA PET/MRI fusion provides precise anatomic localization of tracer uptake and labels enhancing and non-enhancing tumor well. In a small minority of cases, 18 F-FDOPA activity may identify tumor not visible on MRI.

  17. Adversity in childhood linked to elevated striatal dopamine function in adulthood.

    Science.gov (United States)

    Egerton, Alice; Valmaggia, Lucia R; Howes, Oliver D; Day, Fern; Chaddock, Christopher A; Allen, Paul; Winton-Brown, Toby T; Bloomfield, Michael A P; Bhattacharyya, Sagnik; Chilcott, Jack; Lappin, Julia M; Murray, Robin M; McGuire, Philip

    2016-10-01

    Childhood adversity increases the risk of psychosis in adulthood. Theoretical and animal models suggest that this effect may be mediated by increased striatal dopamine neurotransmission. The primary objective of this study was to examine the relationship between adversity in childhood and striatal dopamine function in early adulthood. Secondary objectives were to compare exposure to childhood adversity and striatal dopamine function in young people at ultra high risk (UHR) of psychosis and healthy volunteers. Sixty-seven young adults, comprising 47 individuals at UHR for psychosis and 20 healthy volunteers were recruited from the same geographic area and were matched for age, gender and substance use. Presynaptic dopamine function in the associative striatum was assessed using 18F-DOPA positron emission tomography. Childhood adversity was assessed using the Childhood Experience of Care and Abuse questionnaire. Within the sample as a whole, both severe physical or sexual abuse (T63=2.92; P=0.005), and unstable family arrangements (T57=2.80; P=0.007) in childhood were associated with elevated dopamine function in the associative striatum in adulthood. Comparison of the UHR and volunteer subgroups revealed similar incidence of childhood adverse experiences, and there was no significant group difference in dopamine function. This study provides evidence that childhood adversity is linked to elevated striatal dopamine function in adulthood. Copyright © 2016 The Authors. Published by Elsevier B.V. All rights reserved.

  18. Loss of metabolites from monkey striatum during PET with FDOPA

    DEFF Research Database (Denmark)

    Cumming, P; Munk, O L; Doudet, D

    2001-01-01

    diffusion of [(18)F]fluorodopamine metabolites from brain. Consequently, time-radioactivity recordings of striatum are progressively influenced by metabolite loss. In linear analyses, the net blood-brain clearance of FDOPA (K(D)(i), ml g(-1) min(-1)) can be corrected for this loss by the elimination rate...... constant k(Lin)(cl) (min(-1)). Similarly, the DOPA decarboxylation rate constant (k(D)(3), min(-1)) calculated by compartmental analysis can also be corrected for metabolite loss by the elimination rate constant k(DA)(9) (min(-1)). To compare the two methods, we calculated the two elimination rate...... of the estimate was substantially improved upon correction for metabolite loss. The rate constants for metabolite loss were higher in MPTP-lesioned monkey striatum than in normal striatum. The high correlation between individual estimates of k(Lin)(cl) and k(DA)(9) suggests that both rate constants reveal loss...

  19. Brain 18F-DOPA PET and cognition in de novo Parkinson's disease

    International Nuclear Information System (INIS)

    Picco, Agnese; Arnaldi, Dario; Brugnolo, Andrea; Nobili, Flavio; Morbelli, Silvia; Bossert, Irene; Piccardo, Arnoldo; Girtler, Nicola; Marinelli, Lucio; Abbruzzese, Giovanni; Castaldi, Antonio; De Carli, Fabrizio; Campus, Claudio

    2015-01-01

    The role of mesocortical dopaminergic pathways in the cognitive function of patients with early Parkinson's disease (PD) needs to be further clarified. The study groups comprised 15 drug-naive patients with de novo PD and 10 patients with essential tremor (controls) who underwent 18 F-DOPA PET (static acquisition, normalization on mean cerebellar counts) and an extended neuropsychological test battery. Factor analysis with varimax rotation was applied to the neuropsychological test scores, to yield five factors from 16 original scores, which explained 82 % of the total variance. Correlations between cognitive factors and 18 F-DOPA uptake were assessed with SPM8, taking age and gender as nuisance variables. 18 F-DOPA uptake was significantly lower in PD patients than in controls in the bilateral striatum, mainly in the more affected (right) hemisphere, and in a small right temporal region. Significant positive correlations were found only in PD patients between the executive factor and 18 F-DOPA uptake in the bilateral anterior cingulate cortex (ACC) and the middle frontal gyrus, between the verbal fluency factor and 18 F-DOPA uptake in left BA 46 and the bilateral striatum, and between the visuospatial factor and 18 F-DOPA uptake in the left ACC and bilateral striatum. No correlations were found between 18 F-DOPA uptake and either the verbal memory factor or the abstraction-working memory factor. These data clarify the role of the mesocortical dopaminergic pathways in cognitive function in early PD, highlighting the medial frontal lobe, anterior cingulate, and left BA 46 as the main sites of cortical correlation with executive and language functions. (orig.)

  20. KiWi Vision

    DEFF Research Database (Denmark)

    Schaffert, Sebastian; Bry, Francois; Dolog, Peter

    This deliverable describes the common vision of the KiWi project, ranging from motivation over use cases and usage scenarios to user interaction, system architecture and technologies, and the research that is performed as part of the project. The deliverable is intended for a wide audience to give...

  1. {sup 18}F-FDOPA PET/CT imaging of insulinoma revisited

    Energy Technology Data Exchange (ETDEWEB)

    Imperiale, Alessio; Namer, Izzie-Jacques [University Hospitals of Strasbourg, Department of Biophysics and Nuclear Medicine, Strasbourg (France); University of Strasbourg/CNRS and FMTS, Faculty of Medicine, ICube - UMR 7357, Strasbourg (France); Sebag, Frederic [Aix-Marseille University, Department of Endocrine Surgery, La Timone University Hospital, Marseille (France); Vix, Michel [University of Strasbourg, Department of General, Digestive, and Endocrine Surgery, IRCAD-IHU, Strasbourg (France); Castinetti, Frederic [Aix-Marseille University, Department of Endocrinology, Diabetes and Metabolic Disorders, La Timone University Hospital, Marseille (France); Kessler, Laurence; Moreau, Francois [University of Strasbourg, Department of Diabetology, University Hospital of Strasbourg, Strasbourg (France); Bachellier, Philippe [University Hospitals of Strasbourg, Department of Visceral Surgery and Transplantation, Strasbourg (France); Guillet, Benjamin; Mundler, Olivier [Aix-Marseille University, Department of Nuclear Medicine, La Timone University Hospital, CERIMED, Marseille (France); Taieb, David [Aix-Marseille University, Department of Nuclear Medicine, La Timone University Hospital, CERIMED, Marseille (France); Aix-Marseille University, Biophysics and Nuclear Medecine, La Timone University Hospital, European Center for Research in Medical Imaging, Marseille (France)

    2014-11-01

    {sup 18}F-FDOPA PET imaging is increasingly used in the work-up of patients with neuroendocrine tumours. It has been shown to be of limited value in localizing pancreatic insulin-secreting tumours in adults with hyperinsulinaemic hypoglycaemia (HH) mainly due to {sup 18}F-FDOPA uptake by the whole pancreatic gland. The objective of this study was to review our experience with {sup 18}F-FDOPA PET/CT imaging with carbidopa (CD) premedication in patients with HH in comparison with PET/CT studies performed without CD premedication in an independent population. A retrospective study including 16 HH patients who were investigated between January 2011 and December 2013 using {sup 18}F-FDOPA PET/CT (17 examinations) in two academic endocrine tumour centres was conducted. All PET/CT examinations were performed under CD premedication (200 mg orally, 1 - 2 h prior to tracer injection). The PET/CT acquisition protocol included an early acquisition (5 min after {sup 18}F-FDOPA injection) centred over the upper abdomen and a delayed whole-body acquisition starting 20 - 30 min later. An independent series of eight consecutive patients with HH and investigated before 2011 were considered for comparison. All patients had a reference whole-body PET/CT scan performed about 1 h after {sup 18}F-FDOPA injection. In all cases, PET/CT was performed without CD premedication. In the study group, {sup 18}F-FDOPA PET/CT with CD premedication was positive in 8 out of 11 patients with histologically proven insulinoma (73 %). All {sup 18}F-FDOPA PET/CT-avid insulinomas were detected on early images and 5 of 11 (45 %) on delayed ones. The tumour/normal pancreas uptake ratio was not significantly different between early and delayed acquisitions. Considering all patients with HH, including those without imaging evidence of disease, the detection rate of the primary lesions using CD-assisted {sup 18}F-FDOPA PET/CT was 53 %, showing 9 insulinomas in 17 studies performed. In the control group (without

  2. 18F-FDOPA PET/CT imaging of insulinoma revisited

    International Nuclear Information System (INIS)

    Imperiale, Alessio; Namer, Izzie-Jacques; Sebag, Frederic; Vix, Michel; Castinetti, Frederic; Kessler, Laurence; Moreau, Francois; Bachellier, Philippe; Guillet, Benjamin; Mundler, Olivier; Taieb, David

    2015-01-01

    18 F-FDOPA PET imaging is increasingly used in the work-up of patients with neuroendocrine tumours. It has been shown to be of limited value in localizing pancreatic insulin-secreting tumours in adults with hyperinsulinaemic hypoglycaemia (HH) mainly due to 18 F-FDOPA uptake by the whole pancreatic gland. The objective of this study was to review our experience with 18 F-FDOPA PET/CT imaging with carbidopa (CD) premedication in patients with HH in comparison with PET/CT studies performed without CD premedication in an independent population. A retrospective study including 16 HH patients who were investigated between January 2011 and December 2013 using 18 F-FDOPA PET/CT (17 examinations) in two academic endocrine tumour centres was conducted. All PET/CT examinations were performed under CD premedication (200 mg orally, 1 - 2 h prior to tracer injection). The PET/CT acquisition protocol included an early acquisition (5 min after 18 F-FDOPA injection) centred over the upper abdomen and a delayed whole-body acquisition starting 20 - 30 min later. An independent series of eight consecutive patients with HH and investigated before 2011 were considered for comparison. All patients had a reference whole-body PET/CT scan performed about 1 h after 18 F-FDOPA injection. In all cases, PET/CT was performed without CD premedication. In the study group, 18 F-FDOPA PET/CT with CD premedication was positive in 8 out of 11 patients with histologically proven insulinoma (73 %). All 18 F-FDOPA PET/CT-avid insulinomas were detected on early images and 5 of 11 (45 %) on delayed ones. The tumour/normal pancreas uptake ratio was not significantly different between early and delayed acquisitions. Considering all patients with HH, including those without imaging evidence of disease, the detection rate of the primary lesions using CD-assisted 18 F-FDOPA PET/CT was 53 %, showing 9 insulinomas in 17 studies performed. In the control group (without CD premedication, eight patients), the final

  3. Parsing Heterogeneous Striatal Activity

    Directory of Open Access Journals (Sweden)

    Kae Nakamura

    2017-05-01

    Full Text Available The striatum is an input channel of the basal ganglia and is well known to be involved in reward-based decision making and learning. At the macroscopic level, the striatum has been postulated to contain parallel functional modules, each of which includes neurons that perform similar computations to support selection of appropriate actions for different task contexts. At the single-neuron level, however, recent studies in monkeys and rodents have revealed heterogeneity in neuronal activity even within restricted modules of the striatum. Looking for generality in the complex striatal activity patterns, here we briefly survey several types of striatal activity, focusing on their usefulness for mediating behaviors. In particular, we focus on two types of behavioral tasks: reward-based tasks that use salient sensory cues and manipulate outcomes associated with the cues; and perceptual decision tasks that manipulate the quality of noisy sensory cues and associate all correct decisions with the same outcome. Guided by previous insights on the modular organization and general selection-related functions of the basal ganglia, we relate striatal activity patterns on these tasks to two types of computations: implementation of selection and evaluation. We suggest that a parsing with the selection/evaluation categories encourages a focus on the functional commonalities revealed by studies with different animal models and behavioral tasks, instead of a focus on aspects of striatal activity that may be specific to a particular task setting. We then highlight several questions in the selection-evaluation framework for future explorations.

  4. On the use of [18F]DOPA as an imaging biomarker for transplanted islet mass

    International Nuclear Information System (INIS)

    Eriksson, Olof; Mintz, Akiva; Liu, Chengyang; Yu, Ming; Naji, Ali; Alavi, Abass

    2014-01-01

    Islet transplantation is being developed as a potential cure for patients with type 1 diabetes. There is a need for non-invasive imaging techniques for the quantification of transplanted islets, as current transplantation sites are associated with a substantial loss of islet viability. The dopaminergic metabolic pathway is present in the islets; therefore, we propose Fluorine-18 labeled L-3,4-dihydroxyphenylalanine ([ 18 F]DOPA) as a biomarker for transplanted islet mass. The expression of enzymes involved in the dopaminergic metabolic pathway was investigated in both native and transplanted human islets. The specific uptake of [ 18 F]DOPA in islets and immortalized beta cells was studied in vitro by selective blocking of dopa decarboxylase (DDC). Initial in vivo positron emission tomography (PET) imaging of viable subcutaneous human islets was performed using [ 18 F]DOPA. DDC and vesicular monoamine transporter 2 are co-localized with insulin in the native human pancreas, and the expression is retained after transplantation. Islet uptake of the [ 18 F]DOPA could be modulated by inhibiting DDC, indicating that the uptake followed the normal dopaminergic metabolic pathway. In vivo imaging revealed [ 18 F]DOPA uptake at the site of the functional islet graft. Based on the in vitro and in vivo results presented in this study, we propose to further validate [ 18 F]DOPA-PET as a sensitive imaging modality for imaging extrahepatically transplanted islets. (author)

  5. Automated synthesis of n.c.a. [18F]FDOPA via nucleophilic aromatic substitution with [18F]fluoride

    International Nuclear Information System (INIS)

    Shen, B.; Ehrlichmann, W.; Uebele, M.; Machulla, H.-J.; Reischl, G.

    2009-01-01

    An improved, automated synthesis of [ 18 F]FDOPA including four synthetic steps (fluorination, reductive iodination, alkylation and hydrolysis) is reported with each step optimized individually. In a home-made automatic synthesizer, 9064±3076 MBq of [ 18 F]FDOPA were produced within 120 min from EOB (n=5). Radiochemical purity and enantiomeric excess were both ≥95%. Specific activity was ca. 50 GBq/μmol at EOS. This automatically operable synthesis is well suited for the multi-patient-dose routine production of n.c.a. [ 18 F]FDOPA.

  6. Elevated [(18)F]FDOPA utilization in the periaqueductal gray and medial nucleus accumbens of patients with early Parkinson's disease

    DEFF Research Database (Denmark)

    Kumakura, Yoshitaka; Danielsen, Erik H; Gjedde, Albert

    2009-01-01

    , there have been several reports of focal elevations of FDOPA utilization in brain of patients with Parkinson's disease (PD), all based on reference tissue methods. To investigate this phenomenon further, we used voxel-wise steady-state kinetic analysis to search for regions of elevated FDOPA utilization (K......; ml g(-1) min(-1)) and steady-state trapping (V(d); ml g(-1)) in a group of well-characterized patients with early, asymmetric PD, who were contrasted with an age-matched control group. Subtraction of the population mean parametric maps revealed foci of increased FDOPA utilization K (+25...

  7. The applications of 18F-DOPA PET in Parkinson's disease

    International Nuclear Information System (INIS)

    Zuo Chuantao

    2000-01-01

    The injury of the presynaptic nigro-striae dopaminergic projection is the important mechanism of Parkinson's disease (PD). 18 F-DOPA PET provides a measure of the structure as well as the biochemical integrity of the dopaminergic neurons, which contribute to the early diagnosis, differentiation diagnosis, prognosis evaluation of PD

  8. 18F-FDOPA Accumulation in Traumatic Rib Fractures : A Potential Pitfall

    NARCIS (Netherlands)

    Stormezand, Gilles N.; Glaudemans, Andor W. J. M.; Slart, Riemer H. J. A.

    F-FDOPA (6-[F]fluoro-L-DOPA) is used for the detection and staging of neuroendocrine tumors by visualizing the uptake of amine precursors in these tumors with high sensitivity and specificity. However, as this tracer is only available in a limited number of centers worldwide and the minority of the

  9. Factors affecting 18 F FDOPA standardized uptake value in patients with primary brain tumors after treatment

    International Nuclear Information System (INIS)

    Chiaravalloti, Agostino; Fiorentini, Alessandro; Villani, Veronica; Carapella, Carmine; Pace, Andrea; Di Pietro, Barbara; Di Russo, Carmen; Palumbo, Barbara; Floris, Roberto; Schillaci, Orazio

    2015-01-01

    Aim: To investigate the factors affecting 18 F FDOPA uptake in patients with primary brain tumors (PBT) after treatment. Materials and methods: 97 patients with PBT (6 were grade I, 40 were grade II, 29 were grade III and 22 were grade IV) underwent 18 F FDOPA positron emission tomography/computed tomography (PET/CT) after treatment. Intervals from surgery, chemotherapy (CHT) and radiotherapy (RT) were 41.48 (± 42.27), 16.04 (± 29.08) and 28.62 (± 34.49) months respectively. Results: 18 F FDOPA uptake in the site of recurrence was not related to the interval from surgery and CHT while a significant relationship has been found with the interval from RT and tumor grade. Conclusions: The results of our study show that the interval from RT and the grade of PBT should be considered carefully when evaluating brain PET/CT scans since these factors could directly affect 18 F FDOPA uptake

  10. 18F-DOPA PET/CT and MRI Findings in a Patient With Multiple Meningiomas.

    Science.gov (United States)

    Calabria, Ferdinando F; Chiaravalloti, Agostino; Calabria, Eros N; Grillea, Giovanni; Schillaci, Orazio

    2016-08-01

    A 56-year-old man was referred to our Department for a 2-year story of upper limb tremor, severe headache, and episodes of confusion. Brain F-DOPA PET/CT showed multiple areas of tracer uptake in the two hemispheres of the brain. Subsequent MRI displayed demyelinating foci with high contrast enhancement. Histological specimen confirmed the diagnosis of multiple meningiomas.

  11. Total {sup 18}F-dopa PET tumour uptake reflects metabolic endocrine tumour activity in patients with a carcinoid tumour

    Energy Technology Data Exchange (ETDEWEB)

    Fiebrich, Helle-Brit; Walenkamp, Annemiek M.; Vries, Elisabeth G.E. de [University Medical Centre Groningen, Department of Medical Oncology, Groningen (Netherlands); Jong, Johan R. de; Koopmans, Klaas Pieter; Dierckx, Rudi A.J.O.; Brouwers, Adrienne H. [University Medical Centre Groningen, Department of Nuclear Medicine and Molecular Imaging, Groningen (Netherlands); Kema, Ido P. [University Medical Centre Groningen, Department of Laboratory Medicine, Groningen (Netherlands); Sluiter, Wim; Links, Thera P. [University Medical Centre Groningen, Department of Endocrinology, Groningen (Netherlands)

    2011-10-15

    Positron emission tomography (PET) using 6-[{sup 18}F]fluoro-L-dihydroxyphenylalanine ({sup 18}F-dopa) has an excellent sensitivity to detect carcinoid tumour lesions. {sup 18}F-dopa tumour uptake and the levels of biochemical tumour markers are mediated by tumour endocrine metabolic activity. We evaluated whether total {sup 18}F-dopa tumour uptake on PET, defined as whole-body metabolic tumour burden (WBMTB), reflects tumour load per patient, as measured with tumour markers. Seventy-seven consecutive carcinoid patients who underwent an {sup 18}F-dopa PET scan in two previously published studies were analysed. For all tumour lesions mean standardised uptake values (SUVs) at 40% of the maximal SUV and tumour volume on {sup 18}F-dopa PET were determined and multiplied to calculate a metabolic burden per lesion. WBMTB was the sum of the metabolic burden of all individual lesions per patient. The 24-h urinary serotonin, urine and plasma 5-hydroxindoleacetic acid (5-HIAA), catecholamines (nor)epinephrine, dopamine and their metabolites, measured in urine and plasma, and serum chromogranin A served as tumour markers. All but 1 were evaluable for WBMTB; 74 patients had metastatic disease. {sup 18}F-dopa PET detected 979 lesions. SUV{sub max} on {sup 18}F-dopa PET varied up to 29-fold between individual lesions within the same patients. WBMTB correlated with urinary serotonin (r = 0.51) and urinary and plasma 5-HIAA (r = 0.78 and 0.66). WBMTB also correlated with urinary norepinephrine, epinephrine, dopamine and plasma dopamine, but not with serum chromogranin A. Tumour load per patient measured with {sup 18}F-dopa PET correlates with tumour markers of the serotonin and catecholamine pathway in urine and plasma in carcinoid patients, reflecting metabolic tumour activity. (orig.)

  12. Ageing effect on 18F-DOPA and 123I-MIBG uptake: a cross-sectional study.

    Science.gov (United States)

    Chiaravalloti, Agostino; Barbagallo, Gaetano; Ricci, Maria; Sannino, Pasqualina; Karalis, Georgios; Ursini, Francesco; Schillaci, Orazio

    2018-06-01

    The aim of this study was to investigate the relationship between age and uptake of fluorine-18-L-dihydroxyphenylalanine (F-DOPA) in the brain and myocardial uptake of iodine-123-metaiodobenzylguanidine (I-MIBG) in normal adult participants. To this end, a total of 72 healthy participants were enroled. Of these, 37 individuals (male, 21; female, 16; mean age: 60±12 years; age range: 38-85 years) underwent F-DOPA PET/CT, whereas 35 individuals (male, 19; female, 16; mean age: 61±17 years; age range: 17-87 years) underwent I-MIBG scintigraphy. For F-DOPA PET/CT, regions of interest were placed on the caudate nucleus, globus pallidus and putamen by means of the WFU Pickatlas tool implemented in SPM8 and further analysed after a normalization process. For I-MIBG scintigraphy, regions of interest were set over the upper mediastinum and a heart-to-mediastinum count ratio was calculated. The relation between age and normalized F-DOPA values or heart-to-mediastinum ratio values was examined using correlation analysis of variance and Pearson's correlation coefficient. We did not find any significant relationship between age and F-DOPA and I-MIBG uptake, respectively. Our findings suggest that both brain F-DOPA PET/CT and cardiac I-MIBG scintigraphy represent age-independent biomarkers whose analyses of quantitative uptake may not require adjustment for patients' age.

  13. Usefulness of [18F]-DA and [18F]-DOPA for PET imaging in a mouse model of pheochromocytoma

    International Nuclear Information System (INIS)

    Martiniova, Lucia; Cleary, Susannah; Lai, Edwin W.; Kiesewetter, Dale O.; Seidel, Jurgen; Dawson, Linda F.; Phillips, Jacqueline K.; Thomasson, David; Chen Xiaoyuan; Eisenhofer, Graeme; Powers, James F.; Kvetnansky, Richard

    2012-01-01

    Purpose: To evaluate the usefulness of [ 18 F]-6-fluorodopamine ([ 18 F]-DA) and [ 18 F]-L-6-fluoro-3,4-dihydroxyphenylalanine ([ 18 F]-DOPA) positron emission tomography (PET) in the detection of subcutaneous (s.c.) and metastatic pheochromocytoma in mice; to assess the expression of the norepinephrine transporter (NET) and vesicular monoamine transporters 1 and 2 (VMAT1 and VMAT2), all important for [ 18 F]-DA and [ 18 F]-DOPA uptake. Furthermore, to compare tumor detection by micro-computed tomography (microCT) to magnetic resonance imaging (MRI) in individual mouse. Methods: SUV max values were calculated from [ 18 F]-DA and [ 18 F]-DOPA PET, tumor-to-liver ratios (TLR) were obtained and expression of NET, VMAT1 and VMAT2 was evaluated. Results: [ 18 F]-DA detected less metastatic lesions compared to [ 18 F]-DOPA. TLR values for liver metastases were 2.26–2.71 for [ 18 F]-DOPA and 1.83–2.83 for [ 18 F]-DA. A limited uptake of [ 18 F]-DA was found in s.c. tumors (TLR=0.22-0.27) compared to [ 18 F]-DOPA (TLR=1.56-2.24). Overall, NET and VMAT2 were expressed in all organ and s.c. tumors. However, s.c. tumors lacked expression of VMAT1. We confirmed [ 18 F]-DA's high affinity for the NET for its uptake and VMAT1 and VMAT2 for its storage and retention in pheochromocytoma cell vesicles. In contrast, [ 18 F]-DOPA was found to utilize only VMAT2. Conclusion: MRI was superior in the detection of all organ tumors compared to microCT and PET. [ 18 F]-DOPA had overall better sensitivity than [ 18 F]-DA for the detection of metastases. Subcutaneous tumors were localized only with [ 18 F]-DOPA, a finding that may reflect differences in expression of VMAT1 and VMAT2, perhaps similar to some patients with pheochromocytoma where [ 18 F]-DOPA provides better visualization of lesions than [ 18 F]-DA.

  14. Brain {sup 18}F-DOPA PET and cognition in de novo Parkinson's disease

    Energy Technology Data Exchange (ETDEWEB)

    Picco, Agnese; Arnaldi, Dario; Brugnolo, Andrea; Nobili, Flavio [University of Genoa and IRCCS AOU San Martino-IST, Clinical Neurology, Department of Neuroscience (DINOGMI), Genoa (Italy); Morbelli, Silvia; Bossert, Irene [University of Genoa and IRCCS AOU San Martino-IST, Nuclear Medicine, Department of Health Sciences (DISSAL), Genoa (Italy); Piccardo, Arnoldo [Ospedali Galliera, Nuclear Medicine, Department of Imaging Diagnostics, Genoa (Italy); Girtler, Nicola [University of Genoa and IRCCS AOU San Martino-IST, Clinical Neurology, Department of Neuroscience (DINOGMI), Genoa (Italy); IRCCS San Martino-IST, Clinical Psychology and Psychotherapy Unit, Genoa (Italy); Marinelli, Lucio; Abbruzzese, Giovanni [University of Genoa and IRCCS AOU San Martino-IST, Neurological Rehabilitation, Department of Neuroscience (DINOGMI), Genoa (Italy); Castaldi, Antonio [Ospedali Galliera, Radiology, Department of Imaging Diagnostics, Genoa (Italy); De Carli, Fabrizio [Consiglio Nazionale delle Ricerche (CNR), Institute of Bioimaging and Molecular Physiology, Genoa (Italy); Campus, Claudio [Istituto Italiano di Tecnologia, Genoa (Italy)

    2015-03-28

    The role of mesocortical dopaminergic pathways in the cognitive function of patients with early Parkinson's disease (PD) needs to be further clarified. The study groups comprised 15 drug-naive patients with de novo PD and 10 patients with essential tremor (controls) who underwent {sup 18}F-DOPA PET (static acquisition, normalization on mean cerebellar counts) and an extended neuropsychological test battery. Factor analysis with varimax rotation was applied to the neuropsychological test scores, to yield five factors from 16 original scores, which explained 82 % of the total variance. Correlations between cognitive factors and {sup 18}F-DOPA uptake were assessed with SPM8, taking age and gender as nuisance variables. {sup 18}F-DOPA uptake was significantly lower in PD patients than in controls in the bilateral striatum, mainly in the more affected (right) hemisphere, and in a small right temporal region. Significant positive correlations were found only in PD patients between the executive factor and {sup 18}F-DOPA uptake in the bilateral anterior cingulate cortex (ACC) and the middle frontal gyrus, between the verbal fluency factor and {sup 18}F-DOPA uptake in left BA 46 and the bilateral striatum, and between the visuospatial factor and {sup 18}F-DOPA uptake in the left ACC and bilateral striatum. No correlations were found between {sup 18}F-DOPA uptake and either the verbal memory factor or the abstraction-working memory factor. These data clarify the role of the mesocortical dopaminergic pathways in cognitive function in early PD, highlighting the medial frontal lobe, anterior cingulate, and left BA 46 as the main sites of cortical correlation with executive and language functions. (orig.)

  15. Volumetric assessment of recurrent or progressive gliomas: comparison between F-DOPA PET and perfusion-weighted MRI

    Energy Technology Data Exchange (ETDEWEB)

    Cicone, Francesco [Sant' Andrea Hospital, Rome (Italy). Unit of Nuclear Medicine; Rome Sapienza Univ. (Italy). Dept. of Surgical and Medical Sciences and tranlational Medicine; Research Centre Juelich (Germany). Inst. of Neureoscience and Medicine; Filss, Christian P.; Langen, Karl-Josef [Research Centre Juelich (Germany). Inst. of Neureoscience and Medicine; RWTH Aachen Univ. Hospital (Germany). Dept. of Nuclear Medicine; Minniti, Giuseppe; Scaringi, Claudia [Rome Sapienza Univ. (Italy). Dept. of Surgical and Medical Sciences and tranlational Medicine; Sant' Andrea Hospital, Rome (Italy). Unit of Radiotherapy; Rossi-Espagnet, Camilla; Bozzao, Alessandro [Sant' Andrea Hospital, Rome (Italy). Unit of Neuroradiology; Rome Sapienza Univ. (Italy). Dept. of Neurosciences, Mental Health and Sensory Organs (Ne.S.M.O.S.); Papa, Annalisa; Scopinaro, Francesco [Sant' Andrea Hospital, Rome (Italy). Unit of Nuclear Medicine; Rome Sapienza Univ. (Italy). Dept. of Surgical and Medical Sciences and tranlational Medicine; Galldiks, Norbert [Research Centre Juelich (Germany). Inst. of Neureoscience and Medicine; Cologne Univ. (Germany). Dept. of Neurology; Shah, N. Jon [Research Centre Juelich (Germany). Inst. of Neureoscience and Medicine

    2015-05-01

    To compare the diagnostic information obtained with 6-[{sup 18}F]-fluoro-l-3,4-dihydroxyphenylalanine (F-DOPA) PET and relative cerebral blood volume (rCBV) maps in recurrent or progressive glioma. All patients with recurrent or progressive glioma referred for F-DOPA imaging at our institution between May 2010 and May 2014 were retrospectively included, provided that macroscopic disease was visible on conventional MRI images and that rCBV maps were available for comparison. The final analysis included 50 paired studies (44 patients). After image registration, automatic tumour segmentation of both sets of images was performed using the average signal in a large reference VOI including grey and white matter multiplied by 1.6. Tumour volumes identified by both modalities were compared and their spatial congruence calculated. The distances between F-DOPA uptake and rCBV hot spots, tumour-to-brain ratios (TBRs) and normalized histograms were also computed. On visual inspection, 49 of the 50 F-DOPA and 45 of the 50 rCBV studies were classified as positive. The tumour volume delineated using F-DOPA (F-DOPA{sub vol} {sub 1.6}) greatly exceeded that of rCBV maps (rCBV{sub vol} {sub 1.6}). The median F-DOPA{sub vol} {sub 1.6} and rCBV{sub vol} {sub 1.6} were 11.44 ml (range 0 - 220.95 ml) and 1.04 ml (range 0 - 26.30 ml), respectively (p < 0.00001). Overall, the median overlapping volume was 0.27 ml, resulting in a spatial congruence of 1.38 % (range 0 - 39.22 %). The mean hot spot distance was 27.17 mm (±16.92 mm). F-DOPA uptake TBR was significantly higher than rCBV TBR (1.76 ± 0.60 vs. 1.15 ± 0.52, respectively; p < 0.0001). The histogram analysis showed that F-DOPA provided better separation of tumour from background. In 6 of the 50 studies (12 %), however, physiological uptake in the striatum interfered with tumour delineation. The information provided by F-DOPA PET and rCBV maps are substantially different. Image interpretation is easier and a larger tumour extent

  16. Acute effects of three club drugs on the striatum of rats: Evaluation by quantitative autoradiography with [18F]FDOPA

    International Nuclear Information System (INIS)

    Fang, Chun-Kai; Chen, Hong-Wen; Wang, Wei-Hsun; Liu, Ren-Shen; Hwang, Jeng-Jong

    2013-01-01

    In this work, we used quantitative autoradiography to study the acute effect of cocaine, methamphetamine, and ketamine on the uptake of [ 18 F]FDOPA in the striatum of rats. Drugs were treated 0.5 h before (pre-treated), and 1.5 h after (post-treated) [ 18 F]FDOPA injections, rats were then sacrificed at 2 h post [ 18 F]FDOPA injections to determine the striatum/frontal cortex binding ratios in the striatum. The ratios were lower in the post-treated groups than those of the pre-treated groups, suggesting a net effect of inhibition of trapping of the tracer. The order of uptake inhibition is: ketamine>methamphetamine>cocaine

  17. Ekološki porezi

    OpenAIRE

    Šinković, Zoran

    2013-01-01

    Ekološki porezi uvode se u porezne sustave suvremenih zemalja s ciljem da se njihovom primjenom utječe na ponašanje gospodarskih subjekata i fizičkih osoba. Ekološki porezi trebali bi rezultirati poboljšanjem, odnosno sprečavanjem pogoršanja čovjekova okoliša. Kao instrumenti politike zaštite okoliša imaju tri uloge: ulogu internalizacije eksternih troškova, odgojnu ulogu i ulogu financiranja. Drugim riječima, suvremena politika zaštite okoliša treba ostvariti ciljeve održivog gospodarskog ra...

  18. GMP production of [18F]FDOPA and issues concerning its quality analyses as in USP 'Fluorodopa F 18 Injection'

    International Nuclear Information System (INIS)

    Kao, C.K.; Hsu Wenlin; Xie Hengli; Lin Mingchi; Lan Wenchun; Chao Haoyu

    2011-01-01

    Lately, 6-[ 18 F]fluoro-L-DOPA (FDOPA) has found increase in its clinical demand for whole-body positron emission tomography (PET) scans, and two key issues in fulfilling this demand are the difficulties in producing FDOPA under the recently imposed PET drug good manufacturing practice (GMP) regulations and in providing it in the quality meeting the terms of major compendia. This paper describes the approaches for the GMP production of FDOPA and for the product testing to meet the standard of United States Pharmacopeia (USP) 'Fluorodopa F 18 Injection.' FDOPA was produced by the carrier-added electrophilic aromatic substitution reaction in the facility complying Pharmaceutical Inspection Cooperation Scheme clean room standard. The special aseptic handling technique was applied to minimize the bioburden. The product quality control followed all testing items and procedures, including three different settings of high performance liquid chromatography (HPLC). The process yielded FDOPA average 2.60±0.26 GBq (N=22) in every batch. All qualities of the product were within the specifications described in the USP 'Fluorodopa F 18 Injection.' The entire production was audited by the government authority and certified to comply with the latest PET drug GMP regulation. Our efforts in producing FDOPA following all aspects of GMP requirements have resulted in a product with the USP quality and certified as GMP complied. The routine production yields enough doses for three to four whole-body scans in each batch. The issues discussed in the report provide good reference for producers planning in routine production for PET drugs that are not commonly produced or with complicated compendial quality control tests. (author)

  19. {sup 18}F-DOPA PET/CT in the diagnosis and localization of persistent medullary thyroid carcinoma

    Energy Technology Data Exchange (ETDEWEB)

    Archier, Aurelien; Mundler, Olivier [Aix-Marseille University, Department of Nuclear Medicine, La Timone University Hospital, Marseille (France); Aix-Marseille University, European Center for Research in Medical Imaging, Marseille (France); Heimburger, Celine [University Hospitals of Strasbourg, Department of Biophysics and Nuclear Medicine, Strasbourg (France); Guerin, Carole; Palazzo, Fausto F.; Henry, Jean-Francois; Sebag, Frederic [Aix-Marseille University, Department of Endocrine Surgery, Conception Hospital, Marseille (France); Morange, Isabelle [Aix-Marseille University, Department of Endocrinology, Conception Hospital, Marseille (France); Schneegans, Olivier [Paul Strauss Cancer Center, Department of Nuclear Medicine, Strasbourg (France); Abdullah, Ahmad Esmaeel [Aix-Marseille University, Department of Nuclear Medicine, La Timone University Hospital, Marseille (France); Imperiale, Alessio [University Hospitals of Strasbourg, Department of Biophysics and Nuclear Medicine, Strasbourg (France); ICube, UMR 7357 University of Strasbourg/CNRS and FMTS, Faculty of Medicine, Strasbourg (France); Taieb, David [Aix-Marseille University, Department of Nuclear Medicine, La Timone University Hospital, Marseille (France); Aix-Marseille University, European Center for Research in Medical Imaging, Marseille (France); Institut Paoli-Calmettes, Inserm UMR1068 Marseille Cancerology Research Center, Marseille (France)

    2016-06-15

    To evaluate the performance of {sup 18}F-l-dihydroxyphenylalanine ({sup 18}F-DOPA) PET/CT in the detection of locoregional and distant medullary thyroid carcinoma (MTC) metastases and to compare imaging findings with histological data. We retrospectively evaluated 86 MTC patients with persistently high serum calcitonin levels after initial surgery who had undergone {sup 18}F-DOPA PET/CT between January 2007 and December 2014 in two referral centres. They were followed up for at least 6 months after the PET/CT assessment. The results were compared with histological data or with the findings obtained during follow-up using a complementary imaging modality. {sup 18}F-DOPA PET/CT was positive in 65 of the 86 patients, corresponding to a patient-based sensitivity of 75.6 %. Distant metastatic disease (M1) was seen in 29 patients including 11 with previously unknown metastases revealed only by PET/CT. Among the 36 patients without distant metastatic spread, 25 had nodal involvement limited to the neck, and 10 of these 25 patients underwent reoperation. The lymph node compartment-based sensitivity of {sup 18}F-DOPA PET/CT was 100 % in the two institutions but lesion-based sensitivity was only 24 %. Preoperative and postoperative median calcitonin levels were 405 pg/mL (range 128 - 1,960 pg/mL) and 259 pg/mL (range 33 - 1,516 pg/mL), respectively. None of the patients achieved normalization of serum calcitonin after reoperation. {sup 18}F-DOPA PET/CT enables early diagnosis of a significant number of patients with distant metastasis. It has a limited sensitivity in the detection of residual disease but provides high performance for regional analysis. A surgical compartment-oriented approach could be the approach of choice whatever the number of nodes revealed by {sup 18}F-DOPA PET/CT. (orig.)

  20. 18F-DOPA PET/CT in the diagnosis and localization of persistent medullary thyroid carcinoma

    International Nuclear Information System (INIS)

    Archier, Aurelien; Mundler, Olivier; Heimburger, Celine; Guerin, Carole; Palazzo, Fausto F.; Henry, Jean-Francois; Sebag, Frederic; Morange, Isabelle; Schneegans, Olivier; Abdullah, Ahmad Esmaeel; Imperiale, Alessio; Taieb, David

    2016-01-01

    To evaluate the performance of 18 F-l-dihydroxyphenylalanine ( 18 F-DOPA) PET/CT in the detection of locoregional and distant medullary thyroid carcinoma (MTC) metastases and to compare imaging findings with histological data. We retrospectively evaluated 86 MTC patients with persistently high serum calcitonin levels after initial surgery who had undergone 18 F-DOPA PET/CT between January 2007 and December 2014 in two referral centres. They were followed up for at least 6 months after the PET/CT assessment. The results were compared with histological data or with the findings obtained during follow-up using a complementary imaging modality. 18 F-DOPA PET/CT was positive in 65 of the 86 patients, corresponding to a patient-based sensitivity of 75.6 %. Distant metastatic disease (M1) was seen in 29 patients including 11 with previously unknown metastases revealed only by PET/CT. Among the 36 patients without distant metastatic spread, 25 had nodal involvement limited to the neck, and 10 of these 25 patients underwent reoperation. The lymph node compartment-based sensitivity of 18 F-DOPA PET/CT was 100 % in the two institutions but lesion-based sensitivity was only 24 %. Preoperative and postoperative median calcitonin levels were 405 pg/mL (range 128 - 1,960 pg/mL) and 259 pg/mL (range 33 - 1,516 pg/mL), respectively. None of the patients achieved normalization of serum calcitonin after reoperation. 18 F-DOPA PET/CT enables early diagnosis of a significant number of patients with distant metastasis. It has a limited sensitivity in the detection of residual disease but provides high performance for regional analysis. A surgical compartment-oriented approach could be the approach of choice whatever the number of nodes revealed by 18 F-DOPA PET/CT. (orig.)

  1. Intraindividual comparison of 68Ga-DOTA-TATE and 18F-DOPA PET in patients with well-differentiated metastatic neuroendocrine tumours

    International Nuclear Information System (INIS)

    Haug, Alexander; Auernhammer, Christoph J.; Goeke, Burkhard; Waengler, Bjoern; Tiling, Reinhold; Bartenstein, Peter; Poepperl, Gabriele; Schmidt, Gerwin

    2009-01-01

    To compare the diagnostic impact of 68 Ga-DOTA-TATE and 18 F-DOPA PET in the diagnosis of well-differentiated metastatic neuroendocrine tumours (NET). PET/CT using both 68 Ga-DOTA-TATE and 18 F-DOPA was performed in 25 patients with histologically proven metastatic NET (nine gut, five pancreas, six lung, one paranasal sinus, four with unknown primary). Analyses of PET examinations were patient-based (pathological uptake: yes/no), and based on tumour regions (primary tumour if present and metastases of liver, lung, bones and lymph nodes). The results were compared with the results of contrast enhanced CT, and with plasma serotonin levels, which were available in 24 of the 25 patients. Patient-based sensitivities were 96% for 68 Ga-DOTA-TATE PET and 56% for 18 F-DOPA PET. 68 Ga-DOTA-TATE PET delineated metastases in 54 of 55 positive metastatic tumour regions in contrast to 29 of 55 delineated by 18 F-DOPA PET. Overall, 68 Ga-DOTA-TATE was superior to 18 F-DOPA in 13 patients (two patients showed fewer positive tumour regions with 18 F-DOPA PET). The results were comparable in 12 patients. In 13 of 24 patients, plasma serotonin levels were elevated, and 11 of these 13 patients showed pathological uptake of 18 F-DOPA. Of the 11 patients with normal levels of serotonin, 3 also showed positive 18 F-DOPA uptake. In patients positive for 18 F-DOPA uptake the maximum tumour SUVs were correlated with the levels of serotonin (r=0.66, p=0.01). In this study 68 Ga-DOTA-TATE PET proved clearly superior to 18 F-DOPA PET for detection and staging of NET. 18 F-DOPA uptake tended to be increased in those patients with elevated plasma serotonin. We conclude that 18 F-DOPA PET should be employed in patients with NET with negative 68 Ga-DOTA-TATE PET and elevated plasma serotonin. (orig.)

  2. Factors affecting ¹⁸F FDOPA standardized uptake value in patients with primary brain tumors after treatment.

    Science.gov (United States)

    Chiaravalloti, Agostino; Fiorentini, Alessandro; Villani, Veronica; Carapella, Carmine; Pace, Andrea; Di Pietro, Barbara; Di Russo, Carmen; Palumbo, Barbara; Floris, Roberto; Schillaci, Orazio

    2015-04-01

    To investigate the factors affecting (18)F FDOPA uptake in patients with primary brain tumors (PBT) after treatment. 97 patients with PBT (6 were grade I, 40 were grade II, 29 were grade III and 22 were grade IV) underwent (18)F FDOPA positron emission tomography/computed tomography (PET/CT) after treatment. Intervals from surgery, chemotherapy (CHT) and radiotherapy (RT) were 41.48 (±42.27), 16.04 (±29.08) and 28.62 (±34.49) months respectively. (18)F FDOPA uptake in the site of recurrence was not related to the interval from surgery and CHT while a significant relationship has been found with the interval from RT and tumor grade. The results of our study show that the interval from RT and the grade of PBT should be considered carefully when evaluating brain PET/CT scans since these factors could directly affect (18)F FDOPA uptake. Copyright © 2015 Elsevier Inc. All rights reserved.

  3. Quantitative {sup 18}F-DOPA PET/CT in pheochromocytoma. The relationship between tumor secretion and its biochemical phenotype

    Energy Technology Data Exchange (ETDEWEB)

    Amodru, Vincent; Brue, Thierry; Castinetti, Frederic [Aix-Marseille University, Department of Endocrinology, Conception University Hospital, Marseille (France); Guerin, Carole; Sebag, Frederic [Aix-Marseille University, Department of Endocrine Surgery, Conception University Hospital, Marseille (France); Delcourt, Sarkis; Taieb, David [Aix-Marseille University, Department of Nuclear Medicine, La Timone University Hospital, European Center for Research in Medical Imaging, Marseille (France); Romanet, Pauline [Aix-Marseille University, Laboratory of Molecular Biology, Conception Hospital and CNRS, CRN2M UMR 7286, Marseille (France); Loundou, Anderson [Aix-Marseille University, Department of Public Health, EA3279 Self-perceived Health Assessment Research Unit, La Timone University, Marseille (France); Viana, Bruna; Pacak, Karel [National Institutes of Health, Section on Medical Neuroendocrinology, Eunice Kennedy Shriver National Institute of Child Health and Human Development, Bethesda, MD (United States)

    2018-02-15

    {sup 18}F-FDOPA illustrates the properties of uptake and storage of catecholamines in pheochromocytomas (PHEOs). Until now, the relationship between {sup 18}F-FDOPA quantitative parameters and a PHEO secretory profile has not been specifically evaluated. Fifty-six patients (56% females, median age: 47.5 yrs) with non-metastatic PHEO, evaluated by {sup 18}F-FDOPA PET/CT, were included in this retrospective study. Forty-five patients had negative genetic testing (80.4%); five patients (8.9%) had RET, two patients (3.6%) had SDHB, two had SDHD (3.6%), one patient (1.8%) had NF1, and one patient had a VHL (1.8%) mutation. Correlation between {sup 18}F-FDOPA metabolic parameters (tumor SUVmax, tumor SUVmean, tumor SUVmax/liver SUVmax, MTV 42%, total lesion uptake), urinary metanephrines (MNs), and plasma chromogranin A (CgA) were evaluated. All patients had positive {sup 18}F-FDOPA PET/CT. On univariate analysis, there was a strong correlation between all metabolic parameters and urinary MNs and plasma chromogranin A (CgA). The highest correlations were observed between total lesion (TL) uptake and the value of urinary MNs regardless of their nature (p = 8.10{sup -15} and r = 0.80) and between MTV 42% and plasma CgA levels (p = 2.10{sup -9}, r = 0.74). On multivariate analysis, the correlation of uptake parameters and CgA levels did not persist further due to the relation of CgA and tumor diameter. A correlation between TL uptake and the normetanephrine/metanephrine ratio (NMN/MN) was also found, a finding that was in accordance with in vitro studies, which were found to have a higher catecholamine content in epinephrine producing PHEOs. This retrospective study shows a correlation between {sup 18}F-FDOPA uptake, especially using TL uptake, urinary MNs, and a PHEO biochemical phenotype. This illustrates that beyond its localization value, {sup 18}F-FDOPA PET further enables PHEO characterization at a specific metabolic level. (orig.)

  4. 18F-DOPA PET and enhanced CT imaging for congenital hyperinsulinism: initial UK experience from a technologist's perspective.

    Science.gov (United States)

    Meintjes, Marguerite; Endozo, Raymond; Dickson, John; Erlandsson, Kjel; Hussain, Khalid; Townsend, Caroline; Menezes, Leon; Bomanji, Jamshed

    2013-06-01

    Congenital hyperinsulinism (CHI) is the most common cause of persistent hypoglycaemia in infants and children. Histologically, there are two subgroups, diffuse and focal. The aim of this study was to evaluate the accuracy of (18)F-fluoro-L-dihydroxyphenylalanine ((18)F-DOPA) PET/computed tomography (CT) and contrast-enhanced CT in distinguishing between focal and diffuse lesions in infants with CHI who are unresponsive to medical therapy. In addition, this paper describes the detailed protocol used for imaging and analysis of (18)F-DOPA PET/CT images in our clinical practice. Twenty-two (18)F-DOPA PET/CT and contrast-enhanced CT imaging studies were carried out on 18 consecutive patients (nine boys and nine girls) with CHI (median age, 2 years and 1 month; range, 1-84 months) who had positive dominant ABCC8 mutation genetic results or negative ABCC8/t results but did not respond to first-line medical therapy with high-dose diazoxide. (18)F-DOPA was produced by the cyclotron unit of Woolfson Molecular Imaging Centre, Manchester, and transported to our centre in central London after synthesis and implementation of quality control measures. (18)F-DOPA was administered intravenously at a dose of 4 MBq/kg, and iodine contrast medium was injected intravenously at a dose of 1.5 ml/kg. Single bed position PET/CT images of the pancreas were acquired under light sedation with oral chloral hydrate. Four PET dynamic data acquisition scans were taken 20, 40, 50 and 60 min after injection for a duration of 10 min each. The results were assessed by visual interpretation and quantitative measurements of standardized uptake values (SUVs) in the head, body, and tail of the pancreas. Of the 18 patients, 13 showed diffuse and five showed focal (18)F-DOPA PET pancreatic uptake. Three regions of interest were drawn over the head, body and tail of the pancreas to calculate the SUV(max). Using the formula - highest SUV(max)/next highest SUV(max) - a ratio was calculated. Five patients had

  5. Estimation of patient dose in 18 F-FDG and 18 F-FDOPA PET/CT examinations

    Directory of Open Access Journals (Sweden)

    Aruna Kaushik

    2013-01-01

    Full Text Available Purpose: To estimate specific organ and effective doses to patients resulting from the 18 F-FDG ( 18 F-2-deoxy-D-glucose and 18 F-FDOPA (6-fluoro-( 18 F-L-3, 4-dihydroxyphenylalanine PET/CT examinations for whole body and brain. Materials and Methods: Three protocols for whole body and three for brain PET/CT were used. The CTDI values were measured using standard head and body CT phantoms and also computed using a software CT-Expo for dose evaluation from the CT component. OLINDA software based on MIRD method was used for estimating doses from the PET component of the PET/CT examination. Results: The organ doses from 18 F-FDG and 18 F-FDOPA whole body and brain PET/CT studies were estimated. The total effective dose from a typical protocol of whole body PET/CT examination was 14.4 mSv for females and 11.8 mSv for male patients from 18 F-FDG, whereas it was 11 mSv for female and 9.1 mSv for male patients from 18 F-FDOPA. The total effective doses from a typical protocol for PET/CT studies of brain was 6.5 mSv for females and 5.1 mSv for males from 18 F-FDG whereas it was 3.7 mSv for females and 2.8 mSv for males from 18 F-FDOPA. Conclusions: The effective radiation doses from whole body PET/CT examination was approximately 4-8 times higher than the background radiation dose from both 18 F-FDG and 18 F-FDOPA scans, while it was 1-3 times the background radiation dose from PET/CT scans of brain.

  6. 18F-FDOPA PET-CT vs 99mTc-GHA SPECT-CT in evaluation of recurrent brain gliomas

    International Nuclear Information System (INIS)

    Karunanithi, Sellam; Bal, C.; Malhotra, A.; Kumar, Abhishek; Bandopadhyay, G.P.; Gupta, D.

    2010-01-01

    Full text: Purpose of this study was to compare the role of 18 F-FDOPA PET-CT(FDOPA) and 99m Tc-GHA SPECT-CT (GHA) in detecting recurrence in glioma patients. Materials and Methods: Thirty patients of clinically suspected recurrent glioma of varying grades (ten with low grade and twenty with high grade primary tumor), previously treated with surgery and/or radiotherapy were evaluated using FDOPA and GHA. FDOPA images were interpreted positive for any abnormal tracer uptake noted in brain parenchyma. GHA images were interpreted as positive for abnormal tracer uptake noted in brain parenchyma. Final outcome was judged on the basis of biopsy report and/or clinical follow-up and serial MRI/MR spectroscopy imaging results. Results: Twenty- three patients were considered positive (death in 5, biopsy in 2, clinical progression in 6 and progression on imaging in 10) while 7 were negative for recurrence. FDOPA scan was positive in 22, negative in 8 patients. GHA was positive in 21, negative in 9 patients. Sensitivity, specificity, PPV and NPV of FDOPA were 95.6%, 100%, 100% and 87.5%, respectively. Sensitivity, specificity, PPV and NPV of GHA were 82.6%, 71.4%, 90.4% and 55.5%, respectively. Conclusions: FDOPA has the highest detection rate for recurrent glioma irrespective of the grade. FDOPA was found to be superior especially in detecting low grade viable gliomas. GHA, however due to high occurrence of false-positive results, prospective differentiation of recurrent tumor from treatment-induced changes is not possible in most patients

  7. Accuracy of F-DOPA PET and perfusion-MRI for differentiating radionecrotic from progressive brain metastases after radiosurgery

    Energy Technology Data Exchange (ETDEWEB)

    Cicone, Francesco; Papa, Annalisa; Scopinaro, Francesco [Sant' Andrea Hospital, Rome (Italy). Unit of Nuclear Medicine; ' ' Sapienza' ' Univ., Rome (Italy). Dept. of Surgical and Medicine Sciences and Translational Medicine; Minniti, Giuseppe; Scaringi, Claudia; Maurizi Enrici, Riccardo [' ' Sapienza' ' Univ., Rome (Italy). Dept. of Surgical and Medicine Sciences and Translational Medicine; Sant' Andrea Hospital, Rome (Italy). Unit of Radiotherapy; Romano, Andrea; Tavanti, Francesca; Bozzao, Alessandro [Sant' Andrea Hospital, Rome (Italy). Unit of Neuroradiology; Rome Univ. (Italy). Dept. of Neurosciences, Mental Health and Sensory Organs (Ne.S.M.O.S.)

    2015-01-15

    We assessed the performance of 6-[{sup 18}F]-fluoro-l-3,4-dihydroxyphenylalanine (F-DOPA) PET for differentiating radionecrosis (RN) from tumour progression (PD) in a population of patients with brain metastases, treated with stereotactic radiosurgery. The accuracy of F-DOPA PET was compared with that of perfusion-weighted magnetic resonance (perfusion-MR). In 42 patients with a total of 50 brain metastases from various primaries F-DOPA PET/CT was performed because of suspected radiological progression at the site of previously irradiated brain metastasis. Several semiquantitative PET parameters were recorded, and their diagnostic accuracy was compared by receiver operating characteristic curve analyses. The diagnosis was established by either surgery or follow-up. A comparison was made between F-DOPA PET and perfusion-MR sequences acquired no more than 3 weeks apart. Definitive outcome was available in 46 of the 50 lesions (20 PD, 26 RN). Of the 46 lesions, 11 were surgically excised while in the remaining 35 lesions the diagnosis was established by radiological and clinical criteria. The best diagnostic performance was obtained using the semiquantitative PET parameter maximum lesion to maximum background uptake ratio (SUVL{sub max}/Bkgr{sub max}). With a cut-off value of 1.59, a sensitivity of 90 % and a specificity of 92.3 % were achieved in differentiating RN from PD lesions (accuracy 91.3 %). Relative cerebral blood volume (rCBV) derived from perfusion-MR was available for comparison in 37 of the 46 metastases. Overall accuracy of rCBV was lower than that of all semiquantitative PET parameters under study. The best differentiating rCBV cut-off value was 2.14; this yielded a sensitivity of 86.7 % and a specificity of 68.2 % (accuracy 75.6 %). F-DOPA PET is a highly accurate tool for differentiating RN from PD brain metastases after stereotactic radiosurgery. In this specific setting, F-DOPA PET seems to perform better than perfusion-MR. (orig.)

  8. Carbidopa and physiological distribution of the 6-L-[{sup 18}F]-fluoro-dihydroxy-phenylalanine ({sup 18}F-DOPA); Carbidopa et biodistribution physiologique de la 6-L-[{sup 18}F]-fluorodihydroxyphenylalanine ({sup 18}F-DOPA)

    Energy Technology Data Exchange (ETDEWEB)

    Detour, J.; Hammer, C.; Lucas, A. [Hopitaux universitaires de Strasbourg, Service de radiopharmacie, 67 (France); Imperiale, A.; Constantinesco, A. [Hopitaux universitaires de Strasbourg, Service de biophysique et medecine nucleaire, 67 (France); Beretz, L. [Hopitaux universitaires de Strasbourg, pole de pharmacie-pharmacologie, 67 (France)

    2010-07-01

    Purpose: The administration of carbidopa, an peripheral inhibitor of decarboxylase DOPA, may be performed prior to a full body PET scan {sup 18}F-DOPA. There is currently no consensus regarding the routine use of this metabolic preparation (200 mg, 100 mg, 2 mg / kg, no pre-medication). Conclusions: The absence of pre-medication clearly increases pancreatic uptake of {sup 18}F-D.O.P.A.. These results suggest to reconsider the metabolic preparation based on carbidopa, particularly in cases of suspected clinico biological forms of diffuse hyper-insulinism (nesidioblastosis). Pre-medication in cases of digestive neuroendocrine tumors should be reconsidered. The dose-dependent effect of pre-medication on the tumor uptake remains to be explored. (N.C.)

  9. FDOPA-(18F: a PET radiopharmaceutical recently registered for diagnostic use in countries of the European Union

    Directory of Open Access Journals (Sweden)

    Yanna-Marina Chevalme

    2007-09-01

    Full Text Available Positron emission tomography (PET and its recent update PET/CT are very effective diagnostic tools for non-invasive imaging of metabolic or functional disorders in target tissues. The clinical usefulness of fluorodeoxyglucose-(18F (FDG has been now widely accepted. Recently, the clinical usefulness of fluoroDOPA-(18F or FDOPA, an aminoacid labelled with the same positron emitter fluorine-18, has been evaluated and recognised in France and subsequently in several EU countries. FDOPA is diagnostic PET agent, which has been used for decades in imaging the loss of dopaminergic neurons in Parkinson's disease, and more recently to detect, stage and restage neuroendocrine tumours and to search for recurrence of viable glioma tissue. The present article summarises the body of evidence that led the French Medicines Agency (AFSSAPS to grant a marketing authorisation to IASOdopa, a commercial preparation of FDOPA. Brief case reports and figures illustrate the diagnostic performance of FDOPA PET or PET/CT in the different settings that are currently approved in oncology.Tomografia por emissão de positrons (PET e sua recente atualização PET/CT são ferramentas de diagnóstico muito eficientes para imagens não invasivas de desordens metabólicas ou funcionais em tecido alvo. A utilidade clínica da fluordesoxiglicose-(18F(FDG tem sido agora largamente aceita. Recentemente, a utilidade clinica de fluoroDOPA-(18F ou FDOPA, um aminoácido marcado com o mesmo emissor de pósitron, flúor-18, tem sido avaliado e reconhecido na França e subsequentemente em alguns países da União Européia. FDOPA é o radiofármaco para diagnóstico em PET, o qual tem sido usado por décadas para obtenção de imagens da perda de neurônios dopaminérgicos na doença de Parkinson e, mais recentemente, para identificar inicialmente o estágio e a reavaliação de tumores neuroendócrinos e para a pesquisa da recorrência de glioma viável. O presente artigo resume o conjunto

  10. Novel use of F-DOPA PET/CT imaging in a child with paraganglioma/pheochromocytoma syndrome

    International Nuclear Information System (INIS)

    Levine, Daniel S.; Nadel, Helen R.; Metzger, Daniel L.; Oviedo, Angelica; Adam, Michael J.; Skarsgard, Erik

    2011-01-01

    We report the use of F-DOPA PET/CT imaging in the evaluation of a teenager with marked hypertension and right pararenal, left adrenal and left para-aortic mass lesions. The use of the modality for this clinical application has not been described previously within the pediatric imaging literature. The value of this technique relative to conventional imaging modalities is discussed and warrants consideration of its use, if available, for evaluating children with suspected paragangliomas/pheochromocytomas. (orig.)

  11. Novel use of F-DOPA PET/CT imaging in a child with paraganglioma/pheochromocytoma syndrome

    Energy Technology Data Exchange (ETDEWEB)

    Levine, Daniel S.; Nadel, Helen R. [University of British Columbia, Department of Radiology and Nuclear Medicine, British Columbia Children' s Hospital, Vancouver (Canada); Metzger, Daniel L. [University of British Columbia, Department of Pediatrics, Division of Endocrinology, British Columbia Children' s Hospital, Vancouver (Canada); Oviedo, Angelica [University of British Columbia, Department of Pathology, British Columbia Children' s Hospital, Vancouver (Canada); Adam, Michael J. [University of British Columbia, Department of PET Chemistry, Tri-University Meson Facility (TRIUMF), Vancouver (Canada); Skarsgard, Erik [University of British Columbia, Department of Surgery, British Columbia Children' s Hospital, Vancouver (Canada)

    2011-10-15

    We report the use of F-DOPA PET/CT imaging in the evaluation of a teenager with marked hypertension and right pararenal, left adrenal and left para-aortic mass lesions. The use of the modality for this clinical application has not been described previously within the pediatric imaging literature. The value of this technique relative to conventional imaging modalities is discussed and warrants consideration of its use, if available, for evaluating children with suspected paragangliomas/pheochromocytomas. (orig.)

  12. Clinical value of {sup 18}F-fluorodihydroxyphenylalanine positron emission tomography/computed tomography ({sup 18}F-DOPA PET/CT) for detecting pheochromocytoma

    Energy Technology Data Exchange (ETDEWEB)

    Luster, Markus; Zeich, Katrin; Glatting, Gerhard; Buck, Andreas K.; Solbach, Christoph; Reske, Sven N. [University of Ulm, Department of Nuclear Medicine, Ulm (Germany); Karges, Wolfram [RWTH Aachen, Division of Endocrinology and Diabetes, Aachen (Germany); Pauls, Sandra [University of Ulm, Department of Radiology, Ulm (Germany); Verburg, Frederik A. [University of Wuerzburg, Department of Nuclear Medicine, Wuerzburg (Germany); Dralle, Henning [University Halle-Wittenberg, Department of General, Visceral and Vascular Surgery, Halle (Germany); Neumaier, Bernd [University of Ulm, Department of Nuclear Medicine, Ulm (Germany); Max-Planck-Institut fuer Neurologische Forschung, Section for Radiochemistry, Cologne (Germany); Mottaghy, Felix M. [University of Ulm, Department of Nuclear Medicine, Ulm (Germany); RWTH Aachen, Department of Nuclear Medicine, Aachen (Germany)

    2010-03-15

    In detecting pheochromocytoma (PHEO), positron emission tomography (PET) with the radiolabelled amine precursor {sup 18}F-fluorodihydroxyphenylalanine ({sup 18}F-DOPA) offers excellent specificity, while computed tomography (CT) provides high sensitivity and ability to localize lesions; therefore, the combination of these modalities could be advantageous in this setting. The aim of this study was to investigate whether combined {sup 18}F-DOPA PET/CT more accurately detects and localizes PHEO lesions than does each modality alone. {sup 18}F-DOPA PET, CT and {sup 18}F-DOPA PET/CT images of 25 consecutive patients undergoing diagnostic scanning of suspected sporadic or multiple endocrine neoplasia type 2 syndrome-associated PHEO were reviewed retrospectively in randomized sequence. Two blinded observers scored the images regarding the likelihood of PHEO being present and localizable. Results were correlated with subsequent clinical history and, when available, histology. Of the 19 lesions detected by all three modalities, PET identified each as positive for PHEO, but was unable to definitively localize 15 of 19 (79%). CT could definitively localize all 19 lesions, but could not definitively diagnose or exclude PHEO in 18 of 19 (95%) lesions. Furthermore, CT falsely identified as negative for PHEO one lesion which was judged to be positive for this tumor by both PET and PET/CT. Only in PET/CT scans were all 19 lesions accurately characterized and localized. On a per-patient basis, the sensitivity of {sup 18}F-DOPA PET/CT for PHEO was 100% and the specificity 88%, with a 100% positive predictive value and an 88% negative predictive value. {sup 18}F-DOPA PET/CT more accurately diagnoses and localizes adrenal and extra-adrenal masses suspicious for PHEO than do {sup 18}F-DOPA PET or CT alone. (orig.)

  13. Clinical value of 18F-fluorodihydroxyphenylalanine positron emission tomography/computed tomography (18F-DOPA PET/CT) for detecting pheochromocytoma

    International Nuclear Information System (INIS)

    Luster, Markus; Zeich, Katrin; Glatting, Gerhard; Buck, Andreas K.; Solbach, Christoph; Reske, Sven N.; Karges, Wolfram; Pauls, Sandra; Verburg, Frederik A.; Dralle, Henning; Neumaier, Bernd; Mottaghy, Felix M.

    2010-01-01

    In detecting pheochromocytoma (PHEO), positron emission tomography (PET) with the radiolabelled amine precursor 18 F-fluorodihydroxyphenylalanine ( 18 F-DOPA) offers excellent specificity, while computed tomography (CT) provides high sensitivity and ability to localize lesions; therefore, the combination of these modalities could be advantageous in this setting. The aim of this study was to investigate whether combined 18 F-DOPA PET/CT more accurately detects and localizes PHEO lesions than does each modality alone. 18 F-DOPA PET, CT and 18 F-DOPA PET/CT images of 25 consecutive patients undergoing diagnostic scanning of suspected sporadic or multiple endocrine neoplasia type 2 syndrome-associated PHEO were reviewed retrospectively in randomized sequence. Two blinded observers scored the images regarding the likelihood of PHEO being present and localizable. Results were correlated with subsequent clinical history and, when available, histology. Of the 19 lesions detected by all three modalities, PET identified each as positive for PHEO, but was unable to definitively localize 15 of 19 (79%). CT could definitively localize all 19 lesions, but could not definitively diagnose or exclude PHEO in 18 of 19 (95%) lesions. Furthermore, CT falsely identified as negative for PHEO one lesion which was judged to be positive for this tumor by both PET and PET/CT. Only in PET/CT scans were all 19 lesions accurately characterized and localized. On a per-patient basis, the sensitivity of 18 F-DOPA PET/CT for PHEO was 100% and the specificity 88%, with a 100% positive predictive value and an 88% negative predictive value. 18 F-DOPA PET/CT more accurately diagnoses and localizes adrenal and extra-adrenal masses suspicious for PHEO than do 18 F-DOPA PET or CT alone. (orig.)

  14. Classification of typical and atypical antipsychotic drugs on the basis of dopamine D-1, D-2 and serotonin2 pKi values.

    Science.gov (United States)

    Meltzer, H Y; Matsubara, S; Lee, J C

    1989-10-01

    The pKi values of 13 reference typical and 7 reference atypical antipsychotic drugs (APDs) for rat striatal dopamine D-1 and D-2 receptor binding sites and cortical serotonin (5-HT2) receptor binding sites were determined. The atypical antipsychotics had significantly lower pKi values for the D-2 but not 5-HT2 binding sites. There was a trend for a lower pKi value for the D-1 binding site for the atypical APD. The 5-HT2 and D-1 pKi values were correlated for the typical APD whereas the 5-HT2 and D-2 pKi values were correlated for the atypical APD. A stepwise discriminant function analysis to determine the independent contribution of each pKi value for a given binding site to the classification as a typical or atypical APD entered the D-2 pKi value first, followed by the 5-HT2 pKi value. The D-1 pKi value was not entered. A discriminant function analysis correctly classified 19 of 20 of these compounds plus 14 of 17 additional test compounds as typical or atypical APD for an overall correct classification rate of 89.2%. The major contributors to the discriminant function were the D-2 and 5-HT2 pKi values. A cluster analysis based only on the 5-HT2/D2 ratio grouped 15 of 17 atypical + one typical APD in one cluster and 19 of 20 typical + two atypical APDs in a second cluster, for an overall correct classification rate of 91.9%. When the stepwise discriminant function was repeated for all 37 compounds, only the D-2 and 5-HT2 pKi values were entered into the discriminant function.(ABSTRACT TRUNCATED AT 250 WORDS)

  15. Head-to-head comparison between {sup 18}F-FDOPA PET/CT and MR/CT angiography in clinically recurrent head and neck paragangliomas

    Energy Technology Data Exchange (ETDEWEB)

    Heimburger, Celine; Hubele, Fabrice; Namer, Izzie Jacques [University Hospitals of Strasbourg, Department of Biophysics and Nuclear Medicine, Strasbourg (France); CNRS/University of Strasbourg, ICube, UMR 7357, Strasbourg (France); University of Strasbourg, FMTS, Faculty of Medicine, Strasbourg (France); Veillon, Francis; Riehm, Sophie; Cavalcanti, Marcela [University Hospitals of Strasbourg, Department of Radiology, Strasbourg (France); Taieb, David [Aix-Marseille University, Department of Nuclear Medicine, La Timone University Hospital, Marseille (France); Aix-Marseille University, European Center for Research in Medical Imaging, Marseille (France); Institut Paoli-Calmettes, Inserm UMR1068 Marseille Cancerology Research Center, Marseille (France); Goichot, Bernard; Chabrier, Gerard [University Hospitals of Strasbourg, Department of Internal Medicine, Strasbourg (France); Petit-Thomas, Julie; Charpiot, Anne [University Hospitals of Strasbourg, Department of Otolaryngology and Maxillofacial Surgery, Strasbourg (France); Averous, Gerlinde [University Hospitals of Strasbourg, Department of Pathology, Strasbourg (France); Imperiale, Alessio [University Hospitals of Strasbourg, Department of Biophysics and Nuclear Medicine, Strasbourg (France); CNRS/University of Strasbourg, ICube, UMR 7357, Strasbourg (France); University of Strasbourg, FMTS, Faculty of Medicine, Strasbourg (France); Hautepierre University Hospital, Biophysics and Nuclear Medicine, Strasbourg Cedex (France)

    2017-06-15

    Head and neck paragangliomas (HNPGLs) can relapse after primary treatment. Optimal imaging protocols have not yet been established for posttreatment evaluation. The aim of the present study was to assess the diagnostic value of {sup 18}F-FDOPA PET/CT and MR/CT angiography (MRA/CTA) in HNPGL patients with clinical relapse during their follow-up. Sixteen consecutive patients presenting with local pain, tinnitus, dysphagia, hoarse voice, cranial nerve involvement, deafness, or retrotympanic mass appearing during follow-up after the initial treatment of HNPGLs were retrospectively evaluated. Patients underwent both {sup 18}F-FDOPA PET/CT and MRA (15 patents) or CTA (1 patent). Both methods were first assessed under blinded conditions and afterwards correlated. Head and neck imaging abnormalities without histological confirmation were considered true-positive results based on a consensus between radiologists and nuclear physicians and on further {sup 18}F-FDOPA PET/CT and/or MRA. {sup 18}F-FDOPA PET/CT and MRA/CTA were concordant in 14 patients and in disagreement in 2 patients. {sup 18}F-FDOPA PET/CT and MRA/CTA identified, respectively, 12 and 10 presumed recurrent HNPGLs in 12 patients. The two lesions diagnosed by PET/CT only were confirmed during follow-up by otoscopic examination and MRA performed 29 and 17 months later. {sup 18}F-FDOPA PET/CT images were only slightly influenced by the posttreatment sequelae, showing a better interobserver reproducibility than MRA/CTA. Finally, in 2 of the 16 studied patients, {sup 18}F-FDOPA PET/CT detected two additional synchronous primary HNPGLs. {sup 18}F-FDOPA PET/CT is highly sensitive in posttreatment evaluation of patients with HNPGLs, and also offers better interobserver reproducibility than MRA/CTA and whole-body examination. We therefore suggest that {sup 18}F-FDOPA PET/CT is performed as the first diagnostic imaging modality in symptomatic patients with suspicion of HNPGL relapse after primary treatment when {sup 68

  16. A retrospective comparison between 68Ga-DOTA-TOC PET/CT and 18F-DOPA PET/CT in patients with extra-adrenal paraganglioma

    International Nuclear Information System (INIS)

    Kroiss, Alexander; Putzer, Daniel; Decristoforo, Clemens; Uprimny, Christian; Virgolini, Irene Johanna; Frech, Andreas; Fraedrich, Gustav; Gasser, Rudolf Wolfgang; Shulkin, Barry Lynn; Url, Christoph; Widmann, Gerlig; Prommegger, Rupert; Sprinzl, Georg Mathias

    2013-01-01

    18 F-Fluoro-l-dihydroxyphenylalanine ( 18 F-DOPA) PET offers high sensitivity and specificity in the imaging of nonmetastatic extra-adrenal paragangliomas (PGL) but lower sensitivity in metastatic or multifocal disease. These tumours are of neuroendocrine origin and can be detected by 68 Ga-DOTA-Tyr 3 -octreotide ( 68 Ga-DOTA-TOC) PET. Therefore, we compared 68 Ga-DOTA-TOC and 18 F-DOPA as radiolabels for PET/CT imaging for the diagnosis and staging of extra-adrenal PGL. Combined cross-sectional imaging was the reference standard. A total of 5 men and 15 women (age range 22 to 73 years) with anatomical and/or histologically proven extra-adrenal PGL were included in this study. Of these patients, 5 had metastatic or multifocal lesions and 15 had single sites of disease. Comparative evaluation included morphological imaging with CT and functional imaging with 68 Ga-DOTA-TOC PET and 18 F-DOPA PET. The imaging results were analysed on a per-patient and a per-lesion basis. The maximum standardized uptake value (SUV max ) of each functional imaging modality in concordant tumour lesions was measured. Compared with anatomical imaging, 68 Ga-DOTA-TOC PET and 18 F-DOPA PET each had a per-patient and per-lesion detection rate of 100 % in nonmetastatic extra-adrenal PGL. However, in metastatic or multifocal disease, the per-lesion detection rate of 68 Ga-DOTA-TOC was 100 % and that of 18 F-DOPA PET was 56.0 %. Overall, 68 Ga-DOTA-TOC PET identified 45 lesions; anatomical imaging identified 43 lesions, and 18 F-DOPA PET identified 32 lesions. The overall per-lesion detection rate of 68 Ga-DOTA-TOC PET was 100 % (McNemar, P 18 F-DOPA PET was 71.1 % (McNemar, P max (mean ± SD) of all 32 concordant lesions was 67.9 ± 61.5 for 68 Ga-DOTA-TOC PET and 11.8 ± 7.9 for 18 F-DOPA PET (Mann-Whitney U test, P 68 Ga-DOTA-TOC PET may be superior to 18 F-DOPA PET and diagnostic CT in providing valuable information for pretherapeutic staging of extra-adrenal PGL, particularly in surgically

  17. Head-to-head comparison between "1"8F-FDOPA PET/CT and MR/CT angiography in clinically recurrent head and neck paragangliomas

    International Nuclear Information System (INIS)

    Heimburger, Celine; Hubele, Fabrice; Namer, Izzie Jacques; Veillon, Francis; Riehm, Sophie; Cavalcanti, Marcela; Taieb, David; Goichot, Bernard; Chabrier, Gerard; Petit-Thomas, Julie; Charpiot, Anne; Averous, Gerlinde; Imperiale, Alessio

    2017-01-01

    Head and neck paragangliomas (HNPGLs) can relapse after primary treatment. Optimal imaging protocols have not yet been established for posttreatment evaluation. The aim of the present study was to assess the diagnostic value of "1"8F-FDOPA PET/CT and MR/CT angiography (MRA/CTA) in HNPGL patients with clinical relapse during their follow-up. Sixteen consecutive patients presenting with local pain, tinnitus, dysphagia, hoarse voice, cranial nerve involvement, deafness, or retrotympanic mass appearing during follow-up after the initial treatment of HNPGLs were retrospectively evaluated. Patients underwent both "1"8F-FDOPA PET/CT and MRA (15 patents) or CTA (1 patent). Both methods were first assessed under blinded conditions and afterwards correlated. Head and neck imaging abnormalities without histological confirmation were considered true-positive results based on a consensus between radiologists and nuclear physicians and on further "1"8F-FDOPA PET/CT and/or MRA. "1"8F-FDOPA PET/CT and MRA/CTA were concordant in 14 patients and in disagreement in 2 patients. "1"8F-FDOPA PET/CT and MRA/CTA identified, respectively, 12 and 10 presumed recurrent HNPGLs in 12 patients. The two lesions diagnosed by PET/CT only were confirmed during follow-up by otoscopic examination and MRA performed 29 and 17 months later. "1"8F-FDOPA PET/CT images were only slightly influenced by the posttreatment sequelae, showing a better interobserver reproducibility than MRA/CTA. Finally, in 2 of the 16 studied patients, "1"8F-FDOPA PET/CT detected two additional synchronous primary HNPGLs. "1"8F-FDOPA PET/CT is highly sensitive in posttreatment evaluation of patients with HNPGLs, and also offers better interobserver reproducibility than MRA/CTA and whole-body examination. We therefore suggest that "1"8F-FDOPA PET/CT is performed as the first diagnostic imaging modality in symptomatic patients with suspicion of HNPGL relapse after primary treatment when "6"8Ga-labeled somatostatin analogues are

  18. IDH mutation is paradoxically associated with higher {sup 18}F-FDOPA PET uptake in diffuse grade II and grade III gliomas

    Energy Technology Data Exchange (ETDEWEB)

    Verger, A. [APHM, La Timone Hospital, Department of Nuclear Medicine, Marseille (France); Lorraine University, Department of Nuclear Medicine and Nancyclotep Imaging Platform, CHRU Nancy, Nancy (France); Lorraine University, IADI, INSERM, UMR 947, Nancy (France); Metellus, P. [Centre Hospitalier Prive Clairval, Department of Neurosurgery, Marseille (France); Aix-Marseille University, INSERM, UMR 911, Marseille (France); Sala, Q. [APHM, La Timone Hospital, Department of Nuclear Medicine, Marseille (France); Colin, C. [Aix-Marseille University, INSERM, UMR 911, Marseille (France); Bialecki, E. [Centre Hospitalier Prive Clairval, Department of Neurosurgery, Marseille (France); Taieb, D. [APHM, La Timone Hospital, Department of Nuclear Medicine, Marseille (France); Aix-Marseille University, CERIMED, Marseille (France); Chinot, O. [Aix-Marseille University, INSERM, UMR 911, Marseille (France); APHM, La Timone Hospital, Department of Neuro-Oncology, Marseille (France); Figarella-Branger, D. [Aix-Marseille University, INSERM, UMR 911, Marseille (France); APHM, La Timone Hospital, Department of Anatomopathology, Marseille (France); Guedj, E. [APHM, La Timone Hospital, Department of Nuclear Medicine, Marseille (France); Aix-Marseille University, CERIMED, Marseille (France); Aix-Marseille University, Institut de Neurosciences de la Timone, CNRS, UMR 7289, Marseille (France); Hopital de la Timone, Service Central de Biophysique et Medecine Nucleaire, Marseille (France)

    2017-08-15

    The World Health Organization Classification of Tumors of the Central Nervous System has recently been updated by the integration of diagnostic and prognostic molecular parameters, giving pivotal attention to IDH mutation as a favourable factor. Amino acid PET is increasingly used in the management of gliomas, but its prognostic value is a matter of debate. The aim of this study was to assess the relationship between IDH mutation and {sup 18}F-FDOPA uptake on PET in newly diagnosed gliomas. A total of 43 patients, presenting with diffuse astrocytic and oligodendroglial grade II and III gliomas, reclassified according to the 2016 WHO classification of tumours of the CNS, were retrospectively included. They had all undergone {sup 18}F-FDOPA PET at an initial stage before surgery and histological diagnosis. {sup 18}F-FDOPA uptake values were compared between patients with and without IDH mutation in terms of maximum standardized uptake value (SUVmax) ratios between tumour and normal contralateral brain (T/N), and between tumour and striatum (T/S). Patients with IDH mutation showed higher {sup 18}F-FDOPA T/N SUVmax ratios (1.6 vs. 1.2) and T/S SUVmax ratios (0.9 vs. 0.6) than patients without IDH mutation (p < 0.05). This study showed paradoxically higher {sup 18}F-FDOPA uptake in diffuse grade II and III gliomas with IDH mutation. Despite evident interest in the management of gliomas, and especially in relation to posttherapy evaluation, our findings raise the question of the prognostic value of {sup 18}F-FDOPA uptake on PET uptake in this group of patients. This may be related to differences in amino acid integration, metabolism, or cell differentiation. (orig.)

  19. Ki67 and proliferation in breast cancer.

    Science.gov (United States)

    Pathmanathan, Nirmala; Balleine, Rosemary L

    2013-06-01

    New approaches to the prognostic assessment of breast cancer have come from molecular profiling studies. A major feature of this work has been to emphasise the importance of cancer cell proliferation as a key discriminative indicator of recurrence risk for oestrogen receptor positive breast cancer in particular. Mitotic count scoring, as a component of histopathological grade, has long formed part of a routine evaluation of breast cancer biology. However, there is an increasingly compelling case to include a specific proliferation score in breast cancer pathology reports based on expression of the cell cycle regulated protein Ki67. Immunohistochemical staining for Ki67 is a widely available and economical test with good tolerance of pre-analytical variations and staining conditions. However, there is currently no evidence based protocol established to derive a reliable and informative Ki67 score for routine clinical use. In this circumstance, pathologists must establish a standardised framework for scoring Ki67 and communicating results to a multidisciplinary team.

  20. A retrospective comparison between 68Ga-DOTA-TOC PET/CT and 18F-DOPA PET/CT in patients with extra-adrenal paraganglioma.

    Science.gov (United States)

    Kroiss, Alexander; Putzer, Daniel; Frech, Andreas; Decristoforo, Clemens; Uprimny, Christian; Gasser, Rudolf Wolfgang; Shulkin, Barry Lynn; Url, Christoph; Widmann, Gerlig; Prommegger, Rupert; Sprinzl, Georg Mathias; Fraedrich, Gustav; Virgolini, Irene Johanna

    2013-12-01

    (18)F-Fluoro-L-dihydroxyphenylalanine ((18)F-DOPA) PET offers high sensitivity and specificity in the imaging of nonmetastatic extra-adrenal paragangliomas (PGL) but lower sensitivity in metastatic or multifocal disease. These tumours are of neuroendocrine origin and can be detected by (68)Ga-DOTA-Tyr(3)-octreotide ((68)Ga-DOTA-TOC) PET. Therefore, we compared (68)Ga-DOTA-TOC and (18)F-DOPA as radiolabels for PET/CT imaging for the diagnosis and staging of extra-adrenal PGL. Combined cross-sectional imaging was the reference standard. A total of 5 men and 15 women (age range 22 to 73 years) with anatomical and/or histologically proven extra-adrenal PGL were included in this study. Of these patients, 5 had metastatic or multifocal lesions and 15 had single sites of disease. Comparative evaluation included morphological imaging with CT and functional imaging with (68)Ga-DOTA-TOC PET and (18)F-DOPA PET. The imaging results were analysed on a per-patient and a per-lesion basis. The maximum standardized uptake value (SUVmax) of each functional imaging modality in concordant tumour lesions was measured. Compared with anatomical imaging, (68)Ga-DOTA-TOC PET and (18)F-DOPA PET each had a per-patient and per-lesion detection rate of 100% in nonmetastatic extra-adrenal PGL. However, in metastatic or multifocal disease, the per-lesion detection rate of (68)Ga-DOTA-TOC was 100% and that of (18)F-DOPA PET was 56.0%. Overall, (68)Ga-DOTA-TOC PET identified 45 lesions; anatomical imaging identified 43 lesions, and (18)F-DOPA PET identified 32 lesions. The overall per-lesion detection rate of (68)Ga-DOTA-TOC PET was 100% (McNemar, P TOC PET and 11.8 ± 7.9 for (18)F-DOPA PET (Mann-Whitney U test, P TOC PET may be superior to (18)F-DOPA PET and diagnostic CT in providing valuable information for pretherapeutic staging of extra-adrenal PGL, particularly in surgically inoperable tumours and metastatic or multifocal disease.

  1. Prognostic value of {sup 18}F-DOPA PET/CT at the time of recurrence in patients affected by neuroblastoma

    Energy Technology Data Exchange (ETDEWEB)

    Piccardo, Arnoldo [Galliera Hospital, Nuclear Medicine Unit, Genoa (Italy); E.O. Ospedali Galliera, Department of Nuclear Medicine, Genoa (Italy); Puntoni, Matteo [Galliera Hospital, Clinical Trial Research Unit, Genoa (Italy); Lopci, Egesta; Fanti, Stefano [Sant' Orsola-Malpighi Hospital, Nuclear Medicine Unit, Bologna (Italy); Conte, Massimo; Sorrentino, Stefania; Garaventa, Alberto [G. Gaslini Children' s Hospital, Department of Hematology-Oncology, Genoa (Italy); Foppiani, Luca [Galliera Hospital, Internal Medicine, Genoa (Italy); Morana, Giovanni [G. Gaslini Children' s Hospital, Department of Pathology and Radiology, Genoa (Italy); Naseri, Mehrdad; Villavecchia, Giampiero [Galliera Hospital, Nuclear Medicine Unit, Genoa (Italy); Cistaro, Angelina [IRMET, PET Centre, Turin (Italy)

    2014-06-15

    The aim of this study was to investigate the relationship between {sup 123}I-metaiodobenzylguanidine (MIBG) scan semi-quantification and a new {sup 18}F-DOPA positron emission tomography (PET)/CT score in patients with suspected or documented neuroblastoma (NB) relapse and to assess the association between these two parameters and progression-free survival (PFS)/overall survival (OS). We analysed 24 NB patients who had undergone {sup 123}I-MIBG and {sup 18}F-DOPA PET/CT scans at the time of suspected relapse, after applying a proper scoring system for each scan. In time-to-event analyses, the score distributions were regarded as continuous and were categorized in tertiles and medians. We used Kaplan-Meier curves and Cox proportional hazard models for PFS and OS in order to estimate the independent prognostic impact of {sup 123}I-MIBG and {sup 18}F-DOPA PET/CT scans. The {sup 123}I-MIBG and {sup 18}F-DOPA scores were highly and positively correlated (Spearman's rho = 0.8, p < 0.001). Over a median follow-up of 14 months (range 6-82), 12 cases of disease progression and 6 deaths occurred. Multivariate Cox models showed a higher risk of disease progression [hazard ratio (HR) 17.0, 95 % confidence interval (CI) 2.7-109] in NB patients with {sup 123}I-MIBG score > 3 (3rd tertile) and an even higher risk (HR:37.2, 95 % CI 2.4-574) in those with {sup 18}F-DOPA whole-body metabolic burden (WBMB) >7.5 (median), after adjustment for all main clinical/pathological factors considered. Kaplan-Meier analyses showed a significant association with OS (log-rank p = 0.01 and p = 0.03 for {sup 123}I-MIBG and {sup 18}F-DOPA WBMB, respectively). Our results confirm the good agreement between {sup 18}F-DOPA PET/CT and {sup 123}I-MIBG scan in patients affected by NB relapse. In time-to-event analyses, {sup 123}I-MIBG scan and {sup 18}F-DOPA PET/CT scores were independently and significantly associated with disease progression. (orig.)

  2. LibKiSAO: a Java library for Querying KiSAO.

    Science.gov (United States)

    Zhukova, Anna; Adams, Richard; Laibe, Camille; Le Novère, Nicolas

    2012-09-24

    The Kinetic Simulation Algorithm Ontology (KiSAO) supplies information about existing algorithms available for the simulation of Systems Biology models, their characteristics, parameters and inter-relationships. KiSAO enables the unambiguous identification of algorithms from simulation descriptions. Information about analogous methods having similar characteristics and about algorithm parameters incorporated into KiSAO is desirable for simulation tools. To retrieve this information programmatically an application programming interface (API) for KiSAO is needed. We developed libKiSAO, a Java library to enable querying of the KiSA Ontology. It implements methods to retrieve information about simulation algorithms stored in KiSAO, their characteristics and parameters, and methods to query the algorithm hierarchy and search for similar algorithms providing comparable results for the same simulation set-up. Using libKiSAO, simulation tools can make logical inferences based on this knowledge and choose the most appropriate algorithm to perform a simulation. LibKiSAO also enables simulation tools to handle a wider range of simulation descriptions by determining which of the available methods are similar and can be used instead of the one indicated in the simulation description if that one is not implemented. LibKiSAO enables Java applications to easily access information about simulation algorithms, their characteristics and parameters stored in the OWL-encoded Kinetic Simulation Algorithm Ontology. LibKiSAO can be used by simulation description editors and simulation tools to improve reproducibility of computational simulation tasks and facilitate model re-use.

  3. Application of 18F-FDOPA PET imaging in gliomas%18F-FDOPA PET显像在脑胶质瘤中的临床应用价值

    Institute of Scientific and Technical Information of China (English)

    葛璟洁; 张政伟; 陆秀宏(综述); 管一晖(审校)

    2016-01-01

    脑胶质瘤是发病率最高的神经系统来源肿瘤。目前临床上诊断胶质瘤的方法主要为MRI平扫及增强,但存在一定的局限性。近年来,随着PET与核素显像剂的不断发展和改进,其在胶质瘤领域的研究越来越深入,尤其是18F-FDOPA PET显像在原发性及复发性胶质瘤的诊断、鉴别、分级、定位、治疗和预后评估中具有较高的临床应用价值。本文就此进行综述。%Glioma is one of the most common neurologically originated tumor. Although MRI scanning is the major approach to make diagnosis of glioma at present, it still has some limitations. With the development and improvement of positron emission tomography imaging techniques and radionuclide agents, PET imaging such as 18F-FDOPA PET imaging has played a more and more important role in the diagnosis, discrimination, grading, localization and prognosis evaluation of primary and recurrent gliomas. The present paper summarizes the research progress in this ifeld.

  4. Characterization of glial tumors in PET/CT 18F-dopa and in perfusion MRI

    International Nuclear Information System (INIS)

    Nioche, Christophe

    2011-01-01

    MRI provides morphological information about a tumour, as well as information regarding its micro-vascularisation of the tumour. In PET/CT, accumulation of 18 F-Dopa in tumour cells results from the metabolic activity greater than that of healthy tissues.We studied 28 gliomas for which we analysed data from MRI and PET/CT. A registration method has been developed to combine information from both PET and MRI and to extract volumes of interest consistent with the information included in the two modalities. In these volumes, the tumour compartment and normal tissue compartment were identified using a Gaussian mixture model. Parameters from PET or MRI data were then calculated in these compartments. ROC analyses combined with linear discriminant analyses were used to assess whether joint observation of standardized uptake value (SUVmax) and relative Cerebral Blood Volume (rCBV) or of relative rk1 and rCBV could distinguish between low grade and high grade tumours. We found that using this joint analysis, 82% of high-grade tumors and 70% of low grade tumors were correctly classified (AUC of 0.88 for [SUVmax, rCBV] and of 0.92 for [rk1, rCBV]). Considering the combined information from [SUVmax, rCBV], the sensitivity for detecting high-grade tumors was 95% with a specificity of 60%. The negative predictive value was 52% for a positive predictive value of 95%. Similarly, considering the combined information from [rk1, rCBV], we also obtain a specificity of 60% associated with a 95% sensitivity for detecting high-grade tumors, with a negative predictive value of 60% and positive predictive value of 95%. Our work shows that joint analysis of information from microvascular and metabolic is possible by combining PET and MR imaging data. However, we found that, in our patient population, the microvascular information obtained through MR did not achieve better discrimination than the metabolic information derived from PET only. (author)

  5. Quantification of [18F]FDOPA and [18F]-3-OMFD in pig serum - a new TLC method in comparison with HPLC

    International Nuclear Information System (INIS)

    Pawelke, B.; Fuechtner, F.; Bergmann, R.; Brust, P.

    2002-01-01

    A novel TLC method for convenient quantification of [ 18 F]FDOPA and [ 18 F]-3-OMFD in routine operation was developed and the results assessed in comparison with an HPLC analysis. The two methods were found to correlate well. [ 18 F]fluoride which resisted determination on HPLC RP-18 columns was also quantified by TLC. (orig.)

  6. 18F-DOPA PET/CT and 68Ga-DOTANOC PET/CT scans as diagnostic tools in focal congenital hyperinsulinism. A blinded evaluation

    International Nuclear Information System (INIS)

    Dahl Christiansen, Charlotte; Helleskov Rasmussen, Annett; Petersen, Henrik; Lerberg Nielsen, Anne; Detlefsen, Soenke; Brusgaard, Klaus; Rasmussen, Lars; Hovendal, Claus; Melikyan, Maria; Ekstroem, Klas; Globa, Evgenia; Christesen, Henrik Thybo

    2018-01-01

    Focal congenital hyperinsulinism (CHI) is curable by surgery, which is why identification of the focal lesion is crucial. We aimed to determine the use of 18F-fluoro-dihydroxyphenylalanine (18F-DOPA) PET/CT vs. 68Ga-1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic-acid-1-Nal3 -octreotide (68Ga-DOTANOC) PET/CT as diagnostic tools in focal CHI. PET/CT scans of children with CHI admitted to Odense University Hospital between August 2005 and June 2016 were retrospectively evaluated visually and by their maximal standardized uptake values (SUV max ) by two independent examiners, blinded for clinical, surgical and pathological data. Pancreatic histology was used as the gold standard. For patients without surgery, the genetic profile served as the gold standard. Fifty-five CHI patients were examined by PET/CT (18F-DOPA n = 53, 68Ga-DOTANOC n = 18). Surgery was performed in 34 patients, no surgery in 21 patients. Fifty-one patients had a classifiable outcome, either by histology (n = 33, 22 focal lesions, 11 non-focal) or by genetics (n = 18, all non-focal). The predictive performance of 18F-DOPA PET/CT to identify focal CHI was identical by visual- and cut-off-based evaluation: sensitivity (95% CI) of 1 (0.85-1); specificity of 0.96 (0.82-0.99). The optimal 18F-DOPA PET SUV max ratio cut-off was 1.44 and the optimal 68Ga-DOTANOC PET SUV max cut-off was 6.77 g/ml. The area under the receiver operating curve was 0.98 (0.93-1) for 18F-DOPA PET vs. 0.71 (0.43-0.95) for 68Ga-DOTANOC PET (p < 0.03). In patients subjected to surgery, localization of the focal lesion was correct in 91%, and 100%, by 18F-DOPA PET/CT and 68Ga-DOTANOC PET/CT, respectively. 18F-DOPA PET/CT was excellent in predicting focal CHI and superior compared to 68Ga-DOTANOC PET/CT. Further use of 68GA-DOTANOC PET/CT in predicting focal CHI is discouraged. (orig.)

  7. Grading and outcome prediction of pediatric diffuse astrocytic tumors with diffusion and arterial spin labeling perfusion MRI in comparison with 18F-DOPA PET

    Energy Technology Data Exchange (ETDEWEB)

    Morana, Giovanni; Tortora, Domenico; Severino, Mariasavina; Rossi, Andrea [Istituto Giannina Gaslini, Neuroradiology Unit, Genoa (Italy); Piccardo, Arnoldo; Cabria, Manlio [Ente Ospedaliero Ospedali Galliera, Nuclear Medicine Unit, Genoa (Italy); Puntoni, Matteo [Ente Ospedaliero Ospedali Galliera, Clinical Trial Unit, Scientific Directorate, Genoa (Italy); Nozza, Paolo [Istituto Giannina Gaslini, Pathology Unit, Genoa (Italy); Ravegnani, Marcello; Consales, Alessandro; Mascelli, Samantha; Raso, Alessandro [Istituto Giannina Gaslini, Neurosurgery Unit, Genoa (Italy); Verrico, Antonio; Milanaccio, Claudia [Istituto Giannina Gaslini, Neuro-oncology Unit, Genoa (Italy)

    2017-11-15

    The aim of this study was to investigate MRI-derived diffusion weighted imaging (DWI) and arterial spin labeling (ASL) perfusion imaging in comparison with {sup 18}F-dihydroxyphenylalanine (DOPA) PET with respect to diagnostic performance in tumor grading and outcome prediction in pediatric patients with diffuse astrocytic tumors (DAT). We retrospectively analyzed 26 children with histologically proven treatment naive low and high grade DAT who underwent ASL and DWI performed within 2 weeks of {sup 18}F-DOPA PET. Relative ASL-derived cerebral blood flow max (rCBF max) and DWI-derived minimum apparent diffusion coefficient (rADC min) were compared with {sup 18}F-DOPA uptake tumor/normal tissue (T/N) and tumor/striatum (T/S) ratios, and correlated with World Health Organization (WHO) tumor grade and progression-free survival (PFS). Statistics included Pearson's chi-square and Mann-Whitney U tests, Spearman's rank correlation, receiver operating characteristic (ROC) analysis, discriminant function analysis (DFA), Kaplan-Meier survival curve, and Cox analysis. A significant correlation was demonstrated between rCBF max, rADC min, and {sup 18}F-DOPA PET data (p < 0.001). Significant differences in terms of rCBF max, rADC min, and {sup 18}F-DOPA uptake were found between low- and high-grade DAT (p ≤ 0.001). ROC analysis and DFA demonstrated that T/S and T/N values were the best parameters for predicting tumor progression (AUC 0.93, p < 0.001). On univariate analysis, all diagnostic tools correlated with PFS (p ≤ 0.001); however, on multivariate analysis, only {sup 18}F-DOPA uptake remained significantly associated with outcome (p ≤ 0.03), while a trend emerged for rCBF max (p = 0.09) and rADC min (p = 0.08). The combination of MRI and PET data increased the predictive power for prognosticating tumor progression (AUC 0.97, p < 0.001). DWI, ASL and {sup 18}F-DOPA PET provide useful complementary information for pediatric DAT grading. {sup 18}F-DOPA uptake

  8. Comparison between 68Ga-DOTA-NOC and 18F-DOPA PET for the detection of gastro-entero-pancreatic and lung neuro-endocrine tumours

    International Nuclear Information System (INIS)

    Ambrosini, Valentina; Tomassetti, Paola; Castellucci, Paolo; Campana, Davide; Montini, Giancarlo; Rubello, Domenico; Nanni, Cristina; Rizzello, Anna; Franchi, Roberto; Fanti, Stefano

    2008-01-01

    18 F-FDG positron emission tomography (PET) value for the assessment of neuro-endocrine tumours (NET) is limited. Preliminary studies indicate that 18 F-DOPA and 68 Ga-DOTA-NOC are more accurate for disease assessment and 68 Ga-DOTA peptides provide additional data on receptor status that are crucial for targeted radionuclide therapy. At present, there are no comparative studies investigating their role in NET. The aim of this study was to compare 68 Ga-DOTA-NOC and 18 F-DOPA for the evaluation of gastro-entero-pancreatic and lung neuro-endocrine tumours. Thirteen patients with biopsy-proven NET (gastro-entero-pancreatic or pulmonary) were prospectively enrolled and scheduled for 18 F-DOPA and 68 Ga-DOTA-NOC PET. PET results obtained with both tracers were compared with each other, with other conventional diagnostic procedures (CT, ultrasound) and with follow-up (clinical, imaging). The most common primary tumour site was the pancreas (8/13) followed by the ileum (2/13), the lung (2/13) and the duodenum (1/13). The carcinoma was well differentiated in 10/13 and poorly differentiated in 3/13 cases. 68 Ga-DOTA-NOC PET was positive, showing at least one lesion, in 13/13 cases while 18 F-DOPA PET was positive in 9/13. On a lesions basis, 68 Ga-DOTA-NOC identified more lesions than 18 F-DOPA (71 vs 45), especially at liver, lung and lymph node level. 68 Ga-DOTA-NOC correctly identified the primary site in six of eight non-operated cases (in five cases, the primary was surgically removed before PET), while 18 F-DOPA identified the primary only in two of eight cases. Although the patients studied are few and heterogeneous, our data show that 68 Ga-DOTA-NOC is accurate for the detection of gastro-entero-pancreatic and lung neuro-endocrine tumours in either the primary or metastatic site and that it offers several advantages over 18 F-DOPA. (orig.)

  9. Comparison between 68Ga-DOTA-NOC and 18F-DOPA PET for the detection of gastro-entero-pancreatic and lung neuro-endocrine tumours.

    Science.gov (United States)

    Ambrosini, Valentina; Tomassetti, Paola; Castellucci, Paolo; Campana, Davide; Montini, Giancarlo; Rubello, Domenico; Nanni, Cristina; Rizzello, Anna; Franchi, Roberto; Fanti, Stefano

    2008-08-01

    (18)F-FDG positron emission tomography (PET) value for the assessment of neuro-endocrine tumours (NET) is limited. Preliminary studies indicate that (18)F-DOPA and (68)Ga-DOTA-NOC are more accurate for disease assessment and (68)Ga-DOTA peptides provide additional data on receptor status that are crucial for targeted radionuclide therapy. At present, there are no comparative studies investigating their role in NET. The aim of this study was to compare (68)Ga-DOTA-NOC and (18)F-DOPA for the evaluation of gastro-entero-pancreatic and lung neuro-endocrine tumours. Thirteen patients with biopsy-proven NET (gastro-entero-pancreatic or pulmonary) were prospectively enrolled and scheduled for (18)F-DOPA and (68)Ga-DOTA-NOC PET. PET results obtained with both tracers were compared with each other, with other conventional diagnostic procedures (CT, ultrasound) and with follow-up (clinical, imaging). The most common primary tumour site was the pancreas (8/13) followed by the ileum (2/13), the lung (2/13) and the duodenum (1/13). The carcinoma was well differentiated in 10/13 and poorly differentiated in 3/13 cases. (68)Ga-DOTA-NOC PET was positive, showing at least one lesion, in 13/13 cases while (18)F-DOPA PET was positive in 9/13. On a lesions basis, (68)Ga-DOTA-NOC identified more lesions than (18)F-DOPA (71 vs 45), especially at liver, lung and lymph node level. (68)Ga-DOTA-NOC correctly identified the primary site in six of eight non-operated cases (in five cases, the primary was surgically removed before PET), while (18)F-DOPA identified the primary only in two of eight cases. Although the patients studied are few and heterogeneous, our data show that (68)Ga-DOTA-NOC is accurate for the detection of gastro-entero-pancreatic and lung neuro-endocrine tumours in either the primary or metastatic site and that it offers several advantages over (18)F-DOPA.

  10. 18F-DOPA PET/CT and 68Ga-DOTANOC PET/CT scans as diagnostic tools in focal congenital hyperinsulinism. A blinded evaluation

    Energy Technology Data Exchange (ETDEWEB)

    Dahl Christiansen, Charlotte; Helleskov Rasmussen, Annett [Hans Christian Andersen Children' s Hospital, Odense University Hospital, Odense (Denmark); University of Southern Denmark, Department of Clinical Research, Odense (Denmark); Petersen, Henrik; Lerberg Nielsen, Anne [Odense University Hospital, Department of Nuclear Medicine, Odense (Denmark); Detlefsen, Soenke [University of Southern Denmark, Department of Clinical Research, Odense (Denmark); Odense University Hospital, Department of Pathology, Odense (Denmark); Brusgaard, Klaus [Odense University Hospital, Department of Clinical Genetics, Odense (Denmark); Rasmussen, Lars; Hovendal, Claus [Odense University Hospital, Department of Abdominal Surgery, Odense (Denmark); Melikyan, Maria [Endocrine Research Centre, Moscow (Russian Federation); Ekstroem, Klas [Karolinska Hospital, Astrid Lindgren Children' s Hospital, Stockholm (Sweden); Globa, Evgenia [MOH of Ukraine, Ukrainian Center of Endocrine Surgery, Endocrine Organs and Tissue Transplantation, Kyiv (Ukraine); Christesen, Henrik Thybo [Hans Christian Andersen Children' s Hospital, Odense University Hospital, Odense (Denmark); University of Southern Denmark, Department of Clinical Research, Odense (Denmark); Odense University Hospital, Odense Pancreas Center (OPAC), Odense (Denmark); Odense University Hospital, Department of Paediatrics, Odense C (Denmark)

    2018-02-15

    Focal congenital hyperinsulinism (CHI) is curable by surgery, which is why identification of the focal lesion is crucial. We aimed to determine the use of 18F-fluoro-dihydroxyphenylalanine (18F-DOPA) PET/CT vs. 68Ga-1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic-acid-1-Nal3 -octreotide (68Ga-DOTANOC) PET/CT as diagnostic tools in focal CHI. PET/CT scans of children with CHI admitted to Odense University Hospital between August 2005 and June 2016 were retrospectively evaluated visually and by their maximal standardized uptake values (SUV{sub max}) by two independent examiners, blinded for clinical, surgical and pathological data. Pancreatic histology was used as the gold standard. For patients without surgery, the genetic profile served as the gold standard. Fifty-five CHI patients were examined by PET/CT (18F-DOPA n = 53, 68Ga-DOTANOC n = 18). Surgery was performed in 34 patients, no surgery in 21 patients. Fifty-one patients had a classifiable outcome, either by histology (n = 33, 22 focal lesions, 11 non-focal) or by genetics (n = 18, all non-focal). The predictive performance of 18F-DOPA PET/CT to identify focal CHI was identical by visual- and cut-off-based evaluation: sensitivity (95% CI) of 1 (0.85-1); specificity of 0.96 (0.82-0.99). The optimal 18F-DOPA PET SUV{sub max} ratio cut-off was 1.44 and the optimal 68Ga-DOTANOC PET SUV{sub max} cut-off was 6.77 g/ml. The area under the receiver operating curve was 0.98 (0.93-1) for 18F-DOPA PET vs. 0.71 (0.43-0.95) for 68Ga-DOTANOC PET (p < 0.03). In patients subjected to surgery, localization of the focal lesion was correct in 91%, and 100%, by 18F-DOPA PET/CT and 68Ga-DOTANOC PET/CT, respectively. 18F-DOPA PET/CT was excellent in predicting focal CHI and superior compared to 68Ga-DOTANOC PET/CT. Further use of 68GA-DOTANOC PET/CT in predicting focal CHI is discouraged. (orig.)

  11. A high 18F-FDOPA uptake is associated with a slow growth rate in diffuse Grade II-III gliomas.

    Science.gov (United States)

    Isal, Sibel; Gauchotte, Guillaume; Rech, Fabien; Blonski, Marie; Planel, Sophie; Chawki, Mohammad B; Karcher, Gilles; Marie, Pierre-Yves; Taillandier, Luc; Verger, Antoine

    2018-04-01

    In diffuse Grade II-III gliomas, a high 3,4-dihydroxy-6-( 18 F)-fluoro-L-phenylalanine ( 18 F-FDOPA) positron emission tomography (PET) uptake, with a standardized uptake value (SUV max )/contralateral brain tissue ratio greater than 1.8, was previously found to be consistently associated with the presence of an isocitrate dehydrogenase (IDH) mutation, whereas this mutation is typically associated with a better prognosis. This pilot study was aimed to ascertain the prognostic value of this high 18 F-FDOPA uptake in diffuse Grade II-III gliomas with regard to the velocity of diameter expansion (VDE), which represents an established landmark of better prognosis when below 4 mm per year. 20 patients (42 ± 10 years, 10 female) with newly-diagnosed diffuse Grade II-III gliomas (17 with IDH mutation) were retrospectively included. All had a 18 F-FDOPA PET, quantified with SUV max ratio, along with a serial MRI enabling VDE determination. SUV max ratio was above 1.8 in 5 patients (25%) all of whom had a VDE VDE <4 mm/year in the overall population (45 vs 0%, p = 0.04) and also in the subgroup of patients with IDH mutation (45 vs 0%, p = 0.10). This pilot study shows that in diffuse Grade II-III gliomas, a high 18 F-FDOPA uptake would be predictive of low tumour growth, with a different prognostic significance than IDH mutation. Advances in knowledge: 18 F-FDOPA PET in a single session imaging could have prognostic value in initial diagnosis of diffuse Grade II-III gliomas.

  12. Behavioral sensitivity of temporally modulated striatal neurons

    Directory of Open Access Journals (Sweden)

    George ePortugal

    2011-07-01

    Full Text Available Recent investigations into the neural mechanisms that underlie temporal perception have revealed that the striatum is an important contributor to interval timing processes, and electrophysiological recording studies have shown that the firing rates of striatal neurons are modulated by the time in a trial at which an operant response is made. However, it remains unclear whether striatal firing rate modulations are related to the passage of time alone (i.e., whether temporal information is represented in an abstract manner independent of other attributes of biological importance, or whether this temporal information is embedded within striatal activity related to co-occurring contextual information, such as motor behaviors. This study evaluated these two hypotheses by recording from striatal neurons while rats performed a temporal production task. Rats were trained to respond at different nosepoke apertures for food reward under two simultaneously active reinforcement schedules: a variable-interval (VI-15 sec schedule and a fixed-interval (FI-15 sec schedule of reinforcement. Responding during a trial occurred in a sequential manner composing 3 phases; VI responding, FI responding, VI responding. The vast majority of task-sensitive striatal neurons (95% varied their firing rates associated with equivalent behaviors (e.g., periods in which their snout was held within the nosepoke across these behavioral phases, and 96% of cells varied their firing rates for the same behavior within a phase, thereby demonstrating their sensitivity to time. However, in a direct test of the abstract timing hypothesis, 91% of temporally modulated hold cells were further modulated by the overt motor behaviors associated with transitioning between nosepokes. As such, these data are inconsistent with the striatum representing time in an abstract’ manner, but support the hypothesis that temporal information is embedded within contextual and motor functions of the

  13. Kaurismäki Soome parim

    Index Scriptorium Estoniae

    2007-01-01

    Soome filmiauhinna Jussi võitis A. Kaurismäki "Äärelinna tuled" ("Laitakaupungin valot"), viis Jussit sai Aku Louhimiehe film "Jäine linn" ("Valkoinen kaupunki") ja kaks Jussit Eesti osalusega "Igavese armastuse sõdalane - Jade Warrior"

  14. Personalization Component for KiWi Framework

    DEFF Research Database (Denmark)

    Durao, Frederico; Xu, Guandong; Kotowski, Jakub

    2010-01-01

    In this report we present the personalization component implemented for KiWi addressing diverse aspects such as motivation scenarios, configuration management, formal models, implementations and some real case scenarios on how personalization can be applied to support software project management...

  15. 18F-DOPA PET/CT and 68Ga-DOTANOC PET/CT scans as diagnostic tools in focal congenital hyperinsulinism: a blinded evaluation.

    Science.gov (United States)

    Christiansen, Charlotte Dahl; Petersen, Henrik; Nielsen, Anne Lerberg; Detlefsen, Sönke; Brusgaard, Klaus; Rasmussen, Lars; Melikyan, Maria; Ekström, Klas; Globa, Evgenia; Rasmussen, Annett Helleskov; Hovendal, Claus; Christesen, Henrik Thybo

    2018-02-01

    Focal congenital hyperinsulinism (CHI) is curable by surgery, which is why identification of the focal lesion is crucial. We aimed to determine the use of 18F-fluoro-dihydroxyphenylalanine (18F-DOPA) PET/CT vs. 68Ga-1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic-acid-1-Nal3-octreotide (68Ga-DOTANOC) PET/CT as diagnostic tools in focal CHI. PET/CT scans of children with CHI admitted to Odense University Hospital between August 2005 and June 2016 were retrospectively evaluated visually and by their maximal standardized uptake values (SUV max ) by two independent examiners, blinded for clinical, surgical and pathological data. Pancreatic histology was used as the gold standard. For patients without surgery, the genetic profile served as the gold standard. Fifty-five CHI patients were examined by PET/CT (18F-DOPA n = 53, 68Ga-DOTANOC n = 18). Surgery was performed in 34 patients, no surgery in 21 patients. Fifty-one patients had a classifiable outcome, either by histology (n = 33, 22 focal lesions, 11 non-focal) or by genetics (n = 18, all non-focal). The predictive performance of 18F-DOPA PET/CT to identify focal CHI was identical by visual- and cut-off-based evaluation: sensitivity (95% CI) of 1 (0.85-1); specificity of 0.96 (0.82-0.99). The optimal 18F-DOPA PET SUV max ratio cut-off was 1.44 and the optimal 68Ga-DOTANOC PET SUV max cut-off was 6.77 g/ml. The area under the receiver operating curve was 0.98 (0.93-1) for 18F-DOPA PET vs. 0.71 (0.43-0.95) for 68Ga-DOTANOC PET (p PET/CT and 68Ga-DOTANOC PET/CT, respectively. 18F-DOPA PET/CT was excellent in predicting focal CHI and superior compared to 68Ga-DOTANOC PET/CT. Further use of 68GA-DOTANOC PET/CT in predicting focal CHI is discouraged.

  16. KiCad challenges the big ones

    CERN Document Server

    Antonella Del Rosso

    2015-01-01

    Printed Circuit Boards (PCB) are the heart of any electronic device, including your toaster and your smartphone. Designing PCBs is the job of electronic engineers who, so far, have often had no option but to use proprietary tools to design complex circuits. Thanks to the efforts that CERN experts have put in to improve the free KiCad software, that situation is about to change.   KiCad's development started in 1992 as a way to design PCBs, the units that control how an electronic device works. Since 2013, experts in the Beams department have made important contributions to KiCad as part of the Open Hardware Initiative (OHI), which provides a framework to facilitate knowledge exchange across the electronic design community. “Our vision is to allow the hardware developers to share as easily as their software colleagues,” says Javier Serrano, head of the BE-CO-HT section and OHI initiator. “Software sources are easily shared online because they are text ...

  17. 18F-DOPA PET/CT and 68Ga-DOTANOC PET/CT scans as diagnostic tools in focal congenital hyperinsulinism

    DEFF Research Database (Denmark)

    Christiansen, Charlotte Dahl; Petersen, Henrik; Nielsen, Anne Lerberg

    2018-01-01

    (68Ga-DOTANOC) PET/CT as diagnostic tools in focal CHI. Methods: PET/CT scans of children with CHI admitted to Odense University Hospital between August 2005 and June 2016 were retrospectively evaluated visually and by their maximal standardized uptake values (SUVmax) by two independent examiners......, blinded for clinical, surgical and pathological data. Pancreatic histology was used as the gold standard. For patients without surgery, the genetic profile served as the gold standard. Results: Fifty-five CHI patients were examined by PET/CT (18F-DOPA n = 53, 68Ga-DOTANOC n = 18). Surgery was performed...... in 34 patients, no surgery in 21 patients. Fifty-one patients had a classifiable outcome, either by histology (n = 33, 22 focal lesions, 11 non-focal) or by genetics (n = 18, all non-focal). The predictive performance of 18F-DOPA PET/CT to identify focal CHI was identical by visual- and cut...

  18. Politički marketing i politički sustav

    OpenAIRE

    Šiber, Ivan

    2000-01-01

    U ovom radu autor daje određenje političkog marketinga i naglašava njegovu povezanost s demokratskim poretkom, prikazuje razvoj političkog marketinga od stranačkog k marketinškom konceptu, razmatra politički marketing kao svojevrsnu konstrukciju političke zbilje i analizira politički marketing u Hrvatskoj. U radu se naglašava još uvijek svojevrstan otpor političkom marketingu kod onih koji bi ga trebali koristiti, ali i neke objektivne okolnosti koje otežavaju njegovu primjenu poput nedostatk...

  19. Ki aikido: a solution to stress.

    Science.gov (United States)

    Wiles, L

    1990-03-10

    It is common knowledge that the life of the general dental practitioner is extremely stressful. Different dentists resort to various ways of unwinding--perhaps a game of golf, a sailing trip, or mending the odd clock as occupational therapy. These are all ways of getting away from the stress of day-to-day work--but perhaps the time has come to look for a more fundamental solution. How many dentists have considered taking up a martial art to alleviate the problem of stress? Here, we outline the background of ki aikido and its practical applications in daily life.

  20. Diagnostic utility of PET/CT with {sup 18}F-DOPA and {sup 18}F-FDG in persistent or recurrent medullary thyroid carcinoma: the importance of calcitonin and carcinoembryonic antigen cutoff

    Energy Technology Data Exchange (ETDEWEB)

    Romero-Lluch, Ana Reyes; Guerrero-Vazquez, Raquel; Martinez-Ortega, Antonio Jesus; Navarro-Gonzalez, Elena [Hospital Universitario Virgen del Rocio, Unidad de Gestion Clinica de Endocrinologia y Nutricion, Seville (Spain); Cuenca-Cuenca, Juan Ignacio; Tirado-Hospital, Juan Luis; Borrego-Dorado, Isabel [Hospital Universitario Virgen del Rocio, Unidad de Medicina Nuclear, Seville (Spain)

    2017-11-15

    This study sought to evaluate and compare the utility of 18-F-fluorodihydroxyphenylalanine ({sup 18}F-DOPA) and 18-F-fluorodeoxyglucose ({sup 18}F-FDG) positron emission tomography/computed tomography (PET/CT) for identification of lesions in patients with recurrent medullary thyroid carcinoma (MTC). In addition, we analyzed the correlation between the calcitonin (Ct), carcinoembryonic antigen (CEA) levels, each doubling time (DT), and PET positivity. We evaluated the reliability of the 150 pg/mL Ct cutoff set by the American Thyroid Association guidelines for further imaging (including {sup 18}F-DOPA PET/CT). We prospectively recruited 18 patients with recurrent MTC, identified by elevation of Ct or CEA. Each patient underwent a {sup 18}F-FDG PET/CT and a {sup 18}F-DOPA PET/CT. Abnormal uptakes were detected with {sup 18}F-DOPA (n=12) and {sup 18}F-FDG (n=9), (sensitivity of 66.7% vs. 50%; p<0.01). Twenty-eight lesions were detected with {sup 18}F-DOPA vs. 16 lesions with {sup 18}F-FDG (1.56±1.5 vs. 0.89±1.18 lesions per patient; p=0.01). None of our patients showed additional lesions with {sup 18}F-FDG in comparison to {sup 18}F-DOPA. Patient-based detection rate increased significantly with Ct levels ≥150 pg/mL vs. Ct<150 pg/mL for both {sup 18}F-DOPA (sensitivity 90.9% vs. 28.6%; p=0.013) and {sup 18}F-FDG PET/CT (sensitivity 72.7% vs. 14.3%; p=0.025). Using a CEA cutoff of ≥5 ng/mL, detection rates of {sup 18}F-DOPA and {sup 18}F-FDG PET/CT were 81.1% and 72.7%, respectively. No correlation between Ct-DT or CEA-DT and PET positivity was found. Histological confirmation was obtained in eight patients. {sup 18}F-DOPA PET/CT appears to be superior to {sup 18}F-FDG PET/CT in detecting and locating lesions in patients with recurrent MTC. This technique tends to be especially useful in patients with negative results in other imaging modalities and Ct≥150 pg/mL or CEA≥5 ng/mL. (orig.)

  1. A retrospective comparison between {sup 68}Ga-DOTA-TOC PET/CT and {sup 18}F-DOPA PET/CT in patients with extra-adrenal paraganglioma

    Energy Technology Data Exchange (ETDEWEB)

    Kroiss, Alexander; Putzer, Daniel; Decristoforo, Clemens; Uprimny, Christian; Virgolini, Irene Johanna [Innsbruck Medical University, Department of Nuclear Medicine, Innsbruck (Austria); Frech, Andreas; Fraedrich, Gustav [Innsbruck Medical University, Department of Vascular Surgery, Innsbruck (Austria); Gasser, Rudolf Wolfgang [Innsbruck Medical University, Department of Internal Medicine I, Innsbruck (Austria); Shulkin, Barry Lynn [St. Jude Children' s Research Hospital, Department of Radiological Sciences, Memphis, TN (United States); Url, Christoph [Innsbruck Medical University, Department of Otorhinolaryngology, Innsbruck (Austria); Widmann, Gerlig [Innsbruck Medical University, Department of Radiology, Innsbruck (Austria); Prommegger, Rupert [Sanatorium Kettenbruecke, Department of Surgery, Innsbruck (Austria); Sprinzl, Georg Mathias [State Clinic St. Poelten, Department of Otorhinolaryngology, St. Poelten (Austria)

    2013-12-15

    {sup 18}F-Fluoro-l-dihydroxyphenylalanine ({sup 18}F-DOPA) PET offers high sensitivity and specificity in the imaging of nonmetastatic extra-adrenal paragangliomas (PGL) but lower sensitivity in metastatic or multifocal disease. These tumours are of neuroendocrine origin and can be detected by {sup 68}Ga-DOTA-Tyr{sup 3}-octreotide ({sup 68}Ga-DOTA-TOC) PET. Therefore, we compared {sup 68}Ga-DOTA-TOC and {sup 18}F-DOPA as radiolabels for PET/CT imaging for the diagnosis and staging of extra-adrenal PGL. Combined cross-sectional imaging was the reference standard. A total of 5 men and 15 women (age range 22 to 73 years) with anatomical and/or histologically proven extra-adrenal PGL were included in this study. Of these patients, 5 had metastatic or multifocal lesions and 15 had single sites of disease. Comparative evaluation included morphological imaging with CT and functional imaging with {sup 68}Ga-DOTA-TOC PET and {sup 18}F-DOPA PET. The imaging results were analysed on a per-patient and a per-lesion basis. The maximum standardized uptake value (SUV{sub max}) of each functional imaging modality in concordant tumour lesions was measured. Compared with anatomical imaging, {sup 68}Ga-DOTA-TOC PET and {sup 18}F-DOPA PET each had a per-patient and per-lesion detection rate of 100 % in nonmetastatic extra-adrenal PGL. However, in metastatic or multifocal disease, the per-lesion detection rate of {sup 68}Ga-DOTA-TOC was 100 % and that of {sup 18}F-DOPA PET was 56.0 %. Overall, {sup 68}Ga-DOTA-TOC PET identified 45 lesions; anatomical imaging identified 43 lesions, and {sup 18}F-DOPA PET identified 32 lesions. The overall per-lesion detection rate of {sup 68}Ga-DOTA-TOC PET was 100 % (McNemar, P < 0.5), and that of {sup 18}F-DOPA PET was 71.1 % (McNemar, P < 0.001). The SUV{sub max} (mean {+-} SD) of all 32 concordant lesions was 67.9 {+-} 61.5 for {sup 68}Ga-DOTA-TOC PET and 11.8 {+-} 7.9 for {sup 18}F-DOPA PET (Mann-Whitney U test, P < 0.0001). {sup 68}Ga-DOTA-TOC PET

  2. [Effects of acupuncture stimulation of different acupoint groups on sleeping duration and serum and striatal dopamine contents in rats with gastric mucosal injury].

    Science.gov (United States)

    Yang, Ping; Peng, Lei; Li, Jie-Ting; Ma, Hui-Fang

    2014-02-01

    To observe the effect of acupuncture intervention on gastric ulcer (GU) and sleeping quality from the viewpoint of brain-gut axis which plays an important role in the regulation of many vital functions in health and disease. Forty male Wistar rats were randomized into normal control, GU model, acupuncture of "Zhongwan" (CV 12)-"Zusanli" (ST 36, gastric treatment acupoints), acupuncture of "Shenmai" (BL 62)-"Zhaohai" (KI 6, sleep-promotion acupoints), and acupuncture of CV 12-ST 36-BL 62-KI 6 (combined treatment) groups, with 8 rats in each group. GU model was established by intragastric perfusion of dehydrated alcohol (1 mL/rat), and sleep model established by intraperitoneal injection of pentobarbital sodium (40 mg/kg) after the last treatment. The abovementioned acupoints were punctured with filiform needles and stimulated by manipulating the needle for about 30 s, once every 5 mm during 20 mm of needle retention. The treatment was conducted once daily for five days. Gastric mucosal lesion index was assessed by Guth's method, and the mucosal pathological changes were observed under microscope after H. E. staining. The contents of dopamine (DA) in the serum and striatal tissues were detected by ELISA kit. Compared with the normal control group, the rats' sleeping duration, and serum DA content were markedly decreased and the gastric mucosal lesion index, and the striatal DA content remarkably increased in the model group (P sleeping duration, and serum DA content were significantly increased, and the gastric mucosal lesion index, and the striatal DA content remarkably down-regulated in the CV 12-ST 36 (gastric treatment acupoints), BL 62-KI 6 (sleep-promotion acupoints) and CV 12-ST 36-BL 62-KI 6 (combined treatment) groups (P sleep promotion acupoints group in reducing mucosal lesion index and in increasing serum DA level (P sleeping duration in gastric lesion rats, which may be related to its effects in increasing blood DA and lowering striatal DA level

  3. Seksistički diskurs rodnog identiteta

    OpenAIRE

    Galić, Branka

    2004-01-01

    To što smo rođeni kao žene i muškarci nužno znači da živimo različite živote. Oslanjajući se na razvijene feminističke pristupe, koji problematiziraju odnose raspodjele moći između rodova nastoji se pokazati seksistički diskurs koji se u varijantama tradicionalne i moderne forme prepoznaje u svijesti ispitivane populacije Hrvatske, i to u nizu društvenih odnosa - pojedinaca, obitelji, rada u kući i na tržištu, politici, itd. Razotkrivanje seksističkog diskursa rodnog identiteta u hrvatskom...

  4. Haloperidol Selectively Remodels Striatal Indirect Pathway Circuits

    Science.gov (United States)

    Sebel, Luke E; Graves, Steven M; Chan, C Savio; Surmeier, D James

    2017-01-01

    Typical antipsychotic drugs are widely thought to alleviate the positive symptoms of schizophrenia by antagonizing dopamine D2 receptors expressed by striatal spiny projection neurons (SPNs). What is less clear is why antipsychotics have a therapeutic latency of weeks. Using a combination of physiological and anatomical approaches in ex vivo brain slices from transgenic mice, it was found that 2 weeks of haloperidol treatment induced both intrinsic and synaptic adaptations specifically within indirect pathway SPNs (iSPNs). Perphenazine treatment had similar effects. Some of these adaptations were homeostatic, including a drop in intrinsic excitability and pruning of excitatory corticostriatal glutamatergic synapses. However, haloperidol treatment also led to strengthening of a subset of excitatory corticostriatal synapses. This slow remodeling of corticostriatal iSPN circuitry is likely to play a role in mediating the delayed therapeutic action of neuroleptics. PMID:27577602

  5. Preparation and characterization of PAN–KI complexed gel polymer

    Indian Academy of Sciences (India)

    The structural, miscibility and the chemical rapport between PAN and KI are investigated using X-ray diffraction, Fourier transform infrared spectroscopy and differential scanning calorimetry methods. The conductivity is enhanced with the increase in KI concentration and temperature. The maximum conductivity at 30 ∘ C is ...

  6. Interlaboratory variability of Ki67 staining in breast cancer

    NARCIS (Netherlands)

    Focke, Cornelia M.; Bürger, Horst; van Diest, Paul J.; Finsterbusch, Kai; Gläser, Doreen; Korsching, Eberhard; Decker, Thomas; Anders, M.; Bollmann, R.; Eiting, Fr; Friedrich, K.; Habeck, J. O.; Haroske, G.; Hinrichs, B.; Behrens, A.; Krause, Lars Udo; Braun-Lang, U.; Lorenzen, J.; Minew, N.; Mlynek-Kersjes, M.; Nenning, H.; Packeisen, J.; Poche-de Vos, F.; Reyher-Klein, S.; Rothacker, D.; Schultz, M.; Sturm, U.; Tawfik, M.; Berghäuser, K. H.; Böcker, W; Cserni, G.; Habedank, S.; Lax, S.; Moinfar, F.; Regitnig, P.; Reiner-Concin, A.; Rüschoff, J.; Varga, Z.; Woziwodski, J.

    2017-01-01

    Background Postanalytic issues of Ki67 assessment in breast cancers like counting method standardisation and interrater bias have been subject of various studies, but little is known about analytic variability of Ki67 staining between pathology labs. Our aim was to study interlaboratory variability

  7. 18F-FDOPA PET/CT-Guided Radiofrequency Ablation of Liver Metastases from Neuroendocrine Tumours: Technical Note on a Preliminary Experience

    Energy Technology Data Exchange (ETDEWEB)

    Cazzato, Roberto Luigi, E-mail: gigicazzato@hotmail.it; Garnon, Julien, E-mail: juleiengarnon@gmail.com [Nouvel Hôpital Civil (Hôpitaux Universitaires de Strasbourg, HUS), Department of Interventional Radiology (France); Ramamurthy, Nitin, E-mail: nitin-ramamurthy@hotmail.com [Norfolk and Norwich University Hospital, Department of Radiology (United Kingdom); Tsoumakidou, Georgia, E-mail: georgia.tsoumakidou@chru-strasbourg.fr [Nouvel Hôpital Civil (Hôpitaux Universitaires de Strasbourg, HUS), Department of Interventional Radiology (France); Imperiale, Alessio, E-mail: alessio.imperiale@chru-strasbourg.fr; Namer, Izzie Jacques, E-mail: izzie.jacques.namer@chru-strasbourg.fr [Hôpital de Hautepierre (Hôpitaux Universitaires de Strasbourg, HUS), Department of Biophysics and Nuclear Medicine (France); Bachellier, Philippe, E-mail: philippe.bachellier@chru-strasbourg.fr [Hôpital de Hautepierre (Hôpitaux Universitaires de Strasbourg, HUS), Hepato-Pancreato-Biliary Surgery and Liver Transplantation (France); Caudrelier, Jean, E-mail: jean.caudrelier@chru-strasbourg.fr; Rao, Pramod, E-mail: pramodrao@me.com; Koch, Guillaume, E-mail: guillaume.koch@chru-strasbourg.fr; Gangi, Afshin, E-mail: gangi@unistra.fr [Nouvel Hôpital Civil (Hôpitaux Universitaires de Strasbourg, HUS), Department of Interventional Radiology (France)

    2016-09-15

    AimTo review our preliminary experience with 6-l-18F-fluorodihydroxyphenylalanine (18F-FDOPA) PET/CT-guided radiofrequency ablation (RFA) of liver metastases from neuroendocrine tumours (NETs).Materials and MethodsThree patients (mean age 51.3 years; range 43–56) with gastro-entero pancreatic NET (GEP-NET) liver metastases underwent 18F-FDOPA PET/CT-guided RFA. Patients were referred with oligometastatic hepatic-confined disease (1–6 metastases; <3 cm) on 18F-FDOPA PET/CT; poor lesion visualisation on US, CT, and MR; and ongoing symptoms. Procedures were performed in an interventional PET/CT scanner under general anaesthesia using a split-dose protocol. Lesion characteristics, procedural duration and technical success (accurate probe placement and post-procedural ablation-zone photopaenia), complications, patient and operator dose, and clinical outcomes were evaluated.ResultsThirteen liver metastases (mean size 11.4 mm, range 8–16) were treated in three patients (two presented with “carcinoid syndrome”). Technical success was 100 % with a mean procedural duration of 173.3 min (range 90–210) and no immediate complications. Mean patient dose was 2844 mGy·cm (range 2104–3686). Operator and radiographer doses were acceptable other than the operator’s right hand in the first case (149 µSv); this normalised in the second case. There was no local tumour or extra-hepatic disease progression at mid-term follow-up (mean 12.6 months; range 6–20); however, two cases progressed with new liver metastases at different sites. There was 100 % clinical success (n = 2) in resolving carcinoid syndrome symptoms.Conclusion18F-FDOPA PET/CT-guided RFA appears technically feasible, safe, and effective in patients with GEP-NETs and low-burden hepatic metastases. Further prospective studies are required to elucidate its precise role in tailored multimodality management of GEP-NET liver metastases.

  8. Striatal dysfunction in attention deficit and hyperkinetic disorder

    International Nuclear Information System (INIS)

    Lou, H.C.; Henriksen, L.; Bruhn, P.; Borner, H.; Nielsen, J.B.

    1989-01-01

    We have previously reported that periventricular structures are hypoperfused in attention deficit and hyperactivity disorder (ADHD). This study has expanded the number of patients, who were divided into two groups: six patients with pure ADHD, and 13 patients with ADHD in combination with other neurologic symptoms. By using xenon 133 inhalation and emission tomography, the regional cerebral blood flow distribution was determined and compared with a control group. Striatal regions were found to be hypoperfused and, by inference, hypofunctional in both groups. This hypoperfusion was statistically significant in the right striatum in ADHD, and in both striatal regions in ADHD with other neuropsychologic and neurologic symptoms. The primary sensory and sensorimotor cortical regions were highly perfused. Methylphenidate increased flow to striatal and posterior periventricular regions, and tended to decrease flow to primary sensory regions. Low striatal activity, partially reversible with methylphenidate, appears to be a cardinal feature in ADHD

  9. Assessment of striatal & postural deformities in patients with Parkinson's disease

    Directory of Open Access Journals (Sweden)

    Sanjay Pandey

    2016-01-01

    Interpretation & conclusions: Our results showed that striatal and postural deformities were common and present in about half of the patients with PD. These deformities we more common in patients with advanced stage of PD.

  10. Striatal dysfunction in attention deficit and hyperkinetic disorder

    Energy Technology Data Exchange (ETDEWEB)

    Lou, H.C.; Henriksen, L.; Bruhn, P.; Borner, H.; Nielsen, J.B.

    1989-01-01

    We have previously reported that periventricular structures are hypoperfused in attention deficit and hyperactivity disorder (ADHD). This study has expanded the number of patients, who were divided into two groups: six patients with pure ADHD, and 13 patients with ADHD in combination with other neurologic symptoms. By using xenon 133 inhalation and emission tomography, the regional cerebral blood flow distribution was determined and compared with a control group. Striatal regions were found to be hypoperfused and, by inference, hypofunctional in both groups. This hypoperfusion was statistically significant in the right striatum in ADHD, and in both striatal regions in ADHD with other neuropsychologic and neurologic symptoms. The primary sensory and sensorimotor cortical regions were highly perfused. Methylphenidate increased flow to striatal and posterior periventricular regions, and tended to decrease flow to primary sensory regions. Low striatal activity, partially reversible with methylphenidate, appears to be a cardinal feature in ADHD.

  11. Prefrontal cortex and striatal activation by feedback in Parkinson's disease

    NARCIS (Netherlands)

    Keitz, Martijn; Koerts, Janneke; Kortekaas, Rudie; Renken, Remco; de Jong, Bauke M.; Leenders, Klaus L.

    2008-01-01

    Positive feedbacks reinforce goal-directed behavior and evoke pleasure. in Parkinson's disease (PD) the striatal dysfunction impairs motor performance, but also may lead to decreased positive feedback (reward) processing. This study investigates two types of positive feedback processing (monetary

  12. Global actions of nicotine on the striatal microcircuit

    Directory of Open Access Journals (Sweden)

    Victor E Plata

    2013-11-01

    Full Text Available The question to solve in the present work is: what is the predominant action induced by the activation of cholinergic-nicotinic receptors (nAChrs in the striatal network given that nAChrs are expressed by several elements of the circuit: cortical terminals, dopamine terminals, and various striatal GABAergic interneurons. To answer this question some type of multicellular recording has to be used without losing single cell resolution. Here, we used calcium imaging and nicotine. It is known that in the presence of low micromolar N-Methyl-D-aspartate (NMDA, the striatal microcircuit exhibits neuronal activity consisting in the spontaneous synchronization of different neuron pools that interchange their activity following determined sequences. The striatal circuit also exhibits profuse spontaneous activity in pathological states (without NMDA such as dopamine depletion. However, in this case, most pathological activity is mostly generated by the same neuron pool. Here, we show that both types of activity are inhibited during the application of nicotine. Nicotine actions were blocked by mecamylamine, a non specific antagonist of nAChrs. Interestingly, inhibitory actions of nicotine were also blocked by the GABAA-receptor antagonist bicuculline, in which case, the actions of nicotine on the circuit became excitatory and facilitated neuronal synchronization. We conclude that the predominant action of nicotine in the striatal microcircuit is indirect, via the activation of networks of inhibitory interneurons. This action inhibits striatal pathological activity in early Parkinsonian animals almost as potently as L-DOPA.

  13. Global actions of nicotine on the striatal microcircuit.

    Science.gov (United States)

    Plata, Víctor; Duhne, Mariana; Pérez-Ortega, Jesús; Hernández-Martinez, Ricardo; Rueda-Orozco, Pavel; Galarraga, Elvira; Drucker-Colín, René; Bargas, José

    2013-01-01

    what is the predominant action induced by the activation of cholinergic-nicotinic receptors (nAChrs) in the striatal network given that nAChrs are expressed by several elements of the circuit: cortical terminals, dopamine terminals, and various striatal GABAergic interneurons. To answer this question some type of multicellular recording has to be used without losing single cell resolution. Here, we used calcium imaging and nicotine. It is known that in the presence of low micromolar N-Methyl-D-aspartate (NMDA), the striatal microcircuit exhibits neuronal activity consisting in the spontaneous synchronization of different neuron pools that interchange their activity following determined sequences. The striatal circuit also exhibits profuse spontaneous activity in pathological states (without NMDA) such as dopamine depletion. However, in this case, most pathological activity is mostly generated by the same neuron pool. Here, we show that both types of activity are inhibited during the application of nicotine. Nicotine actions were blocked by mecamylamine, a non-specific antagonist of nAChrs. Interestingly, inhibitory actions of nicotine were also blocked by the GABAA-receptor antagonist bicuculline, in which case, the actions of nicotine on the circuit became excitatory and facilitated neuronal synchronization. We conclude that the predominant action of nicotine in the striatal microcircuit is indirect, via the activation of networks of inhibitory interneurons. This action inhibits striatal pathological activity in early Parkinsonian animals almost as potently as L-DOPA.

  14. Interobserver Variability of Ki-67 Measurement in Breast Cancer

    Directory of Open Access Journals (Sweden)

    Yul Ri Chung

    2016-03-01

    Full Text Available Background: As measurement of Ki-67 proliferation index is an important part of breast cancer diagnostics, we conducted a multicenter study to examine the degree of concordance in Ki-67 counting and to find factors that lead to its variability. Methods: Thirty observers from thirty different institutions reviewed Ki-67–stained slides of 20 different breast cancers on whole sections and tissue microarray (TMA by online system. Ten of the 20 breast cancers had hot spots of Ki-67 expression. Each observer scored Ki-67 in two different ways: direct counting (average vs. hot spot method and categorical estimation. Intraclass correlation coefficient (ICC of Ki-67 index was calculated for comparative analysis. Results: For direct counting, ICC of TMA was slightly higher than that of whole sections using average method (0.895 vs 0.858. The ICC of tumors with hot spots was lower than that of tumors without (0.736 vs 0.874. In tumors with hot spots, observers took an additional counting from the hot spot; the ICC of whole sections using hot spot method was still lower than that of TMA (0.737 vs 0.895. In categorical estimation, Ki-67 index showed a wide distribution in some cases. Nevertheless, in tumors with hot spots, the range of distribution in Ki-67 categories was decreased with hot spot method and in TMA platform. Conclusions: Interobserver variability of Ki-67 index for direct counting and categorical estimation was relatively high. Tumors with hot spots showed greater interobserver variability as opposed to those without, and restricting the measurement area yielded lower interobserver variability.

  15. [18F]DOPA PET/ceCT in diagnosis and staging of primary medullary thyroid carcinoma prior to surgery.

    Science.gov (United States)

    Rasul, Sazan; Hartenbach, Sabrina; Rebhan, Katharina; Göllner, Adelina; Karanikas, Georgios; Mayerhoefer, Marius; Mazal, Peter; Hacker, Marcus; Hartenbach, Markus

    2018-05-15

    Medullary thyroid carcinoma (MTC) is characterized by a high rate of metastasis. In this study we evaluated the ability of [ 18 F]DOPA PET/ceCT to stage MTC in patients with suspicious thyroid nodules and pathologically elevated serum calcitonin (Ctn) levels prior to total thyroidectomy and lymph node (LN) dissection. A group of 32 patients with sonographically suspicious thyroid nodules and pathologically elevated basal Ctn (bCtn) and stimulated Ctn (sCtn) levels underwent DOPA PET/ceCT prior to surgery. Postoperative histology served as the standard of reference for ultrasonography and DOPA PET/ceCT region-based LN staging. Univariate and multivariate regression analyses as well as receiver operating characteristic analysis were used to evaluate the correlations between preoperative and histological parameters and postoperative tumour persistence or relapse. Primary MTC was histologically verified in all patients. Of the 32 patients, 28 showed increased DOPA decarboxylase activity in the primary tumour (sensitivity 88%, mean SUVmax 10.5). Undetected tumours were exclusively staged pT1a. The sensitivities of DOPA PET in the detection of central and lateral metastatic neck LN were 53% and 73%, in contrast to 20% and 39%, respectively, for neck ultrasonography. Preoperative bCtn and carcinoembryonic antigen levels as well as cN1b status and the number of involved neck regions on DOPA PET/ceCT were predictive of postoperative tumour persistence/relapse in the univariate regression analysis (P PET/ceCT cN1b status remained significant in the multivariate analysis (P = 0.016, relative risk 4.02). This study revealed that DOPA PET/ceCT has high sensitivity in the detection of primary MTC and superior sensitivity in the detection of LN metastases compared to ultrasonography. DOPA PET/ceCT identification of N1b status predicts postoperative tumour persistence. Thus, implementation of a DOPA-guided LN dissection might improve surgical success.

  16. Local control of striatal dopamine release

    Directory of Open Access Journals (Sweden)

    Roger eCachope

    2014-05-01

    Full Text Available The mesolimbic and nigrostriatal dopamine (DA systems play a key role in the physiology of reward seeking, motivation and motor control. Importantly, they are also involved in the pathophysiology of Parkinson’s and Huntington’s disease, schizophrenia and addiction. Control of DA release in the striatum is tightly linked to firing of DA neurons in the ventral tegmental area (VTA and the substantia nigra (SN. However, local influences in the striatum affect release by exerting their action directly on axon terminals. For example, endogenous glutamatergic and cholinergic activity is sufficient to trigger striatal DA release independently of cell body firing. Recent developments involving genetic manipulation, pharmacological selectivity or selective stimulation have allowed for better characterization of these phenomena. Such termino-terminal forms of control of DA release transform considerably our understanding of the mesolimbic and nigrostriatal systems, and have strong implications as potential mechanisms to modify impaired control of DA release in the diseased brain. Here, we review these and related mechanisms and their implications in the physiology of ascending DA systems.

  17. Ki wa ja loodus / Martin Rünkla

    Index Scriptorium Estoniae

    Rünk, Martin

    2010-01-01

    Ki wa näitus "Wildlife documentaries" ("Looduse valetõlked") Tallinnas Draakoni galeriis 23. jaanuarini 2010. Eksponeeritud mustvalged tekstimaalid. Kunstnik tõlgendab looduspilte ja helisid tekstina

  18. Does human presynaptic striatal dopamine function predict social conformity?

    Science.gov (United States)

    Stokes, Paul R A; Benecke, Aaf; Puraite, Julita; Bloomfield, Michael A P; Shotbolt, Paul; Reeves, Suzanne J; Lingford-Hughes, Anne R; Howes, Oliver; Egerton, Alice

    2014-03-01

    Socially desirable responding (SDR) is a personality trait which reflects either a tendency to present oneself in an overly positive manner to others, consistent with social conformity (impression management (IM)), or the tendency to view one's own behaviour in an overly positive light (self-deceptive enhancement (SDE)). Neurochemical imaging studies report an inverse relationship between SDR and dorsal striatal dopamine D₂/₃ receptor availability. This may reflect an association between SDR and D₂/₃ receptor expression, synaptic dopamine levels or a combination of the two. In this study, we used a [¹⁸F]-DOPA positron emission tomography (PET) image database to investigate whether SDR is associated with presynaptic dopamine function. Striatal [¹⁸F]-DOPA uptake, (k(i)(cer), min⁻¹), was determined in two independent healthy participant cohorts (n=27 and 19), by Patlak analysis using a cerebellar reference region. SDR was assessed using the revised Eysenck Personality Questionnaire (EPQ-R) Lie scale, and IM and SDE were measured using the Paulhus Deception Scales. No significant associations were detected between Lie, SDE or IM scores and striatal [¹⁸F]-DOPA k(i)(cer). These results indicate that presynaptic striatal dopamine function is not associated with social conformity and suggests that social conformity may be associated with striatal D₂/₃ receptor expression rather than with synaptic dopamine levels.

  19. Američki gangster: „Crnački don“ kao socio-kulturna kontradikcija

    Directory of Open Access Journals (Sweden)

    Dragana Antonijević

    2017-08-01

    Full Text Available U radu se analizira film Američki gangster (2007 u režiji Ridlija Skota, o životu crnačkog gangstera Frenka Lukasa, neobičnog i sposobnog čoveka. Na početku je dat komentar o razlozima za izbor ovog filma, posle čega sledi filmska dijegeza u okviru koje su dati svi relevantni podaci o filmu i njegovom sadržaju, kao i sažeta biografija Frenka Lukasa koja predstavlja jedan od konteksta za analizu i ujedno osnovni sinopsis filma. Potom je primenjena generička analiza u kojoj su dati najvažniji elementi žanrovskog obrasca gangsterskih filmova i njihov kratak istorijat, da bi bilo sagledano koje karakteristike u okviru žanra ima analizirani film. U okviru žanra, detaljnije su razmatrana dva specifična problema: istorijska rekonstrukcija i mitizacija gangstera kroz folklorizaciju i popularizaciju tog lika. Kontekstualna analiza je bila posvećena odnosu kriminala, kompeticije, agresivnosti i „američkog sna“ kao ideala i načina života. S druge strane, razmotren je problem etničkog i posebno crnačkog kriminala u getoiziranim delovima američkih gradova kao kontekst u kome je Lukas delao. Semantička analiza je sažela neke od osnovnih socio-kulturnih kontradikcija u filmu određujući njegov ideološki okvir i poruke.

  20. Prothymosin-alpha and Ki-67 expression in pituitary adenomas

    Directory of Open Access Journals (Sweden)

    Iga Wierzbicka-Tutka

    2016-11-01

    Full Text Available Introduction: Prothymosin alpha (PTMA, a nuclear oncoprotein involved in cell cycle regulation, is used as a prognostic marker in many cancers. The histopathology of pituitary carcinomas and locally invasive adenomas is indistinguishable from that of benign tumors. A new marker is needed to differentiate these lesions. We evaluated PTMA in pituitary adenomas to determine its usefulness as a prognostic factor of tumor proliferation.Material/Methods: We conducted a retrospective analysis of a group of 27 patients, including 15 females (56% and 12 males (44% with a mean age of 58.6±12 years, who underwent pituitary tumor surgery between 2003 and 2012. The Ki-67 and PTMA-nuclear (PTMA-n and PTMA-cytoplasmic (PTMA-c indices were determined by immunohistochemical staining. We studied histopathological features, clinical symptoms, and magnetic resonance imaging or computed tomography performed before surgery and one year following surgery to evaluate tumor size and progression.Results: The expression of Ki-67 was revealed in 77.8% of adenomas, PTMA-n in 81.5% and PTMA-c in 92.6%. The mean value of the Ki-67 index was 1.8%, PTMA-n was 1.84%, and PTMA-c was 35.6%. There was a significant positive correlation between Ki-67 and PTMA-n (p=0.009. We did not find any correlation between Ki-67, PTMA-c, and tumor progression. PTMA-n was found to be correlated with tumor size (p=0.045 and was higher in the case of gonadotropinomas (p=0.026.Conclusions: The positive nuclear expression of Ki-67 and PTMA was observed in the majority of pituitary adenomas. Neither the expression of Ki-67 nor that of PTMA-c was related to tumor recurrence or local invasion.

  1. Reduced striatal D2 receptor binding in myoclonus-dystonia

    International Nuclear Information System (INIS)

    Beukers, R.J.; Weisscher, N.; Tijssen, M.A.J.; Booij, J.; Zijlstra, F.; Amelsvoort, T.A.M.J. van

    2009-01-01

    To study striatal dopamine D 2 receptor availability in DYT11 mutation carriers of the autosomal dominantly inherited disorder myoclonus-dystonia (M-D). Fifteen DYT11 mutation carriers (11 clinically affected) and 15 age- and sex-matched controls were studied using 123 I-IBZM SPECT. Specific striatal binding ratios were calculated using standard templates for striatum and occipital areas. Multivariate analysis with corrections for ageing and smoking showed significantly lower specific striatal to occipital IBZM uptake ratios (SORs) both in the left and right striatum in clinically affected patients and also in all DYT11 mutation carriers compared to control subjects. Our findings are consistent with the theory of reduced dopamine D 2 receptor (D2R) availability in dystonia, although the possibility of increased endogenous dopamine, and consequently, competitive D2R occupancy cannot be ruled out. (orig.)

  2. No association between striatal dopamine transporter binding and body mass index

    DEFF Research Database (Denmark)

    van de Giessen, Elsmarieke; Hesse, Swen; Caan, Matthan W A

    2013-01-01

    Dopamine is one among several neurotransmitters that regulate food intake and overeating. Thus, it has been linked to the pathophysiology of obesity and high body mass index (BMI). Striatal dopamine D(2) receptor availability is lower in obesity and there are indications that striatal dopamine...... transporter (DAT) availability is also decreased. In this study, we tested whether BMI and striatal DAT availability are associated....

  3. FILSAFAT PENDIDIKAN KI HADJAR DEWANTARA DAN SUMBANGANNYA BAGI PENDIDIKAN INDONESIA

    Directory of Open Access Journals (Sweden)

    Henricus Suparlan

    2016-08-01

    Full Text Available Globalization is influenced by fundamentalist spirit of the market has resulted in education is not fully regarded as an effort to educate the nation and the liberation of man, but began to shift toward education as a commodity. To counteract this kind of educational model, the concepts of Ki Hadjar Dewantara education is offered as a solution to the distortions implementation of education in Indonesia today. According to Ki Hadjar Dewantara, the essence of education is to incorporate culture in the child, and put the child into the culture so that children become human beings. Educational philosophy Ki Hadjar Dewantara Among these so-called philosophy of education in which the convergence of the philosophy of progressivism about the child's natural ability to resolve the problems faced by giving the widest freedom of thought, but it also uses culture that has stood the test of time, according to essentialism, as the basic education of the child to achieve his goal. In this case Ki Hadjar Dewantara using native Indonesian culture while the values of the West are taken in accordance with the theory of selective adaptative Trikon (continuity, convergent and concentric. Three contributions of Ki Hadjar Dewantara’s educational philosophy for the Indonesian education are the application of a trilogy of leadership in education, three centers of education and the paguron system.

  4. P04.02 Analysis of 18F-DOPA PET imaging for target volume definition in patients with recurrent glioblastoma treated with proton therapy

    Science.gov (United States)

    Amelio, D.; Scartoni, D.; Palucci, A.; Vennarini, S.; Giacomelli, I.; Lemoine, S.; Donner, D.; Farace, P.; Chierichetti, F.; Amichetti, M.

    2017-01-01

    Abstract Introduction: Target volume definition is of critical relevance when re-irradiation is delivered and steep dose gradient irradiation techniques, such as proton therapy (PT), are employed. Aim of the study is to investigate the impact of 18F-DOPA on target volume contouring in recurrent glioblastoma (rGBM) patients (pts) undergoing re-irradiation with PT. MATERIAL AND METHODS: We investigated the differences in volume and relationship of magnetic resonance imaging (MRI)- vs. DOPA PET-derived gross tumor volumes (GTVs) of 14 rGBM pts re-irradiated with PT between January and November 2016. All pts had been previously treated with photon radiotherapy (60 Gy) with concomitant and adjuvant temozolomide. All the pts received morphological MRI with contrast enhancement medium administration and 18F-DOPA PET-CT study. We used the pathological distribution of 18F-DOPA in brain tissue to identify the so-called Biological Tumor Volume (BTV). Such areas were assessed using a tumor to normal brain ratio > 2. Moreover, any area of contrast enhancement on MRI was used to identify the MRI-based GTV (MRGTV). Definitive GTV included MRGTV plus BTV. Clinical target volume was generated by adding to GTV a 3-mm uniform margin manually corrected in proximity of anatomical barriers. CTV was expanded by 4 mm to create planning target volume. All pts received 36 GyRBE in 18 fractions. Mean values of differently delineated GTVs were compared each other by paired Student’s t-test; p < 0.05 was considered significant. To further compare MRGTV and BTV, the overlapping (MRGTV ^ BTV) and the composite (MRGTV U BTV) volumes were calculated, and a concordance index (CI) was defined as the ratio between the overlap and composite volumes. Results: MRGTV (mean 14.9 ± 14.5 cc) was larger than BTV (mean 10.9 ± 9.8 cc) although this difference was not statistically significant. The composite volume (mean 20.9 ± 14.7 cc) was significantly larger than each single volume (p < 0

  5. Guideline for PET/CT imaging of neuroendocrine neoplasms with {sup 68}Ga-DOTA-conjugated somatostatin receptor targeting peptides and {sup 18}F-DOPA

    Energy Technology Data Exchange (ETDEWEB)

    Bozkurt, Murat Fani [Hacettepe University Faculty of Medicine Department of Nuclear Medicine, Ankara (Turkey); Virgolini, Irene; Decristoforo, Clemens [Medical University Innsbruck, Department of Nuclear Medicine, Innsbruck (Austria); Balogova, Sona [Comenius University and St. Elisabeth Oncology Institute, Department of Nuclear Medicine, Bratislava (Slovakia); Tenon Hospital AP-HP and Universite Pierre et Marie Curie, Department of Nuclear Medicine, Paris (France); Beheshti, Mohsen [St. Vincent' s Hospital, PET-CT Center, Department of Nuclear Medicine and Endocrinology, Linz (Austria); Paracelsus Medical University, Department of Nuclear Medicine, Salzburg (Austria); Rubello, Domenico [Santa Maria della Misericordia Hospital, Department of Nuclear Medicine, PET Center and Medical Physics and Radiology, Rovigo (Italy); Ambrosini, Valentina; Fanti, Stefano [University of Bologna, Department of Experimental, Diagnostic and Specialty Medicine-DIMES, Bologna (Italy); Kjaer, Andreas [National University Hospital and University of Copenhagen, Department of Clinical Physiology, Nuclear Medicine and PET, Rigshospitalet, Copenhagen (Denmark); Delgado-Bolton, Roberto [San Pedro Hospital and Centre for Biomedical Research of La Rioja (CIBIR), Department of Diagnostic Imaging (Radiology) and Nuclear Medicine, Logrono (Spain); Kunikowska, Jolanta [Medical University of Warsaw, Nuclear Medicine, Warsaw (Poland); Oyen, Wim J.G. [Institute of Cancer Research and Royal Marsden NHS Foundation Trust, London (United Kingdom); Chiti, Arturo [Humanitas University, Nuclear Medicine Department, Rozzano, MI (Italy); Giammarile, Francesco [University of Lyon, Nuclear Medicine, Lyon (France)

    2017-08-15

    Neuroendocrine neoplasms are a heterogenous group of tumours, for which nuclear medicine plays an important role in the diagnostic work-up as well as in the targeted therapeutic options. This guideline is aimed to assist nuclear medicine physicians in recommending, performing, reporting and interpreting the results of somatostatin receptor (SSTR) PET/CT imaging using {sup 68}Ga-DOTA-conjugated peptides, as well as {sup 18}F-DOPA imaging for various neuroendocrine neoplasms. The previous procedural guideline by EANM regarding the use PET/CT tumour imaging with {sup 68}Ga-conjugated peptides has been revised and updated with the relevant and recent literature in the field with contribution of distinguished experts. (orig.)

  6. Assessment of dopamine metabolism in brain of patients with dementia by means of 18F-fluorodopa and PET

    International Nuclear Information System (INIS)

    Itoh, Masatoshi; Fujiwara, Takehiko; Meguro, Kenichi; Hatazawa, Jun; Iwata, Ren; Ishiwata, Kiichi; Takahashi, Toshihiro; Ido, Tatsuo; Sasaki, Hidetada.

    1994-01-01

    By means of positron emission tomography (PET) and 18 F-fluorodopa (FDOPA), a study was initiated to analyze the cerebral dopamine (DA) metabolism of 32 subjects including those with AD/SDAT and vascular dementia (VD, multi-infarct type). A semiautomated irregular ROI drawing routine to identify the striatum was developed that interactively defined the PET threshold pixels referring to the count histograms and location of the corresponding pixels. A comparative study by five examiners showed significant improvement in the area size definition and count linearity particularly for low contrast objects. The graphical plot was employed to calculate the FDOPA influx rate (Ki) for the ROI data with cerebellar radioactivity as an input function. The striatal Ki value was found to be relatively stable and did not show signs of a significant age-related change. The vascular patients had smaller Ki to the striatum than the aged control. Although the mean Ki of AD/SDAT was almost compatible with that of age-matched normals, their Ki was more scattered with higher and lower Ki cases. The multiple regression analysis revealed that the Ki could be predicted by age and the mini-mental state (MMS) performance (r 2 =0.590, p 2 =0.401, and p<0.05 for VD). MMS was found to be a more dominant factor than age. We conclude that dopamine metabolism became disturbed as dementia became progressively severe. (author)

  7. Quality assurance trials for Ki67 assessment in pathology.

    Science.gov (United States)

    Raap, M; Ließem, S; Rüschoff, J; Fisseler-Eckhoff, A; Reiner, A; Dirnhofer, S; von Wasielewski, R; Kreipe, H

    2017-10-01

    Ki67 is a broadly used proliferation marker in surgical pathology with an obvious need for standardization to improve reproducibility of assessment. Here, we present results of the so far only existing round robin tests on Ki67, organized annually in Germany, Austria, and Switzerland from 2010 to 2015 with up to 160 participating laboratories (QuIP). In each quality assessment trial, eight probes from each breast cancer, neuroendocrine tumor, and malignant lymphoma were compiled on a tissue microarray (TMA). TMAs were stained in the participants' laboratories with antibodies and procedures also applied in their daily routine. Participating pathologists were expected to assign Ki67 values to one of four different categories for each tumor type. All local stainings and evaluations were reassessed by the organizing panel and compared to a preset standard. On average, 95% of participants reached the benchmark of over 80% concordance rates with the Ki67 category pre-established by the panel. Automatization and type of antibody did not affect the success rate. Concordance rates differed between tumor entities being highest in each tumor type with either very high or very low labeling indices. Lower rates were seen for intermediate Ki67 levels. Staining quality improved during the observation period as did inter-observer concordance with 85% of participants achieving excellent agreement (kappa > 0.8) in the first year and over 95% in 2015. In conclusion, regular external quality assurance trials have been established as a tool to improve the reproducibility and reliability of the prognostic and predictive proliferation marker Ki67.

  8. Current status of PET imaging of neuroendocrine tumours ([18F]FDOPA, [68Ga]traces, [11C/[18F]-HTP)

    International Nuclear Information System (INIS)

    Ambrosini, A.; Morgini, J.J.; Nanni, C.; Castellucci, P.; Fanti, S.

    2015-01-01

    Neuroendocrine neoplasms (NEN) functional imaging is an evolving field that witnessed major advances in the past two decades. The routine use of PET/CT with an array of new radiotracers to specifically study NEN resulted in an increase in lesions detection. Currently, PET radiopharmaceuticals for NEN imaging include both metabolic ([18F]DOPA, [18F]FDG, [11C]/[18F]-HTP) and receptor-mediated compounds ([68Ga]DOTA-peptides). Discussion is still on-going regarding the clinical setting that may benefit the most from the use of one tracer over the other. [68Ga]DOTA-peptides are accurate for the detection of well differentiated NEN and are increasingly employed. Moreover, providing data on somatostatin receptors expression on NEN cells, they represent a fundamental procedure to be performed before starting therapy, as well as to guide treatment, with either hot or cold somatostatin analogues. The easy and economic synthesis process also favours their clinical employment even in centres without an on-site cyclotron. [18F]DOPA is accurate for studying well differentiated tumours however the difficult and expensive synthesis have limited its clinical employment. It currently can be successfully used for imaging tumours with variable to low expression of SSR (medullary thyroid carcinoma, neuroblastoma, pheocromocytoma), that cannot be accurately studied with [68Ga]DOTA-peptides. [11C]/[18F]-HTP has also been proposed to image well differentiated NEN, on the basis of serotonin pathway activity, for which [11C]/[18F]-HTP can be used as precursor. However, although preliminary data are encouraging, the feasibility of its widespread clinical use is still under discussion, mainly limited by a complex synthesis process and more proven advantages over other currently employed compounds. This review aims to provide an overview of the current status and clinical application of PET tracers to image well differentiated NEN and to focus on the still open-issues of debate

  9. Alterations in Striatal Circuits Underlying Addiction-Like Behaviors.

    Science.gov (United States)

    Kim, Hyun Jin; Lee, Joo Han; Yun, Kyunghwa; Kim, Joung-Hun

    2017-06-30

    Drug addiction is a severe psychiatric disorder characterized by the compulsive pursuit of drugs of abuse despite potential adverse consequences. Although several decades of studies have revealed that psychostimulant use can result in extensive alterations of neural circuits and physiology, no effective therapeutic strategies or medicines for drug addiction currently exist. Changes in neuronal connectivity and regulation occurring after repeated drug exposure contribute to addiction-like behaviors in animal models. Among the involved brain areas, including those of the reward system, the striatum is the major area of convergence for glutamate, GABA, and dopamine transmission, and this brain region potentially determines stereotyped behaviors. Although the physiological consequences of striatal neurons after drug exposure have been relatively well documented, it remains to be clarified how changes in striatal connectivity underlie and modulate the expression of addiction-like behaviors. Understanding how striatal circuits contribute to addiction-like behaviors may lead to the development of strategies that successfully attenuate drug-induced behavioral changes. In this review, we summarize the results of recent studies that have examined striatal circuitry and pathway-specific alterations leading to addiction-like behaviors to provide an updated framework for future investigations.

  10. Dysregulation of striatal projection neurons in Parkinson's disease.

    Science.gov (United States)

    Beck, Goichi; Singh, Arun; Papa, Stella M

    2018-03-01

    The loss of nigrostriatal dopamine (DA) is the primary cause of motor dysfunction in Parkinson's disease (PD), but the underlying striatal mechanisms remain unclear. In spite of abundant literature portraying structural, biochemical and plasticity changes of striatal projection neurons (SPNs), in the past there has been a data vacuum from the natural human disease and its close model in non-human primates. Recently, single-cell recordings in advanced parkinsonian primates have generated new insights into the altered function of SPNs. Currently, there are also human data that provide direct evidence of profoundly dysregulated SPN activity in PD. Here, we review primate recordings that are impacting our understanding of the striatal dysfunction after DA loss, particularly through the analysis of physiologic correlates of parkinsonian motor behaviors. In contrast to recordings in rodents, data obtained in primates and patients demonstrate similar major abnormalities of the spontaneous SPN firing in the alert parkinsonian state. Furthermore, these studies also show altered SPN responses to DA replacement in the advanced parkinsonian state. Clearly, there is yet much to learn about the striatal discharges in PD, but studies using primate models are contributing unique information to advance our understanding of pathophysiologic mechanisms.

  11. Striatal volume predicts level of video game skill acquisition.

    Science.gov (United States)

    Erickson, Kirk I; Boot, Walter R; Basak, Chandramallika; Neider, Mark B; Prakash, Ruchika S; Voss, Michelle W; Graybiel, Ann M; Simons, Daniel J; Fabiani, Monica; Gratton, Gabriele; Kramer, Arthur F

    2010-11-01

    Video game skills transfer to other tasks, but individual differences in performance and in learning and transfer rates make it difficult to identify the source of transfer benefits. We asked whether variability in initial acquisition and of improvement in performance on a demanding video game, the Space Fortress game, could be predicted by variations in the pretraining volume of either of 2 key brain regions implicated in learning and memory: the striatum, implicated in procedural learning and cognitive flexibility, and the hippocampus, implicated in declarative memory. We found that hippocampal volumes did not predict learning improvement but that striatal volumes did. Moreover, for the striatum, the volumes of the dorsal striatum predicted improvement in performance but the volumes of the ventral striatum did not. Both ventral and dorsal striatal volumes predicted early acquisition rates. Furthermore, this early-stage correlation between striatal volumes and learning held regardless of the cognitive flexibility demands of the game versions, whereas the predictive power of the dorsal striatal volumes held selectively for performance improvements in a game version emphasizing cognitive flexibility. These findings suggest a neuroanatomical basis for the superiority of training strategies that promote cognitive flexibility and transfer to untrained tasks.

  12. Quantum dots-based quantitative and in situ multiple imaging on ki67 and cytokeratin to improve ki67 assessment in breast cancer.

    Directory of Open Access Journals (Sweden)

    Jing Ping Yuan

    Full Text Available As a marker for tumor cell proliferation, Ki67 has important impacts on breast cancer (BC prognosis. Although immunohistochemical staining is the current standard method, variations in analytical practice make it difficult for pathologists to manually measure Ki67 index. This study was to develop a fluorescent spectrum-based quantitative analysis of Ki67 expression by quantum-dots (QDs multiple imaging technique.A QDs-based in situ multiple fluorescent imaging method was developed, which stained nuclear Ki67 as red signal and cytoplasmic cytokeratin (CK as green signal. Both Ki67 and CK signals were automatically separated and quantified by professional spectrum analysis software. This technique was applied to tissue microarrays from 240 BC patients. Both Ki67 and CK values, and Ki67/CK ratio were obtained for each patient, and their prognostic value on 5-year disease free survival was assessed.This method simultaneously stains nuclear Ki67 and cytoplasmic CK with clear signal contrast, making it easy for signal separation and quantification. The total fluorescent signal intensities of both Ki67 sum and CK sum were obtained, and Ki67/CK ratio calculated. Ki67 sum and Ki67/CK ratio were each attributed into two grades by X-tile software based on the best P value principle. Multivariate analysis showed Ki67 grade (P = 0.047 and Ki67/CK grade (P = 0.004 were independent prognostic factors. Furthermore, area under curve (AUC of ROC analysis for Ki67/CK grade (AUC: 0.683, 95%CI: 0.613-0.752 was higher than Ki67 grade (AUC: 0.665, 95%CI: 0.596-0.734 and HER-2 gene (AUC: 0.586, 95%CI: 0.510-0.661, but lower than N stage (AUC: 0.760, 95%CI: 0.696-0.823 and histological grade (AUC: 0.756, 95%CI: 0.692-0.820 on predicting the risk for recurrence.A QDs-based quantitative and in situ multiple imaging on Ki67 and CK was developed to improve Ki67 assessment in BC, and Ki67/CK grade had better performance than Ki67 grade in predicting prognosis.

  13. An international study to increase concordance in Ki67 scoring

    DEFF Research Database (Denmark)

    Polley, Mei-Yin C; Leung, Samuel C Y; Gao, Dongxia

    2015-01-01

    these data are potentially encouraging, suggesting that it may be possible to standardize scoring of Ki67 among pathology laboratories, clinically important discrepancies persist. Before this biomarker could be recommended for clinical use, future research will need to extend this approach to biopsies...

  14. Coenite seiklused ja Kim Ki-duki huumor / Merit Kask

    Index Scriptorium Estoniae

    Kask, Merit

    2007-01-01

    60-nda Cannes'i filmifestivali filme : Ethan ja Joel Coen'i "Pole maad vanadele meestele" ("No Country for Old Men" ; Ameerika Ühendriigid), Kim Ki-duki "Hingetõmme" ("Soom"/"Breath" ; Lõuna-Korea) ja Raphael Nadjari "Tehilim" (Prantsusmaa - Iisrael - Ameerika Ühendriigid)

  15. Prikljutshenija Koenov i jumor Kim Ki-duka / Merit Kask

    Index Scriptorium Estoniae

    Kask, Merit

    2007-01-01

    60-nda Cannes'i filmifestivali filme : Ethan ja Joel Coen'i "Pole maad vanadele meestele" ("No Country for Old Men" ; Ameerika Ühendriigid), Kim Ki-duki "Hingetõmme" ("Soom"/"Breath" ; Lõuna-Korea) ja Raphael Nadjari "Tehilim" (Prantsusmaa - Iisrael - Ameerika Ühendriigid)

  16. KiT: a MATLAB package for kinetochore tracking.

    Science.gov (United States)

    Armond, Jonathan W; Vladimirou, Elina; McAinsh, Andrew D; Burroughs, Nigel J

    2016-06-15

    During mitosis, chromosomes are attached to the mitotic spindle via large protein complexes called kinetochores. The motion of kinetochores throughout mitosis is intricate and automated quantitative tracking of their motion has already revealed many surprising facets of their behaviour. Here, we present 'KiT' (Kinetochore Tracking)-an easy-to-use, open-source software package for tracking kinetochores from live-cell fluorescent movies. KiT supports 2D, 3D and multi-colour movies, quantification of fluorescence, integrated deconvolution, parallel execution and multiple algorithms for particle localization. KiT is free, open-source software implemented in MATLAB and runs on all MATLAB supported platforms. KiT can be downloaded as a package from http://www.mechanochemistry.org/mcainsh/software.php The source repository is available at https://bitbucket.org/jarmond/kit and under continuing development. Supplementary data are available at Bioinformatics online. jonathan.armond@warwick.ac.uk. © The Author 2016. Published by Oxford University Press.

  17. Statistical inconsistencies in the KiDS-450 data set

    Science.gov (United States)

    Efstathiou, George; Lemos, Pablo

    2018-05-01

    The Kilo-Degree Survey (KiDS) has been used in several recent papers to infer constraints on the amplitude of the matter power spectrum and matter density at low redshift. Some of these analyses have claimed tension with the Planck Λ cold dark matter cosmology at the ˜2σ-3σ level, perhaps indicative of new physics. However, Planck is consistent with other low-redshift probes of the matter power spectrum such as redshift-space distortions and the combined galaxy-mass and galaxy-galaxy power spectra. Here, we perform consistency tests of the KiDS data, finding internal tensions for various cuts of the data at ˜2.2σ-3.5σ significance. Until these internal tensions are understood, we argue that it is premature to claim evidence for new physics from KiDS. We review the consistency between KiDS and other weak lensing measurements of S8, highlighting the importance of intrinsic alignments for precision cosmology.

  18. Ki67 Proliferative Index in Carcinoid Tumors Involving Ovary.

    Science.gov (United States)

    Zhang, Xiaotun; Jones, Andrea; Jenkins, Sarah M; Huang, Yajue

    2018-03-01

    Primary ovarian carcinoid tumors are rare neoplasms that constitute less than 0.1% of all ovarian carcinomas. However, carcinoid tumors metastatic to ovaries are more common. Cell proliferative rate is an important factor in the determination of neuroendocrine tumor prognosis. Limited data are available as regards Ki67 proliferation index in predicting the physiological features of carcinoid tumors involving the ovary. Pathology files of Mayo Clinic Rochester (1995-2014) were searched, and clinical information was collected from medical records. All cases were stained with an antibody against Ki67, and digital analysis was performed with digital imaging analysis. A total of 36 cases (median age 64 years, range 33-83 years), including 9 primary (median age 68 years, range 33-73 years) and 27 metastatic carcinoid cases (median age 64 years, range 36-83 years), were investigated in the current study. Seven out of nine (77.8%) primary ovarian carcinoids are associated with mature teratoma. Twenty two metastatic carcinoids (81.5%) were from the GI tract, four (14.8%) from the pancreas, and one (3.7%) from the posterior thorax location. There was significant difference of Ki67 index between primary (median 2.3%, range, 0.6-8.4%) and metastatic carcinoid tumors (median 9.7%, range, 1.3-46.7%) (p = 0.002). The survival time is much shorter among patients with metastatic carcinoid tumor (median survival 5.8 years) comparing to primary ovarian carcinoid tumor (median 14.2 years) (p = 0.0005). A strong association between Ki67 index and patient survival time was identified (Hazard ratio for 1-percentage point increase 1.11, p = 0.001). Comparing to primary ovarian carcinoid tumor, metastatic carcinoid usually exhibits a higher Ki67 index and a worse outcome.

  19. Ki-67 immunoreactivity in meningiomas--determination of the proliferative potential of meningiomas using the monoclonal antibody Ki-67

    DEFF Research Database (Denmark)

    Madsen, C; Schrøder, H D

    1997-01-01

    The proliferative potential of 66 human intracranial meningiomas (15 benign, 15 atypical, 15 recurrent, 13 bone-invasive, and 8 brain-invasive) was investigated by means of immunohisto-chemistry using the monoclonal antibody Ki-67. This antibody recognizes a nuclear antigen present in human cells...

  20. Fronto-striatal atrophy in behavioural variant frontotemporal dementia & Alzheimer’s disease

    Directory of Open Access Journals (Sweden)

    Maxime eBertoux

    2015-07-01

    Full Text Available Behavioural variant frontotemporal dementia (bvFTD has only recently been associated with significant striatal atrophy, whereas the striatum appears to be relatively preserved in Alzheimer’s disease (AD. Considering the critical role the striatum has in cognition and behaviour, striatal degeneration, together with frontal atrophy, could be responsible of some characteristic symptoms in bvFTD and emerges therefore as promising novel diagnostic biomarker to distinguish bvFTD and AD. Previous studies have, however, only taken either cortical or striatal atrophy into account when comparing the two diseases. In this study, we establish for the first time a profile of fronto-striatal atrophy in 23 bvFTD and 29 AD patients at presentation, based on the structural connectivity of striatal and cortical regions. Patients are compared to 50 healthy controls by using a novel probabilistic connectivity atlas, which defines striatal regions by their cortical white matter connectivity, allowing us to explore the degeneration of the frontal and striatal regions that are functionally linked. Comparisons with controls revealed that bvFTD showed substantial fronto-striatal atrophy affecting the ventral as well as anterior and posterior dorso-lateral prefrontal cortices and the related striatal subregions. By contrast, AD showed few fronto-striatal atrophy, despite having significant posterior dorso-lateral prefrontal degeneration. Direct comparison between bvFTD and AD revealed significantly more atrophy in the ventral striatal-ventromedial prefrontal cortex regions in bvFTD. Consequently, deficits in ventral fronto-striatal regions emerge as promising novel and efficient diagnosis biomarker for bvFTD. Future investigations into the contributions of these fronto-striatal loops on bvFTD symptomology are needed to develop simple diagnostic and disease tracking algorithms.

  1. Striatal dopamine release codes uncertainty in pathological gambling

    DEFF Research Database (Denmark)

    Linnet, Jakob; Mouridsen, Kim; Peterson, Ericka

    2012-01-01

    Two mechanisms of midbrain and striatal dopaminergic projections may be involved in pathological gambling: hypersensitivity to reward and sustained activation toward uncertainty. The midbrain—striatal dopamine system distinctly codes reward and uncertainty, where dopaminergic activation is a linear...... function of expected reward and an inverse U-shaped function of uncertainty. In this study, we investigated the dopaminergic coding of reward and uncertainty in 18 pathological gambling sufferers and 16 healthy controls. We used positron emission tomography (PET) with the tracer [11C]raclopride to measure...... dopamine release, and we used performance on the Iowa Gambling Task (IGT) to determine overall reward and uncertainty. We hypothesized that we would find a linear function between dopamine release and IGT performance, if dopamine release coded reward in pathological gambling. If, on the other hand...

  2. Centrality of striatal cholinergic transmission in basal ganglia function

    Directory of Open Access Journals (Sweden)

    Paola eBonsi

    2011-02-01

    Full Text Available Work over the past two decades revealed a previously unexpected role for striatal cholinergic interneurons in the context of basal ganglia function. The recognition that these interneurons are essential in synaptic plasticity and motor learning represents a significant step ahead in deciphering how the striatum processes cortical inputs, and why pathological circumstances cause motor dysfunction.Loss of the reciprocal modulation between dopaminergic inputs and the intrinsic cholinergic innervation within the striatum appears to be the trigger for pathophysiological changes occurring in basal ganglia disorders. Accordingly, there is now compelling evidence showing profound changes in cholinergic markers in these disorders, in particular Parkinson’s disease and dystonia.Based on converging experimental and clinical evidence, we provide an overview of the role of striatal cholinergic transmission in physiological and pathological conditions, in the context of the pathogenesis of movement disorders.

  3. Distinctive striatal dopamine signaling after dieting and gastric bypass.

    Science.gov (United States)

    Hankir, Mohammed K; Ashrafian, Hutan; Hesse, Swen; Horstmann, Annette; Fenske, Wiebke K

    2015-05-01

    Highly palatable and/or calorically dense foods, such as those rich in fat, engage the striatum to govern and set complex behaviors. Striatal dopamine signaling has been implicated in hedonic feeding and the development of obesity. Dieting and bariatric surgery have markedly different outcomes on weight loss, yet how these interventions affect central homeostatic and food reward processing remains poorly understood. Here, we propose that dieting and gastric bypass produce distinct changes in peripheral factors with known roles in regulating energy homeostasis, resulting in differential modulation of nigrostriatal and mesolimbic dopaminergic reward circuits. Enhancement of intestinal fat metabolism after gastric bypass may also modify striatal dopamine signaling contributing to its unique long-term effects on feeding behavior and body weight in obese individuals. Copyright © 2015 Elsevier Ltd. All rights reserved.

  4. Striatal dopamine release codes uncertainty in pathological gambling

    DEFF Research Database (Denmark)

    Linnet, Jakob; Mouridsen, Kim; Peterson, Ericka

    2012-01-01

    Two mechanisms of midbrain and striatal dopaminergic projections may be involved in pathological gambling: hypersensitivity to reward and sustained activation toward uncertainty. The midbrain-striatal dopamine system distinctly codes reward and uncertainty, where dopaminergic activation is a linear...... function of expected reward and an inverse U-shaped function of uncertainty. In this study, we investigated the dopaminergic coding of reward and uncertainty in 18 pathological gambling sufferers and 16 healthy controls. We used positron emission tomography (PET) with the tracer [(11)C......]raclopride to measure dopamine release, and we used performance on the Iowa Gambling Task (IGT) to determine overall reward and uncertainty. We hypothesized that we would find a linear function between dopamine release and IGT performance, if dopamine release coded reward in pathological gambling. If, on the other hand...

  5. Enhanced striatal sensitivity to aversive reinforcement in adolescents versus adults.

    Science.gov (United States)

    Galván, Adriana; McGlennen, Kristine M

    2013-02-01

    Neurodevelopmental changes in mesolimbic regions are associated with adolescent risk-taking behavior. Numerous studies have shown exaggerated activation in the striatum in adolescents compared with children and adults during reward processing. However, striatal sensitivity to aversion remains elusive. Given the important role of the striatum in tracking both appetitive and aversive events, addressing this question is critical to understanding adolescent decision-making, as both positive and negative factors contribute to this behavior. In this study, human adult and adolescent participants performed a task in which they received squirts of appetitive or aversive liquid while undergoing fMRI, a novel approach in human adolescents. Compared with adults, adolescents showed greater behavioral and striatal sensitivity to both appetitive and aversive stimuli, an effect that was exaggerated in response to delivery of the aversive stimulus. Collectively, these findings contribute to understanding how neural responses to positive and negative outcomes differ between adolescents and adults and how they may influence adolescent behavior.

  6. Striatal grafts in a rat model of Huntington's disease

    DEFF Research Database (Denmark)

    Guzman, R; Meyer, M; Lövblad, K O

    1999-01-01

    Survival and integration into the host brain of grafted tissue are crucial factors in neurotransplantation approaches. The present study explored the feasibility of using a clinical MR scanner to study striatal graft development in a rat model of Huntington's disease. Rat fetal lateral ganglionic...... time-points graft location could not be further verified. Measures for graft size and ventricle size obtained from MR images highly correlated with measures obtained from histologically processed sections (R = 0.8, P fetal rat lateral ganglionic...

  7. Control of striatal signaling by G protein regulators

    Directory of Open Access Journals (Sweden)

    Keqiang eXie

    2011-08-01

    Full Text Available Signaling via heterotrimeric G proteins plays a crucial role in modulating the responses of striatal neurons that ultimately shape core behaviors mediated by the basal ganglia circuitry, such as reward valuation, habit formation and movement coordination. Activation of G-protein-coupled receptors (GPCRs by extracellular signals activates heterotrimeric G proteins by promoting the binding of GTP to their α subunits. G proteins exert their effects by influencing the activity of key effector proteins in this region, including ion channels, second messenger enzymes and protein kinases. Striatal neurons express a staggering number of GPCRs whose activation results in the engagement of downstream signaling pathways and cellular responses with unique profiles but common molecular mechanisms. Studies over the last decade have revealed that the extent and duration of GPCR signaling are controlled by a conserved protein family named Regulator of G protein Signaling (RGS. RGS proteins accelerate GTP hydrolysis by the α subunits of G proteins, thus promoting deactivation of GPCR signaling. In this review, we discuss the progress made in understanding the roles of RGS proteins in controlling striatal G protein signaling and providing integration and selectivity of signal transmission. We review evidence on the formation of a macromolecular complex between RGS proteins and other components of striatal signaling pathways, their molecular regulatory mechanisms and impacts on GPCR signaling in the striatum obtained from biochemical studies and experiments involving genetic mouse models. Special emphasis is placed on RGS9-2, a member of the RGS family that is highly enriched in the striatum and plays critical roles in drug addiction and motor control.

  8. Motor tics evoked by striatal disinhibition in the rat

    Science.gov (United States)

    Bronfeld, Maya; Yael, Dorin; Belelovsky, Katya; Bar-Gad, Izhar

    2013-01-01

    Motor tics are sudden, brief, repetitive movements that constitute the main symptom of Tourette syndrome (TS). Multiple lines of evidence suggest the involvement of the cortico-basal ganglia system, and in particular the basal ganglia input structure—the striatum in tic formation. The striatum receives somatotopically organized cortical projections and contains an internal GABAergic network of interneurons and projection neurons' collaterals. Disruption of local striatal GABAergic connectivity has been associated with TS and was found to induce abnormal movements in model animals. We have previously described the behavioral and neurophysiological characteristics of motor tics induced in monkeys by local striatal microinjections of the GABAA antagonist bicuculline. In the current study we explored the abnormal movements induced by a similar manipulation in freely moving rats. We targeted microinjections to different parts of the dorsal striatum, and examined the effects of this manipulation on the induced tic properties, such as latency, duration, and somatic localization. Tics induced by striatal disinhibition in monkeys and rats shared multiple properties: tics began within several minutes after microinjection, were expressed solely in the contralateral side, and waxed and waned around a mean inter-tic interval of 1–4 s. A clear somatotopic organization was observed only in rats, where injections to the anterior or posterior striatum led to tics in the forelimb or hindlimb areas, respectively. These results suggest that striatal disinhibition in the rat may be used to model motor tics such as observed in TS. Establishing this reliable and accessible animal model could facilitate the study of the neural mechanisms underlying motor tics, and the testing of potential therapies for tic disorders. PMID:24065893

  9. Neuroglial plasticity at striatal glutamatergic synapses in Parkinson's disease

    Directory of Open Access Journals (Sweden)

    Rosa M Villalba

    2011-08-01

    Full Text Available Striatal dopamine denervation is the pathological hallmark of Parkinson’s disease (PD. Another major pathological change described in animal models and PD patients is a significant reduction in the density of dendritic spines on medium spiny striatal projection neurons. Simultaneously, the ultrastructural features of the neuronal synaptic elements at the remaining corticostriatal and thalamostriatal glutamatergic axo-spinous synapses undergo complex ultrastructural remodeling consistent with increased synaptic activity (Villalba et al., 2011. The concept of tripartite synapses (TS was introduced a decade ago, according to which astrocytes process and exchange information with neuronal synaptic elements at glutamatergic synapses (Araque et al., 1999a. Although there has been compelling evidence that astrocytes are integral functional elements of tripartite glutamatergic synaptic complexes in the cerebral cortex and hippocampus, their exact functional role, degree of plasticity and preponderance in other CNS regions remain poorly understood. In this review, we discuss our recent findings showing that neuronal elements at cortical and thalamic glutamatergic synapses undergo significant plastic changes in the striatum of MPTP-treated parkinsonian monkeys. We also present new ultrastructural data that demonstrate a significant expansion of the astrocytic coverage of striatal TS synapses in the parkinsonian state, providing further evidence for ultrastructural compensatory changes that affect both neuronal and glial elements at TS. Together with our limited understanding of the mechanisms by which astrocytes respond to changes in neuronal activity and extracellular transmitter homeostasis, the role of both neuronal and glial components of excitatory synapses must be considered, if one hopes to take advantage of glia-neuronal communication knowledge to better understand the pathophysiology of striatal processing in parkinsonism, and develop new PD

  10. Molecular substrates of action control in cortico-striatal circuits.

    Science.gov (United States)

    Shiflett, Michael W; Balleine, Bernard W

    2011-09-15

    The purpose of this review is to describe the molecular mechanisms in the striatum that mediate reward-based learning and action control during instrumental conditioning. Experiments assessing the neural bases of instrumental conditioning have uncovered functional circuits in the striatum, including dorsal and ventral striatal sub-regions, involved in action-outcome learning, stimulus-response learning, and the motivational control of action by reward-associated cues. Integration of dopamine (DA) and glutamate neurotransmission within these striatal sub-regions is hypothesized to enable learning and action control through its role in shaping synaptic plasticity and cellular excitability. The extracellular signal regulated kinase (ERK) appears to be particularly important for reward-based learning and action control due to its sensitivity to combined DA and glutamate receptor activation and its involvement in a range of cellular functions. ERK activation in striatal neurons is proposed to have a dual role in both the learning and performance factors that contribute to instrumental conditioning through its regulation of plasticity-related transcription factors and its modulation of intrinsic cellular excitability. Furthermore, perturbation of ERK activation by drugs of abuse may give rise to behavioral disorders such as addiction. Copyright © 2011 Elsevier Ltd. All rights reserved.

  11. Adrenergic receptor-mediated modulation of striatal firing patterns.

    Science.gov (United States)

    Ohta, Hiroyuki; Kohno, Yu; Arake, Masashi; Tamura, Risa; Yukawa, Suguru; Sato, Yoshiaki; Morimoto, Yuji; Nishida, Yasuhiro; Yawo, Hiromu

    2016-11-01

    Although noradrenaline and adrenaline are some of the most important neurotransmitters in the central nervous system, the effects of noradrenergic/adrenergic modulation on the striatum have not been determined. In order to explore the effects of adrenergic receptor (AR) agonists on the striatal firing patterns, we used optogenetic methods which can induce continuous firings. We employed transgenic rats expressing channelrhodopsin-2 (ChR2) in neurons. The medium spiny neuron showed a slow rising depolarization during the 1-s long optogenetic striatal photostimulation and a residual potential with 8.6-s half-life decay after the photostimulation. As a result of the residual potential, five repetitive 1-sec long photostimulations with 20-s onset intervals cumulatively increased the number of spikes. This 'firing increment', possibly relating to the timing control function of the striatum, was used to evaluate the AR modulation. The β-AR agonist isoproterenol decreased the firing increment between the 1st and 5th stimulation cycles, while the α 1 -AR agonist phenylephrine enhanced the firing increment. Isoproterenol and adrenaline increased the early phase (0-0.5s of the photostimulation) firing response. This adrenergic modulation was inhibited by the β-antagonist propranolol. Conversely, phenylephrine and noradrenaline reduced the early phase response. β-ARs and α 1 -ARs work in opposition controlling the striatal firing initiation and the firing increment. Copyright © 2016 Elsevier Ireland Ltd and Japan Neuroscience Society. All rights reserved.

  12. The role of striatal NMDA receptors in drug addiction.

    Science.gov (United States)

    Ma, Yao-Ying; Cepeda, Carlos; Cui, Cai-Lian

    2009-01-01

    The past decade has witnessed an impressive accumulation of evidence indicating that the excitatory amino acid glutamate and its receptors, in particular the N-methyl-D-aspartate (NMDA) receptor subtype, play an important role in drug addiction. Various lines of research using animal models of drug addiction have demonstrated that drug-induced craving is accompanied by significant upregulation of NR2B subunit expression. Furthermore, selective blockade of NR2B-containing NMDA receptors in the striatum, especially in the nucleus accumbens (NAc) can inhibit drug craving and reinstatement. The purpose of this review is to examine the role of striatal NMDA receptors in drug addiction. After a brief description of glutamatergic innervation and NMDA receptor subunit distribution in the striatum, we discuss potential mechanisms to explain the role of striatal NMDA receptors in drug addiction by elucidating signaling cascades involved in the regulation of subunit expression and redistribution, phosphorylation of receptor subunits, as well as activation of intracellular signals triggered by drug experience. Understanding the mechanisms regulating striatal NMDA receptor changes in drug addiction will provide more specific and rational targets to counteract the deleterious effects of drug addiction.

  13. In vivo neurochemical characterization of clothianidin induced striatal dopamine release.

    Science.gov (United States)

    Faro, L R F; Oliveira, I M; Durán, R; Alfonso, M

    2012-12-16

    Clothianidin (CLO) is a neonicotinoid insecticide with selective action on nicotinic acetylcholine receptors. The aim of this study was to determine the neurochemical basis for CLO-induced striatal dopamine release using the microdialysis technique in freely moving and conscious rats. Intrastriatal administration of CLO (3.5mM), produced an increase in both spontaneous (2462 ± 627% with respect to basal values) and KCl-evoked (4672 ± 706% with respect to basal values) dopamine release. This effect was attenuated in Ca(2+)-free medium, and was prevented in reserpine pre-treated animals or in presence of tetrodotoxin (TTX). To investigate the involvement of dopamine transporter (DAT), the effect of CLO was observed in presence of nomifensine. The coadministration of CLO and nomifensine produced an additive effect on striatal dopamine release. The results suggest that the effect of CLO on striatal dopamine release is predominantly mediated by an exocytotic mechanism, Ca(2+), vesicular and TTX-dependent and not by a mechanism mediated by dopamine transporter. Published by Elsevier Ireland Ltd.

  14. Fractal analysis of striatal dopamine re-uptake sites

    International Nuclear Information System (INIS)

    Kuikka, J.T.; Bergstroem, K.A.; Tiihonen, J.; Raesaenen, P.; Karhu, J.

    1997-01-01

    Spatial variation in regional blood flow, metabolism and receptor density within the brain and in other organs is measurable even with a low spatial resolution technique such as emission tomography. It has been previously shown that the observed variance increases with increasing number of subregions in the organ/tissue studied. This resolution-dependent variance can be described by fractal analysis. We studied striatal dopamine re-uptake sites in 39 healthy volunteers with high-resolution single-photon emission tomography using iodine-123 labelled 2β-carbomethoxy-3β-(4-iodophenyl)tropane ([ 123 I]β-CIT). The mean fractal dimension was 1.15±0.07. The results indicate that regional striatal dopamine re-uptake sites involve considerable spatial heterogeneity which is higher than the uniform density (dimension=1.00) but much lower than complete randomness (dimension=1.50). There was a gender difference, with females having a higher heterogeneity in both the left and the right striatum. In addition, we found striatal asymmetry (left-to-right heterogeneity ratio of 1.19±0.15; P<0.001), suggesting functional hemispheric lateralization consistent with the control of motor behaviour and integrative functions. (orig.). With 5 figs., 1 tab

  15. Fractal analysis of striatal dopamine re-uptake sites

    Energy Technology Data Exchange (ETDEWEB)

    Kuikka, J.T.; Bergstroem, K.A. [Department of Clinical Physiology, Kuopio University Hospital, Kuopio (Finland); Tiihonen, J.; Raesaenen, P. [Department of Forensic Psychiatry, University of Kuopio and Niuvanniemi Hospital, Kuopio (Finland); Karhu, J. [Department of Clinical Neurophysiology, Kuopio University Hospital, Kuopio (Finland)

    1997-09-01

    Spatial variation in regional blood flow, metabolism and receptor density within the brain and in other organs is measurable even with a low spatial resolution technique such as emission tomography. It has been previously shown that the observed variance increases with increasing number of subregions in the organ/tissue studied. This resolution-dependent variance can be described by fractal analysis. We studied striatal dopamine re-uptake sites in 39 healthy volunteers with high-resolution single-photon emission tomography using iodine-123 labelled 2{beta}-carbomethoxy-3{beta}-(4-iodophenyl)tropane ([{sup 123}I]{beta}-CIT). The mean fractal dimension was 1.15{+-}0.07. The results indicate that regional striatal dopamine re-uptake sites involve considerable spatial heterogeneity which is higher than the uniform density (dimension=1.00) but much lower than complete randomness (dimension=1.50). There was a gender difference, with females having a higher heterogeneity in both the left and the right striatum. In addition, we found striatal asymmetry (left-to-right heterogeneity ratio of 1.19{+-}0.15; P<0.001), suggesting functional hemispheric lateralization consistent with the control of motor behaviour and integrative functions. (orig.). With 5 figs., 1 tab.

  16. Transient and steady-state selection in the striatal microcircuit

    Directory of Open Access Journals (Sweden)

    Adam eTomkins

    2014-01-01

    Full Text Available Although the basal ganglia have been widely studied and implicated in signal processing and action selection, little information is known about the active role the striatal microcircuit plays in action selection in the basal ganglia-thalamo-cortical loops. To address this knowledge gap we use a large scale three dimensional spiking model of the striatum, combined with a rate coded model of the basal ganglia-thalamo-cortical loop, to asses the computational role the striatum plays in action selection. We identify a robust transient phenomena generated by the striatal microcircuit, which temporarily enhances the difference between two competing cortical inputs. We show that this transient is sufficient to modulate decision making in the basal ganglia-thalamo-cortical circuit. We also find that the transient selection originates from a novel adaptation effect in single striatal projection neurons, which is amenable to experimental testing. Finally, we compared transient selection with models implementing classical steady-state selection. We challenged both forms of model to account for recent reports of paradoxically enhanced response selection in Huntington's Disease patients. We found that steady-state selection was uniformly impaired under all simulated Huntington's conditions, but transient selection was enhanced given a sufficient Huntington's-like increase in NMDA receptor sensitivity. Thus our models provide an intriguing hypothesis for the mechanisms underlying the paradoxical cognitive improvements in manifest Huntington's patients.

  17. Prospective comparison of {sup 68}Ga-DOTATATE and {sup 18}F-FDOPA PET/CT in patients with various pheochromocytomas and paragangliomas with emphasis on sporadic cases

    Energy Technology Data Exchange (ETDEWEB)

    Archier, Aurelien; Taieb, David [Aix-Marseille University, Department of Nuclear Medicine, La Timone and North University Hospital, Marseille (France); Aix-Marseille University, European Center for Research in Medical Imaging, Marseille (France); Inserm UMR1068 Marseille Cancerology Research Center, Institut Paoli-Calmettes, Marseille (France); Varoquaux, Arthur; Beschmout, Eva [Aix-Marseille University, Department of Medical Imaging, Conception Hospital, Marseille (France); Garrigue, Philippe; Guillet, Benjamin [Aix-Marseille University, Department of Nuclear Medicine, La Timone and North University Hospital, Marseille (France); Aix-Marseille University, Department of Radiopharmacy, La Timone and North University Hospital, Marseille (France); Montava, Marion; Fakhry, Nicolas [Aix-Marseille University, Department of Otorhinolaryngology-Head and Neck Surgery, Conception Hospital, Marseille (France); Guerin, Carole; Sebag, Frederic [Aix-Marseille University, Department of Endocrine Surgery, Conception Hospital, Marseille (France); Gabriel, Sophie [Aix-Marseille University, Department of Nuclear Medicine, La Timone and North University Hospital, Marseille (France); Aix-Marseille University, European Center for Research in Medical Imaging, Marseille (France); Morange, Isabelle; Castinetti, Frederic [Aix-Marseille University, Department of Endocrinology, Conception Hospital, Marseille (France); Barlier, Anne [Aix-Marseille, University, Laboratory of Biochemistry and Molecular Biology, Conception Hospital, Marseille (France); Loundou, Anderson [Aix-Marseille University, Department of Public Health, Marseille (France); Pacak, Karel [National Institutes of Health, Program in Reproductive and Adult Endocrinology, Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD), Bethesda, MD (United States)

    2016-07-15

    Pheochromocytomas/paragangliomas (PHEOs/PGLs) overexpress somatostatin receptors and recent studies have already shown excellent results in the localization of these tumors using {sup 68}Ga-labeled somatostatin analogs ({sup 68}Ga-DOTA-SSA), especially in patients with germline succinate dehydrogenase subunit B gene (SDHB) mutations and head and neck PGLs (HNPGLs). The value of {sup 68}Ga-DOTA-SSA has to be established in sporadic cases, including PHEOs. Thus, the aim of this study was to compare {sup 68}Ga-DOTATATE PET/CT, {sup 18}F-FDOPA PET/CT, and conventional imaging in patients with various PHEOs/PGLs with a special emphasis on sporadic cases, including those located in the adrenal gland. {sup 68}Ga-DOTATATE, {sup 18}F-FDOPA PET/CT, and conventional imaging (contrast-enhanced CT and MRI with MR angiography sequences) were prospectively performed in 30 patients (8 with SDHD mutations, 1 with a MAX mutation and 21 sporadic cases) with PHEO/PGL at initial diagnosis or relapse. The patient-based sensitivities were 93 % (28/30), 97 % (29/30), and 93 % (28/30) for {sup 68}Ga-DOTATATE PET/CT, {sup 18}F-FDOPA PET/CT, and conventional imaging, respectively. The lesion-based sensitivities were 93 % (43/46), 89 % (41/46), and 76 % (35/46) for {sup 68}Ga-DOTATATE PET/CT, {sup 18}F-FDOPA PET/CT, and conventional imaging respectively (p = 0.042). {sup 68}Ga-DOTATATE PET/CT detected a higher number of HNPGLs (30/30) than {sup 18}F-FDOPA PET/CT (26/30; p = 0.112) and conventional imaging (24/30; p = 0.024). {sup 68}Ga-DOTATATE PET/CT missed two PHEOs of a few millimeters in size and a large recurrent PHEO. One lesion was considered false-positive on {sup 68}Ga-DOTATATE PET/CT and corresponded to a typical focal lesion of fibrous dysplasia on MRI. Among the 11 lesions missed by conventional imaging, 7 were detected by conventional imaging with knowledge of the PET results (4 HNPGLs, 2 LNs, and 1 recurrent PHEO). {sup 68}Ga-DOTATATE PET/CT is the most sensitive tool in the

  18. The role of 18FDG, 18FDOPA PET/CT and 99mTc bone scintigraphy imaging in Erdheim–Chester disease

    Energy Technology Data Exchange (ETDEWEB)

    García-Gómez, F.J., E-mail: javier191185@gmail.com [Department of Nuclear Medicine, Virgen del Rocío Universitary Hospital, Seville (Spain); Acevedo-Báñez, I.; Martínez-Castillo, R.; Tirado-Hospital, J.L.; Cuenca-Cuenca, J.I.; Pachón-Garrudo, V.M.; Álvarez-Pérez, R.M.; García-Jiménez, R. [Department of Nuclear Medicine, Virgen del Rocío Universitary Hospital, Seville (Spain); Rivas-Infante, E. [Department of Pathology, Virgen del Rocío Universitary Hospital, Seville (Spain); García-Morillo, J.S. [Department of Internal Medicine, Virgen del Rocío Universitary Hospital, Seville (Spain); Borrego-Dorado, I. [Department of Nuclear Medicine, Virgen del Rocío Universitary Hospital, Seville (Spain)

    2015-08-15

    Highlights: • Erdheim–Chester disease (ECD) is a rare non-Langerhans cell histiocitosis, characterized by multisystemic xanthogranulomatous infiltration by foamy histiocytes. Etiology and pathogenesis are still unknown and only about 500 cases are related in the literature. • Multifocal nature of involvement in ECD can produce a wide variety of clinical signs. In our experience, neurological involvement is associated with mortality in all cases. Characteristic long bone osteosclerosis was a quasi-pathognomonic finding in bone scintigraphy. • To the best of our knowledge, the 18FDOPA-PET/CT not seem useful in the initial staging of ECD based on a single case report. • Bone scintigraphy and the 18FDG-PET/CT that were particularly useful in despite systemic involvement, locate the optimum site for biopsy and treatment response evaluation. In this context, a baseline 18FDG-PET/CT with an optional bone scintigraphy may help in monitoring the disease and could be considered when patients were incidentally diagnosed and periodically follow-up 18FDG-PET/CT must be performed in the follow up to evaluate the treatment response. - Abstract: Erdheim–Chester disease (ECD) is a rare non-Langerhans cell histiocitosis, characterized by multisystemic xanthogranulomatous infiltration by foamy histiocytes that stain positively for CD68 marker but not express CD1a and S100 proteins. Etiology and pathogenesis are still unknown and only about 500 cases are related in the literature. Multisystemic involvement leads to a wide variety of clinical manifestations that results in a poor prognosis although recent advances in treatment. We present the clinical, nuclear medicine findings and therapeutic aspects of a serie of 6 patients with histopathological diagnosis of ECD, who have undergone both bone scintigraphy (BS) and 18F-fluorodeoxyglucose (18FDG)-PET/CT scans in our institution. A complementary 18F-fluorodopa (18FDOPA)-PET/CT was performed in one case. Three different

  19. The role of 18FDG, 18FDOPA PET/CT and 99mTc bone scintigraphy imaging in Erdheim–Chester disease

    International Nuclear Information System (INIS)

    García-Gómez, F.J.; Acevedo-Báñez, I.; Martínez-Castillo, R.; Tirado-Hospital, J.L.; Cuenca-Cuenca, J.I.; Pachón-Garrudo, V.M.; Álvarez-Pérez, R.M.; García-Jiménez, R.; Rivas-Infante, E.; García-Morillo, J.S.; Borrego-Dorado, I.

    2015-01-01

    Highlights: • Erdheim–Chester disease (ECD) is a rare non-Langerhans cell histiocitosis, characterized by multisystemic xanthogranulomatous infiltration by foamy histiocytes. Etiology and pathogenesis are still unknown and only about 500 cases are related in the literature. • Multifocal nature of involvement in ECD can produce a wide variety of clinical signs. In our experience, neurological involvement is associated with mortality in all cases. Characteristic long bone osteosclerosis was a quasi-pathognomonic finding in bone scintigraphy. • To the best of our knowledge, the 18FDOPA-PET/CT not seem useful in the initial staging of ECD based on a single case report. • Bone scintigraphy and the 18FDG-PET/CT that were particularly useful in despite systemic involvement, locate the optimum site for biopsy and treatment response evaluation. In this context, a baseline 18FDG-PET/CT with an optional bone scintigraphy may help in monitoring the disease and could be considered when patients were incidentally diagnosed and periodically follow-up 18FDG-PET/CT must be performed in the follow up to evaluate the treatment response. - Abstract: Erdheim–Chester disease (ECD) is a rare non-Langerhans cell histiocitosis, characterized by multisystemic xanthogranulomatous infiltration by foamy histiocytes that stain positively for CD68 marker but not express CD1a and S100 proteins. Etiology and pathogenesis are still unknown and only about 500 cases are related in the literature. Multisystemic involvement leads to a wide variety of clinical manifestations that results in a poor prognosis although recent advances in treatment. We present the clinical, nuclear medicine findings and therapeutic aspects of a serie of 6 patients with histopathological diagnosis of ECD, who have undergone both bone scintigraphy (BS) and 18F-fluorodeoxyglucose (18FDG)-PET/CT scans in our institution. A complementary 18F-fluorodopa (18FDOPA)-PET/CT was performed in one case. Three different

  20. Body and Ki in Gicheon : practices of self-cultivation in contemporary Korea

    NARCIS (Netherlands)

    Jeon, Y.

    2017-01-01

    In this dissertation I study the social phenomenon of ki suryŏn (ki-training) as an invented tradition and examine how it functions within Korean society. Mind-body practices referred to as qigong in China and ki suryŏn in Korea are re-constructed in modernity on the basis of ancient East-Asian

  1. DNA synapsis through transient tetramerization triggers cleavage by Ecl18kI restriction enzyme

    NARCIS (Netherlands)

    Zaremba, M.; Lyubchenko, Y.L.; Laurens, N.; van den Broek, B.; Wuite, G.J.L.; Siksnys, V.

    2010-01-01

    To cut DNA at their target sites, restriction enzymes assemble into different oligomeric structures. The Ecl18kI endonuclease in the crystal is arranged as a tetramer made of two dimers each bound to a DNA copy. However, free in solution Ecl18kI is a dimer. To find out whether the Ecl18kI dimer or

  2. Astro-WISE for KiDS survey production and quality control

    NARCIS (Netherlands)

    Kleijn, G.V.; de Jong, Jelte; Valentijn, E.; Kuijken, K.; Consortiums, KiDS; Consortium, Astro-WISE; Ballester, P.; Egret, D.; Lorente, N.P.F.

    The Kilo Degree Survey (KiDS) is a 1500 square degree optical imaging survey with the recently commissioned OmegaCAM wide-field imager on the VLT Survey Telescope (VST). A suite of data products will be delivered to ESO and the community by the KiDS survey team. Spread over Europe, the KiDS team

  3. Clinical impact of ki-67 labeling index in non-small cell lung cancer

    DEFF Research Database (Denmark)

    Jakobsen, Jan Nyrop; Sørensen, Jens Benn

    2013-01-01

    The ki-67 index is a marker of proliferation in malignant tumors. Studies from the period 2000 to 2012 on the prognostic and predictive value of ki-67 labeling index (LI) in non-small cell cancer (NSCLC) are reviewed. Twenty-eight studies reported on the prognostic value of ki-67 index with various...

  4. PSIHOLOŠKI VIDIKI BARV PRI IZDELAVI LOGOTIPA

    OpenAIRE

    Bauman, Anja

    2015-01-01

    Osrednja tema diplomske naloge so psihološki vidiki barv pri izdelavi logotipa. Diplomska naloga zajema tako teoretični kot tudi empirični del. V teoretičnem delu je predstavljen logotip in njegovi kriteriji uspešnosti. Prav tako pa so predstavljene tudi barve, njeni učinki ter značilnosti. Empirični del diplomske naloge pa se ukvarja z analizo obstoječih in izdelanih logotipov.

  5. Automating proliferation rate estimation from Ki-67 histology images

    Science.gov (United States)

    Al-Lahham, Heba Z.; Alomari, Raja S.; Hiary, Hazem; Chaudhary, Vipin

    2012-03-01

    Breast cancer is the second cause of women death and the most diagnosed female cancer in the US. Proliferation rate estimation (PRE) is one of the prognostic indicators that guide the treatment protocols and it is clinically performed from Ki-67 histopathology images. Automating PRE substantially increases the efficiency of the pathologists. Moreover, presenting a deterministic and reproducible proliferation rate value is crucial to reduce inter-observer variability. To that end, we propose a fully automated CAD system for PRE from the Ki-67 histopathology images. This CAD system is based on a model of three steps: image pre-processing, image clustering, and nuclei segmentation and counting that are finally followed by PRE. The first step is based on customized color modification and color-space transformation. Then, image pixels are clustered by K-Means depending on the features extracted from the images derived from the first step. Finally, nuclei are segmented and counted using global thresholding, mathematical morphology and connected component analysis. Our experimental results on fifty Ki-67-stained histopathology images show a significant agreement between our CAD's automated PRE and the gold standard's one, where the latter is an average between two observers' estimates. The Paired T-Test, for the automated and manual estimates, shows ρ = 0.86, 0.45, 0.8 for the brown nuclei count, blue nuclei count, and proliferation rate, respectively. Thus, our proposed CAD system is as reliable as the pathologist estimating the proliferation rate. Yet, its estimate is reproducible.

  6. [3H]Dopamine accumulation and release from striatal slices in young, mature and senescent rats

    International Nuclear Information System (INIS)

    Thompson, J.M.

    1981-01-01

    Examinations of [ 3 H]dopamine ([ 3 H]DA) release following KCl or amphetamine administration in striatal slices from young (7 month), mature (12 month) and senescent (24 month) Wistar rats showed no age-related changes. Further, the amount of [ 3 H]DA accumulated in the striatal slices showed no changes with age. Thus, previously reported age-related deficits in motor behavior (i.e. rotational) are not produced by changes in striatal DA accumulation or release. (Auth.)

  7. Adversity in childhood linked to elevated striatal dopamine function in adulthood

    OpenAIRE

    Egerton, A.; Valmaggia, L. R.; Howes, O. D.; Day, F.; Chaddock, C. A.; Allen, P.; Winton-Brown, T. T.; Bloomfield, M. A. P.; Bhattacharyya, S.; Chilcott, J.; Lappin, J. M.; Murray, R. M.; McGuire, P.

    2016-01-01

    Childhood adversity increases the risk of psychosis in adulthood. Theoretical and animal models suggest that this effect may be mediated by increased striatal dopamine neurotransmission. The primary objective of this study was to examine the relationship between adversity in childhood and striatal dopamine function in early adulthood. Secondary objectives were to compare exposure to childhood adversity and striatal dopamine function in young people at ultra high risk (UHR) of psychosis and he...

  8. Impaired striatal Akt signaling disrupts dopamine homeostasis and increases feeding.

    Directory of Open Access Journals (Sweden)

    Nicole Speed

    Full Text Available The prevalence of obesity has increased dramatically worldwide. The obesity epidemic begs for novel concepts and therapeutic targets that cohesively address "food-abuse" disorders. We demonstrate a molecular link between impairment of a central kinase (Akt involved in insulin signaling induced by exposure to a high-fat (HF diet and dysregulation of higher order circuitry involved in feeding. Dopamine (DA rich brain structures, such as striatum, provide motivation stimuli for feeding. In these central circuitries, DA dysfunction is posited to contribute to obesity pathogenesis. We identified a mechanistic link between metabolic dysregulation and the maladaptive behaviors that potentiate weight gain. Insulin, a hormone in the periphery, also acts centrally to regulate both homeostatic and reward-based HF feeding. It regulates DA homeostasis, in part, by controlling a key element in DA clearance, the DA transporter (DAT. Upon HF feeding, nigro-striatal neurons rapidly develop insulin signaling deficiencies, causing increased HF calorie intake.We show that consumption of fat-rich food impairs striatal activation of the insulin-activated signaling kinase, Akt. HF-induced Akt impairment, in turn, reduces DAT cell surface expression and function, thereby decreasing DA homeostasis and amphetamine (AMPH-induced DA efflux. In addition, HF-mediated dysregulation of Akt signaling impairs DA-related behaviors such as (AMPH-induced locomotion and increased caloric intake. We restored nigro-striatal Akt phosphorylation using recombinant viral vector expression technology. We observed a rescue of DAT expression in HF fed rats, which was associated with a return of locomotor responses to AMPH and normalization of HF diet-induced hyperphagia.Acquired disruption of brain insulin action may confer risk for and/or underlie "food-abuse" disorders and the recalcitrance of obesity. This molecular model, thus, explains how even short-term exposure to "the fast food

  9. Mechanisms mediating parallel action monitoring in fronto-striatal circuits.

    Science.gov (United States)

    Beste, Christian; Ness, Vanessa; Lukas, Carsten; Hoffmann, Rainer; Stüwe, Sven; Falkenstein, Michael; Saft, Carsten

    2012-08-01

    Flexible response adaptation and the control of conflicting information play a pivotal role in daily life. Yet, little is known about the neuronal mechanisms mediating parallel control of these processes. We examined these mechanisms using a multi-methodological approach that integrated data from event-related potentials (ERPs) with structural MRI data and source localisation using sLORETA. Moreover, we calculated evoked wavelet oscillations. We applied this multi-methodological approach in healthy subjects and patients in a prodromal phase of a major basal ganglia disorder (i.e., Huntington's disease), to directly focus on fronto-striatal networks. Behavioural data indicated, especially the parallel execution of conflict monitoring and flexible response adaptation was modulated across the examined cohorts. When both processes do not co-incide a high integrity of fronto-striatal loops seems to be dispensable. The neurophysiological data suggests that conflict monitoring (reflected by the N2 ERP) and working memory processes (reflected by the P3 ERP) differentially contribute to this pattern of results. Flexible response adaptation under the constraint of high conflict processing affected the N2 and P3 ERP, as well as their delta frequency band oscillations. Yet, modulatory effects were strongest for the N2 ERP and evoked wavelet oscillations in this time range. The N2 ERPs were localized in the anterior cingulate cortex (BA32, BA24). Modulations of the P3 ERP were localized in parietal areas (BA7). In addition, MRI-determined caudate head volume predicted modulations in conflict monitoring, but not working memory processes. The results show how parallel conflict monitoring and flexible adaptation of action is mediated via fronto-striatal networks. While both, response monitoring and working memory processes seem to play a role, especially response selection processes and ACC-basal ganglia networks seem to be the driving force in mediating parallel conflict

  10. Neuroinflammation alters voltage-dependent conductance in striatal astrocytes.

    Science.gov (United States)

    Karpuk, Nikolay; Burkovetskaya, Maria; Kielian, Tammy

    2012-07-01

    Neuroinflammation has the capacity to alter normal central nervous system (CNS) homeostasis and function. The objective of the present study was to examine the effects of an inflammatory milieu on the electrophysiological properties of striatal astrocyte subpopulations with a mouse bacterial brain abscess model. Whole cell patch-clamp recordings were performed in striatal glial fibrillary acidic protein (GFAP)-green fluorescent protein (GFP)(+) astrocytes neighboring abscesses at postinfection days 3 or 7 in adult mice. Cell input conductance (G(i)) measurements spanning a membrane potential (V(m)) surrounding resting membrane potential (RMP) revealed two prevalent astrocyte subsets. A1 and A2 astrocytes were identified by negative and positive G(i) increments vs. V(m), respectively. A1 and A2 astrocytes displayed significantly different RMP, G(i), and cell membrane capacitance that were influenced by both time after bacterial exposure and astrocyte proximity to the inflammatory site. Specifically, the percentage of A1 astrocytes was decreased immediately surrounding the inflammatory lesion, whereas A2 cells were increased. These changes were particularly evident at postinfection day 7, revealing increased cell numbers with an outward current component. Furthermore, RMP was inversely modified in A1 and A2 astrocytes during neuroinflammation, and resting G(i) was increased from 21 to 30 nS in the latter. In contrast, gap junction communication was significantly decreased in all astrocyte populations associated with inflamed tissues. Collectively, these findings demonstrate the heterogeneity of striatal astrocyte populations, which experience distinct electrophysiological modifications in response to CNS inflammation.

  11. PSIHOLOŠKI UČINKI MOČI

    OpenAIRE

    Ropert, Tadevž

    2015-01-01

    V zadnjem desetletju je v socialni psihologiji opazen izjemen porast raziskav o moči, zlasti o njenih številnih psiholoških učinkih. Pričujoče magistrsko delo v ospredje postavlja vpliv moči na neetično vedenje, ki je po dosedanjih ugotovitvah kompleksen in vsebuje več moderatorjev. Ker je nedavna raziskava pokazala, da del dneva vpliva na pojavnost neetičnega vedenja (Kouchaki in Smith, 2014), tj., da se pojavi učinek jutranje moralnosti, smo poskusili ugotovitve obeh področij integrirati. N...

  12. MOBING - POJAV, KI ŠKODUJE DELODAJALCU IN DELAVCU

    OpenAIRE

    Bogataj, Alenka

    2012-01-01

    Živimo v času, ko so pri nas delo, zaposlitev, poklic, kariera in delovni uspeh uvrščeni visoko na lestvici družbenih vrednot. Posledično postaja vse pomembnejše tudi dostojanstvo na delovnem mestu. Dostojanstvo na delovnem mestu pa je ključna sestavina obče človeške potrebe in pravice do dostojanstvenega življenja, je temeljna civilizacijska norma in nesporno dejstvo. Delovno mesto je kraj, ki nam omogoča dostojno preživetje. Je tudi kraj, kjer preživimo vsaj osem ur dnevno in kamor naj ...

  13. Simbolisme Kompleks Bangunan Situs Ki Buyut Trusmi Cirebon

    Directory of Open Access Journals (Sweden)

    Muhammad Al Mujabuddawat

    2016-12-01

    Full Text Available Ki Buyut Trusmi Site is a burial site bounded by walls surrounding the complex site. In the complex area of the site, several buildings scattered in the barrier wall of the spatial division sites as many as 4 cemetery yard; West, East, Central, and North. The buildings are in the midst of hundreds of tombs in the complex area of the site. Based on the results of an overview of the physical form and position of the object of those buildings, it is understood that every buildings has its function and symbolic meaning. The position of the components of the building symbolically form a plan groove toward the main location of the most sanctified, the graves of Ki Gede Trusmi and Prince Trusmi in North yard site. Based on symbolic significance and hundred of tombs scattered in the area of the site, they are clearly show a blend of Islamic buildings affected by local culture which already existed, with the animism and Hindu-Buddhist. Those cultural blends form a pre-Islamic cultural treasures material which tangible on the architecture of the building full of symbolism outside the real Islamic law. Local culture become part of construction to the Islamization of local communities, Islam developed in the area Trusmi shows Islamic character integrative and accommodating to the local indigenous community.   Situs Ki Buyut Trusmi merupakan situs pemakaman yang dibatasi oleh tembok keliling yang mengelilingi kompleks situs. Dalam area kompleks situs, berdiri sejumlah bangunan yang tersebar dalam sekat-sekat tembok pembagian halaman situs sebanyak 4 halaman, yaitu Halaman barat, Halaman timur, Halaman tengah, dan Halaman utara. Bangunan-bangunan tersebut berdiri ditengah-tengah ratusan makam di dalam area kompleks situs. Berdasarkan hasil tinjauan terhadap bentuk fisik dan keletakan dari objek bangunan-bangunan tersebut, diketahui memiliki fungsi dan makna simbolik tersendiri. Keletakan komponen-komponen bangunannya secara simbolis membentuk denah alur

  14. HIV infection results in ventral-striatal reward system hypo-activation during cue processing

    NARCIS (Netherlands)

    Plessis, Stéfan du; Vink, Matthijs; Joska, John A; Koutsilieri, Eleni; Bagadia, Asif; Stein, Dan J; Emsley, Robin

    2015-01-01

    OBJECTIVE: Functional MRI has thus far demonstrated that HIV has an impact on frontal-striatal systems involved in executive functioning. The potential impact of HIV on frontal-striatal systems involved in reward processing has yet to be examined by functional MRI. This study therefore aims to

  15. Fronto-striatal atrophy correlates of neuropsychiatric dysfunction in frontotemporal dementia (FTD and Alzheimer's disease (AD

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    Dong Seok Yi

    Full Text Available ABSTRACT Behavioural disturbances in frontotemporal dementia (FTD are thought to reflect mainly atrophy of cortical regions. Recent studies suggest that subcortical brain regions, in particular the striatum, are also significantly affected and this pathology might play a role in the generation of behavioural symptoms. Objective: To investigate prefrontal cortical and striatal atrophy contributions to behavioural symptoms in FTD. Methods: One hundred and eighty-two participants (87 FTD patients, 39 AD patients and 56 controls were included. Behavioural profiles were established using the Cambridge Behavioural Inventory Revised (CBI-R and Frontal System Behaviour Scale (FrSBe. Atrophy in prefrontal (VMPFC, DLPFC and striatal (caudate, putamen regions was established via a 5-point visual rating scale of the MRI scans. Behavioural scores were correlated with atrophy rating scores. Results: Behavioural and atrophy ratings demonstrated that patients were significantly impaired compared to controls, with bvFTD being most severely affected. Behavioural-anatomical correlations revealed that VMPFC atrophy was closely related to abnormal behaviour and motivation disturbances. Stereotypical behaviours were associated with both VMPFC and striatal atrophy. By contrast, disturbance of eating was found to be related to striatal atrophy only. Conclusion: Frontal and striatal atrophy contributed to the behavioural disturbances seen in FTD, with some behaviours related to frontal, striatal or combined fronto-striatal pathology. Consideration of striatal contributions to the generation of behavioural disturbances should be taken into account when assessing patients with potential FTD.

  16. Adenosine Receptor Heteromers and their Integrative Role in Striatal Function

    Directory of Open Access Journals (Sweden)

    Sergi Ferré

    2007-01-01

    Full Text Available By analyzing the functional role of adenosine receptor heteromers, we review a series of new concepts that should modify our classical views of neurotransmission in the central nervous system (CNS. Neurotransmitter receptors cannot be considered as single functional units anymore. Heteromerization of neurotransmitter receptors confers functional entities that possess different biochemical characteristics with respect to the individual components of the heteromer. Some of these characteristics can be used as a “biochemical fingerprint” to identify neurotransmitter receptor heteromers in the CNS. This is exemplified by changes in binding characteristics that are dependent on coactivation of the receptor units of different adenosine receptor heteromers. Neurotransmitter receptor heteromers can act as “processors” of computations that modulate cell signaling, sometimes critically involved in the control of pre- and postsynaptic neurotransmission. For instance, the adenosine A1-A2A receptor heteromer acts as a concentration-dependent switch that controls striatal glutamatergic neurotransmission. Neurotransmitter receptor heteromers play a particularly important integrative role in the “local module” (the minimal portion of one or more neurons and/or one or more glial cells that operates as an independent integrative unit, where they act as processors mediating computations that convey information from diverse volume-transmitted signals. For instance, the adenosine A2A-dopamine D2 receptor heteromers work as integrators of two different neurotransmitters in the striatal spine module.

  17. Reward inference by primate prefrontal and striatal neurons.

    Science.gov (United States)

    Pan, Xiaochuan; Fan, Hongwei; Sawa, Kosuke; Tsuda, Ichiro; Tsukada, Minoru; Sakagami, Masamichi

    2014-01-22

    The brain contains multiple yet distinct systems involved in reward prediction. To understand the nature of these processes, we recorded single-unit activity from the lateral prefrontal cortex (LPFC) and the striatum in monkeys performing a reward inference task using an asymmetric reward schedule. We found that neurons both in the LPFC and in the striatum predicted reward values for stimuli that had been previously well experienced with set reward quantities in the asymmetric reward task. Importantly, these LPFC neurons could predict the reward value of a stimulus using transitive inference even when the monkeys had not yet learned the stimulus-reward association directly; whereas these striatal neurons did not show such an ability. Nevertheless, because there were two set amounts of reward (large and small), the selected striatal neurons were able to exclusively infer the reward value (e.g., large) of one novel stimulus from a pair after directly experiencing the alternative stimulus with the other reward value (e.g., small). Our results suggest that although neurons that predict reward value for old stimuli in the LPFC could also do so for new stimuli via transitive inference, those in the striatum could only predict reward for new stimuli via exclusive inference. Moreover, the striatum showed more complex functions than was surmised previously for model-free learning.

  18. Pyrethroid insecticides evoke neurotransmitter release from rabbit striatal slices

    International Nuclear Information System (INIS)

    Eells, J.T.; Dubocovich, M.L.

    1988-01-01

    The effects of the synthetic pyrethroid insecticide fenvalerate ([R,S]-alpha-cyano-3-phenoxybenzyl[R,S]-2-(4-chlorophenyl)-3- methylbutyrate) on neurotransmitter release in rabbit brain slices were investigated. Fenvalerate evoked a calcium-dependent release of [ 3 H]dopamine and [ 3 H]acetylcholine from rabbit striatal slices that was concentration-dependent and specific for the toxic stereoisomer of the insecticide. The release of [ 3 H]dopamine and [ 3 H]acetylcholine by fenvalerate was modulated by D2 dopamine receptor activation and antagonized completely by the sodium channel blocker, tetrodotoxin. These findings are consistent with an action of fenvalerate on the voltage-dependent sodium channels of the presynaptic membrane resulting in membrane depolarization, and the release of dopamine and acetylcholine by a calcium-dependent exocytotic process. In contrast to results obtained in striatal slices, fenvalerate did not elicit the release of [ 3 H]norepinephrine or [ 3 H]acetylcholine from rabbit hippocampal slices indicative of regional differences in sensitivity to type II pyrethroid actions

  19. Is Ki67 prognostic for aggressive prostate cancer? A multicenter real-world study.

    Science.gov (United States)

    Fantony, Joseph J; Howard, Lauren E; Csizmadi, Ilona; Armstrong, Andrew J; Lark, Amy L; Galet, Colette; Aronson, William J; Freedland, Stephen J

    2018-06-15

    To test if Ki67 expression is prognostic for biochemical recurrence (BCR) after radical prostatectomy (RP). Ki67 immunohistochemistry was performed on tissue microarrays constructed from specimens obtained from 464 men undergoing RP at the Durham and West LA Veterans Affairs Hospitals. Hazard ratios (HR) for Ki67 expression and time to BCR were estimated using Cox regression. Ki67 was associated with more recent surgery year (p < 0.001), positive margins (p = 0.001) and extracapsular extension (p < 0.001). In center-stratified analyses, the adjusted HR for Ki67 expression and BCR approached statistical significance for west LA (HR: 1.54; p = 0.06), but not Durham (HR: 1.10; p = 0.74). This multi-institutional 'real-world' study provides limited evidence for the prognostic role of Ki67 in predicting outcome after RP.

  20. Digital image analysis of Ki67 in hot spots is superior to both manual Ki67 and mitotic counts in breast cancer.

    Science.gov (United States)

    Stålhammar, Gustav; Robertson, Stephanie; Wedlund, Lena; Lippert, Michael; Rantalainen, Mattias; Bergh, Jonas; Hartman, Johan

    2018-05-01

    During pathological examination of breast tumours, proliferative activity is routinely evaluated by a count of mitoses. Adding immunohistochemical stains of Ki67 provides extra prognostic and predictive information. However, the currently used methods for these evaluations suffer from imperfect reproducibility. It is still unclear whether analysis of Ki67 should be performed in hot spots, in the tumour periphery, or as an average of the whole tumour section. The aim of this study was to compare the clinical relevance of mitoses, Ki67 and phosphohistone H3 in two cohorts of primary breast cancer specimens (total n = 294). Both manual and digital image analysis scores were evaluated for sensitivity and specificity for luminal B versus A subtype as defined by PAM50 gene expression assays, for high versus low transcriptomic grade, for axillary lymph node status, and for prognostic value in terms of prediction of overall and relapse-free survival. Digital image analysis of Ki67 outperformed the other markers, especially in hot spots. Tumours with high Ki67 expression and high numbers of phosphohistone H3-positive cells had significantly increased hazard ratios for all-cause mortality within 10 years from diagnosis. Replacing manual mitotic counts with digital image analysis of Ki67 in hot spots increased the differences in overall survival between the highest and lowest histological grades, and added significant prognostic information. Digital image analysis of Ki67 in hot spots is the marker of choice for routine analysis of proliferation in breast cancer. © 2017 John Wiley & Sons Ltd.

  1. New insight into Ki67 expression at the invasive front in breast cancer.

    Directory of Open Access Journals (Sweden)

    Peng Gong

    Full Text Available To investigate the distribution of Ki67+ cells in breast cancer in relation to clinical-pathological parameters and prognosis.Ki67 expression status was detected in 1,086 breast cancer specimens using immunohistochemistry staining and examining the relationship between the Ki67+ cells' location. Subsequently, clinical-pathological parameters and prognosis were determined.In total, Ki67 protein expression was found in 781 (71.92% of the 1,086 breast cancer specimens. Among the 781 Ki67+ cases, 461 were defined as diffuse type and 320 were defined as borderline type. After universal correlation analysis, significant differences were observed in age, histological grade, metastatic nodes, postoperative distant metastasis, and molecular subtype between Ki67+ and Ki67- cases (P = 0.01, 0.001, 0.001, 0.001, and 0.001, respectively. After subgroup analysis, the borderline cases were found to be characterized by a high distant metastasis rate compared to the diffuse cases as well as the Ki67- cases (P = 0.001. No differences were observed between diffuse type or Ki67- cases (P = 0.105. Multivariate analysis showed that age, tumor size, histological grade, lymph node metastasis, molecular subtype, and the Ki67 distribution pattern were observed to be related to postoperative distant metastasis (all P<0.05. Furthermore, borderline type was shown to attain a significantly more distant bone and liver metastasis and worse disease-specific survival than the other types (P = 0.001. In the Cox regression test, the Ki67 distribution pattern was detected as an independent prognostic factor (P = 0.001.The distribution pattern of Ki67 may be a new independent prognostic factor for breast cancer.

  2. Suppression of cell division by pKi-67 antisense-RNA and recombinant protein.

    Science.gov (United States)

    Duchrow, M; Schmidt, M H; Zingler, M; Anemüller, S; Bruch, H P; Broll, R

    2001-01-01

    The human antigen defined by the monoclonal antibody Ki-67 (pKi-67) is a human nuclear protein strongly associated with cell proliferation and found in all tissues studied. It is widely used as a marker of proliferating cells, yet its function is unknown. To investigate its function we suppressed pKi-67 expression by antisense RNA and overexpressed a partial structure of pKi-67 in HeLa cells. A BrdU-incorporation assay showed a significant decrease in DNA synthesis after antisense inhibition. Cell cycle analysis indicated a higher proportion of cells in G1 phase and a lower proportion of cells in S phase while the number of G(2)/M phase cells remained constant. Overexpression of a recombinant protein encoding three of the repetitive elements from exon 13 of pKi-67 had a similar effect to that obtained by antisense inhibition. The similarity of the effect of expressing 'Ki-67 repeats' and pKi-67 antisense RNA could be explained by a negative effect on the folding of the endogenous protein in the endoplasmatic reticulum. Furthermore excessive self-association of pKi-67 via the repeat structure could inhibit its nuclear transport, preventing it from getting to its presumptive site of action. We conclude that the Ki-67 protein has an important role in the regulation of the cell cycle, which is mediated in part by its repetitive elements. Copyright 2001 S. Karger AG, Basel

  3. Sexualidad violenta en el cine de Kim Ki-duk

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    Daniel Muñoz Ruiz

    2011-07-01

    Full Text Available En sus más de 110 años de vida el cine ha representado la sexualidad humana en todas sus modalidades y desde los más variados puntos de vista. El cine de Kim Ki-duk ha sorprendido y escandalizado al público por su crudeza y, a veces, excesiva violencia. El director surcoreano ha explorado a lo largo de su filmografía el tema del sexo siempre desde puntos de vista dramáticos y hasta truculentos. En sus películas la mayoría de las relaciones sexuales carecen de amor y afecto. Nunca son placenteras. La violación, la prostitución, la violencia de género y las frustraciones sexuales son temas recurrentes en su cine.

  4. Impact of intratumoural heterogeneity on the assessment of Ki67 expression in breast cancer.

    Science.gov (United States)

    Aleskandarany, M A; Green, A R; Ashankyty, I; Elmouna, A; Diez-Rodriguez, M; Nolan, C C; Ellis, I O; Rakha, E A

    2016-07-01

    In breast cancer (BC), the prognostic value of Ki67 expression is well-documented. Intratumoural heterogeneity (ITH) of Ki67 expression is amongst the several technical issues behind the lag of its inclusion into BC prognostic work-up. The immunohistochemical (IHC) expression of anti-Ki67 antibody (MIB1 clone) was assessed in four full-face (FF) sections from different primary tumour blocks and their matched axillary nodal (LN) metastases in a series of 55 BC. Assessment was made using the highest expression hot spots (HS), lowest expression (LS), and overall/average expression scores (AS) in each section. Heterogeneity score (Hes), co-efficient of variation, and correlation co-efficient were used to assess the levels of Ki67 ITH. Ki67 HS, LS, and AS scores were highly variable within the same section and between different sections of the primary tumour, with maximal variation observed in the LS (P < 0.001). The least variability between the different slides was observed with HS scoring. Although the associations between Ki67 and clinicopathological and molecular variables were similar when using HS or AS, the best correlation between AS and HS was observed in tumours with high Ki67 expression only. Ki67 expression in LN deposits was less heterogeneous than in the primary tumours and was perfectly correlated with the HS Ki67 expression in the primary tumour sections (r = 0.98, P < 0.001). In conclusion, assessment of Ki67 expression using HS scoring method on a full-face BC tissue section can represent the primary tumour growth fraction that is likely to metastasise. The association between Ki67 expression pattern in the LN metastasis and the HS in the primary tumour may reflect the temporal heterogeneity through clonal expansion.

  5. Clinical and histopathological factors associated with Ki-67 expression in breast cancer patients

    Science.gov (United States)

    ALCO, GUL; BOZDOGAN, ATILLA; SELAMOGLU, DERYA; PILANCI, KEZBAN NUR; TUZLALI, SITKI; ORDU, CETIN; IGDEM, SEFIK; OKKAN, SAIT; DINCER, MAKTAV; DEMIR, GOKHAN; OZMEN, VAHIT

    2015-01-01

    The aim of the present study was to identify the optimal Ki-67 cut-off value in breast cancer (BC) patients, and investigate the association of Ki-67 expression levels with other prognostic factors. Firstly, a retrospective search was performed to identify patients with stage I–III BC (n=462). A range of Ki-67 index values were then assigned to five groups (<10, 10–14, 15–19, 20–24 and ≥25%). The correlation between the Ki-67 index and other prognostic factors [age, tumor type, histological and nuclear grade, tumor size, multifocality, an in situ component, lymphovascular invasion (LVI), estrogen and progesterone receptor (ER/PR) expression, human epidermal growth factor receptor (HER-2) status, axillary involvement and tumor stage] were investigated in each group. The median Ki-67 value was revealed to be 20% (range, 1–95%). A young age (≤40 years old), tumor type, size and grade, LVI, ER/PR negativity and HER-2 positivity were revealed to be associated with the Ki-67 level. Furthermore, Ki-67 was demonstrated to be negatively correlated with ER/PR expression (P<0.001), but positively correlated with tumor size (P<0.001). The multivariate analysis revealed that a Ki-67 value of ≥15% was associated with the largest number of poor prognostic factors (P=0.036). In addition, a Ki-67 value of ≥15% was identified to be statistically significant in association with certain luminal subtypes. The rate of disease-free survival was higher in patients with luminal A subtype BC (P=0.036). Following the correlation analysis for the Ki-67 index and the other prognostic factors, a Ki-67 value of ≥15% was revealed to be the optimal cut-off level for BC patients. PMID:25663855

  6. Striatal dopamine release induced by repetitive transcranial magnetic stimulation over dorsolateral prefrontal cortex: effect of aging

    International Nuclear Information System (INIS)

    Bang, Seong Ae; Cho, Sang Soo; Yoon, Eun Jin; Kim, Ji Sun; Lee, Byung Chul; Kim, Yu Kyeong; Kim, Sang Eun

    2007-01-01

    We previously demonstrated dopamine (DA) release in the bilateral striatal regions following prefrontal repetitive transcranial magnetic stimulation (rTMS) in young subjects. Several lines of evidence support substantial age-related changes in human dopaminergic neurotransmission. One possible explanation is alteration of cortico striatal neural connection with aging. Therefore, we investigated how frontal activation by rTMS influences striatal DA release in the elderly with SPECT measurements of striatal binding of [123I]iodobenzamide (lBZM), a DA D2 receptor radioligand that is sensitive to endogenous DA. Five healthy elderly male subjects (age, 64 3 y) were studied with brain [123I]IBZM SPECT under three conditions (resting, sham stimulation, and active rTMS over left dorsolateral prefrontal cortex (DLPFC)), while receiving a bolus plus constant infusion of [123I]IBZM. rTMS session consisted of three blocks. In each block, 15 trains of 2 sec duration were delivered with 10 Hz stimulation frequency and 100% motor threshold. Striatal V3', calculated as (striatal - occipital)/occipital radioactivity, was measured under equilibrium condition at baseline and after sham and active rTMS. Sham stimulation did not affect striatal V3'. rTMS over left DLPFC induced no significant change in V3' in the right striatum compared with baseline condition (0.91 0.25 vs. 0.96 0.25, P = NS). Interestingly, left striatal V3' showed a significant increase after rTMS over left DLPFC compared with sham condition (1.09 0.33 vs. 0.93 0.27, P < 0.05; 17.0 11.1% increase). These results are discrepant from previous ones from young subjects, who showed frontal rTMS-induced reduction of striatal V3', indicating rTMS-induced striatal DA release. We found no significant striatal DA release induced by rTMS over DLPFC in healthy elderly subjects using in vivo binding competition techniques. These results may support an altered cortico striatal circuit in normal aging

  7. Striatal dopamine release induced by repetitive transcranial magnetic stimulation over dorsolateral prefrontal cortex: effect of aging

    Energy Technology Data Exchange (ETDEWEB)

    Bang, Seong Ae; Cho, Sang Soo; Yoon, Eun Jin; Kim, Ji Sun; Lee, Byung Chul; Kim, Yu Kyeong; Kim, Sang Eun [Seoul National Univ. College of Medicine, Seoul (Korea, Republic of)

    2007-07-01

    We previously demonstrated dopamine (DA) release in the bilateral striatal regions following prefrontal repetitive transcranial magnetic stimulation (rTMS) in young subjects. Several lines of evidence support substantial age-related changes in human dopaminergic neurotransmission. One possible explanation is alteration of cortico striatal neural connection with aging. Therefore, we investigated how frontal activation by rTMS influences striatal DA release in the elderly with SPECT measurements of striatal binding of [123I]iodobenzamide (lBZM), a DA D2 receptor radioligand that is sensitive to endogenous DA. Five healthy elderly male subjects (age, 64 3 y) were studied with brain [123I]IBZM SPECT under three conditions (resting, sham stimulation, and active rTMS over left dorsolateral prefrontal cortex (DLPFC)), while receiving a bolus plus constant infusion of [123I]IBZM. rTMS session consisted of three blocks. In each block, 15 trains of 2 sec duration were delivered with 10 Hz stimulation frequency and 100% motor threshold. Striatal V3', calculated as (striatal - occipital)/occipital radioactivity, was measured under equilibrium condition at baseline and after sham and active rTMS. Sham stimulation did not affect striatal V3'. rTMS over left DLPFC induced no significant change in V3' in the right striatum compared with baseline condition (0.91 0.25 vs. 0.96 0.25, P = NS). Interestingly, left striatal V3' showed a significant increase after rTMS over left DLPFC compared with sham condition (1.09 0.33 vs. 0.93 0.27, P < 0.05; 17.0 11.1% increase). These results are discrepant from previous ones from young subjects, who showed frontal rTMS-induced reduction of striatal V3', indicating rTMS-induced striatal DA release. We found no significant striatal DA release induced by rTMS over DLPFC in healthy elderly subjects using in vivo binding competition techniques. These results may support an altered cortico striatal circuit in normal aging.

  8. Ventral striatal activity links adversity and reward processing in children.

    Science.gov (United States)

    Kamkar, Niki H; Lewis, Daniel J; van den Bos, Wouter; Morton, J Bruce

    2017-08-01

    Adversity impacts many aspects of psychological and physical development including reward-based learning and decision-making. Mechanisms relating adversity and reward processing in children, however, remain unclear. Here, we show that adversity is associated with potentiated learning from positive outcomes and impulsive decision-making, but unrelated to learning from negative outcomes. We then show via functional magnetic resonance imaging that the link between adversity and reward processing is partially mediated by differences in ventral striatal response to rewards. The findings suggest that early-life adversity is associated with alterations in the brain's sensitivity to rewards accounting, in part, for the link between adversity and altered reward processing in children. Copyright © 2017 The Authors. Published by Elsevier Ltd.. All rights reserved.

  9. Striatal activation reflects urgency in perceptual decision making.

    Science.gov (United States)

    van Maanen, Leendert; Fontanesi, Laura; Hawkins, Guy E; Forstmann, Birte U

    2016-10-01

    Deciding between multiple courses of action often entails an increasing need to do something as time passes - a sense of urgency. This notion of urgency is not incorporated in standard theories of speeded decision making that assume information is accumulated until a critical fixed threshold is reached. Yet, it is hypothesized in novel theoretical models of decision making. In two experiments, we investigated the behavioral and neural evidence for an "urgency signal" in human perceptual decision making. Experiment 1 found that as the duration of the decision making process increased, participants made a choice based on less evidence for the selected option. Experiment 2 replicated this finding, and additionally found that variability in this effect across participants covaried with activation in the striatum. We conclude that individual differences in susceptibility to urgency are reflected by striatal activation. By dynamically updating a response threshold, the striatum is involved in signaling urgency in humans. Copyright © 2016 Elsevier Inc. All rights reserved.

  10. Regulation of drugs affecting striatal cholinergic activity by corticostriatal projections

    International Nuclear Information System (INIS)

    Ladinsky, H.

    1986-01-01

    Research demonstrates that the chronic degeneration of the corticostriatal excitatory pathway makes the cholinergic neurons of the striatum insensitive to the neuropharmacological action of a number of different drugs. Female rats were used; they were killed and after the i.v. infusion of tritium-choline precursor, choline acetyltransferase activity was measured. Striatal noradrenaline, dopamine and serotonin content was measured by electrochemical detection coupled with high pressure liquid chromatography. Uptake of tritium-glutamic acid was estimated. The data were analyzed statistically. It is shown that there is evidence that the effects of a number of drugs capable of depressing cholinergic activity through receptor-mediated responses are operative only if the corticostriatal pathway is integral. Neuropharmacological responses in the brain appear to be the result of an interaction between several major neurotransmitter systems

  11. Ventral striatal activity links adversity and reward processing in children

    Directory of Open Access Journals (Sweden)

    Niki H. Kamkar

    2017-08-01

    Full Text Available Adversity impacts many aspects of psychological and physical development including reward-based learning and decision-making. Mechanisms relating adversity and reward processing in children, however, remain unclear. Here, we show that adversity is associated with potentiated learning from positive outcomes and impulsive decision-making, but unrelated to learning from negative outcomes. We then show via functional magnetic resonance imaging that the link between adversity and reward processing is partially mediated by differences in ventral striatal response to rewards. The findings suggest that early-life adversity is associated with alterations in the brain’s sensitivity to rewards accounting, in part, for the link between adversity and altered reward processing in children.

  12. Speech-induced striatal dopamine release is left lateralized and coupled to functional striatal circuits in healthy humans: A combined PET, fMRI and DTI study

    Science.gov (United States)

    Simonyan, Kristina; Herscovitch, Peter; Horwitz, Barry

    2013-01-01

    Considerable progress has been recently made in understanding the brain mechanisms underlying speech and language control. However, the neurochemical underpinnings of normal speech production remain largely unknown. We investigated the extent of striatal endogenous dopamine release and its influences on the organization of functional striatal speech networks during production of meaningful English sentences using a combination of positron emission tomography (PET) with the dopamine D2/D3 receptor radioligand [11C]raclopride and functional MRI (fMRI). In addition, we used diffusion tensor tractography (DTI) to examine the extent of dopaminergic modulatory influences on striatal structural network organization. We found that, during sentence production, endogenous dopamine was released in the ventromedial portion of the dorsal striatum, in its both associative and sensorimotor functional divisions. In the associative striatum, speech-induced dopamine release established a significant relationship with neural activity and influenced the left-hemispheric lateralization of striatal functional networks. In contrast, there were no significant effects of endogenous dopamine release on the lateralization of striatal structural networks. Our data provide the first evidence for endogenous dopamine release in the dorsal striatum during normal speaking and point to the possible mechanisms behind the modulatory influences of dopamine on the organization of functional brain circuits controlling normal human speech. PMID:23277111

  13. Intratumoral heterogeneity of Ki67 expression in early breast cancers exceeds variability between individual tumours

    NARCIS (Netherlands)

    Focke, Cornelia M.; Decker, Thomas; van Diest, Paul J.

    2016-01-01

    Aims: Regional differences in proliferative activity are commonly seen within breast cancers, but little is known on the extent of intratumoral heterogeneity of Ki67 expression. Our aim was to study the intratumoral heterogeneity of Ki67 expression in early breast cancers and its association with

  14. Standardizing evaluation of sarcoma proliferation- higher Ki-67 expression in the tumor periphery than the center

    DEFF Research Database (Denmark)

    Fernebro, J; Engellau, J; Persson, A

    2007-01-01

    Soft tissue sarcomas often present as large and histopathologically heterogenous tumors. Proliferation has repeatedly been identified as a prognostic factor and immunostaining for Ki-67 represents the most commonly used proliferation marker. There is, however, a lack of consensus on how to evaluate...... of proliferation in soft tissue sarcomas should be standardized for clinical application of Ki-67 as a prognostic marker....

  15. Correlation of diffusion and perfusion MRI with Ki-67 in high-grade meningiomas.

    Science.gov (United States)

    Ginat, Daniel T; Mangla, Rajiv; Yeaney, Gabrielle; Wang, Henry Z

    2010-12-01

    Atypical and anaplastic meningiomas have a greater likelihood of recurrence than benign meningiomas. The risk for recurrence is often estimated using the Ki-67 labeling index. The purpose of this study was to determine the correlation between Ki-67 and regional cerebral blood volume (rCBV) and between Ki-67 and apparent diffusion coefficient (ADC) in atypical and anaplastic meningiomas. A retrospective review of the advanced imaging and immunohistochemical characteristics of atypical and anaplastic meningiomas was performed. The relative minimum ADC, relative maximum rCBV, and specimen Ki-67 index were measured. Pearson's correlation was used to compare these parameters. There were 23 cases with available ADC maps and 20 cases with available rCBV maps. The average Ki-67 among the cases with ADC maps and rCBV maps was 17.6% (range, 5-38%) and 16.7% (range, 3-38%), respectively. The mean minimum ADC ratio was 0.91 (SD, 0.26) and the mean maximum rCBV ratio was 22.5 (SD, 7.9). There was a significant positive correlation between maximum rCBV and Ki-67 (Pearson's correlation, 0.69; p = 0.00038). However, there was no significant correlation between minimum ADC and Ki-67 (Pearson's correlation, -0.051; p = 0.70). Maximum rCBV correlated significantly with Ki-67 in high-grade meningiomas.

  16. An inter-observer Ki67 reproducibility study applying two different assessment methods

    DEFF Research Database (Denmark)

    Laenkholm, Anne-Vibeke; Grabau, Dorthe; Møller Talman, Maj-Lis

    2018-01-01

    INTRODUCTION: In 2011, the St. Gallen Consensus Conference introduced the use of pathology to define the intrinsic breast cancer subtypes by application of immunohistochemical (IHC) surrogate markers ER, PR, HER2 and Ki67 with a specified Ki67 cutoff (>14%) for luminal B-like definition. Reports...

  17. Striatal and extra-striatal dopamine transporter in cannabis and tobacco addiction: a high resolution PET study

    International Nuclear Information System (INIS)

    Leroy, C.; Martinot, J.L.; Duchesnay, E.; Artiges, E.; Ribeiro, M.J.; Trichard, Ch.; Karila, L.; Lukasiewicz, M.; Benyamina, A.; Reynaud, M.; Martinot, J.L.; Duchesnay, E.; Artiges, E.; Comtat, C.; Artiges, E.; Trichard, Ch.

    2011-01-01

    The dopamine (DA) system is known to be involved in the reward and dependence mechanisms of addiction. However, modifications in dopaminergic neurotransmission associated with long-term tobacco and cannabis use have been poorly documented in vivo. In order to assess striatal and extra-striatal dopamine transporter (DAT) availability in tobacco and cannabis addiction, three groups of male age-matched subjects were compared: 11 healthy non-smoker subjects, 14 tobacco-dependent smokers (17.6 ± 5.3 cigarettes/day for 12.1 ± 8.5 years) and 13 cannabis and tobacco smokers (CTS) (4.8 ± 5.3 cannabis joints/day for 8.7 ± 3.9 years). DAT availability was examined in positron emission tomography (HRRT) with a high resolution research tomograph after injection of [ 11 C]PE2I, a selective DAT radioligand. Region of interest and voxel-by-voxel approaches using a simplified reference tissue model were performed for the between-group comparison of DAT availability. Measurements in the dorsal striatum from both analyses were concordant and showed a mean 20% lower DAT availability in drug users compared with controls. Whole-brain analysis also revealed lower DAT availability in the ventral striatum, the midbrain, the middle cingulate and the thalamus (ranging from -15 to -30%). The DAT availability was slightly lower in all regions in CTS than in subjects who smoke tobacco only, but the difference does not reach a significant level. These results support the existence of a decrease in DAT availability associated with tobacco and cannabis addictions involving all dopaminergic brain circuits. These findings are consistent with the idea of a global decrease in cerebral DA activity in dependent subjects. (authors)

  18. Effects of postnatal anoxia on striatal dopamine metabolism and prepulse inhibition in rats

    DEFF Research Database (Denmark)

    Sandager-Nielsen, Karin; Andersen, Maibritt B; Sager, Thomas N

    2004-01-01

    (DOPAC) and homovanillic acid (HVA) concentrations. Furthermore, in the anoxic group only, striatal HVA concentrations were negatively correlated to prefrontal cortical N-acetylaspartate (NAA) levels. Similar findings of distorted prefrontal-subcortical interactions have recently been reported...

  19. Ki67 expression in breast cancer. Correlation with prognostic markers and clinicopathological parameters in Saudi patients

    Directory of Open Access Journals (Sweden)

    Mohamed A. Elkablawy

    2016-02-01

    Full Text Available Objectives: To evaluate Ki67 immunoexpression pattern in Saudi breast cancer (BC patients and investigate any possible predictive or prognostic value for Ki67. Methods: This is a retrospective study designed to quantitatively assess the Ki67 proliferative index (PI in retrieved paraffin blocks of 115 Saudi BC patients diagnosed between January 2005 and March 2015 at the Department of Pathology, King Fahd Hospital, Al Madinah Al Munawarah, Kingdom of Saudi Arabia. The Ki67 PI was correlated with individual and combined immunoprofile data of estrogen receptor (ER, progesterone receptor (PR, and human epidermal growth factor receptor 2 (HER2/neu with their clinicopathological parameters. Results: Ki67 immunoreactivity was highly expressed (greater than 25% of the tumor cells were positive in 85 (73.9% patients. The Ki67 PI was significantly associated with poor prognostic clinicopathological parameters including old age (p less than 0.02, high tumor grade (p less than 0.01, lymph node metastasis (p less than 0.001, and Her-2/neu positivity (p less than 0.009. However, the association with ER positivity, PR positivity, tumor size, and lymphovascular invasion were not statistically significant. The Ki67 PI was significantly associated with BC molecular subtypes that were Her2/neu positive (luminal B and HER-2 subtypes compared with the Her2/neu negative (luminal A subtype (p less than 0.04. Conclusion: The Ki67 PI is significantly higher in Saudi BC patients comparing with the reported literature. Ki67 PI was highest in the HER-2 and luminal-B molecular subtypes. Along with other prognostic indicators, Ki67 PI may be useful in predicting prognosis and management of Saudi BC patients.

  20. Effect of in vitro gamma exposure on rat mesencephalic and striatal cellular types and processes length

    International Nuclear Information System (INIS)

    Coffigny, H.; Court, L.

    1994-01-01

    The isolated mesencephalic and striatal cells were irradiated in a dose-range of 0.25 to 3 Gy followed by 3 day of culture. The proportion of monopolar, bipolar, tripolar and multipolar cell population was not obviously modified by irradiation. The processes length was similar to controls, except after 3 Gy exposure, for monopolar and bipolar mesencephalic cells and the tripolar striatal cells where it was increased. In these populations, only cells with long processes seemed to survive. (author)

  1. A negative relationship between ventral striatal loss anticipation response and impulsivity in borderline personality disorder

    OpenAIRE

    Herbort, Maike C.; Soch, Joram; W?stenberg, Torsten; Krauel, Kerstin; Pujara, Maia; Koenigs, Michael; Gallinat, J?rgen; Walter, Henrik; Roepke, Stefan; Schott, Bj?rn H.

    2016-01-01

    Patients with borderline personality disorder (BPD) frequently exhibit impulsive behavior, and self-reported impulsivity is typically higher in BPD patients when compared to healthy controls. Previous functional neuroimaging studies have suggested a link between impulsivity, the ventral striatal response to reward anticipation, and prediction errors. Here we investigated the striatal neural response to monetary gain and loss anticipation and their relationship with impulsivity in 21 female BP...

  2. Genetically determined measures of striatal D2 signaling predict prefrontal activity during working memory performance.

    Science.gov (United States)

    Bertolino, Alessandro; Taurisano, Paolo; Pisciotta, Nicola Marco; Blasi, Giuseppe; Fazio, Leonardo; Romano, Raffaella; Gelao, Barbara; Lo Bianco, Luciana; Lozupone, Madia; Di Giorgio, Annabella; Caforio, Grazia; Sambataro, Fabio; Niccoli-Asabella, Artor; Papp, Audrey; Ursini, Gianluca; Sinibaldi, Lorenzo; Popolizio, Teresa; Sadee, Wolfgang; Rubini, Giuseppe

    2010-02-22

    Variation of the gene coding for D2 receptors (DRD2) has been associated with risk for schizophrenia and with working memory deficits. A functional intronic SNP (rs1076560) predicts relative expression of the two D2 receptors isoforms, D2S (mainly pre-synaptic) and D2L (mainly post-synaptic). However, the effect of functional genetic variation of DRD2 on striatal dopamine D2 signaling and on its correlation with prefrontal activity during working memory in humans is not known. Thirty-seven healthy subjects were genotyped for rs1076560 (G>T) and underwent SPECT with [123I]IBZM (which binds primarily to post-synaptic D2 receptors) and with [123I]FP-CIT (which binds to pre-synaptic dopamine transporters, whose activity and density is also regulated by pre-synaptic D2 receptors), as well as BOLD fMRI during N-Back working memory. Subjects carrying the T allele (previously associated with reduced D2S expression) had striatal reductions of [123I]IBZM and of [123I]FP-CIT binding. DRD2 genotype also differentially predicted the correlation between striatal dopamine D2 signaling (as identified with factor analysis of the two radiotracers) and activity of the prefrontal cortex during working memory as measured with BOLD fMRI, which was positive in GG subjects and negative in GT. Our results demonstrate that this functional SNP within DRD2 predicts striatal binding of the two radiotracers to dopamine transporters and D2 receptors as well as the correlation between striatal D2 signaling with prefrontal cortex activity during performance of a working memory task. These data are consistent with the possibility that the balance of excitatory/inhibitory modulation of striatal neurons may also affect striatal outputs in relationship with prefrontal activity during working memory performance within the cortico-striatal-thalamic-cortical pathway.

  3. Genetically determined measures of striatal D2 signaling predict prefrontal activity during working memory performance.

    Directory of Open Access Journals (Sweden)

    Alessandro Bertolino

    2010-02-01

    Full Text Available Variation of the gene coding for D2 receptors (DRD2 has been associated with risk for schizophrenia and with working memory deficits. A functional intronic SNP (rs1076560 predicts relative expression of the two D2 receptors isoforms, D2S (mainly pre-synaptic and D2L (mainly post-synaptic. However, the effect of functional genetic variation of DRD2 on striatal dopamine D2 signaling and on its correlation with prefrontal activity during working memory in humans is not known.Thirty-seven healthy subjects were genotyped for rs1076560 (G>T and underwent SPECT with [123I]IBZM (which binds primarily to post-synaptic D2 receptors and with [123I]FP-CIT (which binds to pre-synaptic dopamine transporters, whose activity and density is also regulated by pre-synaptic D2 receptors, as well as BOLD fMRI during N-Back working memory.Subjects carrying the T allele (previously associated with reduced D2S expression had striatal reductions of [123I]IBZM and of [123I]FP-CIT binding. DRD2 genotype also differentially predicted the correlation between striatal dopamine D2 signaling (as identified with factor analysis of the two radiotracers and activity of the prefrontal cortex during working memory as measured with BOLD fMRI, which was positive in GG subjects and negative in GT.Our results demonstrate that this functional SNP within DRD2 predicts striatal binding of the two radiotracers to dopamine transporters and D2 receptors as well as the correlation between striatal D2 signaling with prefrontal cortex activity during performance of a working memory task. These data are consistent with the possibility that the balance of excitatory/inhibitory modulation of striatal neurons may also affect striatal outputs in relationship with prefrontal activity during working memory performance within the cortico-striatal-thalamic-cortical pathway.

  4. Elevated Striatal Dopamine Function in Immigrants and Their Children: A Risk Mechanism for Psychosis

    OpenAIRE

    Egerton, A.; Howes, O. D.; Houle, S.; McKenzie, K.; Valmaggia, L. R.; Bagby, M. R.; Tseng, H-H; Bloomfield, M. A. P.; Kenk, M.; Bhattacharyya, S.; Suridjan, I.; Chaddock, C. A.; Winton-Brown, T. T.; Allen, P.; Rusjan, P.

    2017-01-01

    Migration is a major risk factor for schizophrenia but the neurochemical processes involved are unknown. One candidate mechanism is through elevations in striatal dopamine synthesis and release. The objective of this research was to determine whether striatal dopamine function is elevated in immigrants compared to nonimmigrants and the relationship with psychosis. Two complementary case–control studies of in vivo dopamine function (stress-induced dopamine release and dopamine synthesis capaci...

  5. Opposite Effects of Stimulant and Antipsychotic Drugs on Striatal Fast-Spiking Interneurons

    OpenAIRE

    Wiltschko, Alexander B; Pettibone, Jeffrey R; Berke, Joshua D

    2010-01-01

    Psychomotor stimulants and typical antipsychotic drugs have powerful but opposite effects on mood and behavior, largely through alterations in striatal dopamine signaling. Exactly how these drug actions lead to behavioral change is not well understood, as previous electrophysiological studies have found highly heterogeneous changes in striatal neuron firing. In this study, we examined whether part of this heterogeneity reflects the mixture of distinct cell types present in the striatum, by di...

  6. The pan-Kv7 (KCNQ) Channel Opener Retigabine Inhibits Striatal Excitability by Direct Action on Striatal Neurons In Vivo

    DEFF Research Database (Denmark)

    Hansen, Henrik H; Weikop, Pia; Mikkelsen, Maria D

    2017-01-01

    Central Kv7 (KCNQ) channels are voltage-dependent potassium channels composed of different combinations of four Kv7 subunits, being differently expressed in the brain. Notably, striatal dopaminergic neurotransmission is strongly suppressed by systemic administration of the pan-Kv7 channel opener ...... by acute systemic haloperidol administration in the rat. The relative mRNA levels of Kv7 subunits in the rat striatum were found to be Kv7.2 = Kv7.3 = Kv7.5 > >Kv7.4. These data suggest that intrastriatal Kv7 channels play a direct role in regulating striatal excitability in vivo....

  7. KONSEP PEMIKIRAN PENDIDIKAN MENURUT PAULO FREIRE DAN KI HAJAR DEWANTORO

    Directory of Open Access Journals (Sweden)

    Ahmad Syaikhudin

    2012-06-01

    Full Text Available Abstract: Criticism and alternative education offered by Paulo Freire is very interesting to be used to analyze the problems of education in Indonesia. It must be admitted that the context behind the controversial issue of those educational thought is different from that of Indonesian, however, it must be very suitable. According to Paulo Freire, there should be no dichotomy between the goals of education and educational ways. The goal, the transformation that frees individual to be a real person, should be manifested in the extent to how education must be implemented. The purpose of exemption cannot be separated with the path that frees. In addition, Freire's educational theory remains significant in terms of its role in which education should bring up not only the understanding of the world, but also the transformation of the world. On the other hands, Indonesian national leaders, Ki Hajar Dewantara also has inherited a very important philosophy in our national education, that is ing ngarso sung tulodo, ing madyo mangun karso, tut wuri handayani which means that the front is setting as a good model, the middle is inspiring and in the back provides support.

  8. Risk Factors Associated with Discordant Ki-67 Levels between Preoperative Biopsy and Postoperative Surgical Specimens in Breast Cancers.

    Directory of Open Access Journals (Sweden)

    Hyung Sun Kim

    Full Text Available The Ki-67 labelling index is significant for the management of breast cancer. However, the concordance of Ki-67 expression between preoperative biopsy and postoperative surgical specimens has not been well evaluated. This study aimed to find the correlation in Ki-67 expression between biopsy and surgical specimens and to determine the clinicopathological risk factors associated with discordant values.Ki-67 levels were immunohistochemically measured using paired biopsy and surgical specimens in 310 breast cancer patients between 2008 and 2013. ΔKi-67 was calculated by postoperative Ki-67 minus preoperative levels. The outliers of ΔKi-67 were defined as [lower quartile of ΔKi-67-1.5 × interquartile range (IQR] or (upper quartile + 1.5 × IQR and were evaluated according to clinicopathological parameters by logistic regression analysis.The median preoperative and postoperative Ki-67 levels were 10 (IQR, 15 and 10 (IQR, 25, respectively. Correlation of Ki-67 levels between the two specimens indicated a moderately positive relationship (coefficient = 0.676. Of 310 patients, 44 (14.2% showed outliers of ΔKi-67 (range, ≤-20 or ≥28. A significant association with poor prognostic factors was found among these patients. Multivariate analysis determined that significant risk factors for outliers of ΔKi-67 were tumor size >1 cm, negative progesterone receptor (PR expression, grade III cancer, and age ≤35 years. Among 171 patients with luminal human epidermal growth factor receptor 2-negative tumors, breast cancer subtype according to preoperative or postoperative Ki-67 levels discordantly changed in 46 (26.9% patients and a significant proportion of patients with discordant cases had ≥1 risk factor.Ki-67 expression showed a substantial concordance between biopsy and surgical specimens. Extremely discordant Ki-67 levels may be associated with aggressive tumor biology. In patients with luminal subtype disease, clinical application of Ki-67

  9. Proliferation marker pKi-67 occurs in different isoforms with various cellular effects.

    Science.gov (United States)

    Schmidt, Mirko H H; Broll, Rainer; Bruch, Hans-Peter; Finniss, Susan; Bögler, Oliver; Duchrow, Michael

    2004-04-15

    The Ki-67 antigen, pKi-67, is a commonly used proliferation marker in research and pathology. It has been recognized that the protein exists in two different splice variants that differ in one exon. In the current work, we present three new splice variants of human pKi-67 consisting of two naturally occurring isoforms and one atypical version. Additionally, data is presented indicating that alternative splicing of the pKi-67 N-terminus is common in tumor cell lines. Analyzing 93 tissues mainly consisting of brain tumor specimens, we found evidence that long and short isoform can be expressed independently of each other. Induction of mitosis in human peripheral blood mononuclear cells revealed that short pKi-67 appears earlier in the cell cycle than the long isoform and reaches its expression maximum when transcription of the latter sets in. Finally, transfection of mammalian culture cells with exon 7 (specific for the long pKi-67 isoform and not present in the short isoform) in a tetracycline regulated expression system decreased the rate of cell proliferation without affecting the cell cycle. In summary, we present evidence that the pKi-67 N-terminus is differentially spliced resulting in at least five different isoforms with different functions. Copyright 2004 Wiley-Liss, Inc.

  10. Whole-tumor MRI histogram analyses of hepatocellular carcinoma: Correlations with Ki-67 labeling index.

    Science.gov (United States)

    Hu, Xin-Xing; Yang, Zhao-Xia; Liang, He-Yue; Ding, Ying; Grimm, Robert; Fu, Cai-Xia; Liu, Hui; Yan, Xu; Ji, Yuan; Zeng, Meng-Su; Rao, Sheng-Xiang

    2017-08-01

    To evaluate whether whole-tumor histogram-derived parameters for an apparent diffusion coefficient (ADC) map and contrast-enhanced magnetic resonance imaging (MRI) could aid in assessing Ki-67 labeling index (LI) of hepatocellular carcinoma (HCC). In all, 57 patients with HCC who underwent pretreatment MRI with a 3T MR scanner were included retrospectively. Histogram parameters including mean, median, standard deviation, skewness, kurtosis, and percentiles (5 th , 25 th , 75 th , 95 th ) were derived from the ADC map and MR enhancement. Correlations between histogram parameters and Ki-67 LI were evaluated and differences between low Ki-67 (≤10%) and high Ki-67 (>10%) groups were assessed. Mean, median, 5 th , 25 th , 75 th percentiles of ADC, and mean, median, 25 th , 75 th , 95 th percentiles of enhancement of arterial phase (AP) demonstrated significant inverse correlations with Ki-67 LI (rho up to -0.48 for ADC, -0.43 for AP) and showed significant differences between low and high Ki-67 groups (P Histogram-derived parameters of ADC and AP were potentially helpful for predicting Ki-67 LI of HCC. 3 Technical Efficacy: Stage 3 J. MAGN. RESON. IMAGING 2017;46:383-392. © 2016 International Society for Magnetic Resonance in Medicine.

  11. Breast cancer Ki67 expression preoperative discrimination by DCE-MRI radiomics features

    Science.gov (United States)

    Ma, Wenjuan; Ji, Yu; Qin, Zhuanping; Guo, Xinpeng; Jian, Xiqi; Liu, Peifang

    2018-02-01

    To investigate whether quantitative radiomics features extracted from dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) are associated with Ki67 expression of breast cancer. In this institutional review board approved retrospective study, we collected 377 cases Chinese women who were diagnosed with invasive breast cancer in 2015. This cohort included 53 low-Ki67 expression (Ki67 proliferation index less than 14%) and 324 cases with high-Ki67 expression (Ki67 proliferation index more than 14%). A binary-classification of low- vs. high- Ki67 expression was performed. A set of 52 quantitative radiomics features, including morphological, gray scale statistic, and texture features, were extracted from the segmented lesion area. Three most common machine learning classification methods, including Naive Bayes, k-Nearest Neighbor and support vector machine with Gaussian kernel, were employed for the classification and the least absolute shrink age and selection operator (LASSO) method was used to select most predictive features set for the classifiers. Classification performance was evaluated by the area under receiver operating characteristic curve (AUC), accuracy, sensitivity and specificity. The model that used Naive Bayes classification method achieved the best performance than the other two methods, yielding 0.773 AUC value, 0.757 accuracy, 0.777 sensitivity and 0.769 specificity. Our study showed that quantitative radiomics imaging features of breast tumor extracted from DCE-MRI are associated with breast cancer Ki67 expression. Future larger studies are needed in order to further evaluate the findings.

  12. Proliferation marker pKi-67 affects the cell cycle in a self-regulated manner.

    Science.gov (United States)

    Schmidt, Mirko H H; Broll, Rainer; Bruch, Hans-Peter; Duchrow, Michael

    2002-01-01

    The proliferation marker pKi-67 is commonly used in research and pathology to detect proliferating cells. In a previous work, we found the protein to be associated with regulators of the cell cycle, controlling S-phase progression, as well as entry into and exit from mitosis. Here we investigate whether pKi-67 has a regulative effect on the cell cycle itself. For that purpose we cloned four fragments of pKi-67, together representing nearly the whole protein, and an N-terminal pKi-67 antisense oligonucleotide into a tetracycline inducible gene expression system. The sense fragments were C-terminally modified by addition of either a nuclear localization sequence (NLS) or a STOP codon to address the impact of their intracellular distribution. FACS based cell cycle analysis revealed that expression of nearly all pKi-67 domains and the antisense oligonucleotide led to a decreased amount of cells in S-phase and an increased number of cells in G(2)/M- and G(1)-phase. Subsequent analysis of the endogenous pKi-67 mRNA and protein levels revealed that the constructs with the most significant impact on the cell cycle were able to silence pKi-67 transcription as well. We conclude from the data that pKi-67 influences progression of S-phase and mitosis in a self-regulated manner and, therefore, effects the cell cycle checkpoints within both phases. Furthermore, we found pKi-67 mediates an anti-apoptotic effect on the cell and we verified that this marker, although it is a potential ribosomal catalyst, is not expressed in differentiated tissues with a high transcriptional activity. Copyright 2002 Wiley-Liss, Inc.

  13. Sjenički sir kao nematerijalno kulturno nasleđe: Antropološki pristup problemu

    Directory of Open Access Journals (Sweden)

    Ljiljana Gavrilović

    2017-01-01

    Full Text Available U radu se raspravlja o tradicionalnim tehnologijama kao nematerijalnom kulturnom nasleđu i iznosi se etnografija koja je rezultat rada na projektu pripreme dokumentacije za predlog upisa tehnologije proizvodnje sjeničkog sira u nacinalnu Listu nematerijalnih kulturnih dobara. U okviru toga razmotrena je tradicionalna tehnologija proizvodnje sjeničkog sira, kao i nastojanja lokalnih aktera da tu tehnologiju zaštite i sačuvaju. Zatim sledi analiza građe prikupljene u razgovorima s ispitanicima, pripadnicima lokalne zajednice – od samih proizvođača, pa do pojedinaca koji zauzimaju različite upravljačke pozicije. U ovom segmentu fokus je stavljen na svest i spoznaju koju sami lokalni akteri imaju o značaju proizvoda koji nastoje da zaštite i, kako oni sami kažu, „brendiraju“, ali pre svega na probleme sa kojima se suočavaju u tom procesu. Na kraju, analizirane su potencijalne mogućnosti realizacije projekta izrade aplikacije na osnovu koje bi sjenički sir bio upisan na Nacionalnu listu nematerijalnog kulturnog nasleđa. U tom segmentu, fokus je stavljen na delovanje menadžmenta lokalne zajednice, kao i mogućnosti profesionalnih antropologa da pomognu u realizaciji tog procesa.

  14. Striatal [[sup 11]C]-N-methyl-spiperone binding in patients with focal dystonia (torticollis) using positron emission tomography

    Energy Technology Data Exchange (ETDEWEB)

    Leenders, K [Paul Scherrer Inst. (PSI), Villigen (Switzerland); Hartvig, P [Hospital Pharmacy, Univ. Hospital, Uppsala (Sweden); Forsgren, L; Holmgren, G; Almay, B [Dept. of Neurology, Umeaa Univ., Umeaa (Sweden); Eckernaes, S A [Dept. of Neurology, Univ. Hospital, Uppsala (Sweden); Lundqvist, H; Laangstroem, B [Uppsala Univ. PET-Center, Uppsala (Sweden)

    1993-01-01

    Specific binding of [[sup 11]C]-N-methyl-spiperone to striatal dopamine D2 receptors was assessed using positron emission tomography (PET) in 6 patients with adult-onset focal dystonia (predominantly spasmodic torticollis) and in 5 healthy subjects. No significant difference in average specific striatal tracer uptake between patients and healthy subjects was found. However, in the 5 patients showing lateralisation of clinical signs a trend to higher striatal tracer uptake in the contralateral hemisphere was observed. (authors).

  15. Strateški marketing za popularizacijo ritmične gimnastike

    OpenAIRE

    Möderndorfer, Tjaša

    2018-01-01

    Uvodoma smo predstavili in preučili ključne pojme za lažje razumevanje trženjskih osnov. V nadaljevanju predstavimo metode in tehnike, ki nam pomagajo pri raziskovanju in posledično pri določanju trga in ciljev. Predstavljeni so nekateri osnovni modeli, ki nam pomagajo razumeti, kako trg deluje in kaj vse vpliva nanj. Naša tema se nanaša na šport, zato si v nadaljevanju pogledamo delovanje športnih organizacij. Za pripravo strategije trženja pregledamo okolje in vse deležnike, ki so pos...

  16. Can Histological Grade and Mitotic Index Replace Ki67 to Determine Luminal Breast Cancer Subtypes?

    Science.gov (United States)

    Oddó, David; Pulgar, Dahiana; Elgueta, Nicole; Acevedo, Francisco; Razmiliz, Dravna; Navarro, María Elena; Camus, Mauricio; Merino, Tomás; Retamal, Ignacio; Pérez-Sepúlveda, Alejandra; Villarroel, Alejandra; Galindo, Héctor; Peña, José; Sánchez, César

    2018-01-27

    Introduction: Breast cancer can be classified into subtypes based on immunohistochemical markers, with Ki67 expression levels being used to divide luminal BC tumors in luminal A and B subtypes; however, Ki67 is not routinely determined due to a lack of standardization. Objective: To evaluate histological grade and Eliminate: the mitotic index to determine if they can be used as an alternative method to Ki67 staining for luminal subtype definition. Methods: We evaluated estrogen receptor positive breast cancer tissue samples. Pathological analysis included determination of Ki67. A low level of Ki67 was defined as <14% positive cells. Results: We evaluated 151 breast cancer samples; 24 (15,9%) were classified as I; 74 as HG II (49%), and 53 (35,1%) as HG III. The median value for Ki67 was 13% (range: <1% - 82%) and for MI was 2 (0-12). Histological grade I tumors exhibited Ki67 values significantly lower than HG II and III tumors (Anova, Tamhane test p=0,001). A higher Ki67 value was related to a higher MI (Rho Sperman p=0,336; R2= 0,0273). ROC curve analysis determined that a MI ≥ 3 had a sensibility of 61.9% and specificity of 66.7% in predicting a high Ki67 value (≥14%) (area under the curve: 0,691; p =0,0001). A HG I tumor or HG II-III with MI ≤2, had a high probability of corresponding to a LA tumor (76,3%), as defined using Ki67 expression, while the probability of a LB subtype was higher with HG II-III and a MI ≥3 (57.4%). Global discrimination was 68.1%. Conclusions: For the LA subtype, our predictive model showed a good correlation of HG and MI with the classification based on Ki67<14%. In the LB subtype, the model showed a weak correlation; therefore Ki67 determination seems to be needed for this group of patients. Creative Commons Attribution License

  17. Free radical production induced by methamphetamine in rat striatal synaptosomes

    International Nuclear Information System (INIS)

    Pubill, David; Chipana, Carlos; Camins, Antonio; Pallas, Merce; Camarasa, Jordi; Escubedo, Elena

    2005-01-01

    The pro-oxidative effect of methamphetamine (METH) in dopamine terminals was studied in rat striatal synaptosomes. Flow cytometry analysis showed increased production of reactive oxygen species (ROS) in METH-treated synaptosomes, without reduction in the density of dopamine transporters. In synaptosomes from dopamine (DA)-depleted animals, METH did not induce ROS production. Reserpine, in vitro, completely inhibited METH-induced ROS production. These results point to endogenous DA as the main source of ROS induced by METH. Antioxidants and inhibitors of neuronal nitric oxide synthase and protein kinase C (PKC) prevented the METH-induced oxidative effect. EGTA and the specific antagonist methyllycaconitine (MLA, 50 μM) prevented METH-induced ROS production, thus implicating calcium and α7 nicotinic receptors in such effect. Higher concentrations of MLA (>100 μM) showed nonspecific antioxidant effect. Preincubation of synaptosomes with METH (1 μM) for 30 min reduced [ 3 H]DA uptake by 60%. The METH effect was attenuated by MLA and EGTA and potentiated by nicotine, indicating that activation of α 7 nicotinic receptors and Ca 2+ entry are necessary and take place before DAT inhibition. From these findings, it can be postulated that, in our model, METH induces DA release from synaptic vesicles to the cytosol. Simultaneously, METH activates α 7 nicotinic receptors, probably inducing depolarization and an increase in intrasynaptosomal Ca 2+ . This would lead to DAT inhibition and NOS and PKC activation, initiating oxidation of cytosolic DA

  18. Reduced Striatal Dopamine Transporters in People with Internet Addiction Disorder

    Directory of Open Access Journals (Sweden)

    Haifeng Hou

    2012-01-01

    Full Text Available In recent years, internet addiction disorder (IAD has become more prevalent worldwide and the recognition of its devastating impact on the users and society has rapidly increased. However, the neurobiological mechanism of IAD has not bee fully expressed. The present study was designed to determine if the striatal dopamine transporter (DAT levels measured by T99mc-TRODAT-1 single photon emission computed tomography (SPECT brain scans were altered in individuals with IAD. SPECT brain scans were acquired on 5 male IAD subjects and 9 healthy age-matched controls. The volume (V and weight (W of bilateral corpus striatum as well as the T99mc-TRODAT-1 uptake ratio of corpus striatum/the whole brain (Ra were calculated using mathematical models. It was displayed that DAT expression level of striatum was significantly decreased and the V, W, and Ra were greatly reduced in the individuals with IAD compared to controls. Taken together, these results suggest that IAD may cause serious damages to the brain and the neuroimaging findings further illustrate IAD is associated with dysfunctions in the dopaminergic brain systems. Our findings also support the claim that IAD may share similar neurobiological abnormalities with other addictive disorders.

  19. β1-adrenergic receptors activate two distinct signaling pathways in striatal neurons

    Science.gov (United States)

    Meitzen, John; Luoma, Jessie I.; Stern, Christopher M.; Mermelstein, Paul G.

    2010-01-01

    Monoamine action in the dorsal striatum and nucleus accumbens plays essential roles in striatal physiology. Although research often focuses on dopamine and its receptors, norepinephrine and adrenergic receptors are also crucial in regulating striatal function. While noradrenergic neurotransmission has been identified in the striatum, little is known regarding the signaling pathways activated by β-adrenergic receptors in this brain region. Using cultured striatal neurons, we characterized a novel signaling pathway by which activation of β1-adrenergic receptors leads to the rapid phosphorylation of cAMP Response Element Binding Protein (CREB), a transcription-factor implicated as a molecular switch underlying long-term changes in brain function. Norepinephrine-mediated CREB phosphorylation requires β1-adrenergic receptor stimulation of a receptor tyrosine kinase, ultimately leading to the activation of a Ras/Raf/MEK/MAPK/MSK signaling pathway. Activation of β1-adrenergic receptors also induces CRE-dependent transcription and increased c-fos expression. In addition, stimulation of β1-adrenergic receptors produces cAMP production, but surprisingly, β1-adrenergic receptor activation of adenylyl cyclase was not functionally linked to rapid CREB phosphorylation. These findings demonstrate that activation of β1-adrenergic receptors on striatal neurons can stimulate two distinct signaling pathways. These adrenergic actions can produce long-term changes in gene expression, as well as rapidly modulate cellular physiology. By elucidating the mechanisms by which norepinephrine and β1-adrenergic receptor activation affects striatal physiology, we provide the means to more fully understand the role of monoamines in modulating striatal function, specifically how norepinephrine and β1-adrenergic receptors may affect striatal physiology. PMID:21143600

  20. Beyond the Classic VTA: Extended Amygdala Projections to DA-Striatal Paths in the Primate.

    Science.gov (United States)

    Fudge, Julie L; Kelly, Emily A; Pal, Ria; Bedont, Joseph L; Park, Lydia; Ho, Brian

    2017-07-01

    The central extended amygdala (CEA) has been conceptualized as a 'macrosystem' that regulates various stress-induced behaviors. Consistent with this, the CEA highly expresses corticotropin-releasing factor (CRF), an important modulator of stress responses. Stress alters goal-directed responses associated with striatal paths, including maladaptive responses such as drug seeking, social withdrawal, and compulsive behavior. CEA inputs to the midbrain dopamine (DA) system are positioned to influence striatal functions through mesolimbic DA-striatal pathways. However, the structure of this amygdala-CEA-DA neuron path to the striatum has been poorly characterized in primates. In primates, we combined neuronal tracer injections into various arms of the circuit through specific DA subpopulations to assess: (1) whether the circuit connecting amygdala, CEA, and DA cells follows CEA intrinsic organization, or a more direct topography involving bed nucleus vs central nucleus divisions; (2) CRF content of the CEA-DA path; and (3) striatal subregions specifically involved in CEA-DA-striatal loops. We found that the amygdala-CEA-DA path follows macrostructural subdivisions, with the majority of input/outputs converging in the medial central nucleus, the sublenticular extended amygdala, and the posterior lateral bed nucleus of the stria terminalis. The proportion of CRF+ outputs is >50%, and mainly targets the A10 parabrachial pigmented nucleus (PBP) and A8 (retrorubal field, RRF) neuronal subpopulations, with additional inputs to the dorsal A9 neurons. CRF-enriched CEA-DA projections are positioned to influence outputs to the 'limbic-associative' striatum, which is distinct from striatal regions targeted by DA cells lacking CEA input. We conclude that the concept of the CEA is supported on connectional grounds, and that CEA termination over the PBP and RRF neuronal populations can influence striatal circuits involved in associative learning.

  1. D2 receptor genotype and striatal dopamine signaling predict motor cortical activity and behavior in humans.

    Science.gov (United States)

    Fazio, Leonardo; Blasi, Giuseppe; Taurisano, Paolo; Papazacharias, Apostolos; Romano, Raffaella; Gelao, Barbara; Ursini, Gianluca; Quarto, Tiziana; Lo Bianco, Luciana; Di Giorgio, Annabella; Mancini, Marina; Popolizio, Teresa; Rubini, Giuseppe; Bertolino, Alessandro

    2011-02-14

    Pre-synaptic D2 receptors regulate striatal dopamine release and DAT activity, key factors for modulation of motor pathways. A functional SNP of DRD2 (rs1076560 G>T) is associated with alternative splicing such that the relative expression of D2S (mainly pre-synaptic) vs. D2L (mainly post-synaptic) receptor isoforms is decreased in subjects with the T allele with a putative increase of striatal dopamine levels. To evaluate how DRD2 genotype and striatal dopamine signaling predict motor cortical activity and behavior in humans, we have investigated the association of rs1076560 with BOLD fMRI activity during a motor task. To further evaluate the relationship of this circuitry with dopamine signaling, we also explored the correlation between genotype based differences in motor brain activity and pre-synaptic striatal DAT binding measured with [(123)I] FP-CIT SPECT. Fifty healthy subjects, genotyped for DRD2 rs1076560 were studied with BOLD-fMRI at 3T while performing a visually paced motor task with their right hand; eleven of these subjects also underwent [(123)I]FP-CIT SPECT. SPM5 random-effects models were used for statistical analyses. Subjects carrying the T allele had greater BOLD responses in left basal ganglia, thalamus, supplementary motor area, and primary motor cortex, whose activity was also negatively correlated with reaction time at the task. Moreover, left striatal DAT binding and activity of left supplementary motor area were negatively correlated. The present results suggest that DRD2 genetic variation was associated with focusing of responses in the whole motor network, in which activity of predictable nodes was correlated with reaction time and with striatal pre-synaptic dopamine signaling. Our results in humans may help shed light on genetic risk for neurobiological mechanisms involved in the pathophysiology of disorders with dysregulation of striatal dopamine like Parkinson's disease. Copyright © 2010 Elsevier Inc. All rights reserved.

  2. Inhibition of the striatal specific phosphodiesterase PDE10A ameliorates striatal and cortical pathology in R6/2 mouse model of Huntington's disease.

    Directory of Open Access Journals (Sweden)

    Carmela Giampà

    2010-10-01

    Full Text Available Huntington's disease is a devastating neurodegenerative condition for which there is no therapy to slow disease progression. The particular vulnerability of striatal medium spiny neurons to Huntington's pathology is hypothesized to result from transcriptional dysregulation within the cAMP and CREB signaling cascades in these neurons. To test this hypothesis, and a potential therapeutic approach, we investigated whether inhibition of the striatal-specific cyclic nucleotide phosphodiesterase PDE10A would alleviate neurological deficits and brain pathology in a highly utilized model system, the R6/2 mouse.R6/2 mice were treated with the highly selective PDE10A inhibitor TP-10 from 4 weeks of age until euthanasia. TP-10 treatment significantly reduced and delayed the development of the hind paw clasping response during tail suspension, deficits in rotarod performance, and decrease in locomotor activity in an open field. Treatment prolonged time to loss of righting reflex. These effects of PDE10A inhibition on neurological function were reflected in a significant amelioration in brain pathology, including reduction in striatal and cortical cell loss, the formation of striatal neuronal intranuclear inclusions, and the degree of microglial activation that occurs in response to the mutant huntingtin-induced brain damage. Striatal and cortical levels of phosphorylated CREB and BDNF were significantly elevated.Our findings provide experimental support for targeting the cAMP and CREB signaling pathways and more broadly transcriptional dysregulation as a therapeutic approach to Huntington's disease. It is noteworthy that PDE10A inhibition in the R6/2 mice reduces striatal pathology, consistent with the localization of the enzyme in medium spiny neurons, and also cortical pathology and the formation of neuronal nuclear inclusions. These latter findings suggest that striatal pathology may be a primary driver of these secondary pathological events. More

  3. Immunohistochemical Ki-67/KL1 double stains increase accuracy of Ki-67 indices in breast cancer and simplify automated image analysis

    DEFF Research Database (Denmark)

    Nielsen, Patricia S; Bentzer, Nina K; Jensen, Vibeke

    2014-01-01

    observers and automated image analysis. RESULTS: Indices were predominantly higher for single stains than double stains (P≤0.002), yet the difference between observers was statistically significant (PPearson correlation coefficient for manual and automated indices ranged from 0.......69 to 0.85 (Pcorrelating automated indices with tumor characteristics, for example, tumor size (P... stains, Ki-67 should be quantified on double stains to reach a higher accuracy. Automated indices correlated well with manual estimates and tumor characteristics, and they are thus possibly valuable tools in future exploration of Ki-67 in breast cancer....

  4. Intrastriatal administration of botulinum neurotoxin A normalizes striatal D2 R binding and reduces striatal D1 R binding in male hemiparkinsonian rats.

    Science.gov (United States)

    Wedekind, Franziska; Oskamp, Angela; Lang, Markus; Hawlitschka, Alexander; Zilles, Karl; Wree, Andreas; Bauer, Andreas

    2018-01-01

    Cerebral administration of botulinum neurotoxin A (BoNT-A) has been shown to improve disease-specific motor behavior in a rat model of Parkinson disease (PD). Since the dopaminergic system of the basal ganglia fundamentally contributes to motor function, we investigated the impact of BoNT-A on striatal dopamine receptor expression using in vitro and in vivo imaging techniques (positron emission tomography and quantitative autoradiography, respectively). Seventeen male Wistar rats were unilaterally lesioned with 6-hydroxydopamine (6-OHDA) and assigned to two treatment groups 7 weeks later: 10 rats were treated ipsilaterally with an intrastriatal injection of 1 ng BoNT-A, while the others received vehicle (n = 7). All animals were tested for asymmetric motor behavior (apomorphine-induced rotations and forelimb usage) and for striatal expression of dopamine receptors and transporters (D 1 R, D 2 R, and DAT). The striatal D 2 R availability was also quantified longitudinally (1.5, 3, and 5 months after intervention) in 5 animals per treatment group. The 6-OHDA lesion alone induced a unilateral PD-like phenotype and a 13% increase of striatal D 2 R. BoNT-A treatment reduced the asymmetry in both apomorphine-induced rotational behavior and D 2 R expression, with the latter returning to normal values 5 months after intervention. D 1 R expression was significantly reduced, while DAT concentrations showed no alteration. Independent of the treatment, higher interhemispheric symmetry in raclopride binding to D 2 R was generally associated with reduced forelimb akinesia. Our findings indicate that striatal BoNT-A treatment diminishes motor impairment and induces changes in D 1 and D 2 binding site density in the 6-OHDA rat model of PD. © 2017 Wiley Periodicals, Inc.

  5. [Research progress on the clinical value of Ki-67 in breast cancer and its cut-off definition].

    Science.gov (United States)

    Chen, Qing; Wu, Kejin

    2015-08-01

    Ki-67 has an important application value in clinical practice. However, it is still a little tough in clinical application because of the debate on the cut-off definition of Ki-67 index. This review summarizes most studies on the prognostic and predictive value of Ki-67, analyzes the reasons for the discrepancies among the studies cited, and presents the necessity and clinical significance of scientifically defining the cut-off of Ki-67 index, providing a theoretical basis for Ki-67 in clinical application.

  6. 500 kodu on pandud sundmüüki / Agnes Ojala

    Index Scriptorium Estoniae

    Ojala, Agnes

    2009-01-01

    Swedbank ja SEB on pannud sundmüüki kokku ligi 500 eluaset. Swedbank Eesti juhi Priit Perensi, Sampo Panga personaal- ja jaepanganduse direktori Tõnu Vanajuure, kohtutäitur Mati Kadaku kommentaare

  7. Beebitoidu müüki hakkab korraldama range koodeks / Eha Laanepere

    Index Scriptorium Estoniae

    Laanepere, Eha, 1963-

    1995-01-01

    Rinnapiima asendajate reklaami ja müüki reguleerivast rahvusvahelisest koodeksist International Baby Food Action Network (IBFAN), mis on vastu võetud 1982. aastal, selle seadustiku vajalikkusest Eestis

  8. Heat enhancement of radiation resistivity of evaporated CsI, KI and KBr photocathodes

    CERN Document Server

    Tremsin, A S

    2000-01-01

    The photoemissive stability of as-deposited and heat-treated CsI, KI and KBr evaporated thin films under UV radiation is examined in this paper. After the deposition, some photocathodes were annealed for several hours at 90 deg. C in vacuum and their performance was then compared to the performance of non-heated samples. We observed that the post-evaporation thermal treatment not only increases the photoyield of CsI and KI photocathodes in the spectral range of 115-190 nm, but also reduces CsI, KI and KBr photocurrent degradation that occurs after UV irradiation. KBr evaporated layers appeared to be more radiation-resistant than CsI and KI layers. Post-deposition heat treatment did not result in any significant variation of KBr UV sensitivity.

  9. Objective Ki-67 Index Quantification In Non-Breast Tumors – Preliminary Data In Timisoara, Romania

    Directory of Open Access Journals (Sweden)

    A. Vaduva

    2016-06-01

    Proper image segmentation was identified on 25 cases. The best segmentation was obtained in lymphoid and central nervous system (CNS tumors. Lower Ki-67 values than the ones manually reported were identified in 16/25 cases (64%. Interestingly, digital quantification showed all 7 lymphoid cases to have a lower Ki-67 index than manually reported, while 6/9 CNS had higher Ki67 indices using automation processing. Valid digital quantification was not possible on skin, cervical and urothelial tumors, as regions of interest could not be defined to restrain the area to be evaluated.   Conclusion: Our preliminary study shows that ImmunoRatio plugin for Fiji in combination with IrfanView preprocessing are free, easy to use and powerful tools to obtain an objective Ki-67 index in non-mammary tumors: CNS, lymphoid, soft tissue, neuroendocrine tumors, choriocarcinomas and malignant melanomas.  

  10. Transformation in Dang-ki Healing: The Embodied Self and Perceived Legitimacy.

    Science.gov (United States)

    Lee, Boon-Ooi

    2016-09-01

    Since spirit possession in mediumship and shamanism resembles psychotic symptoms, early researchers perceived spirit mediums and shamans as psychiatric patients whose psychopathology was culturally sanctioned. However, other researchers have not only challenged this assumption, but also proposed that spirit possession has transformative benefits. The idiom of spirit possession provides cultural meanings for spirit mediums and shamans to express and transform their personal experiences. The present case study focuses on dang-ki healing, a form of Chinese mediumship practiced in Singapore, in which a deity possesses a human (i.e., dang-ki) to offer aid to supplicants. This study seeks to explore whether involvement in dang-ki healing is transformative; and if so, how the dang-ki's transformation is related to his self and the perceived legitimacy of his mediumship. At a shrine, I interviewed 20 participants, including a male dang-ki, 10 temple assistants, and nine clients. The results obtained were supportive of the therapeutic nature of spirit possession. First, there is a relationship between his self-transformation and the perceived legitimacy of his mediumship. As his clients and community have recognized his spirit possession as genuine, and the healing power of his possessing god, he is able to make use of mediumship as a means for spiritual development. Second, he has developed his spirituality by internalizing his god's positive traits (e.g., compassion). Deities worshipped in dang-ki healing can be conceptualized as ideal selves who represent a wide range of positive traits and moral values of Chinese culture. Thus, the possession of a deity is the embodiment of an ideal self. Finally, the dang-ki's transformation may run parallel to his god's transformation. In Chinese religions, gods have to constantly develop their spirituality even though they are already gods. An understanding of the god's spiritual development further sheds light on the dang-ki's self-transformation.

  11. Chromatin preferences of the perichromosomal layer constituent pKi-67.

    Science.gov (United States)

    Traut, Walther; Endl, Elmar; Garagna, Silvia; Scholzen, Thomas; Schwinger, Eberhard; Gerdes, Johannes; Winking, Heinz

    2002-01-01

    The proliferation-associated nuclear protein pKi-67 relocates from the nucleolus to the chromosome surface during the G2/M transition of the cell cycle and contributes to the formation of the 'perichromosomal layer'. We investigated the in-vivo binding preferences of pKi-67 for various chromatin blocks of the mitotic chromosomes from the human and two mouse species, Mus musculus and M. caroli. All chromosomes were decorated with pKi-67 but displayed a gap of pKi-67 decoration in the centromere and NOR regions. pKi-67 distribution in a rearranged mouse chromosome showed that the formation of the centromeric gap was controlled by the specific chromatin in that region. While most chromatin served as a substrate for direct or indirect binding of pKi-67, we identified three types of chromatin that bound less or no pKi-67. These were: (1) the centromeric heterochromatin defined by the alpha satellite DNA in the human, by the mouse minor satellite in M. musculus and the 60- and 79-bp satellites in M. caroli; (2) the pericentromeric heterochromatin in M. musculus defined by the mouse major satellite, and (3) NORs in the human and in M. musculus defined by rDNA repeats. In contrast, the conspicuous blocks of pericentromeric heterochromatin in human chromosomes 1, 9 and 16 containing the 5-bp satellite showed intense pKi-67 decoration. The centromeric gap may have a biological significance for the proper attachment of the chromosomes to the mitotic spindle. In this context, our results suggest a new role for centromeric heterochromatin: the control of the centromeric gap in the perichromosomal layer.

  12. Decrease in specific micronutrient intake in colorectal cancer patients with tumors presenting Ki-ras mutation

    OpenAIRE

    JORDI SALAS; NURIA LASO; SERGI MAS; M. JOSE LAFUENTE; XAVIER CASTERAD; MANUEL TRIAS; ANTONIO BALLESTA; RAFAEL MOLINA; CARLOS ASCASO; SHICHUN ZHENG; JOHN K. WIENCKE; AMALIA LAFUENTE

    2004-01-01

    Decrease in specific micronutrient intake in colorectal cancer patients with tumors presenting Ki-ras mutation BACKGROUND: The diversity of the Mediterranean diet and the heterogeneity of acquired genetic alterations in colorectal cancer (CRC) led us to examine the possible association between dietary factors and mutations, such as Ki-ras mutations, in genes implicated in the pathogenesis of these neoplasms. PATIENTS AND METHODS: The study was based on 246 cases and 296 controls. For th...

  13. Expression and significance of VEGF, CD34, Ki-67 and p21 in pterygium

    Directory of Open Access Journals (Sweden)

    Li-Bo Wang

    2014-07-01

    Full Text Available AIM: To investigate the expression of VEGF, CD34, Ki-67 and p21 in pterygium as well as the correlation between their expression and clinical pathological characteristics; explore its pathogenesis. METHODS: Immunohistochemical S-P staining method was adopted in detecting the expression of VEGF, CD34, Ki-67 and p21 in 62 cases of pterygia and 20 cases of normal conjunctival tissues. Relationship between these markers and clinical pathological characteristics was analyzed. RESULTS:(1The positive expression of VEGF, CD34, Ki-67 and p21 in 62 cases of pterygia was 74.2%(46/62, 77.4%(48/62, 66.1%(41/62and 40.3%(25/62respectively. The differences were statistically significant compared with normal conjunctival tissues(PPP>0.05; the expression of Ki-67 was correlated with clinical stages(PP>0.05; the expression of p21 was correlated with clinical stages and pterygium characters(PP>0.05.(3Spearman correlation showed that there was a positive correlation between VEGF and Ki-67(r=0.279, Pr=0.299, Pr=-0.267, PP>0.05.CONCLUSION:(1Overexpression of VEGF, Ki-67, CD34 and low expression of p21 suggest that these markers are concerned with the development and progression of pterygium.(2Expression of VEGF and CD34 increases along with the increase of clinical types and stages, expression of Ki-67 increases along with the increase of clinical stages, and expression of p21 decreases along with the improvement of clinical types or stages; they suggest that these markers may play important roles in the development and recurrence of pterygium.(3There is positive correlation between VEGF and Ki-67, VEGF and CD34 as well as negative correlation between VEGF and p21. They suggest that there may be synergistic action between two factors during the development and progression of pterygium.

  14. Gender Differences in Age-Related Striatal Dopamine Depletion in Parkinson’s Disease

    Directory of Open Access Journals (Sweden)

    Jae Jung Lee

    2015-09-01

    Full Text Available Objective Gender differences are a well-known clinical characteristic of Parkinson’s disease (PD. In-vivo imaging studies demonstrated that women have greater striatal dopamine transporter (DAT activity than do men, both in the normal population and in PD patients. We hypothesize that women exhibit more rapid aging-related striatal DAT reduction than do men, as the potential neuroprotective effect of estrogen wanes with age. Methods This study included 307 de novo PD patients (152 men and 155 women who underwent DAT scans for an initial diagnostic work-up. Gender differences in age-related DAT decline were assessed in striatal sub-regions using linear regression analysis. Results Female patients exhibited greater DAT activity compared with male patients in all striatal sub-regions. The linear regression analysis revealed that age-related DAT decline was greater in the anterior and posterior caudate, and the anterior putamen in women compared with men; we did not observe this difference in other sub-regions. Conclusions This study demonstrated the presence of gender differences in age-related DAT decline in striatal sub-regions, particularly in the antero-dorsal striatum, in patients with PD, presumably due to aging-related decrease in estrogen. Because this difference was not observed in the sensorimotor striatum, this finding also suggests that women may not have a greater capacity to tolerate PD pathogenesis than do men.

  15. Striatal lesions produce distinctive impairments in reaction time performance in two different operant chambers.

    Science.gov (United States)

    Brasted, P J; Döbrössy, M D; Robbins, T W; Dunnett, S B

    1998-08-01

    The dorsal striatum plays a crucial role in mediating voluntary movement. Excitotoxic striatal lesions in rats have previously been shown to impair the initiation but not the execution of movement in a choice reaction time task in an automated lateralised nose-poke apparatus (the "nine-hole box"). Conversely, when a conceptually similar reaction time task has been applied in a conventional operant chamber (or "Skinner box"), striatal lesions have been seen to impair the execution rather than the initiation of the lateralised movement. The present study was undertaken to compare directly these two results by training the same group of rats to perform a choice reaction time task in the two chambers and then comparing the effects of a unilateral excitotoxic striatal lesion in both chambers in parallel. Particular attention was paid to adopting similar parameters and contingencies in the control of the task in the two test chambers. After striatal lesions, the rats showed predominantly contralateral impairments in both tasks. However, they showed a deficit in reaction time in the nine-hole box but an apparent deficit in response execution in the Skinner box. This finding confirms the previous studies and indicates that differences in outcome are not simply attributable to procedural differences in the lesions, training conditions or tasks parameters. Rather, the pattern of reaction time deficit after striatal lesions depends critically on the apparatus used and the precise response requirements for each task.

  16. Altered resting state cortico-striatal connectivity in mild to moderate stage Parkinson’s disease

    Directory of Open Access Journals (Sweden)

    Youngbin Kwak

    2010-09-01

    Full Text Available Parkinson’s disease (PD is a progressive neurodegenerative disorder that is characterized by dopamine depletion in the striatum. One consistent pathophysiological hallmark of PD is an increase in spontaneous oscillatory activity in the basal ganglia thalamocortical networks. We evaluated these effects using resting state functional connectivity MRI (fcMRI in mild to moderate stage Parkinson’s patients on and off L-DOPA and age-matched controls using six different striatal seed regions. We observed an overall increase in the strength of cortico-striatal functional connectivity in PD patients off L-DOPA compared to controls. This enhanced connectivity was down-regulated by L-DOPA as shown by an overall decrease in connectivity strength, particularly within motor cortical regions. We also performed a frequency content analysis of the BOLD signal time course extracted from the six striatal seed regions. PD off L-DOPA exhibited increased power in the frequency band 0.02 – 0.05 Hz compared to controls and to PD on L-DOPA. The L-DOPA associated decrease in the power of this frequency range modulated the L-DOPA associated decrease in connectivity strength between striatal seeds and the thalamus. In addition, the L-DOPA associated decrease in power in this frequency band also correlated with the L-DOPA associated improvement in cognitive performance. Our results demonstrate that PD and L-DOPA modulate striatal resting state BOLD signal oscillations and corticostriatal network coherence.

  17. Regulation of dopamine synthesis and release in striatal and prefrontal cortical brain slices

    International Nuclear Information System (INIS)

    Wolf, M.E.

    1986-01-01

    Brain slices were used to investigate the role of nerve terminal autoreceptors in modulating dopamine (DA) synthesis and release in striatum and prefrontal cortex. Accumulation of dihydroxyphenylalanine (DOPA) was used as an index of tyrosine hydroxylation in vitro. Nomifensine, a DA uptake blocker, inhibited DOPA synthesis in striatal but not prefrontal slices. This effect was reversed by the DA antagonist sulpiride, suggesting it involved activation of DA receptors by elevated synaptic levels of DA. The autoreceptor-selective agonist EMD-23-448 also inhibited striatal but not prefrontal DOPA synthesis. DOPA synthesis was stimulated in both brain regions by elevated K + , however only striatal synthesis could be further enhanced by sulpiride. DA release was measured by following the efflux of radioactivity from brain slices prelabeled with [ 3 H]-DA. EMD-23-448 and apomorphine inhibited, while sulpiride enhanced, the K + -evoked overflow of radioactivity from both striatal and prefrontal cortical slices. These findings suggest that striatal DA nerve terminals possess autoreceptors which modulate tyrosine hydroxylation as well as autoreceptors which modulate release. Alternatively, one site may be coupled to both functions through distinct transduction mechanisms. In contrast, autoreceptors on prefrontal cortical terminals appear to regulate DA release but not DA synthesis

  18. An inquiry into the semiquantitative parameters of striatal dopamine receptor imaging

    International Nuclear Information System (INIS)

    Cao Guoxiang; Tan Tianzhi; Kuang Anren; Liang Zhenglu

    1998-01-01

    Purpose: To inquire into the optimal striatal reference region for nonspecific IBZM uptake in brain dopamine receptor imaging. Methods: Using in vivo data from rats, the authors compared the results of 125 I-iodobenzamide ( 125 I-IBZM) striatal specific binding that were respectively obtained taking cerebellum and frontal cortex as striatal reference region of nonspecific uptake of ligand. Results: Radioiodination labelled IBZM bound stereoselectively and reversibly to striatal D2 receptors. Frontal cortex and cerebellum showed rapid uptake and rapid washout of ligand. When cerebellar uptake was used as a reference of nonspecific uptake in striatum, IBZM saturation could not be demonstrated. But when the frontal cortex was used as reference region, saturation could be demonstrated with B max = 44 pmol/g striatum tissue. The percentage of haloperidol replacement and the percentage of uptake difference between striatum and other brain regions which were derived from competitive inhibition experiments with a large does of spiperone or haloperidol, suggested that the cerebellar uptake underestimated nonspecific uptake in the striatum while frontal cortex was an appropriate reference region for nonspecific uptake of ligand in striatum. Conclusions: For the calculation of specific IBZM binding and other semiquantitative parameters of striatal dopamine D2 receptor imaging, frontal cortex would be the nonspecific reference region of choice

  19. MK-801 protection against methamphetamine-induced striatal dopamine terminal injury is associated with attenuated dopamine overflow.

    Science.gov (United States)

    Weihmuller, F B; O'Dell, S J; Marshall, J F

    1992-06-01

    Repeated administrations of methamphetamine (m-AMPH) produce high extracellular levels of dopamine (DA) and subsequent striatal DA terminal damage. Pharmacological blockade of N-methyl-D-aspartate (NMDA) receptors has been shown previously to prevent m-AMPH-induced striatal DA terminal injury, but the mechanism for this protection is unclear. In the present study, in vivo microdialysis was used to determine the effects of blockade of NMDA receptors with the noncompetitive antagonist MK-801 on m-AMPH-induced striatal DA overflow. Four injections of MK-801 (0.5 mg/kg, ip) alone did not significantly change extracellular striatal DA concentrations from pretreatment values. Four treatments with m-AMPH (4.0 mg/kg, sc at 2-hr intervals) increased striatal DA overflow, and the overflow was particularly extensive following the fourth injection. This m-AMPH regimen produced a 40% reduction in striatal DA tissue content 1 week later. Treatment with MK-801 15 min before each of the four m-AMPH injections or prior to only the last two m-AMPH administrations attenuated the m-AMPH-induced increase in striatal DA overflow and protected completely against striatal DA depletions. Other MK-801 treatment regimens less effectively reduced the m-AMPH-induced striatal DA efflux and were ineffective in protecting against striatal DA depletions. Linear regression analysis indicated that cumulative DA overflow was strongly predictive (r = -.68) of striatal DA tissue levels measured one week later. These findings suggest that the extensive DA overflow seen during a neurotoxic regimen of m-AMPH is a crucial component of the subsequent neurotoxicity.(ABSTRACT TRUNCATED AT 250 WORDS)

  20. Peran modal sosial dalam implementasi konsep pemikiran Ki Hadjar Dewantara di SD Taman Muda Yogyakarta

    Directory of Open Access Journals (Sweden)

    Sukma Wijayanto

    2017-09-01

    Full Text Available Penelitian ini bertujuan untuk mendeskripsikan: (1 implementasi pendidikan Ki Hadjar Dewantara; dan (2 modal sosial di SD Taman Siswa Jetis. Penelitian menggunakan pendekatan kualitatif dengan jenis penelitian studi kasus. Unit analisis penelitian adalah SD Tamansiswa Jetis. Penentuan subjek dalam penelitian ini menggunakan teknik purposive sampling dengan subjek penelitian adalah pamong, kepala sekolahdan ketua yayasan Majelis Luhur Persatuan Tamansiswa cabang Jetis. Teknik pengumpulan data menggunakan observasi partisipatif, wawancara dan dokumentasi. Teknik analisis penelitian ini menggunakan model interaktif Milles & Huberman. Berdasarkan penelitian diperoleh sebagai berikut: (1 Konsep pemikiran Ki Hadjar terlaksana di SD Taman Siswa Jetis yakni sistem among tidak dapat dipisahkan prinsip kemerdekaan dan kodrat alam. Pelaksanaan sistem among dilaksanakan dengan keteladanan, pembiasaan, pengajaran, serta hukumam, paksaan dan perintah. (2 Trust, Jaringan, dan norm dalam melaksanakan konsep Ki Hadjar Dewantara menggunakan nilai-nilai kekeluargaan. Kekeluargaan modal sosial yang menjadi kekuatan dalam melaksanakan konsep pendidikan Ki Hadjar di SD Taman Siswa Jetis.Kata kunci: Ki Hadjar Dewantara, Konsep Pendidikan Ki Hadjar Dewantara, Modal Sosial

  1. Striatal Activation Predicts Differential Therapeutic Responses to Methylphenidate and Atomoxetine.

    Science.gov (United States)

    Schulz, Kurt P; Bédard, Anne-Claude V; Fan, Jin; Hildebrandt, Thomas B; Stein, Mark A; Ivanov, Iliyan; Halperin, Jeffrey M; Newcorn, Jeffrey H

    2017-07-01

    Methylphenidate has prominent effects in the dopamine-rich striatum that are absent for the selective norepinephrine transporter inhibitor atomoxetine. This study tested whether baseline striatal activation would predict differential response to the two medications in youth with attention-deficit/hyperactivity disorder (ADHD). A total of 36 youth with ADHD performed a Go/No-Go test during functional magnetic resonance imaging at baseline and were treated with methylphenidate and atomoxetine using a randomized cross-over design. Whole-brain task-related activation was regressed on clinical response. Task-related activation in right caudate nucleus was predicted by an interaction of clinical responses to methylphenidate and atomoxetine (F 1,30  = 17.00; p atomoxetine. The rate of robust response was higher for methylphenidate than for atomoxetine in youth with high (94.4% vs. 38.8%; p = .003; number needed to treat = 2, 95% CI = 1.31-3.73) but not low (33.3% vs. 50.0%; p = .375) caudate activation. Furthermore, response to atomoxetine predicted motor cortex activation (F 1,30  = 14.99; p atomoxetine in youth with ADHD, purportedly reflecting the dopaminergic effects of methylphenidate but not atomoxetine in the striatum, whereas motor cortex activation may predict response to atomoxetine. These data do not yet translate directly to the clinical setting, but the approach is potentially important for informing future research and illustrates that it may be possible to predict differential treatment response using a biomarker-driven approach. Stimulant Versus Nonstimulant Medication for Attention Deficit Hyperactivity Disorder in Children; https://clinicaltrials.gov/; NCT00183391. Copyright © 2017 American Academy of Child and Adolescent Psychiatry. Published by Elsevier Inc. All rights reserved.

  2. Logistički informacioni sistem / Logistics information system

    Directory of Open Access Journals (Sweden)

    Marko D. Andrejić

    2010-01-01

    Full Text Available Logistički automatizovani informacioni sistem treba razvijati kao deo jedinstvenog automatizovanog informacionog sistema (JAIS-a. Da bi se logistički automatizovani informacioni sistem uspešno razvijao i primenjivao u operativnoj praksi, neophodno je slediti globalni koncept razvoja JAIS-a i u razvoju više primenjivati timski rad profesionalnog informatičara i poznavaoca realnog logističkog sistema. Bitan uslov za razvoj kvalitetnog logističkog informacionog sistema jeste definisanje informacionih potreba o pojedinim objektima koje tretira logistički informacioni sistem. Zadatak logističkog automatizovanog informacionog sistema jeste da obezbedi: stalni uvid u stanje logističkog sistema; ukazivanje na potrebne i moguće mere poboljšanja; bolje planiranje i upravljanje radom realnog sistema; informisanje ljudstva o stanju realnog sistema i ukazivanje na pravce daljeg razvoja informacionih sistema. Logistički informacioni sistem treba razvijati vodeći računa i o kompatibilnosti sa budućim saveznicima i partnerima. / A logistics automated information system should be developed as a part of a unified automated information system (JAIS. In order to develop a logistics automated information system and to apply it successfully in operational use, it is necessary to follow the JAIS global development concept and rely more on teamwork of IT experts and specialists in real logistics systems. An important condition for the development of a high-quality logistics information system is to define information needs for particular objects treated by a logistics information system. The task of such a system is to provide: permanent insight into the logistics system, pointing to the necessary and possible measures for improvement, better real system planning and management activities, personnel information about the state of the real system, pointing to the directions of further system development. A logistics information system should be developed

  3. Interest of the PET with F DOPA in the exploration of endocrine para neoplastic syndromes (E.P.S.): about four cases; Interet de la TEP a la FDOPA dans l'exploration des syndromes paraneoplasiques endocriniens (SPE): a propos de 4 cas

    Energy Technology Data Exchange (ETDEWEB)

    Moreau Triby, C.; Pina, G.; Bournaud, C. [Centre de medecine nucleaire, groupement hospitalier Est, Lyon, (France); Billotey, C. [CERMEP, Lyon, (France); Raverot, G.; Borson Chazot, F. [service d' endocrinologie, groupement hospitalier Est, Lyon, (France)

    2009-05-15

    In front an ectopic secretion of adrenocorticotropic hormone (ACTH or corticotropin) or growth hormone (GH) the existence of an endocrine tumor must be evoked. The topographical diagnosis of these tumors is often difficult. The positron computed tomography with 6-fluoro-({sup 18}F)-L-dihydroxy-phenylalanine (PET-FDOPA) showed recently a good sensitivity in the detection of well differentiated endocrine tumors. We report our experience of the PET-FDOPA in the explorations of para-neoplasic endocrine syndromes. Our experience was relatively disappointing, this examination being a little contributive for our patients. The scintigraphy of receptors with somatostatin with octreoscan keeps all this place in this indication. (N.C.)

  4. Elevated Striatal Reactivity Across Monetary and Social Rewards in Bipolar I Disorder

    Science.gov (United States)

    Dutra, Sunny J.; Cunningham, William A.; Kober, Hedy; Gruber, June

    2016-01-01

    Bipolar disorder (BD) is associated with increased reactivity to rewards and heightened positive affectivity. It is less clear to what extent this heightened reward sensitivity is evident across contexts and what the associated neural mechanisms might be. The present investigation employed both a monetary and social incentive delay task among adults with remitted BD type I (N=24) and a healthy non-psychiatric control group (HC; N=25) using fMRI. Both whole-brain and region-of-interest analyses revealed elevated ventral and dorsal striatal reactivity across monetary and social reward receipt, but not anticipation, in the BD group. Post-hoc analyses further suggested that greater striatal reactivity to reward receipt across monetary and social reward tasks predicted decreased self-reported positive affect when anticipating subsequent rewards in the HC, but not BD, group. Results point toward elevated striatal reactivity to reward receipt as a potential neural mechanism of reward reactivity. PMID:26390194

  5. Mitochondrial fragmentation in neuronal degeneration: Toward an understanding of HD striatal susceptibility

    International Nuclear Information System (INIS)

    Cherubini, Marta; Ginés, Silvia

    2017-01-01

    Huntington's disease (HD) is an autosomal-dominant progressive neurodegenerative disorder that primarily affects medium spiny neurons within the striatum. HD is caused by inheritance of an expanded CAG repeat in the HTT gene, resulting in a mutant huntingtin (mHtt) protein containing extra glutamine residues. Despite the advances in understanding the molecular mechanisms involved in HD the preferential vulnerability of the striatum remains an intriguing question. This review discusses current knowledge that links altered mitochondrial dynamics with striatal susceptibility in HD. We also highlight how the modulation of mitochondrial function may constitute an attractive therapeutic approach to reduce mHtt-induced toxicity and therefore prevent the selective striatal neurodegeneration. - Highlights: • Mitochondrial dynamics is unbalanced towards fission in HD. • Excessive mitochondrial fragmentation plays a critical role in the selective vulnerability of the striatum in HD. • Therapeutic approaches aimed to inhibit mitochondrial fission could contribute to prevent striatal neurodegeneration in HD.

  6. Decreased spontaneous eye blink rates in chronic cannabis users: evidence for striatal cannabinoid-dopamine interactions.

    Directory of Open Access Journals (Sweden)

    Mikael A Kowal

    Full Text Available Chronic cannabis use has been shown to block long-term depression of GABA-glutamate synapses in the striatum, which is likely to reduce the extent to which endogenous cannabinoids modulate GABA- and glutamate-related neuronal activity. The current study aimed at investigating the effect of this process on striatal dopamine levels by studying the spontaneous eye blink rate (EBR, a clinical marker of dopamine level in the striatum. 25 adult regular cannabis users and 25 non-user controls matched for age, gender, race, and IQ were compared. Results show a significant reduction in EBR in chronic users as compared to non-users, suggesting an indirect detrimental effect of chronic cannabis use on striatal dopaminergic functioning. Additionally, EBR correlated negatively with years of cannabis exposure, monthly peak cannabis consumption, and lifetime cannabis consumption, pointing to a relationship between the degree of impairment of striatal dopaminergic transmission and cannabis consumption history.

  7. Dopamine-Related Disruption of Functional Topography of Striatal Connections in Unmedicated Patients With Schizophrenia.

    Science.gov (United States)

    Horga, Guillermo; Cassidy, Clifford M; Xu, Xiaoyan; Moore, Holly; Slifstein, Mark; Van Snellenberg, Jared X; Abi-Dargham, Anissa

    2016-08-01

    Despite the well-established role of striatal dopamine in psychosis, current views generally agree that cortical dysfunction is likely necessary for the emergence of psychotic symptoms. The topographic organization of striatal-cortical connections is central to gating and integration of higher-order information, so a disruption of such topography via dysregulated dopamine could lead to cortical dysfunction in schizophrenia. However, this hypothesis remains to be tested using multivariate methods ascertaining the global pattern of striatal connectivity and without the confounding effects of antidopaminergic medication. To examine whether the pattern of brain connectivity across striatal subregions is abnormal in unmedicated patients with schizophrenia and whether this abnormality relates to psychotic symptoms and extrastriatal dopaminergic transmission. In this multimodal, case-control study, we obtained resting-state functional magnetic resonance imaging data from 18 unmedicated patients with schizophrenia and 24 matched healthy controls from the New York State Psychiatric Institute. A subset of these (12 and 17, respectively) underwent positron emission tomography with the dopamine D2 receptor radiotracer carbon 11-labeled FLB457 before and after amphetamine administration. Data were acquired between June 16, 2011, and February 25, 2014. Data analysis was performed from September 1, 2014, to January 11, 2016. Group differences in the striatal connectivity pattern (assessed via multivariable logistic regression) across striatal subregions, the association between the multivariate striatal connectivity pattern and extrastriatal baseline D2 receptor binding potential and its change after amphetamine administration, and the association between the multivariate connectivity pattern and the severity of positive symptoms evaluated with the Positive and Negative Syndrome Scale. Of the patients with schizophrenia (mean [SEM] age, 35.6 [11.8] years), 9 (50%) were male and 9

  8. Striatal structure and its association with N-Acetylaspartate and glutamate in autism spectrum disorder and obsessive compulsive disorder

    NARCIS (Netherlands)

    Naaijen, Jilly; Zwiers, Marcel P.; Forde, Natalie J.; Williams, Steven C. R.; Durston, Sarah; Brandeis, Daniel; Glennon, Jeffrey C.; Franke, Barbara; Lythgoe, David J.; Buitelaar, Jan K.

    Autism spectrum disorders (ASD) and obsessive compulsive disorder (OCD) are often comorbid and are associated with changes in striatal volumes and N-Acetylaspartate (NAA) and glutamate levels. Here, we investigated the relation between dorsal striatal volume and NAA and glutamate levels. We

  9. Contribution of vesicular and cytosolic dopamine to the increased striatal dopamine efflux elicited by intrastriatal injection of SKF38393.

    NARCIS (Netherlands)

    Saigusa, T.; Aono, Y.; Sekino, R.; Uchida, T.; Takada, K.; Oi, Y.; Koshikawa, N.; Cools, A.R.

    2009-01-01

    Like dexamphetamine, SKF38393 induces an increase in striatal dopamine efflux which is insensitive for tetrodotoxin, Ca(2+) independent and prevented by a dopamine transporter inhibitor. The dexamphetamine-induced striatal dopamine efflux originates from both the reserpine-sensitive vesicular

  10. Vimentin and Ki67 expression in circulating tumour cells derived from castrate-resistant prostate cancer.

    Science.gov (United States)

    Lindsay, C R; Le Moulec, S; Billiot, F; Loriot, Y; Ngo-Camus, M; Vielh, P; Fizazi, K; Massard, C; Farace, F

    2016-02-29

    High circulating tumor cell (CTC) counts are associated with poor prognosis in advanced prostate cancer, and recently CTC number was suggested to be a surrogate for survival in metastatic castrate-resistant prostate cancer (mCRPC). Ki67 and vimentin are well-characterised markers of tumour cell proliferation and the epithelial-mesenchymal transition (EMT), respectively. Here we asked if the expression of vimentin and Ki67 in CTCs offered prognostic or predictive information in mCRPC. In two separate patient cohorts, anti-vimentin or anti-Ki67 antibodies were added to the free channel in the CellSearch® system for analysis of peripheral blood samples. For each cohort, association of CTC number with clinical characteristics were assessed using Fisher's exact, Mann-Whitney and chi-squared tests. Kaplan-Meier method and log-rank tests were used to analyse overall survival (OS) of vimentin-expressing and Ki67-expressing CTC patient cohorts. In this retrospective analysis, CTC vimentin expression was analysed in 142 blood samples from 93 patients, and CTC Ki67 expression was analysed in 90 blood samples from 51 patients. In the vimentin cohort, 80/93 (86 %) of baseline samples from patients were CTC-positive overall (≥1 total CTC per 7.5 mls blood), and 30/93 (32.3 %) vimentin CTC-positive (≥1 vimentin-positive CTC per 7.5 mls blood). 41/51 (80.4 %) of baseline samples from patients in the Ki67 cohort were CTC-positive overall, and 23/51 (45.1 %) Ki67 CTC-positive (≥1 Ki67-positive CTC per 7.5 mls blood). There was no significant difference in baseline PSA in patients with vimentin-positive CTC at baseline versus those with no vimentin-positive CTC at baseline (p = 0.33). A significant reduction in OS was shown in patients with vimentin-positive CTC compared to those without vimentin-positive CTC (median 305 days vs 453 days, p = 0.0293). There was no significant difference in baseline PSA in patients with Ki67-positive CTC at baseline versus those without Ki67

  11. Vimentin and Ki67 expression in circulating tumour cells derived from castrate-resistant prostate cancer

    International Nuclear Information System (INIS)

    Lindsay, C. R.; Le Moulec, S.; Billiot, F.; Loriot, Y.; Ngo-Camus, M.; Vielh, P.; Fizazi, K.; Massard, C.; Farace, F.

    2016-01-01

    High circulating tumor cell (CTC) counts are associated with poor prognosis in advanced prostate cancer, and recently CTC number was suggested to be a surrogate for survival in metastatic castrate-resistant prostate cancer (mCRPC). Ki67 and vimentin are well-characterised markers of tumour cell proliferation and the epithelial-mesenchymal transition (EMT), respectively. Here we asked if the expression of vimentin and Ki67 in CTCs offered prognostic or predictive information in mCRPC. In two separate patient cohorts, anti-vimentin or anti-Ki67 antibodies were added to the free channel in the CellSearch® system for analysis of peripheral blood samples. For each cohort, association of CTC number with clinical characteristics were assessed using Fisher’s exact, Mann-Whitney and chi-squared tests. Kaplan-Meier method and log-rank tests were used to analyse overall survival (OS) of vimentin-expressing and Ki67-expressing CTC patient cohorts. In this retrospective analysis, CTC vimentin expression was analysed in 142 blood samples from 93 patients, and CTC Ki67 expression was analysed in 90 blood samples from 51 patients. In the vimentin cohort, 80/93 (86 %) of baseline samples from patients were CTC-positive overall (≥1 total CTC per 7.5 mls blood), and 30/93 (32.3 %) vimentin CTC-positive (≥1 vimentin-positive CTC per 7.5 mls blood). 41/51 (80.4 %) of baseline samples from patients in the Ki67 cohort were CTC-positive overall, and 23/51 (45.1 %) Ki67 CTC-positive (≥1 Ki67-positive CTC per 7.5 mls blood). There was no significant difference in baseline PSA in patients with vimentin-positive CTC at baseline versus those with no vimentin-positive CTC at baseline (p = 0.33). A significant reduction in OS was shown in patients with vimentin-positive CTC compared to those without vimentin-positive CTC (median 305 days vs 453 days, p = 0.0293). There was no significant difference in baseline PSA in patients with Ki67-positive CTC at baseline versus those without Ki67

  12. Striatal dopamine in Parkinson disease: A meta-analysis of imaging studies.

    Science.gov (United States)

    Kaasinen, Valtteri; Vahlberg, Tero

    2017-12-01

    A meta-analysis of 142 positron emission tomography and single photon emission computed tomography studies that have investigated striatal presynaptic dopamine function in Parkinson disease (PD) was performed. Subregional estimates of striatal dopamine metabolism are presented. The aromatic L-amino-acid decarboxylase (AADC) defect appears to be consistently smaller than the dopamine transporter and vesicular monoamine transporter 2 defects, suggesting upregulation of AADC function in PD. The correlation between disease severity and dopamine loss appears linear, but the majority of longitudinal studies point to a negative exponential progression pattern of dopamine loss in PD. Ann Neurol 2017;82:873-882. © 2017 American Neurological Association.

  13. Three-dimensional organization of pKi-67: a comparative fluorescence and electron tomography study using FluoroNanogold.

    Science.gov (United States)

    Cheutin, Thierry; O'Donohue, Marie-Françoise; Beorchia, Adrien; Klein, Christophe; Kaplan, Hervé; Ploton, Dominique

    2003-11-01

    The monoclonal antibody (MAb) Ki-67 is routinely used in clinical studies to estimate the growth fraction of tumors. However, the role of pKi-67, the protein detected by the Ki-67 MAb, remains elusive, although some biochemical data strongly suggest that it might organize chromatin. To better understand the functional organization of pKi-67, we studied its three-dimensional distribution in interphase cells by confocal microscopy and electron tomography. FluoroNanogold, a single probe combining a dense marker with a fluorescent dye, was used to investigate pKi-67 organization at the optical and ultrastructural levels. Observation by confocal microscopy followed by 3D reconstruction showed that pKi-67 forms a shell around the nucleoli. Double labeling experiments revealed that pKi-67 co-localizes with perinucleolar heterochromatin. Electron microscopy studies confirmed this close association and demonstrated that pKi-67 is located neither in the fibrillar nor in the granular components of the nucleolus. Finally, spatial analyses by electron tomography showed that pKi-67 forms cords 250-300 nm in diameter, which are themselves composed of 30-50-nm-thick fibers. These detailed comparative in situ analyses strongly suggest the involvement of pKi-67 in the higher-order organization of perinucleolar chromatin.

  14. Analysis of clinically relevant values of Ki-67 labeling index in Japanese breast cancer patients.

    Science.gov (United States)

    Tamaki, Kentaro; Ishida, Takanori; Tamaki, Nobumitsu; Kamada, Yoshihiko; Uehara, Kanou; Miyashita, Minoru; Amari, Masakazu; Tadano-Sato, Akiko; Takahashi, Yayoi; Watanabe, Mika; McNamara, Keely; Ohuchi, Noriaki; Sasano, Hironobu

    2014-05-01

    It has become important to standardize the methods of Ki-67 evaluation in breast cancer patients, especially those used in the interpretation and scoring of immunoreactivity. Therefore, in this study, we examined the Ki-67 immunoreactivity of breast cancer surgical specimens processed and stained in the same manner in one single Japanese institution by counting nuclear immunoreactivity in the same fashion. We examined 408 Japanese breast cancers with invasive ductal carcinoma and studied the correlation between Ki-67 labeling index and ER/HER2 status and histological grade of breast cancer. We also analyzed overall survival (OS) and disease-free survival (DFS) of these patients according to individual Ki-67 labeling index. There were statistically significant differences of Ki-67 labeling index between ER positive/HER2 negative and ER positive/HER2 positive, ER negative/HER2 positive or ER negative/HER2 negative, and ER positive/HER2 positive and ER negative/HER2 negative groups (all P < 0.001). There were also statistically significant differences of Ki-67 labeling index among each histological grade (P < 0.001, respectively). As for multivariate analyses, Ki-67 labeling index was strongly associated with OS (HR 39.12, P = 0.031) and DFS (HR 10.85, P = 0.011) in ER positive and HER2 negative breast cancer patients. In addition, a statistically significant difference was noted between classical luminal A group and "20 % luminal A" in DFS (P = 0.039) but not between classical luminal A group and "25 % luminal A" (P = 0.105). A significant positive correlation was detected between Ki-67 labeling index and ER/HER2 status and histological grades of the cases examined in our study. The suggested optimal cutoff point of Ki-67 labeling index is between 20 and 25 % in ER positive and HER2 negative breast cancer patients.

  15. Ki-67 labeling index as an adjunct in the diagnosis of serous tubal intraepithelial carcinoma.

    Science.gov (United States)

    Kuhn, Elisabetta; Kurman, Robert J; Sehdev, Ann Smith; Shih, Ie-Ming

    2012-09-01

    There is mounting evidence that serous tubal intraepithelial carcinoma (STIC) may be the immediate precursor of ovarian high-grade serous carcinoma (HGSC) but the criteria for its diagnosis are not well established as highlighted in a recent study showing that interobserver reproducibility, even among expert gynecologic pathologists, was moderate at best. Given the clinical significance of a diagnosis of STIC in a patient who has no other evidence of ovarian carcinoma, this is a serious issue that we felt needed to be addressed. Although it is not clear, at this time, whether such a patient should or should not be treated, the importance of an accurate and reproducible diagnosis of precursors of ovarian carcinoma cannot be underestimated. We hypothesized that an elevated Ki-67 labeling index may aid the diagnosis of STIC. Accordingly, we compared the Ki-67 index of STIC and HGSC to normal fallopian tube epithelium (FTE) in the same patients and to a control group of patients without carcinoma, matched for age. A total of 41 STICs were analyzed, of which 35 were associated with a concurrent HGSC. In FTE, immunoreactivity for Ki-67 was restricted to a few scattered cells (mean 2.0%). No statistically significant difference was found between patients with and without HGSC (P>0.05). However, both STICs and HGSC had significantly higher Ki-67 indices than normal FTE (PSTICs uniformly had an elevated Ki-67 labeling index that ranged from 11.7% to 71.1% (average 35.6%). There was no correlation of the Ki-67 labeling index in the STICs and the associated HGSC, as the labeling index was lower in STIC in 18/35 (51.4%) whereas it was higher in 17/35 (48.6%) (P=0.86). In conclusion, the findings in this study indicate that compared with FTE, STICs have a significantly higher Ki-67 index similar to HGSC. Accordingly, the Ki-67 index can aid the diagnosis of intraepithelial tubal proliferations suspicious for STIC. Therefore, we propose that a Ki-67 index of 10% is a useful

  16. PENDIDIKAN KARAKTER KI HADJAR DEWANTARA: STUDI KRITIS PEMIKIRAN KARAKTER DAN BUDI PEKERTI DALAM TINJAUAN ISLAM

    Directory of Open Access Journals (Sweden)

    Muthoifin Muthoifin

    2015-12-01

    Full Text Available What an importance of character, Ki Hadjar makes it as a soul from the concept of his education. Even the government admitted, almost all national educational concepts referring to his idea. the focus of this issue is how the concept of Ki Hadjar's character in the Islamic view. The method used is historical approach, by the technique of content analysis, descriptive and comparative. The data is analyzed to be conclusion from the existing phenomenon. The results of the study, Ki Hadjar's idea about the character is not found the base that is closely related to faith, but rather stands on a universal national identity, it can be seen that the Ki Hadjar wants the Indonesian nation has a good attitude and personality and remain to stand on the personality of the Indonesian nation that has a distinctive culture and personality. While the characters in Islam can not be separated with monotheism and faith.   Keywords: character; Ki Hadjar Dewantara; budi pekerti; Islam.

  17. Application of deconvolution interferometry with both Hi-net and KiK-net data

    Science.gov (United States)

    Nakata, N.

    2013-12-01

    Application of deconvolution interferometry to wavefields observed by KiK-net, a strong-motion recording network in Japan, is useful for estimating wave velocities and S-wave splitting in the near surface. Using this technique, for example, Nakata and Snieder (2011, 2012) found changed in velocities caused by Tohoku-Oki earthquake in Japan. At the location of the borehole accelerometer of each KiK-net station, a velocity sensor is also installed as a part of a high-sensitivity seismograph network (Hi-net). I present a technique that uses both Hi-net and KiK-net records for computing deconvolution interferometry. The deconvolved waveform obtained from the combination of Hi-net and KiK-net data is similar to the waveform computed from KiK-net data only, which indicates that one can use Hi-net wavefields for deconvolution interferometry. Because Hi-net records have a high signal-to-noise ratio (S/N) and high dynamic resolution, the S/N and the quality of amplitude and phase of deconvolved waveforms can be improved with Hi-net data. These advantages are especially important for short-time moving-window seismic interferometry and deconvolution interferometry using later coda waves.

  18. Entropy based quantification of Ki-67 positive cell images and its evaluation by a reader study

    Science.gov (United States)

    Niazi, M. Khalid Khan; Pennell, Michael; Elkins, Camille; Hemminger, Jessica; Jin, Ming; Kirby, Sean; Kurt, Habibe; Miller, Barrie; Plocharczyk, Elizabeth; Roth, Rachel; Ziegler, Rebecca; Shana'ah, Arwa; Racke, Fred; Lozanski, Gerard; Gurcan, Metin N.

    2013-03-01

    Presence of Ki-67, a nuclear protein, is typically used to measure cell proliferation. The quantification of the Ki-67 proliferation index is performed visually by the pathologist; however, this is subject to inter- and intra-reader variability. Automated techniques utilizing digital image analysis by computers have emerged. The large variations in specimen preparation, staining, and imaging as well as true biological heterogeneity of tumor tissue often results in variable intensities in Ki-67 stained images. These variations affect the performance of currently developed methods. To optimize the segmentation of Ki-67 stained cells, one should define a data dependent transformation that will account for these color variations instead of defining a fixed linear transformation to separate different hues. To address these issues in images of tissue stained with Ki-67, we propose a methodology that exploits the intrinsic properties of CIE L∗a∗b∗ color space to translate this complex problem into an automatic entropy based thresholding problem. The developed method was evaluated through two reader studies with pathology residents and expert hematopathologists. Agreement between the proposed method and the expert pathologists was good (CCC = 0.80).

  19. A comparison of Ki-67 counting methods in luminal Breast Cancer: The Average Method vs. the Hot Spot Method.

    Directory of Open Access Journals (Sweden)

    Min Hye Jang

    Full Text Available In spite of the usefulness of the Ki-67 labeling index (LI as a prognostic and predictive marker in breast cancer, its clinical application remains limited due to variability in its measurement and the absence of a standard method of interpretation. This study was designed to compare the two methods of assessing Ki-67 LI: the average method vs. the hot spot method and thus to determine which method is more appropriate in predicting prognosis of luminal/HER2-negative breast cancers. Ki-67 LIs were calculated by direct counting of three representative areas of 493 luminal/HER2-negative breast cancers using the two methods. We calculated the differences in the Ki-67 LIs (ΔKi-67 between the two methods and the ratio of the Ki-67 LIs (H/A ratio of the two methods. In addition, we compared the performance of the Ki-67 LIs obtained by the two methods as prognostic markers. ΔKi-67 ranged from 0.01% to 33.3% and the H/A ratio ranged from 1.0 to 2.6. Based on the receiver operating characteristic curve method, the predictive powers of the KI-67 LI measured by the two methods were similar (Area under curve: hot spot method, 0.711; average method, 0.700. In multivariate analysis, high Ki-67 LI based on either method was an independent poor prognostic factor, along with high T stage and node metastasis. However, in repeated counts, the hot spot method did not consistently classify tumors into high vs. low Ki-67 LI groups. In conclusion, both the average and hot spot method of evaluating Ki-67 LI have good predictive performances for tumor recurrence in luminal/HER2-negative breast cancers. However, we recommend using the average method for the present because of its greater reproducibility.

  20. A comparison of Ki-67 counting methods in luminal Breast Cancer: The Average Method vs. the Hot Spot Method.

    Science.gov (United States)

    Jang, Min Hye; Kim, Hyun Jung; Chung, Yul Ri; Lee, Yangkyu; Park, So Yeon

    2017-01-01

    In spite of the usefulness of the Ki-67 labeling index (LI) as a prognostic and predictive marker in breast cancer, its clinical application remains limited due to variability in its measurement and the absence of a standard method of interpretation. This study was designed to compare the two methods of assessing Ki-67 LI: the average method vs. the hot spot method and thus to determine which method is more appropriate in predicting prognosis of luminal/HER2-negative breast cancers. Ki-67 LIs were calculated by direct counting of three representative areas of 493 luminal/HER2-negative breast cancers using the two methods. We calculated the differences in the Ki-67 LIs (ΔKi-67) between the two methods and the ratio of the Ki-67 LIs (H/A ratio) of the two methods. In addition, we compared the performance of the Ki-67 LIs obtained by the two methods as prognostic markers. ΔKi-67 ranged from 0.01% to 33.3% and the H/A ratio ranged from 1.0 to 2.6. Based on the receiver operating characteristic curve method, the predictive powers of the KI-67 LI measured by the two methods were similar (Area under curve: hot spot method, 0.711; average method, 0.700). In multivariate analysis, high Ki-67 LI based on either method was an independent poor prognostic factor, along with high T stage and node metastasis. However, in repeated counts, the hot spot method did not consistently classify tumors into high vs. low Ki-67 LI groups. In conclusion, both the average and hot spot method of evaluating Ki-67 LI have good predictive performances for tumor recurrence in luminal/HER2-negative breast cancers. However, we recommend using the average method for the present because of its greater reproducibility.

  1. Repeated cocaine administration results in supersensitivity of striatal D-2 dopamine autoreceptors to pergolide

    International Nuclear Information System (INIS)

    Dwoskin, L.P.; Peris, J.; Yasuda, R.P.; Philpott, K.; Zahniser, N.R.

    1988-01-01

    Groups of rats administered cocaine-HCl (10 mg/kg, i.p.) or saline either acutely or once daily for 8 or 14 days were killed 24 hrs after the last dose. In striatal slices prelabelled with [ 3 H]DA, modulation of [ 3 H]-overflow by pergolide was used to measure D-2 autoreceptor activity. Compared to the contemporaneous control group pergolide produced a greater inhibition only in striatal slices from rats treated repeatedly with cocaine. In radioligand binding studies using striatal membranes from control rats, pergolide had a 500-fold greater affinity for the D-2, as opposed to the D-1, dopamine (DA) receptor subtype. These results indicate that repeated treatment with cocaine produces supersensitive striatal D-2 release-modulating autoreceptors consistent with a compensatory change to diminish the effect of elevated synaptic concentrations of DA produced by cocaine. In contrast, supersensitivity of D-2 receptors was not detected in [ 3 H]spiperone binding assays. 31 references, 2 figures, 1 table

  2. De Novo Mutations in PDE10A Cause Childhood-Onset Chorea with Bilateral Striatal Lesions

    NARCIS (Netherlands)

    Mencacci, N.E.; Kamsteeg, E.J.; Nakashima, K.; R'Bibo, L.; Lynch, D.S.; Balint, B.; Willemsen, M.A.A.P.; Adams, M.E.; Wiethoff, S.; Suzuki, K.; Davies, C.H.; Ng, J.; Meyer, E.; Veneziano, L.; Giunti, P.; Hughes, D.; Raymond, F.L.; Carecchio, M.; Zorzi, G.; Nardocci, N.; Barzaghi, C.; Garavaglia, B.; Salpietro, V.; Hardy, J.; Pittman, A.M.; Houlden, H.; Kurian, M.A.; Kimura, H.; Vissers, L.E.L.M.; Wood, N.W.; Bhatia, K.P.

    2016-01-01

    Chorea is a hyperkinetic movement disorder resulting from dysfunction of striatal medium spiny neurons (MSNs), which form the main output projections from the basal ganglia. Here, we used whole-exome sequencing to unravel the underlying genetic cause in three unrelated individuals with a very

  3. Striatal dopamine D2 receptors, metabolism, and volume in preclinical Huntington disease

    NARCIS (Netherlands)

    van Oostrom, JCH; Maguire, RP; Verschuuren-Bemelmans, CC; van der Duin, LV; Pruim, J; Roos, RAC; Leenders, KL

    2005-01-01

    Among 27 preclinical carriers of the Huntington disease mutation (PMC), the authors found normal striatal values for MRI volumetry in 88% and for fluorodesoxyglucose PET metabolic index in 67%. Raclopride PET binding potential (RAC-BP) was decreased in 50% and correlated with increases in the

  4. Abnormal fronto-striatal activation as a marker of threshold and subthreshold Bulimia Nervosa.

    Science.gov (United States)

    Cyr, Marilyn; Yang, Xiao; Horga, Guillermo; Marsh, Rachel

    2018-04-01

    This study aimed to determine whether functional disturbances in fronto-striatal control circuits characterize adolescents with Bulimia Nervosa (BN) spectrum eating disorders regardless of clinical severity. FMRI was used to assess conflict-related brain activations during performance of a Simon task in two samples of adolescents with BN symptoms compared with healthy adolescents. The BN samples differed in the severity of their clinical presentation, illness duration and age. Multi-voxel pattern analyses (MVPAs) based on machine learning were used to determine whether patterns of fronto-striatal activation characterized adolescents with BN spectrum disorders regardless of clinical severity, and whether accurate classification of less symptomatic adolescents (subthreshold BN; SBN) could be achieved based on patterns of activation in adolescents who met DSM5 criteria for BN. MVPA classification analyses revealed that both BN and SBN adolescents could be accurately discriminated from healthy adolescents based on fronto-striatal activation. Notably, the patterns detected in more severely ill BN compared with healthy adolescents accurately discriminated less symptomatic SBN from healthy adolescents. Deficient activation of fronto-striatal circuits can characterize BN early in its course, when clinical presentations are less severe, perhaps pointing to circuit-based disturbances as useful biomarker or risk factor for the disorder, and a tool for understanding its developmental trajectory, as well as the development of early interventions. © 2018 Wiley Periodicals, Inc.

  5. Synthesis and binding to striatal membranes of non carrier added I-123 labeled 4'-iodococaine

    International Nuclear Information System (INIS)

    Metwally, S.A.M.; Gatley, S.J.; Wolf, A.P.; Yu, D.-W.

    1992-01-01

    An 123 I labeled cocaine analog, 4'-[ 123 I]iodococaine, has been prepared by oxidative destannylation of the tributyltin analog and shown to interact with cocaine binding sites in rat brain striatal membranes. It may thus be a suitable SPECT radiotracer for studies of the dopamine reuptake site in neurodegenerative diseases. (Author)

  6. Human striatal recordings reveal abnormal discharge of projection neurons in Parkinson's disease.

    Science.gov (United States)

    Singh, Arun; Mewes, Klaus; Gross, Robert E; DeLong, Mahlon R; Obeso, José A; Papa, Stella M

    2016-08-23

    Circuitry models of Parkinson's disease (PD) are based on striatal dopamine loss and aberrant striatal inputs into the basal ganglia network. However, extrastriatal mechanisms have increasingly been the focus of attention, whereas the status of striatal discharges in the parkinsonian human brain remains conjectural. We now report the activity pattern of striatal projection neurons (SPNs) in patients with PD undergoing deep brain stimulation surgery, compared with patients with essential tremor (ET) and isolated dystonia (ID). The SPN activity in ET was very low (2.1 ± 0.1 Hz) and reminiscent of that found in normal animals. In contrast, SPNs in PD fired at much higher frequency (30.2 ± 1.2 Hz) and with abundant spike bursts. The difference between PD and ET was reproduced between 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine-treated and normal nonhuman primates. The SPN activity was also increased in ID, but to a lower level compared with the hyperactivity observed in PD. These results provide direct evidence that the striatum contributes significantly altered signals to the network in patients with PD.

  7. Diversity in Long-Term Synaptic Plasticity at Inhibitory Synapses of Striatal Spiny Neurons

    Science.gov (United States)

    Rueda-Orozco, Pavel E.; Mendoza, Ernesto; Hernandez, Ricardo; Aceves, Jose J.; Ibanez-Sandoval, Osvaldo; Galarraga, Elvira; Bargas, Jose

    2009-01-01

    Procedural memories and habits are posited to be stored in the basal ganglia, whose intrinsic circuitries possess important inhibitory connections arising from striatal spiny neurons. However, no information about long-term plasticity at these synapses is available. Therefore, this work describes a novel postsynaptically dependent long-term…

  8. Fronto-striatal glutamate in children with Tourette's disorder and attention-deficit/hyperactivity disorder

    Directory of Open Access Journals (Sweden)

    Jilly Naaijen

    2017-01-01

    Conclusion: We found no evidence for glutamatergic neuropathology in TD or ADHD within the fronto-striatal circuits. However, the correlation of OC-symptoms with ACC glutamate concentrations suggests that altered glutamatergic transmission is involved in OC-symptoms within TD, but this needs further investigation.

  9. Fronto-striatal glutamate in children with Tourette's disorder and attention-deficit/hyperactivity disorder

    NARCIS (Netherlands)

    Naaijen, Jilly; Forde, Natalie J.; Lythgoe, David J.; Akkermans, Sophie E. A.; Openneer, Thaira J. C.; Dietrich, Andrea; Zwiers, Marcel P.; Hoekstra, Pieter J.; Buitelaar, Jan K.

    2017-01-01

    Objective: Both Tourette's disorder (TD) and attention-deficit/hyperactivity disorder (ADHD) have been related to abnormalities in glutamatergic neurochemistry in the fronto-striatal circuitry. TD and ADHD often co-occur and the neural underpinnings of this co-occurrence have been insufficiently

  10. Striatal Dopamine Transporter Binding Does Not Correlate with Clinical Severity in Dementia with Lewy Bodies

    DEFF Research Database (Denmark)

    Ziebell, Morten; Andersen, Birgitte B; Pinborg, Lars H

    2013-01-01

    cognitively evaluated with the Mini Mental State Examination. RESULTS: There was no correlation between Mini Mental State Examination, Hoehn and Yahr score, fluctuations or hallucinations, and striatal DAT availability as measured with (123)I-PE2I and SPECT. CONCLUSION: In patients with newly diagnosed DLB...

  11. Functional connectivity modeling of consistent cortico-striatal degeneration in Huntington's disease

    Directory of Open Access Journals (Sweden)

    Imis Dogan

    2015-01-01

    Full Text Available Huntington's disease (HD is a progressive neurodegenerative disorder characterized by a complex neuropsychiatric phenotype. In a recent meta-analysis we identified core regions of consistent neurodegeneration in premanifest HD in the striatum and middle occipital gyrus (MOG. For early manifest HD convergent evidence of atrophy was most prominent in the striatum, motor cortex (M1 and inferior frontal junction (IFJ. The aim of the present study was to functionally characterize this topography of brain atrophy and to investigate differential connectivity patterns formed by consistent cortico-striatal atrophy regions in HD. Using areas of striatal and cortical atrophy at different disease stages as seeds, we performed task-free resting-state and task-based meta-analytic connectivity modeling (MACM. MACM utilizes the large data source of the BrainMap database and identifies significant areas of above-chance co-activation with the seed-region via the activation-likelihood-estimation approach. In order to delineate functional networks formed by cortical as well as striatal atrophy regions we computed the conjunction between the co-activation profiles of striatal and cortical seeds in the premanifest and manifest stages of HD, respectively. Functional characterization of the seeds was obtained using the behavioral meta-data of BrainMap. Cortico-striatal atrophy seeds of the premanifest stage of HD showed common co-activation with a rather cognitive network including the striatum, anterior insula, lateral prefrontal, premotor, supplementary motor and parietal regions. A similar but more pronounced co-activation pattern, additionally including the medial prefrontal cortex and thalamic nuclei was found with striatal and IFJ seeds at the manifest HD stage. The striatum and M1 were functionally connected mainly to premotor and sensorimotor areas, posterior insula, putamen and thalamus. Behavioral characterization of the seeds confirmed that experiments

  12.  Immunohistochemical Expression of ki-67 and p53 in Colorectal Adenomas: A Clinicopathological Study

    Directory of Open Access Journals (Sweden)

    Hussam Hasson Ali

    2011-07-01

    Full Text Available  Objectives: To evaluate the significance of P53 and Ki-67 expression as immunohistochemical markers in early detection of premalignant changes in different types of colorectal adenomas. Also, to correlate immunohistochemical expression of the two markers with different clinicopathological parameters including; age, and sex of the patient, type, site, size and grade of dysplasia of colorectal adenomas.Methods: Forty-seven polypectomy specimens of colorectal adenomas were retrieved from the archival materials of the Gastrointestinal and Hepatic Diseases Teaching Hospital in Baghdad from 2009 - 2010. Four µm section specimens were stained by immunohistochemical technique with Ki-67 and P53 tumor markers. P-values <0.05 were considered statistically significant.Results: Immunohistochemical expressions of Ki-67 and P53 had a significant correlation with the size and grade of dysplasia in colorectal adenomas. However, there was no significant correlation among the immunohistochemical expression of Ki-67 and P53 with the age and gender of the patient, and the type and site of colorectal adenomas. There was no significant correlation between Ki-67 and P53 expressions in colorectal adenomas. Villous adenomas of colorectum showed a significant correlation with the grade of dysplasia, while there was no significant correlation between size and site of colorectal adenoma with the grade of dysplasia.Conclusion: High grade dysplasia with significant positive immunohistochemical markers of Ki-67 and P53 could be valuable parameters for selecting from the total colorectal adenoma population, those most deserving of close surveillance in follow-up cancer prevention programs. It is closely linked with increasing age particularly in patients with a large size adenoma of villous component in their histology.

  13. Expression of PPARγ, p27 and Ki67 in Cervical Cancer and its Clinical Significance

    Directory of Open Access Journals (Sweden)

    Peng-li LI

    2015-03-01

    Full Text Available Objective: To investigate the expression of peroxisome proliferation-activated receptor γ (PPARγ, p27 and Ki67 in cervical cancer and its clinical significance. Methods: The expression of PPARγ, p27 and Ki67 in the tissues of 42 patients with cervical cancer, 28 with cervical intraepithelial neoplasia (CIN and 12 with normal cervix was detected using immunohistochemistry. Results:The positive rate of PPARγ protein in cervical cancer tissue (76.2% was significantly higher than in CIN (53.6% and normal cervical tissue (8.3% (P<0.05 orP<0.01, which was also evidently higher in CIN than in normal cervical tissue (P<0.05. The positive rate of p27 protein in cervical cancer tissue (31.0% was significantly lower than in CIN (57.1% and normal cervical tissue (83.3% (P<0.05 or P<0.01, and that in CIN had a markedly lower tendency compared with normal cervical tissue (P<0.05. The positive rate of Ki67 protein in cervical cancer tissue (100.0% was apparently higher than in CIN (85.7% and normal cervical tissue (33.3% (P<0.05 or P<0.01, which was also markedly higher in CIN than in normal cervical tissue (P<0.01. The expression of PPARγ, p27 and Ki67 proteins was not associated with the clinicopathological features of patients, including the age, histological types, pathological grading and clinical staging (P>0.05.Conclusion: Abnormal expression of PPARγ, p27 and Ki67 may play important roles in occurrence and progression of cervical cancer, and hence, joint detection of PPARγ, p27 and Ki67 can be used to diagnose early CIN and cervical cancer.

  14. [Comparison of digital and visual methods for Ki-67 assessment in invasive breast carcinomas].

    Science.gov (United States)

    Kushnarev, V A; Artemyeva, E S; Kudaybergenova, A G

    2018-01-01

    to compare two methods for quantitative assessment of the proliferative activity index (PAI): a visual estimation method by several investigators and digital image analysis (DIA). The use of the Ki-67 index in the daily clinical practice of a Morbid Anatomy Department is associated with the problem of reproducibility of quantitative assessment of the Ki-67 PAI. Due to the development of digital imaging techniques in morphology, new methods for PAI evaluation using the DIA are proposed. The Ki-67 PAI data obtained during visual assessment and digital image analysis were compared in 104 cases of grades 2-3 breast carcinoma. The histological sections were scanned using a Panoramic III scanner (3D Histech, Hungary) and digital images were obtained. DIA was carried out using the software 3D Histech QuantCenter (3D Histech, Hungary), by marking 3-10 zones. Evaluation of the obtained sections was done independently by two investigators engaged in cancer pathology. The level of agreement between visual and digital methods did not differ significantly (p>0.001). The authors selected a gray area in the range of 10-35% IPA, where the Ki-67 index showed a weak relationship between the analyzed groups (ICC, 0.47). The Ki67 index below 10% and above 35% showed a sufficient reproducibility in the same laboratory. The authors consider that the scanned digital form of a histological section, which can be evaluated using automated software analysis modules, is an independent and objective method to assess proliferative activity for Ki-67 index validation.

  15. Immunohistochemicai study of Ki- 67 expression in unicystic Ameloblastoma and Dentigerous cyst

    Directory of Open Access Journals (Sweden)

    Eslami M.

    2004-06-01

    Full Text Available Statement of Problem: Differentiation of dentigerous cyst from unicystic ameloblastoma, discovering any initial ameloblastic changes in lining epithelium of dentigerous cyst at early stage, and differentiation between hyperplastic odontogenic epithelium in fibrous capsule of dentigerous cyst from ameloblastic proliferation, need to an accurate and reliable technique."nPurpose: The aim of this study was to determine and compare Ki-67 immunoreactivity in various locations of the epithelium of Dentigerous cyst and Unicystic Ameloblastoma."nMaterials and Methods: In this historical Cohort study, 15 cases of dentigerous cyst and 9 cases of unicystic ameloblastoma were selected. Immunohistochemistry staining was performed by M1B-1 (murine monoclonal antibody against Ki-67. The stained nucleous were counted in basal and suprabasal layer of lining epithelium of both lesions in 3000 epithelial cells. Finally, the percentage of positive cells (presented as labeling index was calculated, t- student test was used to analyze the related data."nResults: Ki-67 (LI in basal layer of Dentigerous cyst (2.59±1.66 and Unicystic Ameloblastoma (3.76±79 had no significant differences, but Ki-67 (LI in suprabasal layer of unicystic ameloblastoma (2.15±0.69 was significantly higher than dentigerous cyst (0.77±0.55 P=0.003."nThe difference between the average numbers of positive cells for Ki-67 (LI in these two lesions was statistically significant (P<0.05 and it was higher in Unicystic Ameloblastoma than Dentigerous cyst."nConclusion: Based on the findings of this study, it is suggested that Ki-67 (LI in suprabasal layer or throughout the epithelium can be considered as a useful marker for differential diagnosis between dentigerous cyst and unicystic ameloblastoma.

  16. Role of contingency in striatal response to incentive in adolescents with anxiety.

    Science.gov (United States)

    Benson, Brenda E; Guyer, Amanda E; Nelson, Eric E; Pine, Daniel S; Ernst, Monique

    2015-03-01

    This study examines the effect of contingency on reward function in anxiety. We define contingency as the aspect of a situation in which the outcome is determined by one's action-that is, when there is a direct link between one's action and the outcome of the action. Past findings in adolescents with anxiety or at risk for anxiety have revealed hypersensitive behavioral and neural responses to higher value rewards with correct performance. This hypersensitivity to highly valued (salient) actions suggests that the value of actions is determined not only by outcome magnitude, but also by the degree to which the outcome is contingent on correct performance. Thus, contingency and incentive value might each modulate reward responses in unique ways in anxiety. Using fMRI with a monetary reward task, striatal response to cue anticipation is compared in 18 clinically anxious and 20 healthy adolescents. This task manipulates orthogonally reward contingency and incentive value. Findings suggest that contingency modulates the neural response to incentive magnitude differently in the two groups. Specifically, during the contingent condition, right-striatal response tracks incentive value in anxious, but not healthy, adolescents. During the noncontingent condition, striatal response is bilaterally stronger to low than to high incentive in anxious adolescents, while healthy adolescents exhibit the expected opposite pattern. Both contingency and reward magnitude differentiate striatal activation in anxious versus healthy adolescents. These findings may reflect exaggerated concern about performance and/or alterations of striatal coding of reward value in anxious adolescents. Abnormalities in reward function in anxiety may have treatment implications.

  17. Striatal dopamine transmission is subtly modified in human A53Tα-synuclein overexpressing mice.

    Directory of Open Access Journals (Sweden)

    Nicola J Platt

    Full Text Available Mutations in, or elevated dosage of, SNCA, the gene for α-synuclein (α-syn, cause familial Parkinson's disease (PD. Mouse lines overexpressing the mutant human A53Tα-syn may represent a model of early PD. They display progressive motor deficits, abnormal cellular accumulation of α-syn, and deficits in dopamine-dependent corticostriatal plasticity, which, in the absence of overt nigrostriatal degeneration, suggest there are age-related deficits in striatal dopamine (DA signalling. In addition A53Tα-syn overexpression in cultured rodent neurons has been reported to inhibit transmitter release. Therefore here we have characterized for the first time DA release in the striatum of mice overexpressing human A53Tα-syn, and explored whether A53Tα-syn overexpression causes deficits in the release of DA. We used fast-scan cyclic voltammetry to detect DA release at carbon-fibre microelectrodes in acute striatal slices from two different lines of A53Tα-syn-overexpressing mice, at up to 24 months. In A53Tα-syn overexpressors, mean DA release evoked by a single stimulus pulse was not different from wild-types, in either dorsal striatum or nucleus accumbens. However the frequency responsiveness of DA release was slightly modified in A53Tα-syn overexpressors, and in particular showed slight deficiency when the confounding effects of striatal ACh acting at presynaptic nicotinic receptors (nAChRs were antagonized. The re-release of DA was unmodified after single-pulse stimuli, but after prolonged stimulation trains, A53Tα-syn overexpressors showed enhanced recovery of DA release at old age, in keeping with elevated striatal DA content. In summary, A53Tα-syn overexpression in mice causes subtle changes in the regulation of DA release in the striatum. While modest, these modifications may indicate or contribute to striatal dysfunction.

  18. The basal ganglia matching tools package for striatal uptake semi-quantification: description and validation

    International Nuclear Information System (INIS)

    Calvini, Piero; Rodriguez, Guido; Nobili, Flavio; Inguglia, Fabrizio; Mignone, Alessandro; Guerra, Ugo P.

    2007-01-01

    To design a novel algorithm (BasGan) for automatic segmentation of striatal 123 I-FP-CIT SPECT. The BasGan algorithm is based on a high-definition, three-dimensional (3D) striatal template, derived from Talairach's atlas. A blurred template, obtained by convolving the former with a 3D Gaussian kernel (FWHM = 10 mm), approximates striatal activity distribution. The algorithm performs translations and scale transformation on the bicommissural aligned image to set the striatal templates with standard size in an appropriate initial position. An optimization protocol automatically performs fine adjustments in the positioning of blurred templates to best match the radioactive counts, and locates an occipital ROI for background evaluation. Partial volume effect correction is included in the process of uptake computation of caudate, putamen and background. Experimental validation was carried out by means of six acquisitions of an anthropomorphic striatal phantom. The BasGan software was applied to a first set of patients with Parkinson's disease (PD) versus patients affected by essential tremor. A highly significant correlation was achieved between true binding potential and measured 123 I activity from the phantom. 123 I-FP-CIT uptake was significantly lower in all basal ganglia in the PD group versus controls with both BasGan and a conventional ROI method used for comparison, but particularly with the former. Correlations with the motor UPDRS score were far more significant with the BasGan. The novel BasGan algorithm automatically performs the 3D segmentation of striata. Because co-registered MRI is not needed, it can be used by all nuclear medicine departments, since it is freely available on the Web. (orig.)

  19. Striatal cholinergic interneurons and D2 receptor-expressing GABAergic medium spiny neurons regulate tardive dyskinesia.

    Science.gov (United States)

    Bordia, Tanuja; Zhang, Danhui; Perez, Xiomara A; Quik, Maryka

    2016-12-01

    Tardive dyskinesia (TD) is a drug-induced movement disorder that arises with antipsychotics. These drugs are the mainstay of treatment for schizophrenia and bipolar disorder, and are also prescribed for major depression, autism, attention deficit hyperactivity, obsessive compulsive and post-traumatic stress disorder. There is thus a need for therapies to reduce TD. The present studies and our previous work show that nicotine administration decreases haloperidol-induced vacuous chewing movements (VCMs) in rodent TD models, suggesting a role for the nicotinic cholinergic system. Extensive studies also show that D2 dopamine receptors are critical to TD. However, the precise involvement of striatal cholinergic interneurons and D2 medium spiny neurons (MSNs) in TD is uncertain. To elucidate their role, we used optogenetics with a focus on the striatum because of its close links to TD. Optical stimulation of striatal cholinergic interneurons using cholineacetyltransferase (ChAT)-Cre mice expressing channelrhodopsin2-eYFP decreased haloperidol-induced VCMs (~50%), with no effect in control-eYFP mice. Activation of striatal D2 MSNs using Adora2a-Cre mice expressing channelrhodopsin2-eYFP also diminished antipsychotic-induced VCMs, with no change in control-eYFP mice. In both ChAT-Cre and Adora2a-Cre mice, stimulation or mecamylamine alone similarly decreased VCMs with no further decline with combined treatment, suggesting nAChRs are involved. Striatal D2 MSN activation in haloperidol-treated Adora2a-Cre mice increased c-Fos + D2 MSNs and decreased c-Fos + non-D2 MSNs, suggesting a role for c-Fos. These studies provide the first evidence that optogenetic stimulation of striatal cholinergic interneurons and GABAergic MSNs modulates VCMs, and thus possibly TD. Moreover, they suggest nicotinic receptor drugs may reduce antipsychotic-induced TD. Copyright © 2016 Elsevier Inc. All rights reserved.

  20. Prespektif Pemikiran Ki Hadjar Dewantara Dalam Pendidikan Karakter Dan Kaitannya Dengan Pendidikan Islam

    Directory of Open Access Journals (Sweden)

    Fauziah Mashari

    2016-06-01

    Full Text Available Artikel ini membahas pendidikan karakter dalam perspektif Ki Hadjar Dewantara yang merupakan Bapak Pendidikan Nasional, dan kaitannya dengan pendidikan Islam. Di dalam pembangunan karakter yang dipentingkan adalah keikhlasan, kejujuran, jiwa kemanusiaan yang tinggi, sesuainya kata dengan perbuatan, prestasi kerja, kedisiplinan, jiwa dedikasi dan selalu berorientasi kepada hari depan dan pembaharuan. Pembinaan karakter akhlaq-ul kari>mah harus ditanamkan kepada seluruh lapisan dan tingkatan masyarakat, mulai dari tingkat atas sampai ke lapisan bawah. Lapisan atas itu kemudian memberikan teladan yang baik pada masyarakat dan rakyatnya. Tetapi manakala para pemimpin memberikan contoh yang buruk, maka akan berlaku pepatah yang menyatakan, “kalau guru kencing berdiri, murid akan kencing berlari; andai kata guru kencing berdiri, niscaya murid akan kencing menari-nari.” Berdasarkan latar belakang masalah tersebut diatas, tulisan ini bermaksud mencari jawaban dari pertanyaan-pertanyaan mendasar berikut: (1 bagaimana pengertian pendidikan karakter Ki Hadjar Dewantara? (2 bagaimana pengertian pendidikan agama? (3 bagaimana kaitan pendidikan karakter Ki Hadjar Dewantara dengan pendidikan Islam? Uraian dari jawaban yang dimaksud akan menunjukkan secara gamblang bahwa gagasan Ki Hadjar Dewantara tentang pendidikan karakter seiring dan sejalan dengan pendidikan Islam. || This article discusses character education in the perspective of Ki Hadjar Dewantara who is Father of National Education, and its relation to Islamic education. What is necessary for constructing the character is sincerity, honesty, spirit of humanity, suitability of words and deeds, work performance, discipline, dedication and spirit. Character building of akhlāq-ul karīmah must be imparted to all layers and levels of society, from top to bottom layer. Then, the top layer gives good examples to the society and its people. When the leaders have bad examples, so there is a strong and

  1. Kemija u nastavi: Etimološki pristup učenju kemije

    OpenAIRE

    Raos, Nenad; Raos (ur.), Nenad

    2018-01-01

    Etimološki pristup učenju kemije je u tome da ne objasnimo samo što ime ili termin znači nego i da ukažemo na njegovo izvorno značenje te objasnimo kako je našao svoj put do kemije. U članku se razmatra povijest anorganske kemije kroz povijest imenovanja kemijskih elemenata. Povijest pak organske kemije otkriva, upravo kroz imena spojeva, da se temeljila prije svega na izolaciji čistih tvari iz prirodnih materijala. Etimološki pristup učenju kemije olakšava usvajanje kemijske nomenklature i t...

  2. Ki-67 expression reveals strong, transient influenza specific CD4 T cell responses after adult vaccination

    OpenAIRE

    Li, Xi; Miao, Hongyu; Henn, Alicia; Topham, David J.; Wu, Hulin; Zand, Martin S.; Mosmann, Tim R.

    2012-01-01

    Although previous studies have found minimal changes in CD4 T cell responses after vaccination of adults with trivalent inactivated influenza vaccine, daily sampling and monitoring of the proliferation marker Ki-67 have now been used to reveal that a substantial fraction of influenza-specific CD4 T cells respond to vaccination. At 4–6 days after vaccination, there is a sharp rise in the numbers of Ki-67-expressing PBMC that produce IFNγ, IL-2 and/or TNFα in vitro in response to influenza vacc...

  3. Dejavniki, ki vplivajo na ustanavljanje in uspešnost vrtcev v podjetju

    OpenAIRE

    Klemenšek, Tanja

    2015-01-01

    V magistrski nalogi analiziramo dejavnike, ki bi dvignili raven kakovosti življenja v družini, ter kritično ovrednotimo mnenja različnih avtorjev, ki o tej temi pišejo v strokovni literaturi. Hkrati ugotavljamo tudi razloge, zaradi katerih podjetja in ustanove ustanavljajo svoje vrtce. Analizirani dejavniki so naslednji: pomoč zaposlenim pri usklajevanju delovnih in zasebnih obveznosti v družini oziroma partnerskih zvezah, prihranek časa za skupno družinsko življenje, večja čustvena povezanos...

  4. LIKOVNE DEJAVNOSTI, KI SPODBUJAJO PREDŠOLSKEGA OTROKA K USTVARJALNEMU IZRAŽANJU

    OpenAIRE

    Medved, Andreja

    2015-01-01

    Namen diplomskega dela Likovne dejavnosti, ki spodbujajo predšolskega otroka k ustvarjalnemu izražanju je predstaviti literaturo o likovnem razvoju otrok in njihovi ustvarjalnosti – od česa je ta odvisna in kako prispevamo k njenemu izboljšanju – ter opisati likovne dejavnosti, ki spodbujajo predšolske otroke k ustvarjalnemu izražanju. Diplomsko delo je sestavljeno iz teoretičnega in praktičnega dela. V teoretičnem delu je predstavljen likovni razvoj predšolskih otrok, pomen in značil...

  5. Grafični uporabniški vmesnik za vgrajene sisteme

    OpenAIRE

    MAJERLE, TILEN

    2017-01-01

    Grafični uporabniški vmesnik je način interakcije med uporabnikom in napravo, največkrat osebnim računalnikom. V današnjem času postajajo vgrajeni sistemi vse bolj zmogljivi, s tem pa tudi vse večje zahteve po delovanju. Pri najbolj zmogljivih napravah lahko priključimo zaslon na sistem in tako omogočimo uporabniku grafičen prikaz. Ker imajo vgrajeni sistemi precej manj spominskih kapacitet, moramo razmisliti o grafičnih knjižnicah, ki so namenjene prav takšnim sistemom. ...

  6. Binding of [3H]MSX-2 (3-(3-hydroxypropyl)-7-methyl-8-(m-methoxystyryl)-1-propargylxanthine) to rat striatal membranes--a new, selective antagonist radioligand for A(2A) adenosine receptors.

    Science.gov (United States)

    Müller, C E; Maurinsh, J; Sauer, R

    2000-01-01

    The present study describes the preparation and binding properties of a new, potent, and selective A(2A) adenosine receptor (AR) antagonist radioligand, [3H]3-(3-hydroxypropyl)-7-methyl-8-(m-methoxystyryl)-1-propargy lxanth ine ([3H]MSX-2). [3H]MSX-2 binding to rat striatal membranes was saturable and reversible. Saturation experiments showed that [3H]MSX-2 labeled a single class of binding sites with high affinity (K(d)=8.0 nM) and limited capacity (B(max)=1.16 fmol.mg(-1) of protein). The presence of 100 microM GTP, or 10 mM magnesium chloride, respectively, had no effect on [3H]MSX-2 binding. AR agonists competed with the binding of 1 nM [3H]MSX-2 with the following order of potency: 5'-N-ethylcarboxamidoadenosine (NECA)>2-[4-(carboxyethyl)phenylethylamino]-5'-N-ethylcarboxami doaden osine (CGS-21680)>2-chloroadenosine (2-CADO)>N(6)-cyclopentyladenosine (CPA). AR antagonists showed the following order of potency: 8-(m-bromostyryl)-3, 7-dimethyl-1-propargylxanthine (BS-DMPX)>1, 3-dipropyl-8-cyclopentylxanthine (DPCPX)>(R)-5, 6-dimethyl-7-(1-phenylethyl)-2-(4-pyridyl)-7H-pyrrolo[2, 3-d]pyrimidine-4-amine (SH-128)>3,7-dimethyl-1-propargylxanthine (DMPX)>caffeine. The K(i) values for antagonists were in accordance with data from binding studies with the agonist radioligand [3H]CGS21680, while agonist affinities were 3-7-fold lower. [3H]MSX-2 is a highly selective A(2A) AR antagonist radioligand exhibiting a selectivity of at least two orders of magnitude versus all other AR subtypes. The new radioligand shows high specific radioactivity (85 Ci/mmol, 3150 GBq/mmol) and acceptable nonspecific binding at rat striatal membranes of 20-30%, at 1 nM.

  7. KI-Aikido for Handicapped Students at Leeward Community College: Theory and Practice.

    Science.gov (United States)

    MacGugan, Kirk

    In an effort to provide physical education instruction for handicapped students, Leeward Community College implemented, on a pilot basis, a non-credit course in KI-Aikido, an oriental martial art which combines theory and exercise toward the goal of controlling the body through the power of the mind. The course, offered to both handicapped and…

  8. Proliferating cell nuclear antigen and Ki-67 immunohistochemistry of oligodendrogliomas with special reference to prognosis

    DEFF Research Database (Denmark)

    HEEGAARD, S.; Sommer, Helle Mølgaard; BROHOLM, H.

    1995-01-01

    survival time of 23.5 months and 26.2 months, respectively. No significant correlation between LI (or survival) and tumor size, cerebral localization, radiation, resection/biopsy, sex, age, or cytologic atypia was found. Conclusions. The use of Ki-67 and PCNA LI higher than 3% and 4%, respectively, appears...

  9. Vitamin D Receptor, Retinoid X Receptor, Ki-67, Survivin, and Ezrin Expression in Canine Osteosarcoma

    Directory of Open Access Journals (Sweden)

    John Davies

    2012-01-01

    Full Text Available Canine osteosarcoma (OS is an aggressive malignant bone tumor. Prognosis is primarily determined by clinical parameters. Vitamin D has been postulated as a novel therapeutic option for many malignancies. Upon activation, vitamin D receptors (VDRs combine with retinoid receptor (RXR forming a heterodimer initiating a cascade of events. Vitamin D's antineoplastic activity and its mechanism of action in OS remain to be clearly established. Expression of VDR, RXR, Ki-67, survivin, and ezrin was studied in 33 archived, canine OS specimens. VDR, RXR, survivin, and ezrin were expressed in the majority of cases. There was no statistically significant difference in VDR expression in relationship with tumor grade, type, or locations or animal breed, age, and/or sex. No significant association (p=0.316 between tumor grade and Ki-67 expression was found; in particular, no difference in Ki-67 expression between grades 2 and 3 OSs was found, while a negative correlation was noted between Ki-67 and VDR expression (ρ=−0.466, a positive correlation between survivin and RXR expression was found (p=0.374. A significant relationship exists between VDR and RXR expression in OSs and proliferative/apoptosis markers. These results establish a foundation for elucidating mechanisms by which vitamin D induces antineoplastic activity in OS.

  10. Differences in Expression of EGFR, Ki67 and p-EPK in Oral Cavity ...

    African Journals Online (AJOL)

    Purpose: To evaluate the expression of EGFR, Ki67, and p-EPK in oral cavity and oropharyngeal cancers, and to investigate their clinical significance as prognostic markers. Methods: One hundred patients who underwent curative surgery for oral cavity or oropharyngeal squamous cell carcinoma in a Chinese People's ...

  11. Kriitikud hindavad Cannes'is seni enim Kaurismäki filmi / Jaan Ruus

    Index Scriptorium Estoniae

    Ruus, Jaan, 1938-2017

    2011-01-01

    64. Cannes'i filmifestivalil seni enim köitnud filmidest, pikemalt Aki Kaurismäki filmist "Sadam" ("Le Havre"). Lühidalt enim vaidlusi tekitanud ameerika režissööri Terrence Malicki filmist "Elupuu" ("The Tree of Life") ja taani režissööri Lars von Trieri filmist "Melanhoolia" ("Melancholia")

  12. Ion transport in Au doped/undoped KDP crystals with KI/NaI as ...

    Indian Academy of Sciences (India)

    Unknown

    information regarding the mobility and production of lattice defects in these materials. ... volume of tetra-auro chloric acid solution to the mixture of KDP and KI/NaI. .... two hydrogen at one end and an H bond with no hydro- gen at the other end.

  13. Tallink kaalub müüki pandud Silja Line'i ostu / Priit Rajalo

    Index Scriptorium Estoniae

    Rajalo, Priit, 1975-

    2005-01-01

    Soome Silja Oy AB omanikfirma Sea Containers otsustas 2. novembril Silja Line'i müüki panna, kuna laevafirma kasumlikkus on järsult vähenenud. Tallink Grupi finantsdirektori Janek Stalmeistri sõnul on Tallinki võimalikku ostuhuvi Silja Line'i vastu vara veel kommenteerida. Lisa: Silja laevad

  14. Screening for cervical cancer precursors with p16/Ki-67 dual-stained cytology

    DEFF Research Database (Denmark)

    Ikenberg, Hans; Bergeron, Christine; Schmidt, Dietmar

    2013-01-01

    Pap cytology is known to be more specific but less sensitive than testing for human papillomavirus (HPV) for the detection of high-grade cervical intraepithelial neoplasia (CIN2+). We assessed whether p16/Ki-67 dual-stained cytology, a biomarker combination indicative of transforming HPV infections...

  15. Ki-67 expression reveals strong, transient influenza specific CD4 T cell responses after adult vaccination.

    Science.gov (United States)

    Li, Xi; Miao, Hongyu; Henn, Alicia; Topham, David J; Wu, Hulin; Zand, Martin S; Mosmann, Tim R

    2012-06-29

    Although previous studies have found minimal changes in CD4 T cell responses after vaccination of adults with trivalent inactivated influenza vaccine, daily sampling and monitoring of the proliferation marker Ki-67 have now been used to reveal that a substantial fraction of influenza-specific CD4 T cells respond to vaccination. At 4-6 days after vaccination, there is a sharp rise in the numbers of Ki-67-expressing PBMC that produce IFNγ, IL-2 and/or TNFα in vitro in response to influenza vaccine or peptide. Ki-67(+) cell numbers then decline rapidly, and 10 days after vaccination, both Ki-67(+) and overall influenza-specific cell numbers are similar to pre-vaccination levels. These results provide a tool for assessing the quality and quantity of CD4 T cell responses to different influenza vaccines, and raise the possibility that the anti-influenza T cell memory response may be qualitatively altered by vaccination, even if the overall memory cell numbers do not change significantly. Copyright © 2012. Published by Elsevier Ltd.

  16. The National Heritage of Ki Hadjar Dewantara in Tamansiswa about Culture-Based Education and Learning

    Science.gov (United States)

    Towaf, Siti Malikhah

    2016-01-01

    Global interdependence is a reality; in the security, economics, politics, socio-culture, and especially in the education of a nation;. Relevant to the need for an international dialog on education, this study tries to explore: 1) the concepts of culture-based education and learning of Ki Hadjar Dewantara (KHD) in Tamansiswa, 2) the results of…

  17. Prognostic significance of MCM 2 and Ki-67 in neuroblastic tumors in children.

    Science.gov (United States)

    Lewandowska, Magdalena; Taran, Katarzyna; Sitkiewicz, Anna; Andrzejewska, Ewa

    2015-12-02

    Neuroblastic tumors can be characterized by three features: spontaneous regression, maturation and aggressive proliferation. The most common and routinely used method of assessing tumor cell proliferation is to determine the Ki-67 index in the tumor tissue. Despite numerous studies, neuroblastoma biology is not fully understood, which makes treatment results unsatisfactory. MCM 2 is a potential prognostic factor in the neuroblastoma group. The study is based on retrospective analysis of 35 patients treated for neuroblastic tumors in the Department of Pediatric Surgery and Oncology of the Medical University of Lodz, during the period 2001-2011. The material comprised tissues of 16 tumors excised during the operation and 19 biopsy specimens. Immunohistochemical examinations were performed with immunoperoxidase using mouse monoclonal anti-MCM 2 and anti-Ki-67 antibodies. We observed that MCM 2 expression ranged from 2% to 98% and the Ki-67 index ranged from 0 to 95%. There was a statistically significant correlation between expression of MCM 2 and the value of the Ki-67 index and a correlation close to statistical significance between expression of MCM 2 and unfavorable histopathology. There was no statistical relationship between expression of MCM 2 and age over 1 year and N-myc amplification. The presented research shows that MCM 2 may have prognostic significance in neuroblastic pediatric tumors and as a potential prognostic factor could be the starting point of new individualized therapy.

  18. Analysis on the relation of pterygium with VEGF,SDF-1,Ki-67,PCNA and Survivin

    Directory of Open Access Journals (Sweden)

    Ying Song

    2015-12-01

    Full Text Available AIM:To analyze and study the relation of pterygium with vascular endothelial growth factor(VEGF,stroma cell-derived factor 1(SDF-1,tumor proliferating antigen(Ki-67,proliferating cell nuclear antigen(PCNAand survivin. METHODS:Seventy-nine patients(106 eyeswith pterygium from January 2013 to May 2015 in our hospital were selected as observation group. Seventy-nine persons with normal conjunctiva during the same period were selected as control group. Then the number of positive cells and staining intensity classification of the two groups for VEGF,SDF-1,Ki-67,PCNA and survivin were compared,and the detection results of patients with different gender,stages and types were compared too. Then the relation between pterygium and those indexes were analyzed by the Logistic analysis. RESULTS:The number of positive cells and staining intensity classification of observation group for VEGF,SDF-1,Ki-67,PCNA and survivin were all higher than those of control group,and the detection results of patients with different stages and types had certain differences too(all PP>0.05. All those indexes had close relation to pterygium by the Logistic analysis. CONCLUSION:The expression of VEGF,SDF-1,Ki-67,PCNA and survivin in tissue of patients with pterygium all show abnormal state,and those indexes all have close relation to pterygium.

  19. Nemški Pavliha im Vergleich zu seiner Vorlage Tyll Eulenspiegels wunderbare und seltsame Historien

    Directory of Open Access Journals (Sweden)

    Marija Javor Briški

    2017-12-01

    Full Text Available Unter Berücksichtigung des soziohistorischen Hintergrundes der Zielleser befasst sich der Beitrag auf inhaltlicher, struktureller, medialer und phraseologischer Ebene mit dem Vergleich der slowenischen Übersetzung Nemški Pavliha und seiner wiederentdeckten Vorlage Tyll Eulenspiegels wunderbare und seltsame Historien.

  20. Incorporation of p-53 mutation status and Ki-67 proliferating index in ...

    African Journals Online (AJOL)

    Ayesha Ahmed

    2018-04-26

    Apr 26, 2018 ... gastric cancer. p-53 mutation status and Ki-67 proliferation index are established prognostic ... could not only be predictive in patientLs prognostics but could also form a basis of molecular ... a similar status to Her2-neu in gastric cancer, yet no ..... HER2-based biology in 1,006 cases of gastric cancer in.

  1. Analysis of the Ki-67 index in the vaginal epithelium of castrated rats treated with tamoxifen

    Directory of Open Access Journals (Sweden)

    Afif Rieth Nery-Aguiar

    2016-02-01

    Full Text Available OBJECTIVES: Vaginal atrophy and breast cancer are common conditions in postmenopausal women and tamoxifen is the standard endocrine treatment for hormone-sensitive tumors. The present study aimed to assess the effect of tamoxifen on Ki-67 protein expression in the vaginal epithelium of castrated rats. MATERIAL AND METHODS: Forty Wistar-Hannover adult, virgin, castrated rats were randomly divided into two groups, group I (control, n=20 and group II (tamoxifen, n=20, receiving 0.5 ml of propylene glycol and 250 µg of tamoxifen diluted in 0.5 ml of propylene glycol, respectively, daily by gavage for 30 days. On the 31st day, the rats were euthanized and their vaginas were removed and fixed in 10% buffered formalin for the immunohistochemical study of Ki-67 protein expression. Data were analyzed by the Levene and Student’s t tests (p<0.05. RESULTS: The mean index of Ki-67 expression in the rat vagina of groups I and II was 4.04±0.96 and 26.86±2.19, respectively (p<0.001. CONCLUSIONS: According to the results of the present study, tamoxifen, at the dose and treatment length used, induced a significant increase in the cell proliferation of the vaginal mucosa in castrated rats, as evaluated by Ki-67 protein expression.

  2. The Plant-Derived Bauhinia bauhinioides Kallikrein Proteinase Inhibitor (rBbKI Attenuates Elastase-Induced Emphysema in Mice

    Directory of Open Access Journals (Sweden)

    Bruno Tadeu Martins-Olivera

    2016-01-01

    Full Text Available Background. Elastase mediates important oxidative actions during the development of chronic obstructive pulmonary disease (COPD. However, few resources for the inhibition of elastase have been investigated. Our study evaluated the ability of the recombinant plant derived Bauhinia bauhinioides Kallikrein proteinase Inhibitor (rBbKI to modulate elastase-induced pulmonary inflammation. Methods. C57Bl/6 mice were given intratracheal elastase (ELA group or saline (SAL group and were treated intraperitoneally with rBbKI (ELA-rBbKI and SAL-rBbKI groups. At day 28, the following analyses were performed: (I lung mechanics, (II exhaled nitric oxide (ENO, (III bronchoalveolar lavage fluid (BALF, and (IV lung immunohistochemical staining. Results. In addition to decreasing mechanical alterations and alveolar septum disruption, rBbKI reduced the number of cells in the BALF and decreased the cellular expression of TNF-α, MMP-9, MMP-12, TIMP-1, eNOS, and iNOS in airways and alveolar walls compared with the ELA group. rBbKI decreased the volume proportion of 8-iso-PGF2α, collagen, and elastic fibers in the airways and alveolar walls compared with the ELA group. A reduction in the number of MUC-5-positive cells in the airway walls was also observed. Conclusion. rBbKI reduced elastase-induced pulmonary inflammation and extracellular matrix remodeling. rBbKI may be a potential pharmacological tool for COPD treatment.

  3. Standardized Ki67 Diagnostics Using Automated Scoring--Clinical Validation in the GeparTrio Breast Cancer Study.

    Science.gov (United States)

    Klauschen, Frederick; Wienert, Stephan; Schmitt, Wolfgang D; Loibl, Sibylle; Gerber, Bernd; Blohmer, Jens-Uwe; Huober, Jens; Rüdiger, Thomas; Erbstößer, Erhard; Mehta, Keyur; Lederer, Bianca; Dietel, Manfred; Denkert, Carsten; von Minckwitz, Gunter

    2015-08-15

    Scoring proliferation through Ki67 immunohistochemistry is an important component in predicting therapy response to chemotherapy in patients with breast cancer. However, recent studies have cast doubt on the reliability of "visual" Ki67 scoring in the multicenter setting, particularly in the lower, yet clinically important, proliferation range. Therefore, an accurate and standardized Ki67 scoring is pivotal both in routine diagnostics and larger multicenter studies. We validated a novel fully automated Ki67 scoring approach that relies on only minimal a priori knowledge on cell properties and requires no training data for calibration. We applied our approach to 1,082 breast cancer samples from the neoadjuvant GeparTrio trial and compared the performance of automated and manual Ki67 scoring. The three groups of autoKi67 as defined by low (≤ 15%), medium (15.1%-35%), and high (>35%) automated scores showed pCR rates of 5.8%, 16.9%, and 29.5%, respectively. AutoKi67 was significantly linked to prognosis with overall and progression-free survival P values P(OS) cancer that correlated with clinical endpoints and is deployable in routine diagnostics. It may thus help to solve recently reported reliability concerns in Ki67 diagnostics. ©2014 American Association for Cancer Research.

  4. Cell proliferation-associated nuclear antigen defined by antibody Ki-67: a new kind of cell cycle-maintaining proteins

    International Nuclear Information System (INIS)

    Duchrow, M.; Schlueter, C.; Key, G.; Kubbutat, H.G.; Wohlenberg, C.; Flad, H.D.; Gerdes

    1995-01-01

    A decade of studies on the human nuclear antigen defined by monoclonal antibody Ki-67 (the 'Ki-67 proteins') has made it abundantly clear that this structure is strictly associated with human cell proliferation and the expression of this protein can be used to access the growth fraction of a given cell population. Until recently the Ki-67 protein was described as a nonhistone protein that is highly susceptible to protease treatment. We have isolated and sequenced cDNAs encoding for this antigen and found two isoforms of the full length cDNA of 11.5 and 12.5 kb, respectively, sequence and structure of which are thus far unique. The gene encoding the Ki-67 protein is organized in 15 exons and is localized on chromosome 10. The center of this gene is formed by an extraordinary 6845 bp exon containing 16 successively repeated homologous segments of 366 bp ('Ki-67 repeats'), each containing a highly conserved new motif of 66 bp ('Ki-67 motif'). The deduced peptide sequence of this central exon possesses 10 ProGluSerThr (PEST) motifs which are associated with high turnover proteins such as other cell cycle-related proteins, oncogenes and transcription factors, etc. Like the latter proteins the Ki-67 antigen plays a pivotal role in maintaining cell proliferation because Ki-67 protein antisense oligonucleotides significantly inhibit 3 H-thymidine incorporation in permanent human tumor cell lines in a dose-dependent manner. (author). 30 refs, 2 figs

  5. Striatal response to reward anticipation: evidence for a systems-level intermediate phenotype for schizophrenia.

    Science.gov (United States)

    Grimm, Oliver; Heinz, Andreas; Walter, Henrik; Kirsch, Peter; Erk, Susanne; Haddad, Leila; Plichta, Michael M; Romanczuk-Seiferth, Nina; Pöhland, Lydia; Mohnke, Sebastian; Mühleisen, Thomas W; Mattheisen, Manuel; Witt, Stephanie H; Schäfer, Axel; Cichon, Sven; Nöthen, Markus; Rietschel, Marcella; Tost, Heike; Meyer-Lindenberg, Andreas

    2014-05-01

    Attenuated ventral striatal response during reward anticipation is a core feature of schizophrenia that is seen in prodromal, drug-naive, and chronic schizophrenic patients. Schizophrenia is highly heritable, raising the possibility that this phenotype is related to the genetic risk for the disorder. To examine a large sample of healthy first-degree relatives of schizophrenic patients and compare their neural responses to reward anticipation with those of carefully matched controls without a family psychiatric history. To further support the utility of this phenotype, we studied its test-retest reliability, its potential brain structural contributions, and the effects of a protective missense variant in neuregulin 1 (NRG1) linked to schizophrenia by meta-analysis (ie, rs10503929). Examination of a well-established monetary reward anticipation paradigm during functional magnetic resonance imaging at a university hospital; voxel-based morphometry; test-retest reliability analysis of striatal activations in an independent sample of 25 healthy participants scanned twice with the same task; and imaging genetics analysis of the control group. A total of 54 healthy first-degree relatives of schizophrenic patients and 80 controls matched for demographic, psychological, clinical, and task performance characteristics were studied. Blood oxygen level-dependent response during reward anticipation, analysis of intraclass correlations of functional contrasts, and associations between striatal gray matter volume and NRG1 genotype. Compared with controls, healthy first-degree relatives showed a highly significant decrease in ventral striatal activation during reward anticipation (familywise error-corrected P systems-level functional phenotype is reliable (with intraclass correlation coefficients of 0.59-0.73), independent of local gray matter volume (with no corresponding group differences and no correlation to function, and with all uncorrected P values >.05), and affected by

  6. Imaging of striatal dopamine transporters in rat brain with single pinhole SPECT and co-aligned MRI is highly reproducible

    International Nuclear Information System (INIS)

    Booij, Jan; Bruin, Kora de; Win, Maartje M.L. de; Lavini, Cristina Mphil; Heeten, Gerard J. den; Habraken, Jan

    2003-01-01

    A recently developed pinhole high-resolution SPECT system was used to measure striatal to non-specific binding ratios in rats (n = 9), after injection of the dopamine transporter ligand 123 I-FP-CIT, and to assess its test/retest reproducibility. For co-alignment purposes, the rat brain was imaged on a 1.5 Tesla clinical MRI scanner using a specially developed surface coil. The SPECT images showed clear striatal uptake. On the MR images, cerebral and extra-cerebral structures could be easily delineated. The mean striatal to non-specific [ 123 I]FP-CIT binding ratios of the test/retest studies were 1.7 ± 0.2 and 1.6 ± 0.2, respectively. The test/retest variability was approximately 9%. We conclude that the assessment of striatal [ 123 I]FP-CIT binding ratios in rats is highly reproducible

  7. Pre-pulse inhibition and striatal dopamine in subjects at an ultra-high risk for psychosis

    NARCIS (Netherlands)

    de Koning, Mariken B.; Bloemen, Oswald J. N.; van Duin, Esther D. A.; Booij, Jan; Abel, Kathryn M.; de Haan, Lieuwe; Linszen, Don H.; van Amelsvoort, Thérèse A. M. J.

    2014-01-01

    Reduced prepulse inhibition (PPI) of the acoustic startle response is thought to represent a robust biomarker in schizophrenia. Reduced PPI has been demonstrated in subjects at ultra high risk (UHR) for developing psychosis. Imaging studies report disruption of striatal dopaminergic

  8. Evaluation of Ki-67 Antigen and Protein P53 Expression in Orthokratinized and Parakratinized Odontogenic Keratocyst

    Directory of Open Access Journals (Sweden)

    F. Baghaei

    2004-06-01

    Full Text Available Statement of Problem: Odontogenic Keratocysts (OKC make up 10-12% of all developmental cysts with dental origin. OKCs are classified into parakeratotic and orthokeratotic types, with completely different clinical features. In order to investigate biological behavior of OKCs, an immunohistochemical study was designed, using Ki-67 antigen as proliferation marker and P53 protein as tumor suppressor gene.Purposes: The aim of the present study was to investigate the expression of P53 and Ki-67 markers in two types of OKCs and to determine their relationship with the biological behaviour of OKC.Materials and Methods: A total of 20 OKCs (parakeratotic n=10, orthokeratotic n=10were stained immunohistochemically for Ki-67 and P53 protein by Biotin – Streptavidine method. Then, slides were studied quantitatively through optical lense (magnification=X10and the number of positively stained cells was counted/mm BM.Results: The average number of Positively stained cells for Ki-67 were 62.30±11.96 cells/mm BM in parakeratotic, and 29.90±4.90 cells/mmBM in orthokeratotic OKCs (P<0.05. Positive cells for Ki-67 were dominantly located in parabasal layer. Mean stainedcells for P53 were 4.30± 2.21cells/mmBM in parakeratinized and 4.80±1.75 cells/mmBM in orthokeratotic types that was not statistically significant. (P<0.58Parakeratotic OKCs mostly occur in the lower jaw (90%, whereas just 50% of orthokeratotic OKCs occur in mandible (P=0.05Conclusion: Regarding other clinical features and the existence of daughter cysts, no significant statistical difference was found between two types of OKCs.

  9. Intratumor heterogeneity of DCE-MRI reveals Ki-67 proliferation status in breast cancer

    Science.gov (United States)

    Cheng, Hu; Fan, Ming; Zhang, Peng; Liu, Bin; Shao, Guoliang; Li, Lihua

    2018-03-01

    Breast cancer is a highly heterogeneous disease both biologically and clinically, and certain pathologic parameters, i.e., Ki67 expression, are useful in predicting the prognosis of patients. The aim of the study is to identify intratumor heterogeneity of breast cancer for predicting Ki-67 proliferation status in estrogen receptor (ER)-positive breast cancer patients. A dataset of 77 patients was collected who underwent dynamic contrast enhancement magnetic resonance imaging (DCE-MRI) examination. Of these patients, 51 were high-Ki-67 expression and 26 were low-Ki-67 expression. We partitioned the breast tumor into subregions using two methods based on the values of time to peak (TTP) and peak enhancement rate (PER). Within each tumor subregion, image features were extracted including statistical and morphological features from DCE-MRI. The classification models were applied on each region separately to assess whether the classifiers based on features extracted from various subregions features could have different performance for prediction. An area under a receiver operating characteristic curve (AUC) was computed using leave-one-out cross-validation (LOOCV) method. The classifier using features related with moderate time to peak achieved best performance with AUC of 0.826 than that based on the other regions. While using multi-classifier fusion method, the AUC value was significantly (P=0.03) increased to 0.858+/-0.032 compare to classifier with AUC of 0.778 using features from the entire tumor. The results demonstrated that features reflect heterogeneity in intratumoral subregions can improve the classifier performance to predict the Ki-67 proliferation status than the classifier using features from entire tumor alone.

  10. KiDS-450: testing extensions to the standard cosmological model

    Science.gov (United States)

    Joudaki, Shahab; Mead, Alexander; Blake, Chris; Choi, Ami; de Jong, Jelte; Erben, Thomas; Fenech Conti, Ian; Herbonnet, Ricardo; Heymans, Catherine; Hildebrandt, Hendrik; Hoekstra, Henk; Joachimi, Benjamin; Klaes, Dominik; Köhlinger, Fabian; Kuijken, Konrad; McFarland, John; Miller, Lance; Schneider, Peter; Viola, Massimo

    2017-10-01

    We test extensions to the standard cosmological model with weak gravitational lensing tomography using 450 deg2 of imaging data from the Kilo Degree Survey (KiDS). In these extended cosmologies, which include massive neutrinos, non-zero curvature, evolving dark energy, modified gravity and running of the scalar spectral index, we also examine the discordance between KiDS and cosmic microwave background (CMB) measurements from Planck. The discordance between the two data sets is largely unaffected by a more conservative treatment of the lensing systematics and the removal of angular scales most sensitive to non-linear physics. The only extended cosmology that simultaneously alleviates the discordance with Planck and is at least moderately favoured by the data includes evolving dark energy with a time-dependent equation of state (in the form of the w0 - wa parametrization). In this model, the respective S_8=σ _8√{Ω m/0.3} constraints agree at the 1σ level, and there is 'substantial concordance' between the KiDS and Planck data sets when accounting for the full parameter space. Moreover, the Planck constraint on the Hubble constant is wider than in Λ cold dark matter (ΛCDM) and in agreement with the Riess et al. (2016) direct measurement of H0. The dark energy model is moderately favoured as compared to ΛCDM when combining the KiDS and Planck measurements, and marginalized constraints in the w0-wa plane are discrepant with a cosmological constant at the 3σ level. KiDS further constrains the sum of neutrino masses to 4.0 eV (95% CL), finds no preference for time or scale-dependent modifications to the metric potentials, and is consistent with flatness and no running of the spectral index.

  11. A new framework for cortico-striatal plasticity: behavioural theory meets in vitro data at the reinforcement-action interface.

    Directory of Open Access Journals (Sweden)

    Kevin N Gurney

    2015-01-01

    Full Text Available Operant learning requires that reinforcement signals interact with action representations at a suitable neural interface. Much evidence suggests that this occurs when phasic dopamine, acting as a reinforcement prediction error, gates plasticity at cortico-striatal synapses, and thereby changes the future likelihood of selecting the action(s coded by striatal neurons. But this hypothesis faces serious challenges. First, cortico-striatal plasticity is inexplicably complex, depending on spike timing, dopamine level, and dopamine receptor type. Second, there is a credit assignment problem-action selection signals occur long before the consequent dopamine reinforcement signal. Third, the two types of striatal output neuron have apparently opposite effects on action selection. Whether these factors rule out the interface hypothesis and how they interact to produce reinforcement learning is unknown. We present a computational framework that addresses these challenges. We first predict the expected activity changes over an operant task for both types of action-coding striatal neuron, and show they co-operate to promote action selection in learning and compete to promote action suppression in extinction. Separately, we derive a complete model of dopamine and spike-timing dependent cortico-striatal plasticity from in vitro data. We then show this model produces the predicted activity changes necessary for learning and extinction in an operant task, a remarkable convergence of a bottom-up data-driven plasticity model with the top-down behavioural requirements of learning theory. Moreover, we show the complex dependencies of cortico-striatal plasticity are not only sufficient but necessary for learning and extinction. Validating the model, we show it can account for behavioural data describing extinction, renewal, and reacquisition, and replicate in vitro experimental data on cortico-striatal plasticity. By bridging the levels between the single synapse and

  12. Transgenic mice expressing a Huntington s disease mutation are resistant to quinolinic acid-induced striatal excitotoxicity

    OpenAIRE

    Hansson, Oskar; Petersén, Åsa; Leist, Marcel; Nicotera, Pierluigi; Castilho, Roger F.; Brundin, Patrik

    1999-01-01

    Huntington’s disease (HD) is a hereditary neurodegenerative disorder presenting with chorea, dementia, and extensive striatal neuronal death. The mechanism through which the widely expressed mutant HD gene mediates a slowly progressing striatal neurotoxicity is unknown. Glutamate receptor-mediated excitotoxicity has been hypothesized to contribute to the pathogenesis of HD. Here we show that transgenic HD mice expressing exon 1 of a human HD gene with an expanded number of CAG repeats (line R...

  13. Association of pKi-67 with satellite DNA of the human genome in early G1 cells.

    Science.gov (United States)

    Bridger, J M; Kill, I R; Lichter, P

    1998-01-01

    pKi-67 is a nucleolar antigen that provides a specific marker for proliferating cells. It has been shown previously that pKi-67's distribution varies in a cell cycle-dependent manner: it coats all chromosomes during mitosis, accumulates in nuclear foci during G1 phase (type I distribution) and localizes within nucleoli in late G1 S and G2 phase (type II distribution). Although no function has as yet been ascribed to pKi-67, it has been found associated with centromeres in G1. In the present study the distribution pattern of pKi-67 during G1 in human dermal fibroblasts (HDFs) was analysed in more detail. Synchronization experiments show that in very early G1 cells pKi-67 coincides with virtually all satellite regions analysed, i.e. with centromeric (alpha-satellite), telomeric (minisatellite) and heterochromatic blocks (satellite III) on chromosomes 1 and Y (type Ia distribution). In contrast, later in the G1 phase, a smaller fraction of satellite DNA regions are found collocalized with pKi-67 foci (type Ib distribution). When all pKi-67 becomes localized within nucleoli, even fewer satellite regions remain associated with the pKi-67 staining. However, all centromeric and short arm regions of the acrocentric chromosomes, which are in very close proximity to or even contain the rRNA genes, are collocalized with anti-pKi-67 staining throughout the remaining interphase of the cell cycle. Thus, our data demonstrate that during post-mitotic reformation and nucleogenesis there is a progressive decline in the fraction of specific satellite regions of DNA that remain associated with pKi-67. This may be relevant to nucleolar reformation following mitosis.

  14. The proliferation marker pKi-67 becomes masked to MIB-1 staining after expression of its tandem repeats.

    Science.gov (United States)

    Schmidt, Mirko H H; Broll, Rainer; Bruch, Hans-Peter; Duchrow, Michael

    2002-11-01

    The Ki-67 antigen, pKi-67, is one of the most commonly used markers of proliferating cells. The protein can only be detected in dividing cells (G(1)-, S-, G(2)-, and M-phase) but not in quiescent cells (G(0)). The standard antibody to detect pKi-67 is MIB-1, which detects the so-called 'Ki-67 motif' FKELF in 9 of the protein's 16 tandem repeats. To investigate the function of these repeats we expressed three of them in an inducible gene expression system in HeLa cells. Surprisingly, addition of a nuclear localization sequence led to a complete absence of signal in the nuclei of MIB-1-stained cells. At the same time antibodies directed against different epitopes of pKi-67 did not fail to detect the protein. We conclude that the overexpression of the 'Ki-67 motif', which is present in the repeats, can lead to inability of MIB-1 to detect its antigen as demonstrated in adenocarcinoma tissue samples. Thereafter, in order to prevent the underestimation of Ki-67 proliferation indices in MIB-1-labeled preparations, additional antibodies (for example, MIB-21) should be used. Additionally, we could show in a mammalian two-hybrid assay that recombinant pKi-67 repeats are capable of self-associating with endogenous pKi-67. Speculating that the tandem repeats are intimately involved in its protein-protein interactions, this offers new insights in how access to these repeats is regulated by pKi-67 itself.

  15. Chromophore-assisted light inactivation of pKi-67 leads to inhibition of ribosomal RNA synthesis.

    Science.gov (United States)

    Rahmanzadeh, R; Hüttmann, G; Gerdes, J; Scholzen, T

    2007-06-01

    Expression of the nuclear Ki-67 protein (pKi-67) is strongly associated with cell proliferation. For this reason, antibodies against this protein are widely used as prognostic tools for the assessment of cell proliferation in biopsies from cancer patients. Despite this broad application in histopathology, functional evidence for the physiological role of pKi-67 is still missing. Recently, we proposed a function of pKi-67 in the early steps of ribosomal RNA (rRNA) synthesis. Here, we have examined the involvement of pKi-67 in this process by photochemical inhibition using chromophore-assisted light inactivation (CALI). Anti-pKi-67 antibodies were labelled with the fluorochrome fluorescein 5(6)-isothiocyanate and were irradiated after binding to their target protein. Performing CALI in vitro on cell lysates led to specific cross-linking of pKi-67. Moreover, the upstream binding factor (UBF) necessary for rRNA transcription was also partly subjected to cross-link formation, indicating a close spatial proximity of UBF and pKi-67. CALI in living cells, using micro-injected antibody, caused a striking relocalization of UBF from foci within the nucleoli to spots located at the nucleolar rim or within the nucleoplasm. pKi-67-CALI resulted in dramatic inhibition of RNA polymerase I-dependent nucleolar rRNA synthesis, whereas RNA polymerase II-dependent nucleoplasmic RNA synthesis remained almost unaltered. Our data presented here argue for a crucial role of pKi-67 in RNA polymerase I-dependent nucleolar rRNA synthesis.

  16. Prognostic value of Ki-67 index in adult medulloblastoma after accounting for molecular subgroup: a retrospective clinical and molecular analysis.

    Science.gov (United States)

    Zhao, Fu; Zhang, Jing; Li, Peng; Zhou, Qiangyi; Zhang, Shun; Zhao, Chi; Wang, Bo; Yang, Zhijun; Li, Chunde; Liu, Pinan

    2018-04-23

    Medulloblastoma (MB) is a rare primary brain tumor in adults. We previously evaluated that combining both clinical and molecular classification could improve current risk stratification for adult MB. In this study, we aimed to identify the prognostic value of Ki-67 index in adult MB. Ki-67 index of 51 primary adult MBs was reassessed using a computer-based image analysis (Image-Pro Plus). All patients were followed up ranging from 12 months up to 15 years. Gene expression profiling and immunochemistry were used to establish the molecular subgroups in adult MB. Combined risk stratification models were designed based on clinical characteristics, molecular classification and Ki-67 index, and identified by multivariable Cox proportional hazards analysis. In our cohort, the mean Ki-67 value was 30.0 ± 11.3% (range 6.56-63.55%). The average Ki-67 value was significantly higher in LC/AMB than in CMB and DNMB (P = .001). Among three molecular subgroups, Group 4-tumors had the highest average Ki-67 value compared with WNT- and SHH-tumors (P = .004). Patients with Ki-67 index large than 30% displayed poorer overall survival (OS) and progression free survival (PFS) than those with Ki-67 less than 30% (OS: P = .001; PFS: P = .006). Ki-67 index (i.e. > 30%, < 30%) was identified as an independent significant prognostic factor (OS: P = .017; PFS: P = .024) by using multivariate Cox proportional hazards model. In conclusion, Ki-67 index can be considered as a valuable independent prognostic biomarker for adult patients with MB.

  17. Blunted striatal response to monetary reward anticipation during smoking abstinence predicts lapse during a contingency-managed quit attempt.

    Science.gov (United States)

    Sweitzer, Maggie M; Geier, Charles F; Denlinger, Rachel; Forbes, Erika E; Raiff, Bethany R; Dallery, Jesse; McClernon, F J; Donny, Eric C

    2016-03-01

    Tobacco smoking is associated with dysregulated reward processing within the striatum, characterized by hypersensitivity to smoking rewards and hyposensitivity to non-smoking rewards. This bias toward smoking reward at the expense of alternative rewards is further exacerbated by deprivation from smoking, which may contribute to difficulty maintaining abstinence during a quit attempt. We examined whether abstinence-induced changes in striatal processing of rewards predicted lapse likelihood during a quit attempt supported by contingency management (CM), in which abstinence from smoking was reinforced with money. Thirty-six non-treatment-seeking smokers participated in two functional MRI (fMRI) sessions, one following 24-h abstinence and one following smoking as usual. During each scan, participants completed a rewarded guessing task designed to elicit striatal activation in which they could earn smoking and monetary rewards delivered after the scan. Participants then engaged in a 3-week CM-supported quit attempt. As previously reported, 24-h abstinence was associated with increased striatal activation in anticipation of smoking reward and decreased activation in anticipation of monetary reward. Individuals exhibiting greater decrements in right striatal activation to monetary reward during abstinence (controlling for activation during non-abstinence) were more likely to lapse during CM (p reward. These results are consistent with a growing number of studies indicating the specific importance of disrupted striatal processing of non-drug reward in nicotine dependence and highlight the importance of individual differences in abstinence-induced deficits in striatal function for smoking cessation.

  18. Sexual dimorphism in striatal dopaminergic responses promotes monogamy in social songbirds.

    Science.gov (United States)

    Tokarev, Kirill; Hyland Bruno, Julia; Ljubičić, Iva; Kothari, Paresh J; Helekar, Santosh A; Tchernichovski, Ofer; Voss, Henning U

    2017-08-11

    In many songbird species, males sing to attract females and repel rivals. How can gregarious, non-territorial songbirds such as zebra finches, where females have access to numerous males, sustain monogamy? We found that the dopaminergic reward circuitry of zebra finches can simultaneously promote social cohesion and breeding boundaries. Surprisingly, in unmated males but not in females, striatal dopamine neurotransmission was elevated after hearing songs. Behaviorally too, unmated males but not females persistently exchanged mild punishments in return for songs. Song reinforcement diminished when dopamine receptors were blocked. In females, we observed song reinforcement exclusively to the mate's song, although their striatal dopamine neurotransmission was only slightly elevated. These findings suggest that song-triggered dopaminergic activation serves a dual function in social songbirds: as low-threshold social reinforcement in males and as ultra-selective sexual reinforcement in females. Co-evolution of sexually dimorphic reinforcement systems can explain the coexistence of gregariousness and monogamy.

  19. Overeating Behavior and Striatal Dopamine with 6-[18F]-Fluoro-L--Tyrosine PET

    Directory of Open Access Journals (Sweden)

    Claire E. Wilcox

    2010-01-01

    Full Text Available Eating behavior may be affected by dopamine synthesis capacity. In this study, 6-[18F]-fluoro-L--tyrosine (FMT positron emission tomography (PET uptake in striatal subregions was correlated with BMI (kg/m2 and an estimate of the frequency of prior weight loss attempts in 15 healthy subjects. BMI was negatively correlated with FMT uptake in the dorsal caudate. Although the association between BMI and FMT uptake in the dorsal caudate was not significant upon correction for age and sex, the association fell within the range of a statistical trend. Weight loss attempts divided by years trying was also negatively correlated with FMT uptake in the dorsal putamen (=.05. These results suggest an association between low dorsal striatal presynaptic dopamine synthesis capacity and overeating behavior.

  20. Striatal μ-opioid receptor availability predicts cold pressor pain threshold in healthy human subjects

    DEFF Research Database (Denmark)

    Hagelberg, Nora; Aalto, Sargo; Tuominen, Lauri

    2012-01-01

    the potential associations between μ-opioid receptor BP(ND) and psychophysical measures. The results show that striatal μ-opioid receptor BP(ND) predicts cold pressor pain threshold, but not cold pressor pain tolerance or tactile sensitivity. This finding suggests that striatal μ-opioid receptor density......Previous PET studies in healthy humans have shown that brain μ-opioid receptor activation during experimental pain is associated with reductions in the sensory and affective ratings of the individual pain experience. The aim of this study was to find out whether brain μ-opioid receptor binding...... at the resting state, in absence of painful stimulation, can be a long-term predictor of experimental pain sensitivity. We measured μ-opioid receptor binding potential (BP(ND)) with μ-opioid receptor selective radiotracer [(11)C]carfentanil and positron emission tomography (PET) in 12 healthy male subjects...

  1. Populations of striatal medium spiny neurons encode vibrotactile frequency in rats: modulation by slow wave oscillations.

    Science.gov (United States)

    Hawking, Thomas G; Gerdjikov, Todor V

    2013-01-01

    Dorsolateral striatum (DLS) is implicated in tactile perception and receives strong projections from somatosensory cortex. However, the sensory representations encoded by striatal projection neurons are not well understood. Here we characterized the contribution of DLS to the encoding of vibrotactile information in rats by assessing striatal responses to precise frequency stimuli delivered to a single vibrissa. We applied stimuli in a frequency range (45-90 Hz) that evokes discriminable percepts and carries most of the power of vibrissa vibration elicited by a range of complex fine textures. Both medium spiny neurons and evoked potentials showed tactile responses that were modulated by slow wave oscillations. Furthermore, medium spiny neuron population responses represented stimulus frequency on par with previously reported behavioral benchmarks. Our results suggest that striatum encodes frequency information of vibrotactile stimuli which is dynamically modulated by ongoing brain state.

  2. Effects of the modern food environment on striatal function, cognition and regulation of ingestive behavior.

    Science.gov (United States)

    Burke, Mary V; Small, Dana M

    2016-06-01

    Emerging evidence from human and animal studies suggest that consumption of palatable foods rich in fat and/or carbohydrates may produce deleterious influences on brain function independently of body weight or metabolic disease. Here we consider two mechanisms by which diet can impact striatal circuits to amplify food cue reactivity and impair inhibitory control. First, we review findings demonstrating that the energetic properties of foods regulate nucleus accumbens food cue reactivity, a demonstrated predictor of weight gain susceptibility, which is then sensitized by chronic consumption of an energy dense diet. Second, we consider evidence for diet-induced adaptations in dorsal striatal dopamine signaling that is associated with impaired inhibitory control and negative outcome learning.

  3. Running wheel exercise before a binge regimen of methamphetamine does not protect against striatal dopaminergic damage.

    Science.gov (United States)

    O'dell, Steven J; Marshall, John F

    2014-09-01

    Repeated administration of methamphetamine (mAMPH) to rodents in a single-day "binge" dosing regimen produces long-lasting damage to forebrain dopaminergic nerve terminals as measured by decreases in tissue dopamine (DA) content and levels of the plasmalemmal DA transporter (DAT). However, the midbrain cell bodies from which the DA terminals arise survive, and previous reports show that striatal DA markers return to control levels by 12 months post-mAMPH, suggesting long-term repair or regrowth of damaged DA terminals. We previously showed that when rats engaged in voluntary aerobic exercise for 3 weeks before and 3 weeks after a binge regimen of mAMPH, exercise significantly ameliorated mAMPH-induced decreases in striatal DAT. However, these data left unresolved the question of whether exercise protected against the initial neurotoxicity from the mAMPH binge or accelerated the repair of the damaged DA terminals. The present experiments were designed to test whether exercise protects against the mAMPH-induced injury. Adult male Sprague-Dawley rats were allowed to run in wheels for 3 weeks before an acute binge regimen of mAMPH or saline, then placed into nonwheel cages for an additional week before autoradiographic determination of striatal DAT binding. The autoradiographic findings showed that prior exercise provided no protection against mAMPH-induced damage to striatal DA terminals. These results, together with analyses from our previous experiments, suggest that voluntary exercise may accelerate the repair of mAMPH-damaged DA terminals and that voluntary exercise may be useful as therapeutic adjunct in the treatment mAMPH addicts. © 2014 Wiley Periodicals, Inc.

  4. Ventricular fibrillation cardiac arrest produces a chronic striatal hyperdopaminergic state that is worsened by methylphenidate treatment.

    Science.gov (United States)

    Nora, Gerald J; Harun, Rashed; Fine, David F; Hutchison, Daniel; Grobart, Adam C; Stezoski, Jason P; Munoz, Miranda J; Kochanek, Patrick M; Leak, Rehana K; Drabek, Tomas; Wagner, Amy K

    2017-07-01

    Cardiac arrest survival rates have improved with modern resuscitation techniques, but many survivors experience impairments associated with hypoxic-ischemic brain injury (HIBI). Currently, little is understood about chronic changes in striatal dopamine (DA) systems after HIBI. Given the common empiric clinical use of DA enhancing agents in neurorehabilitation, investigation evaluating dopaminergic alterations after cardiac arrest (CA) is necessary to optimize rehabilitation approaches. We hypothesized that striatal DA neurotransmission would be altered chronically after ventricular fibrillation cardiac arrest (VF-CA). Fast-scan cyclic voltammetry was used with median forebrain bundle (MFB) maximal electrical stimulations (60Hz, 10s) in rats to characterize presynaptic components of DA neurotransmission in the dorsal striatum (D-Str) and nucleus accumbens 14 days after a 5-min VF-CA when compared to Sham or Naïve. VF-CA increased D-Str-evoked overflow [DA], total [DA] released, and initial DA release rate versus controls, despite also increasing maximal velocity of DA reuptake (V max ). Methylphenidate (10 mg/kg), a DA transporter inhibitor, was administered to VF-CA and Shams after establishing a baseline, pre-drug 60 Hz, 5 s stimulation response. Methylphenidate increased initial evoked overflow [DA] more-so in VF-CA versus Sham and reduced D-Str V max in VF-CA but not Shams; these findings are consistent with upregulated striatal DA transporter in VF-CA versus Sham. Our work demonstrates that 5-min VF-CA increases electrically stimulated DA release with concomitant upregulation of DA reuptake 2 weeks after brief VF-CA insult. Future work should elucidate how CA insult duration, time after insult, and insult type influence striatal DA neurotransmission and related cognitive and motor functions. © 2017 International Society for Neurochemistry.

  5. Ventral striatal regulation of CREM mediates impulsive action and drug addiction vulnerability

    OpenAIRE

    Miller, Michael L.; Ren, Yanhua; Szutorisz, Henrietta; Warren, Noël A.; Tessereau, Chloé; Egervári, Gábor; Mlodnicka, Agnieszka; Kapoor, Manav; Chaarani, Bader; Morris, Claudia V.; Schumann, Gunter; Garavan, Hugh; Goate, Alison M.; Bannon, Michael J.; Halperin, Jeffrey M.

    2017-01-01

    Impulsivity, a multifaceted behavioral hallmark of attention-deficit/hyperactivity disorder (ADHD), strongly influences addiction vulnerability and other psychiatric disorders that incur enormous medical and societal burdens yet the neurobiological underpinnings linking impulsivity to disease remain poorly understood. Here we report the critical role of ventral striatal cAMP-response element modulator (CREM) in mediating impulsivity relevant to drug abuse vulnerability. Using an ADHD rat mode...

  6. Chronic exposure to dopamine agonists affects the integrity of striatal D2 receptors in Parkinson's patients

    Directory of Open Access Journals (Sweden)

    Marios Politis

    2017-01-01

    Full Text Available We aimed to investigate the integrity and clinical relevance of striatal dopamine receptor type-2 (D2R availability in Parkinson's disease (PD patients. We studied 68 PD patients, spanning from early to advanced disease stages, and 12 healthy controls. All participants received one [11C]raclopride PET scan in an OFF medication condition for quantification of striatal D2R availability in vivo. Parametric images of [11C]raclopride non-displaceable binding potential were generated from the dynamic [11C]raclopride scans using implementation of the simplified reference tissue model with cerebellum as the reference tissue. PET data were interrogated for correlations with clinical data related to disease burden and dopaminergic treatment. PD patients showed a mean 16.7% decrease in caudate D2R and a mean 3.5% increase in putaminal D2R availability compared to healthy controls. Lower caudate [11C]raclopride BPND correlated with longer PD duration. PD patients on dopamine agonist treatment had 9.2% reduced D2R availability in the caudate and 12.8% in the putamen compared to PD patients who never received treatment with dopamine agonists. Higher amounts of lifetime dopamine agonist therapy correlated with reduced D2Rs availability in both caudate and putamen. No associations between striatal D2R availability and levodopa treatment and dyskinesias were found. In advancing PD the caudate and putamen D2R availability are differentially affected. Chronic exposure to treatment with dopamine agonists, but no levodopa, suppresses striatal D2R availability, which may have relevance to output signaling to frontal lobes and the occurrence of executive deficits, but not dyskinesias.

  7. Basal ganglia disorders associated with imbalances in the striatal striosome and matrix compartments

    Directory of Open Access Journals (Sweden)

    Jill R. Crittenden

    2011-09-01

    Full Text Available The striatum is composed principally of GABAergic, medium spiny projection neurons (MSNs that can be categorized based on their gene expression, electrophysiological profiles and input-output circuits. Major subdivisions of MSN populations include 1 those in ventromedial and dorsolateral striatal regions, 2 those giving rise to the direct and indirect pathways, and 3 those that lie in the striosome and matrix compartments. The first two classificatory schemes have enabled advances in understanding of how basal ganglia circuits contribute to disease. However, despite the large number of molecules that are differentially expressed in the striosomes or the extra-striosomal matrix, and the evidence that these compartments have different input-output connections, our understanding of how this compartmentalization contributes to striatal function is still not clear. A broad view is that the matrix contains the direct and indirect pathway MSNs that form parts of sensorimotor and associative circuits, whereas striosomes contain MSNs that receive input from parts of limbic cortex and project directly or indirectly to the dopamine-containing neurons of the substantia nigra, pars compacta. Striosomes are widely distributed within the striatum and are thought to exert global, as well as local, influences on striatal processing by exchanging information with the surrounding matrix, including through interneurons that send processes into both compartments. It has been suggested that striosomes exert and maintain limbic control over behaviors driven by surrounding sensorimotor and associative parts of the striatal matrix. Consistent with this possibility, imbalances between striosome and matrix functions have been reported in relation to neurological disorders, including Huntington’s disease, L-DOPA-induced dyskinesias, dystonia and drug addiction. Here, we consider how signaling imbalances between the striosomes and matrix might relate to symptomatology in

  8. Concomitant Appearance of Pisa Syndrome and Striatal Hand in Parkinson’s Disease

    Directory of Open Access Journals (Sweden)

    Sanjay Pandey

    2011-10-01

    Full Text Available Pisa syndrome is (PS usually seen in patients receiving antipsychotic drugs and characterised by lateral flexion of trunk and axial dystonia. It is believed that antipsychotic drugs lead to dopamine blockage causing PS. We describe a Parkinson’s disease patient who was doing well with levodopa/carbidopa for 3 years and developed lateral flexion of trunk. His abnormal posture used to completely improve upon lying down position. He also had striatal hand deformity suggestive of focal dystonia.

  9. Prolonged striatal disinhibition as a chronic animal model of tic disorders.

    Science.gov (United States)

    Vinner, Esther; Israelashvili, Michal; Bar-Gad, Izhar

    2017-12-01

    Experimental findings and theoretical models have associated Tourette syndrome with abnormal striatal inhibition. The expression of tics, the hallmark symptom of this disorder, has been transiently induced in non-human primates and rodents by the injection of GABA A antagonists into the striatum, leading to temporary disinhibition. The novel chronic model of tic expression utilizes mini-osmotic pumps implanted subcutaneously in the rat's back for prolonged infusion of bicuculline into the dorsolateral striatum. Tics were expressed on the contralateral side to the infusion over a period of multiple days. Tic expression was stable, and maintained similar properties throughout the infusion period. Electrophysiological recordings revealed the existence of tic-related local field potential spikes and individual neuron activity changes that remained stable throughout the infusion period. The striatal disinhibition model provides a unique combination of face validity (tic expression) and construct validity (abnormal striatal inhibition) but is limited to sub-hour periods. The new chronic model extends the period of tic expression to multiple days and thus enables the study of tic dynamics and the effects of behavior and pharmacological agents on tic expression. The chronic model provides similar behavioral and neuronal correlates of tics as the acute striatal disinhibition model but over prolonged periods of time, thus providing a unique, basal ganglia initiated model of tic expression. Chronic expression of symptoms is the key to studying the time varying properties of Tourette syndrome and the effects of multiple internal and external factors on this disorder. Copyright © 2017 Elsevier B.V. All rights reserved.

  10. Quinolinic acid induces disrupts cytoskeletal homeostasis in striatal neurons. Protective role of astrocyte-neuron interaction.

    Science.gov (United States)

    Pierozan, Paula; Ferreira, Fernanda; de Lima, Bárbara Ortiz; Pessoa-Pureur, Regina

    2015-02-01

    Quinolinic acid (QUIN) is an endogenous metabolite of the kynurenine pathway involved in several neurological disorders. Among the several mechanisms involved in QUIN-mediated toxicity, disruption of the cytoskeleton has been demonstrated in striatally injected rats and in striatal slices. The present work searched for the actions of QUIN in primary striatal neurons. Neurons exposed to 10 µM QUIN presented hyperphosphorylated neurofilament (NF) subunits (NFL, NFM, and NFH). Hyperphosphorylation was abrogated in the presence of protein kinase A and protein kinase C inhibitors H89 (20 μM) and staurosporine (10 nM), respectively, as well as by specific antagonists to N-methyl-D-aspartate (50 µM DL-AP5) and metabotropic glutamate receptor 1 (100 µM MPEP). Also, intra- and extracellular Ca(2+) chelators (10 µM BAPTA-AM and 1 mM EGTA, respectively) and Ca(2+) influx through L-type voltage-dependent Ca(2+) channel (10 µM verapamil) are implicated in QUIN-mediated effects. Cells immunostained for the neuronal markers βIII-tubulin and microtubule-associated protein 2 showed altered neurite/neuron ratios and neurite outgrowth. NF hyperphosphorylation and morphological alterations were totally prevented by conditioned medium from QUIN-treated astrocytes. Cocultured astrocytes and neurons interacted with one another reciprocally, protecting them against QUIN injury. Cocultured cells preserved their cytoskeletal organization and cell morphology together with unaltered activity of the phosphorylating system associated with the cytoskeleton. This article describes cytoskeletal disruption as one of the most relevant actions of QUIN toxicity in striatal neurons in culture with soluble factors secreted by astrocytes, with neuron-astrocyte interaction playing a role in neuroprotection. © 2014 Wiley Periodicals, Inc.

  11. Implantable microencapsulated dopamine (DA): prolonged functional release of DA in denervated striatal tissue.

    Science.gov (United States)

    McRae, A; Hjorth, S; Mason, D; Dillon, L; Tice, T

    1990-01-01

    Biodegradable controlled-release microcapsule systems made with the biocompatible biodegradable polyester excipient poly [DL-lactide-co-gly-colide] constitute an exciting new technology for drug delivery to the central nervous system (CNS). The present study describes functional observations indicating that implantation of dopamine (DA) microcapsules encapsulated within two different polymer excipients into denervated striatal tissue assures a prolonged release of the transmitter in vivo. This technology has a considerable potential for basic and possibly clinical research.

  12. DISC1 and striatal volume: a potential risk phenotype for mental illness

    Directory of Open Access Journals (Sweden)

    M. Mallar eChakravarty

    2012-06-01

    Full Text Available Disrupted-in-schizophrenia 1 was originally discovered in a large Scottish family with abnormally high rates of severe mental illness, including schizophrenia, bipolar disorder, and depression. An accumulating body of evidence from genetic, postmortem, and animal data supports a role for DISC1 in different forms of mental illness. DISC1 may play an important role in determining structure and function of several brain regions. One brain region of particular importance for several mental disorders is the striatum, and DISC1 mutant mice have demonstrated an increase in dopamine (D2 receptors in this structure. However, association between DISC1 functional polymorphisms and striatal structure have not been examined in humans to our knowledge. We, therefore hypothesized that there would be a relationship between human striatal volume and DISC1 genotype, specifically in the Leu607Phe (rs6675281 and Ser704Cys (rs821618 single nucleotide polymorphisms. We tested our hypothesis by automatically identifying the striatum in fifty-four healthy volunteers recruited for this study. We also performed an exploratory analysis of cortical thickness, cortical surface area, and structure volume. Our results demonstrate that Phe allele carriers have larger striatal volume bilaterally (left striatum: p=0.017; right striatum: p=0.016. From the exploratory analyses we found that Phe carriers also had larger right hemisphere volumes and right occipital lobe surface area (p=0.014 compared to LeuLeu homozygotes (p=0.0074. However, these exploratory findings do not survive a conservative correction for multiple comparisons. Our findings demonstrate that a functional DISC1 variant influences striatal volumes. Taken together with animal data that this gene influences D2 receptor levels in striatum, a key risk pathway for mental illnesses such as schizophrenia and bipolar disorder may be conferred via DISC1’s effects on the striatum .

  13. Differences in striatal dopamine transporter density between tremor dominant and non-tremor Parkinson's disease

    International Nuclear Information System (INIS)

    Kaasinen, Valtteri; Kinos, Maija; Joutsa, Juho; Seppaenen, Marko; Noponen, Tommi

    2014-01-01

    Parkinson's disease (PD) can manifest with a tremor-dominant or a non-tremor (akinetic-rigid) phenotype. Although the tremor-dominant subtype may show a better prognosis, there is limited information on the phenotypic differences regarding the level of striatal dopamine transmission. The present study investigated striatal dopamine transporter (DAT) binding characteristics in a large sample of patients with and without tremor. [ 123 I]FP-CIT SPECT scans of 231 patients with a clinical diagnosis of PD and abnormal FP-CIT binding (157 with tremor, 74 without tremor) and 230 control patients with normal FP-CIT binding (148 with tremor, 82 without tremor) were analysed using an automated region-of-interest analysis of the scans (BRASS). Specific striatal binding ratios were compared between phenotypes and groups using age, sex, and symptom duration, predominant side of symptoms, dopaminergic medications and scanner as covariates. Patients with PD had 28.1 - 65.0 % lower binding in all striatal regions compared to controls (p < 0.001). The mean FP-CIT caudate nucleus uptake and the left caudate nucleus uptake were higher in PD patients with tremor than in PD patients without tremor (mean 9.0 % higher, left 10.5 % higher; p < 0.05), whereas there were no differences between tremor and non-tremor control patients. No significant effects of tremor on DAT binding were observed in the anterior or posterior putamen. The motor phenotype is associated with the extent of caudate dopamine terminal loss in PD, as dopamine function is relatively more preserved in tremor patients. Symptom type is related to caudate dopamine function only in association with Parkinsonian dopaminergic degeneration, not in intact dopamine systems in patients with non-PD tremor. (orig.)

  14. Specific reactions of different striatal neuron types in morphology induced by quinolinic acid in rats.

    Directory of Open Access Journals (Sweden)

    Qiqi Feng

    Full Text Available Huntington's disease (HD is a neurological degenerative disease and quinolinic acid (QA has been used to establish HD model in animals through the mechanism of excitotoxicity. Yet the specific pathological changes and the underlying mechanisms are not fully elucidated. We aimed to reveal the specific morphological changes of different striatal neurons in the HD model. Sprague-Dawley (SD rats were subjected to unilaterally intrastriatal injections of QA to mimic the HD model. Behavioral tests, histochemical and immunhistochemical stainings as well as Western blots were applied in the present study. The results showed that QA-treated rats had obvious motor and cognitive impairments when compared with the control group. Immunohistochemical detection showed a great loss of NeuN+ neurons and Darpp32+ projection neurons in the transition zone in the QA group when compared with the control group. The numbers of parvalbumin (Parv+ and neuropeptide Y (NPY+ interneurons were both significantly reduced while those of calretinin (Cr+ and choline acetyltransferase (ChAT+ were not changed notably in the transition zone in the QA group when compared to the controls. Parv+, NPY+ and ChAT+ interneurons were not significantly increased in fiber density while Cr+ neurons displayed an obvious increase in fiber density in the transition zone in QA-treated rats. The varicosity densities of Parv+, Cr+ and NPY+ interneurons were all raised in the transition zone after QA treatment. In conclusion, the present study revealed that QA induced obvious behavioral changes as well as a general loss of striatal projection neurons and specific morphological changes in different striatal interneurons, which may help further explain the underlying mechanisms and the specific functions of various striatal neurons in the pathological process of HD.

  15. Anatomical and electrophysiological changes in striatal TH interneurons after loss of the nigrostriatal dopaminergic pathway.

    Science.gov (United States)

    Ünal, Bengi; Shah, Fulva; Kothari, Janish; Tepper, James M

    2015-01-01

    Using transgenic mice that express enhanced green fluorescent protein (EGFP) under the control of the tyrosine hydroxylase (TH) promoter, we have previously shown that there are approximately 3,000 striatal EGFP-TH interneurons per hemisphere in mice. Here, we report that striatal TH-EGFP interneurons exhibit a small, transient but significant increase in number after unilateral destruction of the nigrostriatal dopaminergic pathway. The increase in cell number is accompanied by electrophysiological and morphological changes. The intrinsic electrophysiological properties of EGFP-TH interneurons ipsilateral to 6-OHDA lesion were similar to those originally reported in intact mice except for a significant reduction in the duration of a characteristic depolarization induced plateau potential. There was a significant change in the distribution of the four previously described electrophysiologically distinct subtypes of striatal TH interneurons. There was a concomitant increase in the frequency of both spontaneous excitatory and inhibitory post-synaptic currents, while their amplitudes did not change. Nigrostriatal lesions did not affect somatic size or dendritic length or branching, but resulted in an increase in the density of proximal dendritic spines and spine-like appendages in EGFP-TH interneurons. The changes indicate that electrophysiology properties and morphology of striatal EGFP-TH interneurons depend on endogenous levels of dopamine arising from the nigrostriatal pathway. Furthermore, these changes may serve to help compensate for the changes in activity of spiny projection neurons that occur following loss of the nigrostriatal innervation in experimental or in early idiopathic Parkinson's disease by increasing feedforward GABAergic inhibition exerted by these interneurons.

  16. Extrasynaptic neurotransmission in the modulation of brain function. Focus on the striatal neuronal-glial networks

    Directory of Open Access Journals (Sweden)

    Kjell eFuxe

    2012-06-01

    Full Text Available Extrasynaptic neurotransmission is an important short distance form of volume transmission (VT and describes the extracellular diffusion of transmitters and modulators after synaptic spillover or extrasynaptic release in the local circuit regions binding to and activating mainly extrasynaptic neuronal and glial receptors in the neuroglial networks of the brain. Receptor-receptor interactions in G protein-coupled receptor (GPCR heteromers play a major role, on dendritic spines and nerve terminals including glutamate synapses, in the integrative processes of the extrasynaptic signaling. Heteromeric complexes between GPCR and ion-channel receptors play a special role in the integration of the synaptic and extrasynaptic signals. Changes in extracellular concentrations of the classical synaptic neurotransmitters glutamate and GABA found with microdialysis is likely an expression of the activity of the neuron-astrocyte unit of the brain and can be used as an index of VT-mediated actions of these two neurotransmitters in the brain. Thus, the activity of neurons may be functionally linked to the activity of astrocytes, which may release glutamate and GABA to the extracellular space where extrasynaptic glutamate and GABA receptors do exist. Wiring transmission (WT and VT are fundamental properties of all neurons of the CNS but the balance between WT and VT varies from one nerve cell population to the other. The focus is on the striatal cellular networks, and the WT and VT and their integration via receptor heteromers are described in the GABA projection neurons, the glutamate, dopamine, 5-hydroxytryptamine (5-HT and histamine striatal afferents, the cholinergic interneurons and different types of GABA interneurons. In addition, the role in these networks of VT signaling of the energy-dependent modulator adenosine and of endocannabinoids mainly formed in the striatal projection neurons will be underlined to understand the communication in the striatal

  17. A direct ROI quantification method for inherent PVE correction: accuracy assessment in striatal SPECT measurements

    Energy Technology Data Exchange (ETDEWEB)

    Vanzi, Eleonora; De Cristofaro, Maria T.; Sotgia, Barbara; Mascalchi, Mario; Formiconi, Andreas R. [University of Florence, Clinical Pathophysiology, Florence (Italy); Ramat, Silvia [University of Florence, Neurological and Psychiatric Sciences, Florence (Italy)

    2007-09-15

    The clinical potential of striatal imaging with dopamine transporter (DAT) SPECT tracers is hampered by the limited capability to recover activity concentration ratios due to partial volume effects (PVE). We evaluated the accuracy of a least squares method that allows retrieval of activity in regions of interest directly from projections (LS-ROI). An Alderson striatal phantom was filled with striatal to background ratios of 6:1, 9:1 and 28:1; the striatal and background ROIs were drawn on a coregistered X-ray CT of the phantom. The activity ratios of these ROIs were derived both with the LS-ROI method and with conventional SPECT EM reconstruction (EM-SPECT). Moreover, the two methods were compared in seven patients with motor symptoms who were examined with N-3-fluoropropyl-2-{beta}-carboxymethoxy-3-{beta}-(4-iodophenyl) (FP-CIT) SPECT, calculating the binding potential (BP). In the phantom study, the activity ratios obtained with EM-SPECT were 3.5, 5.3 and 17.0, respectively, whereas the LS-ROI method resulted in ratios of 6.2, 9.0 and 27.3, respectively. With the LS-ROI method, the BP in the seven patients was approximately 60% higher than with EM-SPECT; a linear correlation between the LS-ROI and the EM estimates was found (r = 0.98, p = 0.03). The LS-ROI PVE correction capability is mainly due to the fact that the ill-conditioning of the LS-ROI approach is lower than that of the EM-SPECT one. The LS-ROI seems to be feasible and accurate in the examination of the dopaminergic system. This approach can be fruitful in monitoring of disease progression and in clinical trials of dopaminergic drugs. (orig.)

  18. Reduced striatal dopamine D2/3 receptor availability in Body Dysmorphic Disorder.

    Science.gov (United States)

    Vulink, Nienke C; Planting, Robin S; Figee, Martijn; Booij, Jan; Denys, Damiaan

    2016-02-01

    Though the dopaminergic system is implicated in Obsessive Compulsive and Related Disorders (OCRD), the dopaminergic system has never been investigated in-vivo in Body Dysmorphic Disorder (BDD). In line with consistent findings of reduced striatal dopamine D2/3 receptor availability in Obsessive Compulsive Disorder (OCD), we hypothesized that the dopamine D2/3 receptor availability in the striatum will be lower in patients with BDD in comparison to healthy subjects. Striatal dopamine D2/3 receptor Binding Potential (BPND) was examined in 12 drug-free BDD patients and 12 control subjects pairwise matched by age, sex, and handedness using [(123)I]iodobenzamide Single Photon Emission Computed Tomography (SPECT; bolus/constant infusion technique). Regions of interest were the caudate nucleus and the putamen. BPND was calculated as the ratio of specific striatal to binding in the occipital cortex (representing nonspecific binding). Compared to controls, dopamine D2/3 receptor BPND was significantly lower in BDD, both in the putamen (p=0.017) and caudate nucleus (p=0.022). This study provides the first evidence of a disturbed dopaminergic system in BDD patients. Although previously BDD was classified as a separate disorder (somatoform disorder), our findings give pathophysiological support for the recent reclassification of BDD to the OCRD in DSM-5. Copyright © 2015 Elsevier B.V. and ECNP. All rights reserved.

  19. Electrical and chemical transmission between striatal GABAergic output neurones in rat brain slices

    Science.gov (United States)

    Venance, Laurent; Glowinski, Jacques; Giaume, Christian

    2004-01-01

    Basal ganglia are interconnected subcortical nuclei, connected to the thalamus and all cortical areas involved in sensory motor control, limbic functions and cognition. The striatal output neurones (SONs), the major striatal population, are believed to act as detectors and integrators of distributed patterns of cerebral cortex inputs. Despite the key role of SONs in cortico-striatal information processing, little is known about their local interactions. Here, we report the existence and characterization of electrical and GABAergic transmission between SONs in rat brain slices. Tracer coupling (biocytin) incidence was high during the first two postnatal weeks and then decreased (postnatal days (P) 5–25, 60%; P25–30, 29%; n = 61). Electrical coupling was observed between 27% of SON pairs (coupling coefficient: 3.1 ± 0.3%, n = 89 at P15) and as shown by single-cell RT-PCR, several connexin (Cx) mRNAs were found to be expressed (Cx31.1, Cx32, Cx36 and Cx47). GABAergic synaptic transmission (abolished by bicuculline, a GABAA receptor antagonist) observed in 19% of SON pairs (n = 62) was reliable (mean failure rate of 6 ± 3%), precise (variation coefficient of latency, 0.06), strong (IPSC amplitudes of 38 ± 12 pA) and unidirectional. Interestingly, electrical and chemical transmission were mutually exclusive. These results suggest that preferential networks of electrically and chemically connected SONs, might be involved in the channelling of cortico-basal ganglia information processing. PMID:15235091

  20. Striatal dopamine D2/3 receptor regulation by stress inoculation in squirrel monkeys

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    Alex G. Lee

    2016-06-01

    Full Text Available Intermittent mildly stressful situations provide opportunities to learn, practice, and improve coping in a process called stress inoculation. Stress inoculation also enhances cognitive control and response inhibition of impulsive motivated behavior. Cognitive control and motivation have been linked to striatal dopamine D2 and/or D3 receptors (DRD2/3 in rodents, monkeys, and humans. Here, we study squirrel monkeys randomized early in life to stress inoculation with or without maternal companionship and a no-stress control treatment condition. Striatal DRD2/3 availability in adulthood was measured in vivo by [11C]raclopride binding using positron emission tomography (PET. DRD2/3 availability was greater in caudate and putamen compared to ventral striatum as reported in PET studies of humans and other non-human primates. DRD2/3 availability in ventral striatum was also consistently greater in stress inoculated squirrel monkeys compared to no-stress controls. Squirrel monkeys exposed to stress inoculation in the presence of their mother did not differ from squirrel monkeys exposed to stress inoculation without maternal companionship. Similar effects in different social contexts extend the generality of our findings and together suggest that stress inoculation increases striatal DRD2/3 availability as a correlate of cognitive control in squirrel monkeys.

  1. Contribution of fronto-striatal regions to emotional valence and repetition under cognitive conflict.

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    Chun, Ji-Won; Park, Hae-Jeong; Kim, Dai Jin; Kim, Eosu; Kim, Jae-Jin

    2017-07-01

    Conflict processing mediated by fronto-striatal regions may be influenced by emotional properties of stimuli. This study aimed to examine the effects of emotion repetition on cognitive control in a conflict-provoking situation. Twenty-one healthy subjects were scanned using functional magnetic resonance imaging while performing a sequential cognitive conflict task composed of emotional stimuli. The regional effects were analyzed according to the repetition or non-repetition of cognitive congruency and emotional valence between the preceding and current trials. Post-incongruence interference in error rate and reaction time was significantly smaller than post-congruence interference, particularly under repeated positive and non-repeated positive, respectively, and post-incongruence interference, compared to post-congruence interference, increased activity in the ACC, DLPFC, and striatum. ACC and DLPFC activities were significantly correlated with error rate or reaction time in some conditions, and fronto-striatal connections were related to the conflict processing heightened by negative emotion. These findings suggest that the repetition of emotional stimuli adaptively regulates cognitive control and the fronto-striatal circuit may engage in the conflict adaptation process induced by emotion repetition. Both repetition enhancement and repetition suppression of prefrontal activity may underlie the relationship between emotion and conflict adaptation. Copyright © 2017 Elsevier B.V. All rights reserved.

  2. Tamoxifen counteracts estradiol induced effects on striatal and hypophyseal dopamine receptors

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    Ferretti, C.; Blengio, M.; Ghi, P.; Racca, S.; Genazzani, E.; Portaleone, P.

    1988-01-01

    We investigated the ability of Tamoxifen (TAM), an antiestrogen drug, to counteract the modification induced by estrogens on dopamine (DA) receptors on striatum and on adenohypophysis of ovex female rats. Subacute treatment with 17..beta..-estradiol (E/sub 2/) at both low (0.1 ..mu..g/kg) and high (20 ..mu..g/kg) doses confirmed its ability to increase the number of striatal /sup 3/H-Spiperone (/sup 3/H-SPI) binding sites in a dose dependent manner. By contrast in the pituitary, only high doses of estrogen were effective in reducing the number of DA receptors. We treated ovex female rats for 15 days with TAM alone or associated with E/sub 2/, to see if these estrogenic effects could be suppressed by an antiestrogenic drug. TAM did not affect the number of striatal DA receptors, but significantly increased the adenohypophy-seal DA binding sites, without varying their affinity. No changes were observed in pituitary and striatal DA receptor density, even when TAM was injected in association with estradiol. In conclusions: TAM is able to counteract the effects estrogens have on DA receptors. However there is some evidence that it could influence the pituitary DA systems independently of it antiestrogenic activity.

  3. Striatal dopamine D2/3 receptor availability in treatment resistant depression.

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    Bart P de Kwaasteniet

    Full Text Available Several studies demonstrated improvement of depressive symptoms in treatment resistant depression (TRD after administering dopamine agonists which suggest abnormal dopaminergic neurotransmission in TRD. However, the role of dopaminergic signaling through measurement of striatal dopamine D(2/3 receptor (D2/3R binding has not been investigated in TRD subjects. We used [(123I]IBZM single photon emission computed tomography (SPECT to investigate striatal D2/3R binding in TRD. We included 6 severe TRD patients, 11 severe TRD patients on antipsychotics (TRD AP group and 15 matched healthy controls. Results showed no significant difference (p = 0.75 in striatal D2/3R availability was found between TRD patients and healthy controls. In the TRD AP group D2/3R availability was significantly decreased (reflecting occupancy of D2/3Rs by antipsychotics relative to TRD patients and healthy controls (p<0.001 but there were no differences in clinical symptoms between TRD AP and TRD patients. This preliminary study therefore does not provide evidence for large differences in D2/3 availability in severe TRD patients and suggests this TRD subgroup is not characterized by altered dopaminergic transmission. Atypical antipsychotics appear to have no clinical benefit in severe TRD patients who remain depressed, despite their strong occupancy of D2/3Rs.

  4. Elevated Striatal Dopamine Function in Immigrants and Their Children: A Risk Mechanism for Psychosis.

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    Egerton, Alice; Howes, Oliver D; Houle, Sylvain; McKenzie, Kwame; Valmaggia, Lucia R; Bagby, Michael R; Tseng, Huai-Hsuan; Bloomfield, Michael A P; Kenk, Miran; Bhattacharyya, Sagnik; Suridjan, Ivonne; Chaddock, Chistopher A; Winton-Brown, Toby T; Allen, Paul; Rusjan, Pablo; Remington, Gary; Meyer-Lindenberg, Andreas; McGuire, Philip K; Mizrahi, Romina

    2017-03-01

    Migration is a major risk factor for schizophrenia but the neurochemical processes involved are unknown. One candidate mechanism is through elevations in striatal dopamine synthesis and release. The objective of this research was to determine whether striatal dopamine function is elevated in immigrants compared to nonimmigrants and the relationship with psychosis. Two complementary case-control studies of in vivo dopamine function (stress-induced dopamine release and dopamine synthesis capacity) in immigrants compared to nonimmigrants were performed in Canada and the United Kingdom. The Canadian dopamine release study included 25 immigrant and 31 nonmigrant Canadians. These groups included 23 clinical high risk (CHR) subjects, 9 antipsychotic naïve patients with schizophrenia, and 24 healthy volunteers. The UK dopamine synthesis study included 32 immigrants and 44 nonimmigrant British. These groups included 50 CHR subjects and 26 healthy volunteers. Both striatal stress-induced dopamine release and dopamine synthesis capacity were significantly elevated in immigrants compared to nonimmigrants, independent of clinical status. These data provide the first evidence that the effect of migration on the risk of developing psychosis may be mediated by an elevation in brain dopamine function. © The Author 2017. Published by Oxford University Press on behalf of the Maryland Psychiatric Research Center.

  5. A negative relationship between ventral striatal loss anticipation response and impulsivity in borderline personality disorder.

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    Herbort, Maike C; Soch, Joram; Wüstenberg, Torsten; Krauel, Kerstin; Pujara, Maia; Koenigs, Michael; Gallinat, Jürgen; Walter, Henrik; Roepke, Stefan; Schott, Björn H

    2016-01-01

    Patients with borderline personality disorder (BPD) frequently exhibit impulsive behavior, and self-reported impulsivity is typically higher in BPD patients when compared to healthy controls. Previous functional neuroimaging studies have suggested a link between impulsivity, the ventral striatal response to reward anticipation, and prediction errors. Here we investigated the striatal neural response to monetary gain and loss anticipation and their relationship with impulsivity in 21 female BPD patients and 23 age-matched female healthy controls using functional magnetic resonance imaging (fMRI). Participants performed a delayed monetary incentive task in which three categories of objects predicted a potential gain, loss, or neutral outcome. Impulsivity was assessed using the Barratt Impulsiveness Scale (BIS-11). Compared to healthy controls, BPD patients exhibited significantly reduced fMRI responses of the ventral striatum/nucleus accumbens (VS/NAcc) to both reward-predicting and loss-predicting cues. BIS-11 scores showed a significant positive correlation with the VS/NAcc reward anticipation responses in healthy controls, and this correlation, while also nominally positive, failed to reach significance in BPD patients. BPD patients, on the other hand, exhibited a significantly negative correlation between ventral striatal loss anticipation responses and BIS-11 scores, whereas this correlation was significantly positive in healthy controls. Our results suggest that patients with BPD show attenuated anticipation responses in the VS/NAcc and, furthermore, that higher impulsivity in BPD patients might be related to impaired prediction of aversive outcomes.

  6. DARPP-32 interaction with adducin may mediate rapid environmental effects on striatal neurons.

    Science.gov (United States)

    Engmann, Olivia; Giralt, Albert; Gervasi, Nicolas; Marion-Poll, Lucile; Gasmi, Laila; Filhol, Odile; Picciotto, Marina R; Gilligan, Diana; Greengard, Paul; Nairn, Angus C; Hervé, Denis; Girault, Jean-Antoine

    2015-12-07

    Environmental enrichment has multiple effects on behaviour, including modification of responses to psychostimulant drugs mediated by striatal neurons. However, the underlying molecular and cellular mechanisms are not known. Here we show that DARPP-32, a hub signalling protein in striatal neurons, interacts with adducins, which are cytoskeletal proteins that cap actin filaments' fast-growing ends and regulate synaptic stability. DARPP-32 binds to adducin MARCKS domain and this interaction is modulated by DARPP-32 Ser97 phosphorylation. Phospho-Thr75-DARPP-32 facilitates β-adducin Ser713 phosphorylation through inhibition of a cAMP-dependent protein kinase/phosphatase-2A cascade. Caffeine or 24-h exposure to a novel enriched environment increases adducin phosphorylation in WT, but not T75A mutant mice. This cascade is implicated in the effects of brief exposure to novel enriched environment on dendritic spines in nucleus accumbens and cocaine locomotor response. Our results suggest a molecular pathway by which environmental changes may rapidly alter responsiveness of striatal neurons involved in the reward system.

  7. Tamoxifen counteracts estradiol induced effects on striatal and hypophyseal dopamine receptors

    International Nuclear Information System (INIS)

    Ferretti, C.; Blengio, M.; Ghi, P.; Racca, S.; Genazzani, E.; Portaleone, P.

    1988-01-01

    We investigated the ability of Tamoxifen (TAM), an antiestrogen drug, to counteract the modification induced by estrogens on dopamine (DA) receptors on striatum and on adenohypophysis of ovex female rats. Subacute treatment with 17β-estradiol (E 2 ) at both low (0.1 μg/kg) and high (20 μg/kg) doses confirmed its ability to increase the number of striatal 3 H-Spiperone ( 3 H-SPI) binding sites in a dose dependent manner. By contrast in the pituitary, only high doses of estrogen were effective in reducing the number of DA receptors. We treated ovex female rats for 15 days with TAM alone or associated with E 2 , to see if these estrogenic effects could be suppressed by an antiestrogenic drug. TAM did not affect the number of striatal DA receptors, but significantly increased the adenohypophy-seal DA binding sites, without varying their affinity. No changes were observed in pituitary and striatal DA receptor density, even when TAM was injected in association with estradiol. In conclusions: TAM is able to counteract the effects estrogens have on DA receptors. However there is some evidence that it could influence the pituitary DA systems independently of it antiestrogenic activity

  8. Beyond Neuronal Activity Markers: Select Immediate Early Genes in Striatal Neuron Subtypes Functionally Mediate Psychostimulant Addiction

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    Ramesh Chandra

    2017-06-01

    Full Text Available Immediate early genes (IEGs were traditionally used as markers of neuronal activity in striatum in response to stimuli including drugs of abuse such as psychostimulants. Early studies using these neuronal activity markers led to important insights in striatal neuron subtype responsiveness to psychostimulants. Such studies have helped identify striatum as a critical brain center for motivational, reinforcement and habitual behaviors in psychostimulant addiction. While the use of IEGs as neuronal activity markers in response to psychostimulants and other stimuli persists today, the functional role and implications of these IEGs has often been neglected. Nonetheless, there is a subset of research that investigates the functional role of IEGs in molecular, cellular and behavioral alterations by psychostimulants through striatal medium spiny neuron (MSN subtypes, the two projection neuron subtypes in striatum. This review article will address and highlight the studies that provide a functional mechanism by which IEGs mediate psychostimulant molecular, cellular and behavioral plasticity through MSN subtypes. Insight into the functional role of IEGs in striatal MSN subtypes could provide improved understanding into addiction and neuropsychiatric diseases affecting striatum, such as affective disorders and compulsive disorders characterized by dysfunctional motivation and habitual behavior.

  9. Rapid eye movement sleep behaviour disorder and striatal dopamine depletion in patients with Parkinson's disease.

    Science.gov (United States)

    Chung, S J; Lee, Y; Lee, J J; Lee, P H; Sohn, Y H

    2017-10-01

    Rapid eye movement sleep behaviour disorder (RBD) is related to striatal dopamine depletion. This study was performed to confirm whether clinically probable RBD (cpRBD) in patients with Parkinson's disease (PD) is associated with a specific pattern of striatal dopamine depletion. A prospective survey was conducted using the RBD Screening Questionnaire (RBDSQ) in 122 patients with PD who had undergone dopamine transporter (DAT) positron emission tomography scan. Patients with cpRBD (RBDSQ ≥ 7) exhibited greater motor deficits, predominantly in the less-affected side and axial symptoms, and were prescribed higher levodopa-equivalent doses at follow-up than those without cpRBD (RBDSQ ≤ 4), despite their similar disease and treatment durations. Compared to patients without cpRBD, those with cpRBD showed lower DAT activities in the putamen, particularly in the less-affected side in all putaminal subregions, and a tendency to be lower in the ventral striatum. In addition, greater motor deficits in patients with cpRBD than in those without cpRBD remained significant after controlling for DAT binding in the putamen and other confounding variables. These results demonstrated that the presence of RBD in patients with PD is associated with different patterns of both motor deficit distribution and striatal DAT depletion, suggesting that the presence of RBD represents a distinct PD subtype with a malignant motor parkinsonism. © 2017 EAN.

  10. Age related changes in striatal resting state functional connectivity in autism

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    Aarthi ePadmanabhan

    2013-11-01

    Full Text Available Characterizing the nature of developmental change is critical to understanding the mechanisms that are impaired in complex neurodevelopment disorders such as autism spectrum disorder (ASD and, pragmatically, may allow us to pinpoint periods of plasticity when interventions are particularly useful. Although aberrant brain development has long been theorized as a characteristic feature of ASD, the neural substrates have been difficult to characterize, in part due to a lack of developmental data and to performance confounds. To address these issues, we examined the development of intrinsic functional connectivity with resting state fMRI from late childhood to early adulthood (8-36 years, using a seed based functional connectivity method with the striatum. Overall, we found that both groups show decreases in cortico-striatal circuits over age. However, when controlling for age, ASD participants showed increased connectivity with parietal cortex and decreased connectivity with prefrontal cortex relative to TD participants. In addition, ASD participants showed aberrant age-related changes in connectivity with anterior aspects of cerebellum, and posterior temporal regions (e.g. fusiform gyrus, inferior and superior temporal gyri. In sum, we found prominent differences in the development of striatal connectivity in ASD, most notably, atypical development of connectivity in striatal networks that may underlie cognitive and social reward processing. Our findings highlight the need to identify the biological mechanisms of perturbations in brain reorganization over development, which also may help clarify discrepant findings in the literature.

  11. Postural & striatal deformities in Parkinson`s disease: Are these rare?

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    Sanjay Pandey

    2016-01-01

    Full Text Available Parkinson`s disease (PD is the most common neurodegenerative disease and is characterized by tremor, rigidity and akinesia. Diagnosis is clinical in the majority of the patients. Patients with PD may have stooped posture but some of them develop different types of postural and striatal deformities. Usually these deformities are more common in atypical parkinsonian disorders such as progressive supranuclear palsy and multisystem atrophy. But in many studies it has been highlighted that these may also be present in approximately one third of PD patients leading to severe disability. These include antecollis or dropped head, camptocormia, p0 isa syndrome, scoliosis, striatal hands and striatal toes. The pathogenesis of these deformities is a complex combination of central and peripheral influences such as rigidity, dystonia and degenerative skeletal changes. Duration of parkinsonism symptoms is an important risk factor and in majority of the patients these deformities are seen in advanced statge of the disease. The patients with such symptoms may initially respond to dopaminergic medications but if not intervened they may become fixed and difficult to treat. Pain and restriction of movement are most common clinical manifestations and these may mimick symptoms of musculoskeletal disorders like rheumatoid arthritis. Early diagnosis is important as the patients may respond to adjustment in dopaminergic medications. Recent advances such as deep brain stimulation (DBS and ultrasound guided botulinum toxin injection are helpful in management of these deformities in patients with PD.

  12. Reduced amygdala and ventral striatal activity to happy faces in PTSD is associated with emotional numbing.

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    Kim L Felmingham

    Full Text Available There has been a growing recognition of the importance of reward processing in PTSD, yet little is known of the underlying neural networks. This study tested the predictions that (1 individuals with PTSD would display reduced responses to happy facial expressions in ventral striatal reward networks, and (2 that this reduction would be associated with emotional numbing symptoms. 23 treatment-seeking patients with Posttraumatic Stress Disorder were recruited from the treatment clinic at the Centre for Traumatic Stress Studies, Westmead Hospital, and 20 trauma-exposed controls were recruited from a community sample. We examined functional magnetic resonance imaging responses during the presentation of happy and neutral facial expressions in a passive viewing task. PTSD participants rated happy facial expression as less intense than trauma-exposed controls. Relative to controls, PTSD participants revealed lower activation to happy (-neutral faces in ventral striatum and and a trend for reduced activation in left amygdala. A significant negative correlation was found between emotional numbing symptoms in PTSD and right ventral striatal regions after controlling for depression, anxiety and PTSD severity. This study provides initial evidence that individuals with PTSD have lower reactivity to happy facial expressions, and that lower activation in ventral striatal-limbic reward networks may be associated with symptoms of emotional numbing.

  13. Increased coherence among striatal regions in the theta range during attentive wakefulness

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    G. Lepski

    2012-08-01

    Full Text Available The striatum, the largest component of the basal ganglia, is usually subdivided into associative, motor and limbic components. However, the electrophysiological interactions between these three subsystems during behavior remain largely unknown. We hypothesized that the striatum might be particularly active during exploratory behavior, which is presumably associated with increased attention. We investigated the modulation of local field potentials (LFPs in the striatum during attentive wakefulness in freely moving rats. To this end, we implanted microelectrodes into different parts of the striatum of Wistar rats, as well as into the motor, associative and limbic cortices. We then used electromyograms to identify motor activity and analyzed the instantaneous frequency, power spectra and partial directed coherence during exploratory behavior. We observed fine modulation in the theta frequency range of striatal LFPs in 92.5 ± 2.5% of all epochs of exploratory behavior. Concomitantly, the theta power spectrum increased in all striatal channels (P 0.7 between the primary motor cortex and the rostral part of the caudatoputamen nucleus, as well as among all striatal channels (P < 0.001. Conclusively, we observed a pattern of strong theta band activation in the entire striatum during attentive wakefulness, as well as a strong coherence between the motor cortex and the entire striatum. We suggest that this activation reflects the integration of motor, cognitive and limbic systems during attentive wakefulness.

  14. Striatal pre-enkephalin overexpression improves Huntington's disease symptoms in the R6/2 mouse model of Huntington's disease.

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    Stéphanie Bissonnette

    Full Text Available The reduction of pre-enkephalin (pENK mRNA expression might be an early sign of striatal neuronal dysfunction in Huntington's disease (HD, due to mutated huntingtin protein. Indeed, striatopallidal (pENK-containing neurodegeneration occurs at earlier stage of the disease, compare to the loss of striatonigral neurons. However, no data are available about the functional role of striatal pENK in HD. According to the neuroprotective properties of opioids that have been recognized recently, the objective of this study was to investigate whether striatal overexpression of pENK at early stage of HD can improve motor dysfunction, and/or reduce striatal neuronal loss in the R6/2 transgenic mouse model of HD. To achieve this goal recombinant adeno-associated-virus (rAAV2-containing green fluorescence protein (GFP-pENK was injected bilaterally in the striatum of R6/2 mice at 5 weeks old to overexpress opioid peptide pENK. Striatal injection of rAAV2-GFP was used as a control. Different behavioral tests were carried out before and/or after striatal injections of rAAV2. The animals were euthanized at 10 weeks old. Our results demonstrate that striatal overexpression of pENK had beneficial effects on behavioral symptoms of HD in R6/2 by: delaying the onset of decline in muscular force; reduction of clasping; improvement of fast motor activity, short-term memory and recognition; as well as normalization of anxiety-like behavior. The improvement of behavioral dysfunction in R6/2 mice having received rAAV2-GFP-pENK associated with upregulation of striatal pENK mRNA; the increased level of enkephalin peptide in the striatum, globus pallidus and substantia nigra; as well as the slight increase in the number of striatal neurons compared with other groups of R6/2. Accordingly, we suggest that at early stage of HD upregulation of striatal enkephalin might play a key role at attenuating illness symptoms.

  15. Effect of doping of OH- and CN- on the liberation of I2 molecules in KI by gamma-irradiation, impurity concentration effect

    International Nuclear Information System (INIS)

    Shirke, A.K.; Pode, R.B.; Deshmukh, B.T.

    1996-01-01

    Photodecomposition of pure and doped KI powder (KI:KOH; KI:KCN; Impurity concentration, 100, 300, 500, 700 and 1000 ppm) to produce free I 2 molecules during gamma irradiation is studied with the help of absorption and IR measurements. Large number of I 2 molecules are formed in pure KI as compared to the doped samples. Hydroxide impurity increases the rate of liberation of I 2 molecules whereas the cyanide impurity decreases the rate of liberation of I 2 molecules. (Author)

  16. Effects of Herbal-Acupuncture with Rosae Laevigatae Fructus Extract at KI10(Umgok on Osteoporosis in Ovariectomized Mice

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    Kim Dong-soo

    2009-12-01

    Full Text Available Objective & Methods : The purpose of this study was to observe the effects of herbal-acupuncture with Rosae Laevigatae Fructus extact(RLF-HA at KI10(Umgok on osteoporosis in ovariectomized(OVX ddy mice. We carried out several experimental items to analyze the changes in body weight, uterine weight, uterus index, tibial length, the ash bone weight, tibial BMD, serum ALP, serum osteocalcin, serum Ca, and the levels of Ca, P, Ca/P ratio in tibia, and we performed histological and histomorphological analysis as well. Results : 1. Herbal-acupuncture with Rosae Laevigatae Fructus at KI10(Umgok and saline injection at KI10(Umgok significantly inhibited the reduction of tibial calcium level in ovariectomized mice. 2. Herbal-acupuncture with Rosae Laevigatae Fructus at KI10(Umgok significantly inhibited the increase of tibial osteoclast cells in ovariectomized mice. 3. Herbal-acupuncture with Rosae Laevigatae Fructus at KI10(Umgok significantly inhibited the reduction of tibial trabecular bone thickness(TBT in ovariectomized mice. 4. Herbal-acupuncture with Rosae Laevigatae Fructus at KI10(Umgok significantly inhibited the overgrowth of tibial growth plate length(GPL in ovariectomized mice. Conclusion : These results suggested that herbal-acupuncture with Rosae Laevigatae Fructus at KI10(Umgok has a therapeutic effect on osteoporosis, and to be put to practical use in the future osteoporosis clinic.

  17. Association of high proliferation marker Ki-67 expression with DCEMR imaging features of breast: a large scale evaluation

    Science.gov (United States)

    Saha, Ashirbani; Harowicz, Michael R.; Grimm, Lars J.; Kim, Connie E.; Ghate, Sujata V.; Walsh, Ruth; Mazurowski, Maciej A.

    2018-02-01

    One of the methods widely used to measure the proliferative activity of cells in breast cancer patients is the immunohistochemical (IHC) measurement of the percentage of cells stained for nuclear antigen Ki-67. Use of Ki-67 expression as a prognostic marker is still under investigation. However, numerous clinical studies have reported an association between a high Ki-67 and overall survival (OS) and disease free survival (DFS). On the other hand, to offer non-invasive alternative in determining Ki-67 expression, researchers have made recent attempts to study the association of Ki-67 expression with magnetic resonance (MR) imaging features of breast cancer in small cohorts (AUC) of the values predicted. Our model was able to predict high versus low Ki-67 in the test set with an AUC of 0.67 (95% CI: 0.58-0.75, p<1.1e-04). Thus, a moderate strength of association of Ki-67 values and MRextracted imaging features was demonstrated in our experiments.

  18. A simple algorithm for subregional striatal uptake analysis with partial volume correction in dopaminergic PET imaging

    International Nuclear Information System (INIS)

    Lue Kunhan; Lin Hsinhon; Chuang Kehshih; Kao Chihhao, K.; Hsieh Hungjen; Liu Shuhsin

    2014-01-01

    In positron emission tomography (PET) of the dopaminergic system, quantitative measurements of nigrostriatal dopamine function are useful for differential diagnosis. A subregional analysis of striatal uptake enables the diagnostic performance to be more powerful. However, the partial volume effect (PVE) induces an underestimation of the true radioactivity concentration in small structures. This work proposes a simple algorithm for subregional analysis of striatal uptake with partial volume correction (PVC) in dopaminergic PET imaging. The PVC algorithm analyzes the separate striatal subregions and takes into account the PVE based on the recovery coefficient (RC). The RC is defined as the ratio of the PVE-uncorrected to PVE-corrected radioactivity concentration, and is derived from a combination of the traditional volume of interest (VOI) analysis and the large VOI technique. The clinical studies, comprising 11 patients with Parkinson's disease (PD) and 6 healthy subjects, were used to assess the impact of PVC on the quantitative measurements. Simulations on a numerical phantom that mimicked realistic healthy and neurodegenerative situations were used to evaluate the performance of the proposed PVC algorithm. In both the clinical and the simulation studies, the striatal-to-occipital ratio (SOR) values for the entire striatum and its subregions were calculated with and without PVC. In the clinical studies, the SOR values in each structure (caudate, anterior putamen, posterior putamen, putamen, and striatum) were significantly higher by using PVC in contrast to those without. Among the PD patients, the SOR values in each structure and quantitative disease severity ratings were shown to be significantly related only when PVC was used. For the simulation studies, the average absolute percentage error of the SOR estimates before and after PVC were 22.74% and 1.54% in the healthy situation, respectively; those in the neurodegenerative situation were 20.69% and 2

  19. Dopamine D(1) receptor-mediated control of striatal acetylcholine release by endogenous dopamine.

    Science.gov (United States)

    Acquas, E; Di Chiara, G

    1999-10-27

    The role of dopamine D(1) and D(2) receptors in the control of acetylcholine release in the dorsal striatum by endogenous dopamine was investigated by monitoring with microdialysis the effect of the separate or combined administration of the dopamine D(1) receptor antagonist, SCH 39166 ¿(-)-trans-6,7,7a,8,9, 13b-exahydro-3-chloro-2-hydroxy-N-methyl-5H-benzo-[d]-nap hto-[2, 1b]-azepine hydrochloride¿ (50 microg/kg subcutaneous (s.c.)), of the dopamine D(2)/D(3) receptor agonist, quinpirole (trans-(-)-4aR, 4a,5,6,7,8,8a,9-octahydro-5-propyl-1H-pyrazolo-(3,4-g)-quinoline hydrochloride) (5 and 10 microg/kg s.c.), and of the D(3) receptor selective agonist, PD 128,907 [S(+)-(4aR,10bR)-3,4,4a, 10b-tetrahydro-4-propyl-2H,5H-[1]benzopyrano-[4,3-b]-1,4-oxazin -9-ol hydrochloride] (50 microg/kg s.c.), on in vivo dopamine and acetylcholine release. Microdialysis was performed with a Ringer containing low concentrations (0.01 microM) of the acetylcholinesterase inhibitor, neostigmine. Quinpirole (10 microg/kg s.c.) decreased striatal dopamine and acetylcholine release. Administration of PD 128,907 (50 microg/kg) decreased dopamine but failed to affect acetylcholine release. SCH 39166 (50 microg/kg s.c.) stimulated dopamine release and reduced acetylcholine release. Pretreatment with quinpirole reduced (5 microg/kg s.c.) or completely prevented (10 microg/kg s.c.) the stimulation of dopamine release elicited by SCH 39166 (50 microg/kg s.c.); on the other hand, pretreatment with quinpirole (5 and 10 microg/kg) potentiated the reduction of striatal acetylcholine release induced by SCH 39166 (50 microg/kg s.c.). Similarly, pretreatment with PD 128,907 (50 microg/kg) which prevented the increase of dopamine release induced by SCH 39166 (50 microg/kg), potentiated the reduction of striatal acetylcholine transmission elicited by SCH 39166. Thus, pretreatment with low doses of quinpirole or PD 128,907 influences in opposite manner the effect of SCH 39166 on striatal dopamine and

  20. A Population of Indirect Pathway Striatal Projection Neurons Is Selectively Entrained to Parkinsonian Beta Oscillations.

    Science.gov (United States)

    Sharott, Andrew; Vinciati, Federica; Nakamura, Kouichi C; Magill, Peter J

    2017-10-11

    Classical schemes of basal ganglia organization posit that parkinsonian movement difficulties presenting after striatal dopamine depletion stem from the disproportionate firing rates of spiny projection neurons (SPNs) therein. There remains, however, a pressing need to elucidate striatal SPN firing in the context of the synchronized network oscillations that are abnormally exaggerated in cortical-basal ganglia circuits in parkinsonism. To address this, we recorded unit activities in the dorsal striatum of dopamine-intact and dopamine-depleted rats during two brain states, respectively defined by cortical slow-wave activity (SWA) and activation. Dopamine depletion escalated striatal net output but had contrasting effects on "direct pathway" SPNs (dSPNs) and "indirect pathway" SPNs (iSPNs); their firing rates became imbalanced, and they disparately engaged in network oscillations. Disturbed striatal activity dynamics relating to the slow (∼1 Hz) oscillations prevalent during SWA partly generalized to the exaggerated beta-frequency (15-30 Hz) oscillations arising during cortical activation. In both cases, SPNs exhibited higher incidences of phase-locked firing to ongoing cortical oscillations, and SPN ensembles showed higher levels of rhythmic correlated firing, after dopamine depletion. Importantly, in dopamine-depleted striatum, a widespread population of iSPNs, which often displayed excessive firing rates and aberrant phase-locked firing to cortical beta oscillations, preferentially and excessively synchronized their firing at beta frequencies. Conversely, dSPNs were neither hyperactive nor synchronized to a large extent during cortical activation. These data collectively demonstrate a cell type-selective entrainment of SPN firing to parkinsonian beta oscillations. We conclude that a population of overactive, excessively synchronized iSPNs could orchestrate these pathological rhythms in basal ganglia circuits. SIGNIFICANCE STATEMENT Chronic depletion of dopamine

  1. Striatal hypometabolism in premanifest and manifest Huntington's disease patients

    Energy Technology Data Exchange (ETDEWEB)

    Lopez-Mora, Diego Alfonso; Camacho, Valle; Fernandez, Alejandro; Montes, Alberto; Carrio, Ignasi [Autonomous University of Barcelona, Nuclear Medicine Department, Hospital Sant Pau, Barcelona (Spain); Perez-Perez, Jesus; Martinez-Horta, Sauel; Kulisevsky, Jaime [Autonomous University of Barcelona, Movement Disorders Unit, Neurology Department, Hospital Sant Pau, Barcelona (Spain); Sampedro, Frederic [University of Barcelona, Barcelona (Spain); Lozano-Martinez, Gloria Andrea; Gomez-Anson, Beatriz [Autonomous University of Barcelona, Neuroradiology, Radiology Department, Hospital Sant Pau, Barcelona (Spain)

    2016-11-15

    To assess metabolic changes in cerebral {sup 18}F-FDG PET/CT in premanifest and manifest Huntington's disease (HD) subjects compared to a control group and to correlate {sup 18}F-FDG uptake patterns with different disease stages. Thirty-three gene-expanded carriers (Eight males; mean age: 43 y/o; CAG > 39) were prospectively included. Based on the Unified Huntington's Disease Rating Scale Total Motor Score and the Total Functional Capacity, subjects were classified as premanifest (preHD = 15) and manifest (mHD = 18). Estimated time disease-onset was calculated using the Langbehn formula, which allowed classifying preHD as far-to (preHD-A) and close-to (PreHD-B) disease-onset. Eighteen properly matched participants were included as a control group (CG). All subjects underwent brain {sup 18}F-FDG PET/CT and MRI. {sup 18}F-FDG PET/CT were initially assessed by two nuclear medicine physicians identifying qualitative metabolic changes in the striatum. Quantitative analysis was performed using SPM8 with gray matter atrophy correction using the BPM toolbox. Visual analysis showed a marked striatal hypometabolism in mHD. A normal striatal distribution of {sup 18}F-FDG uptake was observed for most of the preHD subjects. Quantitative analysis showed a significant striatal hypometabolism in mHD subjects compared to CG (p < 0.001 uncorrected, k = 50 voxels). In both preHD groups we observed a significant striatal hypometabolism with respect to CG (p < 0.001 uncorrected, k = 50 voxels). In mHD subjects we observed a significant striatal hypometabolism with respect to both preHD groups (p < 0.001 uncorrected, k = 50 voxels). {sup 18}F-FDG PET/CT might be a helpful tool to identify patterns of glucose metabolism in the striatum across the stages of HD and might be relevant in assessing the clinical status of gene-expanded HD carriers due to the fact that dysfunctional glucose metabolism begins at early preHD stages of the disease. {sup 18}F-FDG PET/CT appears as a

  2. The Nishino Breathing Method and Ki-energy (Life-energy): A Challenge to Traditional Scientific Thinking

    Science.gov (United States)

    Ohnishi, S. Tsuyoshi; Ohnishi, Tomoko

    2006-01-01

    The breathing method, which was developed and is being taught by Kozo Nishino, a Japanese Ki-expert, is for raising the levels of Ki-energy (life-energy or the vitality) of an individual. It is neither a therapy nor a healing technique. However, many of his students have experienced an improvement in their health, and in some cases, they were able to overcome health problems by themselves. Since this is an interesting subject from the standpoint of complementary and alternative medicine (CAM), we have been collaborating with Nishino to conduct a scientific investigation of his Ki-energy. We found that Nishino's Ki-energy can inhibit cell division of cancer cells, protect isolated mitochondria from heat deterioration and reduce lipid peroxidation in heat-treated mitochondria. Although Ki-energy may consist of several different energy forms, we found that at least one of them is near-infrared radiation between the wavelength range of 0.8 and 2.7 µm. Another interesting observation at his school is the Taiki-practice (paired Ki-practice). During this practice, Nishino can ‘move’ his students without any physical contact. Many of them run, jump or roll on the floor when they receive his Ki-energy. We studied this and propose that ‘information’ is conveyed through the air between two individuals by Ki-energy. This may be called a five sense-independent, life-to-life communication by Ki. All of our results suggest that we should re-evaluate the Cartesian dualism (separation of mind and body) which has been a fundamental principle of modern science for the past three centuries. PMID:16786048

  3. The Nishino Breathing Method and Ki-energy (Life-energy: A Challenge to Traditional Scientific Thinking

    Directory of Open Access Journals (Sweden)

    Tsuyoshi Ohnishi

    2006-01-01

    Full Text Available The breathing method, which was developed and is being taught by Kozo Nishino, a Japanese Ki-expert, is for raising the levels of Ki-energy (life-energy or the vitality of an individual. It is neither a therapy nor a healing technique. However, many of his students have experienced an improvement in their health, and in some cases, they were able to overcome health problems by themselves. Since this is an interesting subject from the standpoint of complementary and alternative medicine (CAM, we have been collaborating with Nishino to conduct a scientific investigation of his Ki-energy. We found that Nishino's Ki-energy can inhibit cell division of cancer cells, protect isolated mitochondria from heat deterioration and reduce lipid peroxidation in heat-treated mitochondria. Although Ki-energy may consist of several different energy forms, we found that at least one of them is near-infrared radiation between the wavelength range of 0.8 and 2.7 µm. Another interesting observation at his school is the Taiki-practice (paired Ki-practice. During this practice, Nishino can ‘move’ his students without any physical contact. Many of them run, jump or roll on the floor when they receive his Ki-energy. We studied this and propose that ‘information’ is conveyed through the air between two individuals by Ki-energy. This may be called a five sense-independent, life-to-life communication by Ki. All of our results suggest that we should re-evaluate the Cartesian dualism (separation of mind and body which has been a fundamental principle of modern science for the past three centuries.

  4. On the r>h Shift in Kiên Giang Khmer

    Directory of Open Access Journals (Sweden)

    James Kirby

    2017-12-01

    Full Text Available This paper presents an acoustic and perceptual study of the r>h shift in the variety of Khmer spoken in Giồng Riềng district, Kiên Giang province, Vietnam. In Phnom Penh Khmer, /r/ is realized as [h] in syllable onsets and onset clusters, and accompanied by lowered pitch, breathiness, and in some cases a change in the quality of the following vowel. In Kiên Giang Khmer, the r>h shift is accompanied by pitch lowering, but without changes in aspiration or vowel quality, and spectral measures did not indicate substantial differences in voice quality. Consistent with their productions, users of this dialect appear to rely solely on differences pitch to identify these lexical items. We discuss the implications of our findings for Khmer dialectology, mechanisms of sound change, and variation in the realization of rhotics more generally.

  5. Obtaining and characterization catalyst Ki/Al_2O_3 by physical dispersion process via wet

    International Nuclear Information System (INIS)

    Silva, M.C. da; Dantas, J.; Costa, A.C.F.M.; Costa, N.C.O.; Freitas, N.L. de

    2014-01-01

    The aim of this study is the Obtention and characterization of catalysts being supported alumina impregnated with KI by physical dispersion in wet via attritor mill in periods of 30 and 60 minutes. Before and after impregnation the catalysts were characterized by XRD, X ray fluorescence, particle size distribution, textural analysis (BET). The results show the presence of the stable crystalline phase Al_2O_3 in all samples after impregnation and the second phase formed from KI and K_2O. There was a decrease in the agglomerates incorporated with the potassium due to the milling process. It was observed that the highest specific surface area was obtained by the impregnated sample into a 60 min. (author)

  6. Thermoluminescence of KI:Eu2+ Stimulated by Ultraviolet Irradiation at Different Temperatures

    International Nuclear Information System (INIS)

    Aguirre de Carcer, I.; Jaque, F.; Townsend, P.D.

    1999-01-01

    The thermoluminescence (TL) of KI:Eu 2+ after ultraviolet (254 nm) irradiation at different temperatures from -40 deg. C to +40 deg. C has been studied. Two main glow peaks and some minor features have been identified on the thermoluminescence glow curves. Irradiating at low temperature gives a strong peak at γ5 deg. C and a less pronounced one at 230 deg. C. The TL glow peak emission spectra were analysed as consisting of the addition of several Gaussian shaped emission bands. The position of the Gaussian peaks, and their widths, are coincident with divalent europium emission at different sites of the KI:Eu 2+ system. A new emission band centred at 3.05 eV, 0.16 eV FWHM for Eu 2+ has been observed from the TL emission spectra. The changes in the spectral distribution of the TL emission with irradiation temperature are discussed. (author)

  7. Correlation Between Ki-67 Index, World Health Organization Grade and Patient Survival in Glial Tumors With Astrocytic Differentiation

    Science.gov (United States)

    Dzhenkov, Deyan L; Kitanova, Martina; Donev, Ivan S; Ghenev, Peter

    2017-01-01

    Background Glioblastoma multiforme (GBM) is a class IV astrocytic tumor, the most malignant of the four groups of World Health Organization (WHO) tumors with astrocytic differentiation. Aim The aim of this study was to estab­lish whether a correlation exists between the Ki-67 index of tumors with astrocytic differentiation, WHO grade, and patient survival. Materials and methods A retrospective non-clinical approach to patient selection was chosen for the aim of the study. A total of 47 patients diagnosed and treated for CNS tumors with astrocytic differentiation in the St. Marina University Hospital, Varna, Bulgaria, from September 2012 to July 2016 were retrospectively included into the study cohort. The cases were tested for their immunohistochemistry (IHC) reaction with Ki-67 after their original Hematoxylin and Eosin and IHC slides were reviewed by a single author and blind coded. The Ki-67 positivity index of the nuclei was estimated after digitalization of the slides and calculated by the ImmunoRatio automated count­ing tool. The individual Ki-67 index and patient survival of each case were statistically compared. Results The histopathological groups, after the blind Ki-67 index automated calculation was carried out, revealed no WHO grade I, two WHO grade II samples, four WHO grade III samples and 41 WHO grade IV cases, and these were included in the analysis. The two samples of WHO grade II astrocytic tumors had a mean Ki-67 index of 25%; however, they comprised tumors with an individual index of 43% and 7%, both individual values with a highly unlikely index for this group. The four samples of WHO grade III had a mean Ki-67 index of 4%, standard deviation ±2.16 (p>0.05), with the lowest index being 1% and the highest one being 6%. Both WHO grade II and III did not include enough samples to allow for a proper statistical analysis of patient survival. The 41 GBM cases had a mean Ki-67 index of 17.34%, standard deviation ±10.79 (p>0

  8. Prognostic value of Ki67 analysed by cytology or histology in primary breast cancer.

    Science.gov (United States)

    Robertson, Stephanie; Stålhammar, Gustav; Darai-Ramqvist, Eva; Rantalainen, Mattias; Tobin, Nicholas P; Bergh, Jonas; Hartman, Johan

    2018-03-27

    The accuracy of biomarker assessment in breast pathology is vital for therapy decisions. The therapy predictive and prognostic biomarkers oestrogen receptor (ER), progesterone receptor, HER2 and Ki67 may act as surrogates to gene expression profiling of breast cancer. The aims of this study were to investigate the concordance of consecutive biomarker assessment by immunocytochemistry on preoperative fine-needle aspiration cytology versus immunohistochemistry (IHC) on the corresponding resected breast tumours. Further, to investigate the concordance with molecular subtype and correlation to stage and outcome. Two retrospective cohorts comprising 385 breast tumours with clinicopathological data including gene expression-based subtype and up to 10-year overall survival data were evaluated. In both cohorts, we identified a substantial variation in Ki67 index between cytology and histology and a switch between low and high proliferation within the same tumour in 121/360 cases. ER evaluations were discordant in only 1.5% of the tumours. From cohort 2, gene expression data with PAM50 subtype were used to correlate surrogate subtypes. IHC-based surrogate classification could identify the correct molecular subtype in 60% and 64% of patients by cytology (n=63) and surgical resections (n=73), respectively. Furthermore, high Ki67 in surgical resections but not in cytology was associated with poor overall survival and higher probability for axillary lymph node metastasis. This study shows considerable differences in the prognostic value of Ki67 but not ER in breast cancer depending on the diagnostic method. Furthermore, our findings show that both methods are insufficient in predicting true molecular subtypes. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2018. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

  9. Euro tulekust lahutab 1,5 miljardit ülejääki / Raimo Poom

    Index Scriptorium Estoniae

    Poom, Raimo

    2010-01-01

    2009. aasta III kvartali lõpus oli Eesti eelarvedefitsiit 4,9% SKT-st, eelarve ülejääk oli III kvartalis 1,4 mld. Rahandusministeeriumi nõunik Sven Kirsipuu on arvamusel, et ka IV kvartal peaks olema ülejäägiga. Euroalaga liitumiseks on vaja vähemalt 1,5-miljardilist ülejääki. Graafikud

  10. Further human evidence for striatal dopamine release induced by administration of ∆9-tetrahydrocannabinol (THC): selectivity to limbic striatum.

    Science.gov (United States)

    Bossong, Matthijs G; Mehta, Mitul A; van Berckel, Bart N M; Howes, Oliver D; Kahn, René S; Stokes, Paul R A

    2015-08-01

    Elevated dopamine function is thought to play a key role in both the rewarding effects of addictive drugs and the pathophysiology of schizophrenia. Accumulating epidemiological evidence indicates that cannabis use is a risk factor for the development of schizophrenia. However, human neurochemical imaging studies that examined the impact of ∆9-tetrahydrocannabinol (THC), the main psychoactive component in cannabis, on striatal dopamine release have provided inconsistent results. The objective of this study is to assess the effect of a THC challenge on human striatal dopamine release in a large sample of healthy participants. We combined human neurochemical imaging data from two previous studies that used [(11)C]raclopride positron emission tomography (PET) (n = 7 and n = 13, respectively) to examine the effect of THC on striatal dopamine neurotransmission in humans. PET images were re-analysed to overcome differences in PET data analysis. THC administration induced a significant reduction in [(11)C]raclopride binding in the limbic striatum (-3.65 %, from 2.39 ± 0.26 to 2.30 ± 0.23, p = 0.023). This is consistent with increased dopamine levels in this region. No significant differences between THC and placebo were found in other striatal subdivisions. In the largest data set of healthy participants so far, we provide evidence for a modest increase in human striatal dopamine transmission after administration of THC compared to other drugs of abuse. This finding suggests limited involvement of the endocannabinoid system in regulating human striatal dopamine release and thereby challenges the hypothesis that an increase in striatal dopamine levels after cannabis use is the primary biological mechanism underlying the associated higher risk of schizophrenia.

  11. Effect of Exercise Training on Striatal Dopamine D2/D3 Receptors in Methamphetamine Users during Behavioral Treatment.

    Science.gov (United States)

    Robertson, Chelsea L; Ishibashi, Kenji; Chudzynski, Joy; Mooney, Larissa J; Rawson, Richard A; Dolezal, Brett A; Cooper, Christopher B; Brown, Amira K; Mandelkern, Mark A; London, Edythe D

    2016-05-01

    Methamphetamine use disorder is associated with striatal dopaminergic deficits that have been linked to poor treatment outcomes, identifying these deficits as an important therapeutic target. Exercise attenuates methamphetamine-induced neurochemical damage in the rat brain, and a preliminary observation suggests that exercise increases striatal D2/D3 receptor availability (measured as nondisplaceable binding potential (BPND)) in patients with Parkinson's disease. The goal of this study was to evaluate whether adding an exercise training program to an inpatient behavioral intervention for methamphetamine use disorder reverses deficits in striatal D2/D3 receptors. Participants were adult men and women who met DSM-IV criteria for methamphetamine dependence and were enrolled in a residential facility, where they maintained abstinence from illicit drugs of abuse and received behavioral therapy for their addiction. They were randomized to a group that received 1 h supervised exercise training (n=10) or one that received equal-time health education training (n=9), 3 days/week for 8 weeks. They came to an academic research center for positron emission tomography (PET) using [(18)F]fallypride to determine the effects of the 8-week interventions on striatal D2/D3 receptor BPND. At baseline, striatal D2/D3 BPND did not differ between groups. However, after 8 weeks, participants in the exercise group displayed a significant increase in striatal D2/D3 BPND, whereas those in the education group did not. There were no changes in D2/D3 BPND in extrastriatal regions in either group. These findings suggest that structured exercise training can ameliorate striatal D2/D3 receptor deficits in methamphetamine users, and warrants further evaluation as an adjunctive treatment for stimulant dependence.

  12. DRD2 genotype-based variation of default mode network activity and of its relationship with striatal DAT binding.

    Science.gov (United States)

    Sambataro, Fabio; Fazio, Leonardo; Taurisano, Paolo; Gelao, Barbara; Porcelli, Annamaria; Mancini, Marina; Sinibaldi, Lorenzo; Ursini, Gianluca; Masellis, Rita; Caforio, Grazia; Di Giorgio, Annabella; Niccoli-Asabella, Artor; Popolizio, Teresa; Blasi, Giuseppe; Bertolino, Alessandro

    2013-01-01

    The default mode network (DMN) comprises a set of brain regions with "increased" activity during rest relative to cognitive processing. Activity in the DMN is associated with functional connections with the striatum and dopamine (DA) levels in this brain region. A functional single-nucleotide polymorphism within the dopamine D2 receptor gene (DRD2, rs1076560 G > T) shifts splicing of the 2 D2 isoforms, D2 short and D2 long, and has been associated with striatal DA signaling as well as with cognitive processing. However, the effects of this polymorphism on DMN have not been explored. The aim of this study was to evaluate the effects of rs1076560 on DMN and striatal connectivity and on their relationship with striatal DA signaling. Twenty-eight subjects genotyped for rs1076560 underwent functional magnetic resonance imaging during a working memory task and 123 55 I-Fluoropropyl-2-beta-carbomethoxy-3-beta(4-iodophenyl) nortropan Single Photon Emission Computed Tomography ([(123)I]-FP-CIT SPECT) imaging (a measure of dopamine transporter [DAT] binding). Spatial group-independent component (IC) analysis was used to identify DMN and striatal ICs. Within the anterior DMN IC, GG subjects had relatively greater connectivity in medial prefrontal cortex (MPFC), which was directly correlated with striatal DAT binding. Within the posterior DMN IC, GG subjects had reduced connectivity in posterior cingulate relative to T carriers. Additionally, rs1076560 genotype predicted connectivity differences within a striatal network, and these changes were correlated with connectivity in MPFC and posterior cingulate within the DMN. These results suggest that genetically determined D2 receptor signaling is associated with DMN connectivity and that these changes are correlated with striatal function and presynaptic DA signaling.

  13. Inspection of feasible calibration conditions for UV radiometer detectors with the KI/KIO3 actinometer.

    Science.gov (United States)

    Qiang, Zhimin; Li, Wentao; Li, Mengkai; Bolton, James R; Qu, Jiuhui

    2015-01-01

    UV radiometers are widely employed for irradiance measurements, but their periodical calibrations not only induce an extra cost but also are time-consuming. In this study, the KI/KIO3 actinometer was applied to calibrate UV radiometer detectors at 254 nm with a quasi-collimated beam apparatus equipped with a low-pressure UV lamp, and feasible calibration conditions were identified. Results indicate that a washer constraining the UV light was indispensable, while the size (10 or 50 mL) of a beaker containing the actinometer solution had little influence when a proper washer was used. The absorption or reflection of UV light by the internal beaker wall led to an underestimation or overestimation of the irradiance determined by the KI/KIO3 actinometer, respectively. The proper range of the washer internal diameter could be obtained via mathematical analysis. A radiometer with a longer service time showed a greater calibration factor. To minimize the interference from the inner wall reflection of the collimating tube, calibrations should be conducted at positions far enough away from the tube bottom. This study demonstrates that after the feasible calibration conditions are identified, the KI/KIO3 actinometer can be applied readily to calibrate UV radiometer detectors at 254 nm. © 2014 The American Society of Photobiology.

  14. FEASIBILITY STUDY FOR POTASSIUM IODIDE (KI) DISTRIBUTION IN NEW YORK CITY

    International Nuclear Information System (INIS)

    MOSS, STEVEN

    2005-01-01

    The New York City Department of Health and Mental Hygiene (DOHMH), Bureau of Environmental Science and Engineering, Office of Radiological Health (ORH) [as the primary local technical consultant in the event of a radiological or nuclear incident within the boundaries of New York City] requested the assistance of Brookhaven National Laboratory (BNL) with the development of a Feasibility Study for Potassium Iodide (KI) distribution in the unlikely event of a significant release of radioactive iodine in or near New York City. Brookhaven National Laboratory had previously provided support for New York City with the development of the radiological/nuclear portions of its All Hazards Emergency Response Plans. The work is funded by Medical and Health Research Association (MHRA) of New York City, Inc., under a work grant by the Federal Centers for Disease Control (CDC) for Public Health Preparedness and Response for Bioterrorism. This report is part of the result of that effort. The conclusions of this report are that: (1) There is no credible radiological scenario that would prompt the need for large segments of the general population of New York City to take KI as a result of a projected plume exposure to radioiodine reaching even the lowest threshold of 5 rem to the thyroid; and (2) KI should be stockpiled in amounts and locations sufficient for use by first responders/emergency responders in response to any localized release of radioiodine

  15. WACANA SOSIAL MITOS KERIS KI BARU GAJAH DALAM TRADISI NGREBEG DI KECAMATAN KEDIRI, TABANAN

    Directory of Open Access Journals (Sweden)

    Anak Agung Ayu Meitridwiastiti

    2017-12-01

    Full Text Available Penelitian wacana sosial atas mitos keris Ki Baru Gajah dalam tradisi Ngrebeg di Kecamatan Kediri, Tabanan dilakukan untuk menganalisis struktur mitos yang bersifat tekstual, menjelaskan implementasi dan fungsi mitos keris Ki Baru Gajah dalam Purana Pura Luhur Pakendungan pada Tradisi Ngrebeg. Penelitian ini juga mengungkapkan wacana sosial yang ada dan berkembang di masyarakat Kecamatan Kediri, Tabanan yang bersifat kontekstual.Teori yang digunakan dalam penelitian ini adalah teori fungsi dan semiotika (Charles Sander Pierce. Pengumpulan data dikumpulkan melalui studi pustaka, wawancara, dan perekaman. Analisis data yang digunakan adalah hermeneutika dan deskriptif analitik.Penyajian hasil analisis data yang digunakan adalah metode informal. Implementasi mitos keris Ki Baru Gajah meliputi tradisi Ngrebeg, sedangkan fungsinya meliputi fungsi pelengkap upacara Dewa Yadnya, sebagai media pendidikan masyarakat, mempererat hubungan sosial masyarakat, dan pengusir wabah penyakit. Wacana sosial meliputi makna dari mitos tersebut, yaitu makna simbolik, loyalitas, dan kesuburan. Diharapkan dengan tradisi yang berasal dari sebuah mitos dapat memberikan keharmonisan dan kesejahteraan kehidupan dalam masyarakat Kecamatan Kediri, Tabanan.

  16. Kraški rob (landscape term Geologic section along the motorway Kozina – Koper (Capodistria

    Directory of Open Access Journals (Sweden)

    Ladislav Placer

    2007-06-01

    Full Text Available Geologic section along the motorway from Kozina to Koper in totality exposed geologic structure of the border belt between Adriatic-Apulian foreland and Dinarides that was formed by subthrusting of Adriatic-Apulian foreland (Istria, Friuli underneath External Dinarides (Kras, Čičarija. During this process within the subthrusting belt a geomorphologic step was formed at sites where limestone became overthrust on flyschbeds.Apartof this geomorphologic step became known in the last decade of 20st century as the Kraški rob (Karst edge. With respect to geologic and geomorphologic considerations the term Kra{ki rob (»Karst Edge« as landscape term for cliffs above the valleys of the Osapska reka and upper Rižana rivers should be distinguished from term karst edge (kra{ki rob as a general term which is a synonym for the geomorphologic step consisting of precipitous cliffs and steep carbonate slopes situated entirely between the mouth of the river Timava and Mt. Učka that form the border belt between the karstic plateaus of Kras and Čičarije from one side, and the flysch Istria with the Trieste flysch coastal zone on the otherside.

  17. FEASIBILITY STUDY FOR POTASSIUM IODIDE (KI) DISTRIBUTION IN NEW YORK CITY.

    Energy Technology Data Exchange (ETDEWEB)

    MOSS, STEVEN

    2005-04-29

    The New York City Department of Health and Mental Hygiene (DOHMH), Bureau of Environmental Science and Engineering, Office of Radiological Health (ORH) [as the primary local technical consultant in the event of a radiological or nuclear incident within the boundaries of New York City] requested the assistance of Brookhaven National Laboratory (BNL) with the development of a Feasibility Study for Potassium Iodide (KI) distribution in the unlikely event of a significant release of radioactive iodine in or near New York City. Brookhaven National Laboratory had previously provided support for New York City with the development of the radiological/nuclear portions of its All Hazards Emergency Response Plans. The work is funded by Medical and Health Research Association (MHRA) of New York City, Inc., under a work grant by the Federal Centers for Disease Control (CDC) for Public Health Preparedness and Response for Bioterrorism. This report is part of the result of that effort. The conclusions of this report are that: (1) There is no credible radiological scenario that would prompt the need for large segments of the general population of New York City to take KI as a result of a projected plume exposure to radioiodine reaching even the lowest threshold of 5 rem to the thyroid; and (2) KI should be stockpiled in amounts and locations sufficient for use by first responders/emergency responders in response to any localized release of radioiodine.

  18. KiDS-450: tomographic cross-correlation of galaxy shear with Planck lensing

    Science.gov (United States)

    Harnois-Déraps, Joachim; Tröster, Tilman; Chisari, Nora Elisa; Heymans, Catherine; van Waerbeke, Ludovic; Asgari, Marika; Bilicki, Maciej; Choi, Ami; Erben, Thomas; Hildebrandt, Hendrik; Hoekstra, Henk; Joudaki, Shahab; Kuijken, Konrad; Merten, Julian; Miller, Lance; Robertson, Naomi; Schneider, Peter; Viola, Massimo

    2017-10-01

    We present the tomographic cross-correlation between galaxy lensing measured in the Kilo Degree Survey (KiDS-450) with overlapping lensing measurements of the cosmic microwave background (CMB), as detected by Planck 2015. We compare our joint probe measurement to the theoretical expectation for a flat Λ cold dark matter cosmology, assuming the best-fitting cosmological parameters from the KiDS-450 cosmic shear and Planck CMB analyses. We find that our results are consistent within 1σ with the KiDS-450 cosmology, with an amplitude re-scaling parameter AKiDS = 0.86 ± 0.19. Adopting a Planck cosmology, we find our results are consistent within 2σ, with APlanck = 0.68 ± 0.15. We show that the agreement is improved in both cases when the contamination to the signal by intrinsic galaxy alignments is accounted for, increasing A by ∼0.1. This is the first tomographic analysis of the galaxy lensing - CMB lensing cross-correlation signal, and is based on five photometric redshift bins. We use this measurement as an independent validation of the multiplicative shear calibration and of the calibrated source redshift distribution at high redshifts. We find that constraints on these two quantities are strongly correlated when obtained from this technique, which should therefore not be considered as a stand-alone competitive calibration tool.

  19. KiKK: An endless story or the long way to come to a conclusion?

    International Nuclear Information System (INIS)

    Michel, Rolf; Mueller, Wolfgang-Ulrich

    2009-01-01

    More than one year after the publication of the KiKK-Study (Epidemiological Study on Childhood Cancer in the Vicinity of Nuclear Power Plants), which reported a statistical correlation between the proximity of a person's residence to the nearest nuclear power plant, at the time of diagnosis, and the person's risk of contracting cancer (or leukaemia) prior to his or her fifth birthday, the SSK presented its assessment and the related scientific explanatory statement to the public on the occasion of an expert discussion in Bonn on February 26, 2009, This article describes the background of the SSK deliberations and gives a survey of its essential results and conclusions. In total, the results are unsatisfactory, since the SSK was not able to explain the findings of the KiKK-Study. However, this was not unexpected considering the international state of knowledge regarding the development of childhood cancer. Considering the fact, that the radiation exposure of members of the public, originating from the nuclear power plants even at the locations of the potentially highest exposures, is by orders of magnitude lower than the natural radiation exposures, the SSK was able to exclude the radiation from the nuclear power plants as cause of the observed increased relative risks. Any more far-reaching explanation attempts would be mere speculation. It is still a long way to know how childhood cancer develops and how the results of the KiKK-Study or other small-scale enhancements of the cancer risk can be explained. (orig.)

  20. [Utilization of Physiotherapy Services by Children and Adolescents - Results of the KiGGS- Baseline Survey].

    Science.gov (United States)

    Weber, A; Karch, D; Thyen, U; Rommel, A; Schlack, R; Hölling, H; von Kries, R

    2017-03-01

    Aim of the study: The use of physical therapy in German children and adolescents has so far solely been analyzed on the basis of health insurance data, which can neither consider case history nor social factors. Using the KiGGS-baseline survey it is possible to examine the use of physical therapy on the basis of parental reported health problems and social factors. Methodology: Identifiable determinants for the use of physical therapy in the last 12 months in the KiGGS-baseline survey were examined bivariate and multivariate in logistic regression models with mutual adjustment. The following determinants were considered: social factors, somatic disorders and psychological abnormalities. The proportion of the use of physical therapy, which can be explained by these determinants, was estimated using population-attributable risk fraction. Results: The frequency of the use of physical therapy in the last 12 months in the 0 to 17-year-olds in the KiGGS-baseline survey was 6,4% with higher use during infancy and adolescence. The socio-economic status of parents was not associated with the use of physical therapy. A migration background decreased the probability of the use of physical therapy, for example, among children aged 0 to 2 years (OR adjusted : 0,5 [95% CI: 0,2-1,0]). In those with scoliosis, the use of physical therapy was almost twice as frequent in infancy as in adolescence (58,4 vs. 34,4%). A maximum of 15% of all children and adolescents with back pain reported the use of physical therapy. When ADHD was diagnosed at preschool age, the probability of using physical therapy was increased (OR adjusted : 5,1 [95% CI: 1,4-18,6]). The health problems, which were assessed in the KiGGS-baseline survey and considered for this analysis could explain 37% of the use of physical therapy in the 0 to 2-year-olds. In the other age groups, 59 to 62% could be explained. Conclusion: Comparison of the KiGGS-baseline survey with health insurance data shows similar frequencies

  1. OPREMLJENOST ŠOL Z DIDAKTIČNIMI PRIPOMOČKI ZA PODROČJE ARITMETIKE IN ALGEBRE V PRVEM TRILETJU IN NJIHOVA RACIONALNA UPORABA

    OpenAIRE

    Sraka, Petra

    2011-01-01

    V diplomskem delu so predstavljeni didaktični pripomočki na splošno, sledi pregled terminov, ki so se zanje uporabljali skozi zgodovino vse do danes, klasifikacija ter lastnosti temeljnih didaktičnih pripomočkov. Podane so osnovne smernice kritične izbire ter racionalne uporabe pripomočkov pri pouku matematike. Bolj podrobno so predstavljeni didaktični pripomočki pri pouku matematike v sklopu aritmetike in algebre v prvem triletju osnovne šole oziroma tisti pripomočki, ki jih predpisuje učni ...

  2. Synthesis H-Zeolite catalyst by impregnation KI/KIO3 and performance test catalyst for biodiesel production

    Science.gov (United States)

    Widayat, W.; Rizky Wicaksono, Adit; Hakim Firdaus, Lukman; Okvitarini, Ndaru

    2016-02-01

    The objective of this research is to produce H-catalyst catalyst that was impregnated with KI/KIO3. The catalyst was analyzed about surface area, X-Ray Diffraction (XRD) and performance test of catalyst for biodiesel production. An H-Zeolite catalyst was synthesized from natural zeolite with chemical treatment processing, impregnation KI/KIO3 and physical treatment. The results shows that the surface area of the catalyst by 27.236 m2/g at a concentration of 5% KI. XRD analysis shows peak 2-θ at 23.627o indicating that KI was impregnated on H-zeolite catalyst. The catalyst was tested in production of biodiesel using palm oil with conventional methods for 3 hour at temperature of 70-80 oC. The result for conversion Fatty Acid Methyl Ester (FAME) reached maximum value on 87.91% under production process using catalyst 5% KIO3-H zeolite.

  3. Kiika Kööki hädas välisuksega / Monica Sikk, Boris Dubovik

    Index Scriptorium Estoniae

    Sikk, Monica

    2000-01-01

    Kunagise Pärli kohviku ruumidesse rajatud kaupluse Kiika Kööki sisekujundusest (Arhitektuuribüroo ITC MCM) ning muinsuskaitsega probleeme tekitanud uuest välisuksest; muinsuskaitsja Boris Duboviku kommentaar

  4. Kaurismäki ja Almodovar võtavad Cannes'is mõõtu / Andres Laasik

    Index Scriptorium Estoniae

    Laasik, Andres, 1960-2016

    2006-01-01

    Filmidest, mis osalevad 17. mail algava Cannes'i filmifestivali võistlusprogrammis : Aki Kaurismäki "Äärelinna tuled" ("Laitakaupungin valot"), Pedro Almodovari "Tagasipöördumine" ("Volver"), Sofia Coppola "Marie-Antoinette" jt

  5. KiVa Antibullying Program: Overview of Evaluation Studies Based on a Randomized Controlled Trial and National Rollout in Finland

    Directory of Open Access Journals (Sweden)

    Christina Salmivalli

    2012-12-01

    Full Text Available The effects of a Finnish national school-based antibullying program (KiVa were evaluated in a randomized controlled trial (2007–2009 and during nationwide implementation (since 2009. The KiVa program is been found to reduce bullying and victimization and increase empathy towards victimized peers and self-efficacy to support and defend them. KiVa increases school liking and motivation and contributes to significant reductions in anxiety, depression, and negative peer perceptions. Somewhat larger reductions in bullying and victimization were found in the randomized controlled trial than in the broad rollout, and the largest effects were obtained in primary school (grades 1–6. The uptake of the KiVa program is remarkable, with 90 percent of Finnish comprehensive schools currently registered as program users.

  6. [Physical activity and electronic media use in children and adolescents: results of the KiGGS study: first follow-up (KiGGS wave 1)].

    Science.gov (United States)

    Manz, K; Schlack, R; Poethko-Müller, C; Mensink, G; Finger, J; Lampert, T

    2014-07-01

    Physical activity during childhood and adolescence has numerous health benefits, while sedentary behavior, especially electronic media use, is associated with the development of overweight. Therefore, the promotion of physical activity during childhood and adolescence is an integral part of national public health efforts. The aim of this article is to describe the physical activity behavior of German children and adolescents based on the nationwide data of the German Health Interview and Examination Survey for Children and Adolescents (KiGGS wave 1). Furthermore, the association between physical activity and sports participation and use of screen-based media in youth aged 11 to 17 years was analyzed. The analyses included data from 10,426 children and adolescents aged 3-17 years collected by telephone interviews. Children older than 11 years answered the questions by themselves, whereas a parent was interviewed for younger children. The descriptive analyses were performed under consideration of social and demographic factors. According to the results of KiGGS wave 1 a total of 77.5% (95% Cl 76.0-78.9 %) of the children and adolescents participated in sports activities, and 59.7% (58.1-61.3 %) were members of a sports club. The recommendation of the World Health Organization (WHO) to be physically active at least 60 min per day was achieved by 27.5% (26.0-28.9 %). Children and adolescents with a low socioeconomic status (SES) participated less in sports activities than children of higher SES groups. Excessive use of screen-based media was more likely to be associated with lack of sports participation than with a lack of physical activity. In the future, preventive measures should promote the daily physical activity of children and adolescents and additionally encourage children and adolescents with low SES to participate in sports activities.

  7. Effects of cholecystokinin octapeptide on striatal dopamine metabolism and on apomorphine-induced stereotyped cage-climbing in mice

    Energy Technology Data Exchange (ETDEWEB)

    Kovacs, G L; Szabo, G; Telegdy, G [Institute of Pathophysiology, University Medical School, Szeged, Hungary; Penke, B [Institute of Medical Chemistry, University Medical School, Szeged, Hungary

    1981-01-29

    The effects of sulfated (CCK-8-SE) and non-sulfated (CCK-8-NS) cholecystokinin octapeptide on striatal dopamine (DA) metabolism have been investigated on mice. CCK-8-NS facilitated the disappearance of striatal DA, measured after synthesis inhibition with 350 mg/kg of ..cap alpha..-methyl-p-tyrosine. CCK-8-SE did not affect DA disappearance. In vitro uptake of (/sup 3/H)DA by striatal slices was affected by neither CCK-8-SE, nor CCK-8-NS (10/sup -5/ M). Potassium-induced in vitro release of (/sup 3/H)DA from striatal slices was significantly increased by 10/sup -5/ M CCK-8-NS: however, CCK-8-SE likewise increased DA release in this model system. Apomorphine-induced (1.0 mg/kg) stereotyped cage-climbing behavior was not affected by CCK-8-SE but was enhanced by CCK-8-NS. This effect could be antagonized by haloperidol, but not by naloxone. The data suggest that CCK-8-NS affects striatal DA release, disappearance and receptor sensitivity in the mouse. Dopaminergic mechanisms should therefore be regarded as a possible mode of action of CCK-8-NS on brain functions.

  8. Effects of cholecystokinin octapeptide on striatal dopamine metabolism and on apomorphine-induced stereotyped cage-climbing in mice

    International Nuclear Information System (INIS)

    Kovacs, G.L.; Szabo, G.; Telegdy, G.; Penke, B.

    1981-01-01

    The effects of sulfated (CCK-8-SE) and non-sulfated (CCK-8-NS) cholecystokinin octapeptide on striatal dopamine (DA) metabolism have been investigated on mice. CCK-8-NS facilitated the disappearance of striatal DA, measured after synthesis inhibition with 350 mg/kg of α-methyl-p-tyrosine. CCK-8-SE did not affect DA disappearance. In vitro uptake of [ 3 H]DA by striatal slices was affected by neither CCK-8-SE, nor CCK-8-NS (10 -5 M). Potassium-induced in vitro release of [ 3 H]DA from striatal slices was significantly increased by 10 -5 M CCK-8-NS: however, CCK-8-SE likewise increased DA release in this model system. Apomorphine-induced (1.0 mg/kg) stereotyped cage-climbing behavior was not affected by CCK-8-SE but was enhanced by CCK-8-NS. This effect could be antagonized by haloperidol, but not by naloxone. The data suggest that CCK-8-NS affects striatal DA release, disappearance and receptor sensitivity in the mouse. Dopaminergic mechanisms should therefore be regarded as a possible mode of action of CCK-8-NS on brain functions. (Auth.)

  9. The temporal and spatial distribution of the proliferation associated Ki-67 protein during female and male meiosis.

    Science.gov (United States)

    Traut, Walther; Endl, Elmar; Scholzen, Thomas; Gerdes, Johannes; Winking, Heinz

    2002-09-01

    We used immunolocalization in tissue sections and cytogenetic preparations of female and male gonads to study the distribution of the proliferation marker pKi-67 during meiotic cell cycles of the house mouse, Mus musculus. During male meiosis, pKi-67 was continuously present in nuclei of all stages from the spermatogonium through spermatocytes I and II up to the earliest spermatid stage (early round spermatids) when it appeared to fade out. It was not detected in later spermatid stages or sperm. During female meiosis, pKi-67 was present in prophase I oocytes of fetal ovaries. It was absent in oocytes from newborn mice and most oocytes of primordial follicles from adults. The Ki-67 protein reappeared in oocytes of growing follicles and was continuously present up to metaphase II. Thus, pKi-67 was present in all stages of cell growth and cell division while it was absent from resting oocytes and during the main stages of spermiocytogenesis. Progression through the meiotic cell cycle was associated with extensive intranuclear relocation of pKi-67. In the zygotene and pachytene stages, most of the pKi-67 colocalized with centromeric (centric and pericentric) heterochromatin and adjacent nucleoli; the heterochromatic XY body in male pachytene, however, was free of pKi-67. At early diplotene, pKi-67 was mainly associated with nucleoli. At late diplotene, diakinesis, metaphase I and metaphase II of meiosis, pKi-67 preferentially bound to the perichromosomal layer and was almost absent from the heterochromatic centromeric regions of the chromosomes. After the second division of male meiosis, the protein reappeared at the centromeric heterochromatin and an adjacent region in the earliest spermatid stage and then faded out. The general patterns of pKi-67 distribution were comparable to those in mitotic cell cycles. With respect to the timing, it is interesting to note that relocation from the nucleolus to the perichromosomal layer takes place at the G2/M-phase transition in

  10. The proliferation marker pKi-67 organizes the nucleolus during the cell cycle depending on Ran and cyclin B.

    Science.gov (United States)

    Schmidt, Mirko H H; Broll, Rainer; Bruch, Hans-Peter; Bögler, Oliver; Duchrow, Michael

    2003-01-01

    The proliferation marker pKi-67 ('Ki-67 antigen') is commonly used in clinical and research pathology to detect proliferating cells, as it is only expressed during cell-cycle progression. Despite the fact that this antigen has been known for nearly two decades, there is still no adequate understanding of its function. This study has therefore identified proteins that interact with pKi-67, using a yeast two-hybrid system. A mammalian two-hybrid system and immunoprecipitation studies were used to verify these interactions. Among other cell-cycle regulatory proteins, two binding partners associated with the small GTPase Ran were identified. In addition, DNA-structural and nucleolus-associated proteins binding to pKi-67 were found. Moreover, it was demonstrated that the N-terminal domain of pKi-67 is capable of self-binding to its own repeat region encoded by exon 13. Since RanBP, a protein involved in the transport of macromolecules over the nuclear lamina, was found to be a binding partner, a possible effect of pKi-67 on the localization of cell-cycle regulatory proteins was proposed. To test this hypothesis, a tetracycline-responsive gene expression system was used to induce the pKi-67 fragments previously used for the two-hybrid screens in HeLa cells. Subsequent immunostaining revealed the translocation of cyclin B1 from cytoplasm to nucleoli in response to this expression. It is suggested that pKi-67 is a Ran-associated protein with a role in the disintegration and reformation of the nucleolus and thereby in entry into and exit from the M-phase. Copyright 2002 John Wiley & Sons, Ltd.

  11. An analysis of potassium iodide (KI) prophylaxis for the general public in the event of a nuclear accident

    Energy Technology Data Exchange (ETDEWEB)

    Behling, H.; Behling, K. [S. Cohen & Associates, Inc., McLean, VA (United States); Amarasooriya, H.; Kotsch, J. [Scientech, Inc., Rockville, MD (United States)

    1995-02-01

    A generic difficulty encountered in cost-benefit analyses is the quantification of major elements that define the costs and the benefits in commensurate units. In this study, the costs of making KI available for public use, and the avoidance of thyroidal health effects predicted to be realized from the availability of that KI (i.e., the benefits), are defined in the commensurate units of dollars.

  12. Comparison of the value of PCNA and Ki-67 as markers of cell proliferation in ameloblastic tumor

    Science.gov (United States)

    Mosqueda-Taylor, Adalberto; Molina-Frechero, Nelly; Mori-Estevez, Ana D.; Sánchez-Acuña, Guillermo

    2013-01-01

    Objectives: The aim of this study was to compare among PCNAand Ki-67 as the most reliable immunohistochemical marker for evaluating cell proliferation in ameloblastic tumors. Study Design: Observational, retrospective, and descriptive study of a large series of ameloblastic tumors, composed of 161 ameloblastomas and four ameloblastic carcinomas, to determine and compare PCNA and Ki-67 expression using immunohistochemistry techniques. Results: When analyzing Ki-67 positivity, the desmoplastic ameloblastoma demonstrated a significantly lower proliferation rate (1.9%) compared with the solid/multicystic and unicystic ameloblastomas and ameloblastic carcinomas (p<0.05), whereas the ameloblastic carcinomas displayed a significantly higher rate compared with all of the other ameloblastomas (48.7%) (p<0.05). When analyzing cell proliferation with PCNA, we found significant differences only between the ameloblastic carcinomas (93.3%) and the desmoplastic ameloblastomas (p<0.05). When differences between the immunopositivity for PCNA and Ki-67 were compared, the percentages were higher for PCNA in all types of ameloblastomas and ameloblastic carcinomas. In all cases, the percentages were greater than 80%, whereas the immunopositivity for Ki-67 was significantly lower; for example, the ameloblastic carcinoma expressed the highest positivity and only reached 48.7%, compared to 93.3% when we used PCNA. Conclusions: In the present study, when we used the proliferation cell marker Ki-67, the percentages of positivity were more specific and varied among the different types of ameloblastomas, suggesting that Ki-67 is a more specific marker for the proliferation of ameloblastic tumor cells. Key words:Ameloblastomas, ameloblastic carcinoma, PCNA, Ki-67, cell proliferation markers. PMID:23229269

  13. An analysis of potassium iodide (KI) prophylaxis for the general public in the event of a nuclear accident

    International Nuclear Information System (INIS)

    Behling, H.; Behling, K.; Amarasooriya, H.; Kotsch, J.

    1995-02-01

    A generic difficulty encountered in cost-benefit analyses is the quantification of major elements that define the costs and the benefits in commensurate units. In this study, the costs of making KI available for public use, and the avoidance of thyroidal health effects predicted to be realized from the availability of that KI (i.e., the benefits), are defined in the commensurate units of dollars

  14. Motor and cortico-striatal-thalamic connectivity alterations in intrauterine growth restriction.

    Science.gov (United States)

    Eixarch, Elisenda; Muñoz-Moreno, Emma; Bargallo, Nuria; Batalle, Dafnis; Gratacos, Eduard

    2016-06-01

    Intrauterine growth restriction is associated with short- and long-term neurodevelopmental problems. Structural brain changes underlying these alterations have been described with the use of different magnetic resonance-based methods that include changes in whole structural brain networks. However, evaluation of specific brain circuits and its correlation with related functions has not been investigated in intrauterine growth restriction. In this study, we aimed to investigate differences in tractography-related metrics in cortico-striatal-thalamic and motor networks in intrauterine growth restricted children and whether these parameters were related with their specific function in order to explore its potential use as an imaging biomarker of altered neurodevelopment. We included a group of 24 intrauterine growth restriction subjects and 27 control subjects that were scanned at 1 year old; we acquired T1-weighted and 30 directions diffusion magnetic resonance images. Each subject brain was segmented in 93 regions with the use of anatomical automatic labeling atlas, and deterministic tractography was performed. Brain regions included in motor and cortico-striatal-thalamic networks were defined based in functional and anatomic criteria. Within the streamlines that resulted from the whole brain tractography, those belonging to each specific circuit were selected and tractography-related metrics that included number of streamlines, fractional anisotropy, and integrity were calculated for each network. We evaluated differences between both groups and further explored the correlation of these parameters with the results of socioemotional, cognitive, and motor scales from Bayley Scale at 2 years of age. Reduced fractional anisotropy (cortico-striatal-thalamic, 0.319 ± 0.018 vs 0.315 ± 0.015; P = .010; motor, 0.322 ± 0.019 vs 0.319 ± 0.020; P = .019) and integrity cortico-striatal-thalamic (0.407 ± 0.040 vs 0.399 ± 0.034; P = .018; motor, 0.417 ± 0.044 vs 0

  15. Oxidative Stress Posttranslationally Regulates the Expression of Ha-Ras and Ki-Ras in Cultured Astrocytes

    Directory of Open Access Journals (Sweden)

    Samantha Messina

    2012-01-01

    Full Text Available Addition of hydrogen peroxide to cultured astrocytes induced a rapid and transient increase in the expression of Ha-Ras and Ki-Ras. Pull-down experiments with the GTP-Ras-binding domain of Raf-1 showed that oxidative stress substantially increased the activation of Ha-Ras, whereas a putative farnesylated activated form of Ki-Ras was only slightly increased. The increase in both Ha-Ras and Ki-Ras was insensitive to the protein synthesis inhibitor, cycloheximide, and was occluded by the proteasomal inhibitor, MG-132. In addition, exposure to hydrogen peroxide reduced the levels of ubiquitinated Ras protein, indicating that oxidative stress leads to a reduced degradation of both isoforms through the ubiquitin/proteasome pathway. Indeed, the late reduction in Ha-Ras and Ki-Ras was due to a recovery of proteasomal degradation because it was sensitive to MG-132. The late reduction of Ha-Ras levels was abrogated by compound PD98059, which inhibits the MAP kinase pathway, whereas the late reduction of Ki-Ras was unaffected by PD98059. We conclude that oxidative stress differentially regulates the expression of Ha-Ras and Ki-Ras in cultured astrocytes, and that activation of the MAP kinase pathway by oxidative stress itself or by additional factors may act as a fail-safe mechanism limiting a sustained expression of the potentially detrimental Ha-Ras.

  16. Effect of KiFAY on Performance, Insulin-like Growth Factor-1, and Thyroid Hormones in Broilers

    Directory of Open Access Journals (Sweden)

    Amit Kini

    2016-10-01

    Full Text Available A comparative study was performed to investigate the efficacy of KiFAY as a feed additive on performance parameters, thyroid, and pancreatic hormone levels in broilers. Ninety birds (Vencobb 400 were randomly divided into three groups viz., Control (no DL-methionine supplementation, Treatment1 (containing added DL-methionine and Treatment 2 (containing KiFAY and without DL-methionine supplementation. The performance parameters (weekly body weight, body weight gain, feed intake, and feed consumption ratio were recorded and calculated during the whole study of 4 weeks. Analyses of insulin and insulin-like growth factor (IGF 1, triiodothyronine (T3, thyroxine (T4 and thyroid stimulating hormone (TSH were performed at the end of the study. The results show that birds on supplementation of KiFAY performed significantly (p<0.001 better than other treatments. The weekly body weight, body weight gain, feed in-take and feed consumption ratio improved in KiFAY treated birds. The study found an increase in insulin and IGF1 levels (p<0.001 in KiFAY compared with the other treatments. Serum T3, T4, and TSH levels in the Treatment 2 were higher than other treatments (p<0.001. The KiFAY supplementation was able to improve performance with associated responses at a hormonal level in broilers.

  17. Cell Proliferation (KI-67) Expression Is Associated with Poorer Prognosis in Nigerian Compared to British Breast Cancer Women

    Science.gov (United States)

    Agboola, Ayodeji O. J.; Banjo, Adekumbiola A. F.; Anunobi, Charles C.; Salami, Babatunde; Agboola, Mopelola Deji; Musa, Adewale A.; Nolan, Christopher C.; Rakha, Emad A.; Ellis, Ian O.; Green, Andrew R.

    2013-01-01

    Background. Black women with breast cancer (BC) in Nigeria have higher mortality rate compared with British women. This study investigated prognostic features of cell proliferation biomarker (Ki-67) in Nigerian breast cancer women. Materials and Methods. The protein expression of Ki-67 was investigated in series of 308 Nigerian women, prepared as a tissue microarray (TMA), using immunohistochemistry. Clinic-pathological parameters, biomarkers, and patient outcome of tumours expressing Ki-67 in Nigerian women were correlated with UK grade-matched series. Results. A significantly larger proportion of breast tumours from Nigerian women showed high Ki-67 expression. Those tumours were significantly correlated with negative expression of the steroid hormone receptors (ER and PgR), p21, p27, E-cadherin, BRCA-1, and Bcl-2 (all P < 0.001), but positively associated with EGFR (P = 0.003), p53, basal cytokeratins: CK56, CK14, triple negative, and basal phenotype using Nielsen's classification (all P < 0.001) compared to UK women. Multivariate analyses showed that race was also associated with BCSS independent of tumour size, lymph node status, and ER status. Conclusion. Ki-67 expression was observed to have contributed to the difference in the BCSS in Nigerian compared with British BC women. Therefore, targeting Ki-67 in the indigenous black women with BC might improve the patient outcome in the black women with BC. PMID:23691362

  18. Suprabasal expression of Ki-67 as a marker for the severity of oral epithelial dysplasia and oral squamous cell carcinoma

    Directory of Open Access Journals (Sweden)

    Nidhi Dwivedi

    2013-01-01

    Full Text Available Background: Transition of the normal oral epithelium to dysplasia and to malignancy is featured by increased cell proliferation. To evaluate the hypothesis of distributional disturbances in proliferating and stem cells in oral epithelial dysplasia and oral squamous cell carcinoma (OSCC. Aim: To evaluate layer wise expression of Ki-67 in oral epithelial dysplasia and in OSCC. Materials and Methods: Thirty histologically confirmed cases of oral epithelial dysplasia, fifteen cases of OSCC and five cases of normal buccal mucosa were immunohistochemically examined and nuclear expression of Ki-67 was counted according to basal, parabasal, and suprabasal layers in epithelial dysplasia and number of positive cells per 100 cells in OSCC as labeling index (LI. Results: Suprabasal expression of Ki-67 increased according to the severity of epithelial dysplasia and the difference was statistically significant ( P < 0.001. The mean Ki-67LI was 12.78 for low risk lesions, 28.68 for high risk lesions, 39.45 for OSCC and 13.6 for normal buccal mucosa. Conclusion: The results of the present study demonstrate the use of proliferative marker Ki-67 in assessing the severity of epithelial dysplasia. Suprabasal expression of Ki-67 provides an objective criteria for determining the severity of epithelial dysplasia and histological grading of OSCC.

  19. The role of Ki67 proliferation assessment in predicting local control in bladder cancer patients treated by radical radiation therapy

    International Nuclear Information System (INIS)

    Lara, P.C.; Gonzalez, G.; Rey, A.; Apolinario, R.; Santana, C.; Afonso, J.L.; Diaz, J.M.

    1998-01-01

    Purpose: To assess whether tumour proliferation as measured by Ki67 immunostaining has any predictive value for local control in bladder cancer patients treated by radiotherapy. Patients and methods: Fifty-five patients suffering from infiltrating bladder carcinoma recommended for radical radiotherapy (66 Gy/6-7weeks) were included in this study. Paraffin-embedded pre-treatment tumour sections were stained with the Ki67 antibody. The percentage of Ki67-positive nuclei was correlated with established prognostic factors, local control and survival. Results27%) Ki67 expression indices (31.5%) (P<0.05; log-rank test). Conclusions: Ki67 immunostaining was a feasible method to estimate tumour proliferation. Patients with very low proliferating tumours seemed to achieve better local control after fractionated radiotherapy compared to other patients. Further studies are needed with a greater number of patients to accurately define the role of Ki67 expression in predicting tumour repopulation during fractionated radiotherapy. (Copyright (c) 1998 Elsevier Science B.V., Amsterdam. All rights reserved.)

  20. Impulse control disorders in Parkinson's disease: decreased striatal dopamine transporter levels.

    Science.gov (United States)

    Voon, Valerie; Rizos, Alexandra; Chakravartty, Riddhika; Mulholland, Nicola; Robinson, Stephanie; Howell, Nicholas A; Harrison, Neil; Vivian, Gill; Ray Chaudhuri, K

    2014-02-01

    Impulse control disorders are commonly associated with dopaminergic therapy in Parkinson's disease (PD). PD patients with impulse control disorders demonstrate enhanced dopamine release to conditioned cues and a gambling task on [(11)C]raclopride positron emission tomography (PET) imaging and enhanced ventral striatal activity to reward on functional MRI. We compared PD patients with impulse control disorders and age-matched and gender-matched controls without impulse control disorders using [(123)I]FP-CIT (2β-carbomethoxy-3β-(4-iodophenyl)tropane) single photon emission computed tomography (SPECT), to assess striatal dopamine transporter (DAT) density. The [(123)I]FP-CIT binding data in the striatum were compared between 15 PD patients with and 15 without impulse control disorders using independent t tests. Those with impulse control disorders showed significantly lower DAT binding in the right striatum with a trend in the left (right: F(1,24)=5.93, p=0.02; left: F(1,24)=3.75, p=0.07) compared to controls. Our findings suggest that greater dopaminergic striatal activity in PD patients with impulse control disorders may be partly related to decreased uptake and clearance of dopamine from the synaptic cleft. Whether these findings are related to state or trait effects is not known. These findings dovetail with reports of lower DAT levels secondary to the effects of methamphetamine and alcohol. Although any regulation of DAT by antiparkinsonian medication appears to be modest, PD patients with impulse control disorders may be differentially sensitive to regulatory mechanisms of DAT expression by dopaminergic medications.

  1. Abstinence duration modulates striatal functioning during monetary reward processing in cocaine patients.

    Science.gov (United States)

    Bustamante, Juan-Carlos; Barrós-Loscertales, Alfonso; Costumero, Víctor; Fuentes-Claramonte, Paola; Rosell-Negre, Patricia; Ventura-Campos, Noelia; Llopis, Juan-José; Ávila, César

    2014-09-01

    Pre-clinical and clinical studies in cocaine addiction highlight alterations in the striatal dopaminergic reward system that subserve maintenance of cocaine use. Using an instrumental conditioning paradigm with monetary reinforcement, we studied striatal functional alterations in long-term abstinent cocaine-dependent patients and striatal functioning as a function of abstinence and treatment duration. Eighteen patients and 20 controls underwent functional magnetic resonance imaging during a Monetary Incentive Delay task. Region of interest analyses based on masks of the dorsal and ventral striatum were conducted to test between-group differences and the functional effects in the cocaine group of time (in months) with no more than two lapses from the first time patients visited the clinical service to seek treatment at the scanning time (duration of treatment), and the functional effects of the number of months with no lapses or relapses at the scanning session time (length of abstinence). We applied a voxel-wise and a cluster-wise FWE-corrected level (pFWE) at a threshold of P reward anticipation than the control group. The regression analyses in the patients group revealed a positive correlation between duration of treatment and brain activity in the left caudate during reward anticipation. Likewise, length of abstinence negatively correlated with brain activity in the bilateral nucleus accumbens during monetary outcome processing. In conclusion, caudate and nucleus accumbens show a different brain response pattern to non-drug rewards during cocaine addiction, which can be modulated by treatment success. © 2013 The Authors, Addiction Biology © 2013 Society for the Study of Addiction.

  2. Striatal Dopamine Depletion Patterns and Early Non-Motor Burden in Parkinsons Disease.

    Directory of Open Access Journals (Sweden)

    Su Jin Chung

    Full Text Available The mechanism underlying non-motor symptoms in Parkinson's disease has not yet been elucidated. In this study, we hypothesized that Parkinson patients with more non-motor symptoms have a different pattern of striatal dopamine depletion, particularly in areas other than the sensorimotor striatum, compared to those with fewer non-motor symptoms.We conducted a prospective survey of the degree of non-motor symptoms (using the Korean version of the Non-Motor Symptoms Scale; K-NMSS in 151 patients with early-stage Parkinson's disease who had undergone a dopamine transporter PET scan as an initial diagnostic procedure. We classified the patients into two groups; high non-motor patients (HNM-PD; K-NMSS score ≥ 41 and low non-motor patients (LNM-PD.Patients in the HNM-PD group (n = 71 were older, had longer symptom duration, exhibited more severe motor deficits, and had been prescribed higher levodopa-equivalent doses at follow-up than those in the LNM-PD group. However, dopamine transporter binding to the striatal sub-regions and inter-sub-regional binding ratios were comparable between the two groups. A general linear model showed that the HNM-PD group had significantly more severe motor deficits than the LNM-PD group after controlling for age, gender, symptom duration, and dopamine transporter binding to the sensorimotor striatum.This study demonstrated that the pattern of striatal dopamine depletion does not contribute to early non-motor burden in Parkinson's disease. Our results suggest that LNM-PD patients may have a more benign course of motor symptom progression than HNM-PD patients.

  3. Homeostatic regulation of excitatory synapses on striatal medium spiny neurons expressing the D2 dopamine receptor.

    Science.gov (United States)

    Thibault, Dominic; Giguère, Nicolas; Loustalot, Fabien; Bourque, Marie-Josée; Ducrot, Charles; El Mestikawy, Salah; Trudeau, Louis-Éric

    2016-05-01

    Striatal medium spiny neurons (MSNs) are contacted by glutamatergic axon terminals originating from cortex, thalamus and other regions. The striatum is also innervated by dopaminergic (DAergic) terminals, some of which release glutamate as a co-transmitter. Despite evidence for functional DA release at birth in the striatum, the role of DA in the establishment of striatal circuitry is unclear. In light of recent work suggesting activity-dependent homeostatic regulation of glutamatergic terminals on MSNs expressing the D2 DA receptor (D2-MSNs), we used primary co-cultures to test the hypothesis that stimulation of DA and glutamate receptors regulates the homeostasis of glutamatergic synapses on MSNs. Co-culture of D2-MSNs with mesencephalic DA neurons or with cortical neurons produced an increase in spines and functional glutamate synapses expressing VGLUT2 or VGLUT1, respectively. The density of VGLUT2-positive terminals was reduced by the conditional knockout of this gene from DA neurons. In the presence of both mesencephalic and cortical neurons, the density of synapses reached the same total, compatible with the possibility of a homeostatic mechanism capping excitatory synaptic density. Blockade of D2 receptors increased the density of cortical and mesencephalic glutamatergic terminals, without changing MSN spine density or mEPSC frequency. Combined blockade of AMPA and NMDA glutamate receptors increased the density of cortical terminals and decreased that of mesencephalic VGLUT2-positive terminals, with no net change in total excitatory terminal density or in mEPSC frequency. These results suggest that DA and glutamate signaling regulate excitatory inputs to striatal D2-MSNs at both the pre- and postsynaptic level, under the influence of a homeostatic mechanism controlling functional output of the circuit.

  4. Lower levels of uric acid and striatal dopamine in non-tremor dominant Parkinson's disease subtype.

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    Ismael Huertas

    Full Text Available Parkinson's disease (PD patients who present with tremor and maintain a predominance of tremor have a better prognosis. Similarly, PD patients with high levels of uric acid (UA, a natural neuroprotectant, have also a better disease course. Our aim was to investigate whether PD motor subtypes differ in their levels of UA, and if these differences correlate with the degree of dopamine transporter (DAT availability. We included 75 PD patients from whom we collected information about their motor symptoms, DAT imaging and UA concentration levels. Based on the predominance of their motor symptoms, patients were classified into postural instability and gait disorder (PIGD, n = 36, intermediate (I, n = 22, and tremor-dominant (TD, n = 17 subtypes. The levels of UA and striatal DAT were compared across subtypes and the correlation between these two measures was also explored. We found that PIGD patients had lower levels of UA (3.7 vs 4.5 vs 5.3 mg/dL; P<0.001 and striatal DAT than patients with an intermediate or TD phenotype. Furthermore, UA levels significantly correlated with the levels of striatal DAT. We also observed that some PIGD (25% and I (45% patients had a predominance of tremor at disease onset. We speculate that UA might be involved in the maintenance of the less damaging TD phenotype and thus also in the conversion from TD to PIGD. Low levels of this natural antioxidant could lead to a major neuronal damage and therefore influence the conversion to a more severe motor phenotype.

  5. Morphine Reward Promotes Cue-Sensitive Learning: Implication of Dorsal Striatal CREB Activity

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    Mathieu Baudonnat

    2017-05-01

    Full Text Available Different parallel neural circuits interact and may even compete to process and store information: whereas stimulus–response (S–R learning critically depends on the dorsal striatum (DS, spatial memory relies on the hippocampus (HPC. Strikingly, despite its potential importance for our understanding of addictive behaviors, the impact of drug rewards on memory systems dynamics has not been extensively studied. Here, we assessed long-term effects of drug- vs food reinforcement on the subsequent use of S–R vs spatial learning strategies and their neural substrates. Mice were trained in a Y-maze cue-guided task, during which either food or morphine injections into the ventral tegmental area (VTA were used as rewards. Although drug- and food-reinforced mice learned the Y-maze task equally well, drug-reinforced mice exhibited a preferential use of an S–R learning strategy when tested in a water-maze competition task designed to dissociate cue-based and spatial learning. This cognitive bias was associated with a persistent increase in the phosphorylated form of cAMP response element-binding protein phosphorylation (pCREB within the DS, and a decrease of pCREB expression in the HPC. Pharmacological inhibition of striatal PKA pathway in drug-rewarded mice limited the morphine-induced increase in levels of pCREB in DS and restored a balanced use of spatial vs cue-based learning. Our findings suggest that drug (opiate reward biases the engagement of separate memory systems toward a predominant use of the cue-dependent system via an increase in learning-related striatal pCREB activity. Persistent functional imbalance between striatal and hippocampal activity could contribute to the persistence of addictive behaviors, or counteract the efficiency of pharmacological or psychotherapeutic treatments.

  6. Dopaminergic modulation of striatal acetylcholine release in rats depleted of dopamine as neonates.

    Science.gov (United States)

    Johnson, B J; Bruno, J P

    1995-02-01

    A repeated sessions, in vivo microdialysis design was used to determine the D1- and D2-like receptor modulation of striatal ACh efflux in intact adult rats and those depleted of DA on postnatal Day 3. Systemic administration of the D1-like agonist SKF 38393 (1.0 or 10.0 mg/kg, or the D2-like antagonist clebopride (1.0 or 10.0 mg/kg) increased ACh efflux in both controls and DA-depleted animals. Systemic administration of the D1-like antagonist SCH 23390 (0.05 or 0.2 mg/kg) or D2-like agonist quinpirole (0.5 or 1.0 mg/kg) decreased ACh efflux in both groups of animals. DA-depleted animals exhibited a larger response than did controls to the lower doses of these drugs. Intrastriatal administration of clebopride (10 microM) increased ACh efflux in DA-depleted animals. Finally, basal and clebopride-stimulated ACh efflux were unaffected by the repeated microdialysis sessions. These data demonstrate that the reciprocal modulation of striatal ACh efflux, seen in controls and in rats depleted of DA as adults, is also present in adults depleted of DA as neonates. Because the roles of D1- and D2-receptors in the expression of motor behavior differ between rats depleted of DA as adults vs as neonates, these data suggest that alterations in the dopaminergic modulation of striatal ACh release do not underlie the sparing from motoric deficits seen in animals depleted of DA as neonates.

  7. Arc mRNA induction in striatal efferent neurons associated with response learning.

    Science.gov (United States)

    Daberkow, D P; Riedy, M D; Kesner, R P; Keefe, K A

    2007-07-01

    The dorsal striatum is involved in motor-response learning, but the extent to which distinct populations of striatal efferent neurons are differentially involved in such learning is unknown. Activity-regulated, cytoskeleton-associated (Arc) protein is an effector immediate-early gene implicated in synaptic plasticity. We examined arc mRNA expression in striatopallidal vs. striatonigral efferent neurons in dorsomedial and dorsolateral striatum of rats engaged in reversal learning on a T-maze motor-response task. Male Sprague-Dawley rats learned to turn right or left for 3 days. Half of the rats then underwent reversal training. The remaining rats were yoked to rats undergoing reversal training, such that they ran the same number of trials but ran them as continued-acquisition trials. Brains were removed and processed using double-label fluorescent in situ hybridization for arc and preproenkephalin (PPE) mRNA. In the reversal, but not the continued-acquisition, group there was a significant relation between the overall arc mRNA signal in dorsomedial striatum and the number of trials run, with rats reaching criterion in fewer trials having higher levels of arc mRNA expression. A similar relation was seen between the numbers of PPE(+) and PPE(-) neurons in dorsomedial striatum with cytoplasmic arc mRNA expression. Interestingly, in behaviourally activated animals significantly more PPE(-) neurons had cytoplasmic arc mRNA expression. These data suggest that Arc in both striatonigral and striatopallidal efferent neurons is involved in striatal synaptic plasticity mediating motor-response learning in the T-maze and that there is differential processing of arc mRNA in distinct subpopulations of striatal efferent neurons.

  8. Abnormal striatal dopaminergic neurotransmission during rest and task production in spasmodic dysphonia.

    Science.gov (United States)

    Simonyan, Kristina; Berman, Brian D; Herscovitch, Peter; Hallett, Mark

    2013-09-11

    Spasmodic dysphonia is a primary focal dystonia characterized by involuntary spasms in the laryngeal muscles during speech production. The pathophysiology of spasmodic dysphonia is thought to involve structural and functional abnormalities in the basal ganglia-thalamo-cortical circuitry; however, neurochemical correlates underpinning these abnormalities as well as their relations to spasmodic dysphonia symptoms remain unknown. We used positron emission tomography with the radioligand [(11)C]raclopride (RAC) to study striatal dopaminergic neurotransmission at the resting state and during production of symptomatic sentences and asymptomatic finger tapping in spasmodic dysphonia patients. We found that patients, compared to healthy controls, had bilaterally decreased RAC binding potential (BP) to striatal dopamine D2/D3 receptors on average by 29.2%, which was associated with decreased RAC displacement (RAC ΔBP) in the left striatum during symptomatic speaking (group average difference 10.2%), but increased RAC ΔBP in the bilateral striatum during asymptomatic tapping (group average difference 10.1%). Patients with more severe voice symptoms and subclinically longer reaction time to initiate the tapping sequence had greater RAC ΔBP measures, while longer duration of spasmodic dysphonia was associated with a decrease in task-induced RAC ΔBP. Decreased dopaminergic transmission during symptomatic speech production may represent a disorder-specific pathophysiological trait involved in symptom generation, whereas increased dopaminergic function during unaffected task performance may be explained by a compensatory adaptation of the nigrostriatal dopaminergic system possibly due to decreased striatal D2/D3 receptor availability. These changes can be linked to the clinical and subclinical features of spasmodic dysphonia and may represent the neurochemical basis of basal ganglia alterations in this disorder.

  9. Striatal fast-spiking interneurons: from firing patterns to postsynaptic impact

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    Andreas eKlaus

    2011-07-01

    Full Text Available In the striatal microcircuit, fast-spiking (FS interneurons have an important role in mediating inhibition onto neighboring medium spiny (MS projection neurons. In this study, we combined computational modeling with in vitro and in vivo electrophysiological measurements to investigate FS cells in terms of their discharge properties and their synaptic efficacies onto MS neurons. In vivo firing of striatal FS interneurons is characterized by a high firing variability. It is not known, however, if this variability results from the input that FS cells receive, or if it is promoted by the stuttering spike behavior of these neurons. Both our model and measurements in vitro show that FS neurons that exhibit random stuttering discharge in response to steady depolarization, do not show the typical stuttering behavior when they receive fluctuating input. Importantly, our model predicts that electrically coupled FS cells show substantial spike synchronization only when they are in the stuttering regime. Therefore, together with the lack of synchronized firing of striatal FS interneurons that has been reported in vivo, these results suggest that neighboring FS neurons are not in the stuttering regime simultaneously and that in vivo FS firing variability is more likely determined by the input fluctuations. Furthermore, the variability in FS firing is translated to variability in the postsynaptic amplitudes in MS neurons due to the strong synaptic depression of the FS-to-MS synapse. Our results support the idea that these synapses operate over a wide range from strongly depressed to almost fully recovered. The strong inhibitory effects that FS cells can impose on their postsynaptic targets, and the fact that the FS-to-MS synapse model showed substantial depression over extended periods of time might indicate the importance of cooperative effects of multiple presynaptic FS interneurons and the precise orchestration of their activity.

  10. Striatal Activity and Reward Relativity: Neural Signals Encoding Dynamic Outcome Valuation.

    Science.gov (United States)

    Webber, Emily S; Mankin, David E; Cromwell, Howard C

    2016-01-01

    The striatum is a key brain region involved in reward processing. Striatal activity has been linked to encoding reward magnitude and integrating diverse reward outcome information. Recent work has supported the involvement of striatum in the valuation of outcomes. The present work extends this idea by examining striatal activity during dynamic shifts in value that include different levels and directions of magnitude disparity. A novel task was used to produce diverse relative reward effects on a chain of instrumental action. Rats ( Rattus norvegicus ) were trained to respond to cues associated with specific outcomes varying by food pellet magnitude. Animals were exposed to single-outcome sessions followed by mixed-outcome sessions, and neural activity was compared among identical outcome trials from the different behavioral contexts. Results recording striatal activity show that neural responses to different task elements reflect incentive contrast as well as other relative effects that involve generalization between outcomes or possible influences of outcome variety. The activity that was most prevalent was linked to food consumption and post-food consumption periods. Relative encoding was sensitive to magnitude disparity. A within-session analysis showed strong contrast effects that were dependent upon the outcome received in the immediately preceding trial. Significantly higher numbers of responses were found in ventral striatum linked to relative outcome effects. Our results support the idea that relative value can incorporate diverse relationships, including comparisons from specific individual outcomes to general behavioral contexts. The striatum contains these diverse relative processes, possibly enabling both a higher information yield concerning value shifts and a greater behavioral flexibility.

  11. Loss of Balance between Striatal Feedforward Inhibition and Corticostriatal Excitation Leads to Tremor.

    Science.gov (United States)

    Oran, Yael; Bar-Gad, Izhar

    2018-02-14

    Fast-spiking interneurons (FSIs) exert powerful inhibitory control over the striatum and are hypothesized to balance the massive excitatory cortical and thalamic input to this structure. We recorded neuronal activity in the dorsolateral striatum and globus pallidus (GP) concurrently with the detailed movement kinematics of freely behaving female rats before and after selective inhibition of FSI activity using IEM-1460 microinjections. The inhibition led to the appearance of episodic rest tremor in the body part that depended on the somatotopic location of the injection within the striatum. The tremor was accompanied by coherent oscillations in the local field potential (LFP). Individual neuron activity patterns became oscillatory and coherent in the tremor frequency. Striatal neurons, but not GP neurons, displayed additional temporal, nonoscillatory correlations. The subsequent reduction in the corticostriatal input following muscimol injection to the corresponding somatotopic location in the primary motor cortex led to disruption of the tremor and a reduction of the LFP oscillations and individual neuron's phase-locked activity. The breakdown of the normal balance of excitation and inhibition in the striatum has been shown previously to be related to different motor abnormalities. Our results further indicate that the balance between excitatory corticostriatal input and feedforward FSI inhibition is sufficient to break down the striatal decorrelation process and generate oscillations resulting in rest tremor typical of multiple basal ganglia disorders. SIGNIFICANCE STATEMENT Fast-spiking interneurons (FSIs) play a key role in normal striatal processing by exerting powerful inhibitory control over the network. FSI malfunctions have been associated with abnormal processing of information within the striatum that leads to multiple movement disorders. Here, we study the changes in neuronal activity and movement kinematics following selective inhibition of these

  12. Sensory Entrainment Mechanisms in Auditory Perception: Neural Synchronization Cortico-Striatal Activation.

    Science.gov (United States)

    Sameiro-Barbosa, Catia M; Geiser, Eveline

    2016-01-01

    The auditory system displays modulations in sensitivity that can align with the temporal structure of the acoustic environment. This sensory entrainment can facilitate sensory perception and is particularly relevant for audition. Systems neuroscience is slowly uncovering the neural mechanisms underlying the behaviorally observed sensory entrainment effects in the human sensory system. The present article summarizes the prominent behavioral effects of sensory entrainment and reviews our current understanding of the neural basis of sensory entrainment, such as synchronized neural oscillations, and potentially, neural activation in the cortico-striatal system.

  13. Dopaminergic differentiation of human neural stem cells mediated by co-cultured rat striatal brain slices

    DEFF Research Database (Denmark)

    Anwar, Mohammad Raffaqat; Andreasen, Christian Maaløv; Lippert, Solvej Kølvraa

    2008-01-01

    differentiation, we co-cultured cells from a human neural forebrain-derived stem cell line (hNS1) with rat striatal brain slices. In brief, coronal slices of neonatal rat striatum were cultured on semiporous membrane inserts placed in six-well trays overlying monolayers of hNS1 cells. After 12 days of co......Properly committed neural stem cells constitute a promising source of cells for transplantation in Parkinson's disease, but a protocol for controlled dopaminergic differentiation is not yet available. To establish a setting for identification of secreted neural compounds promoting dopaminergic...

  14. Sensory Entrainment Mechanisms in Auditory Perception: Neural Synchronization Cortico-Striatal Activation

    Science.gov (United States)

    Sameiro-Barbosa, Catia M.; Geiser, Eveline

    2016-01-01

    The auditory system displays modulations in sensitivity that can align with the temporal structure of the acoustic environment. This sensory entrainment can facilitate sensory perception and is particularly relevant for audition. Systems neuroscience is slowly uncovering the neural mechanisms underlying the behaviorally observed sensory entrainment effects in the human sensory system. The present article summarizes the prominent behavioral effects of sensory entrainment and reviews our current understanding of the neural basis of sensory entrainment, such as synchronized neural oscillations, and potentially, neural activation in the cortico-striatal system. PMID:27559306

  15. Ventral striatal activity correlates with memory confidence for old- and new-responses in a difficult recognition test.

    Directory of Open Access Journals (Sweden)

    Ulrike Schwarze

    Full Text Available Activity in the ventral striatum has frequently been associated with retrieval success, i.e., it is higher for hits than correct rejections. Based on the prominent role of the ventral striatum in the reward circuit, its activity has been interpreted to reflect the higher subjective value of hits compared to correct rejections in standard recognition tests. This hypothesis was supported by a recent study showing that ventral striatal activity is higher for correct rejections than hits when the value of rejections is increased by external incentives. These findings imply that the striatal response during recognition is context-sensitive and modulated by the adaptive significance of "oldness" or "newness" to the current goals. The present study is based on the idea that not only external incentives, but also other deviations from standard recognition tests which affect the subjective value of specific response types should modulate striatal activity. Therefore, we explored ventral striatal activity in an unusually difficult recognition test that was characterized by low levels of confidence and accuracy. Based on the human uncertainty aversion, in such a recognition context, the subjective value of all high confident decisions is expected to be higher than usual, i.e., also rejecting items with high certainty is deemed rewarding. In an accompanying behavioural experiment, participants rated the pleasantness of each recognition response. As hypothesized, ventral striatal activity correlated in the current unusually difficult recognition test not only with retrieval success, but also with confidence. Moreover, participants indicated that they were more satisfied by higher confidence in addition to perceived oldness of an item. Taken together, the results are in line with the hypothesis that ventral striatal activity during recognition codes the subjective value of different response types that is modulated by the context of the recognition test.

  16. Striatal dopamine D1 and D2 receptors: widespread influences on methamphetamine-induced dopamine and serotonin neurotoxicity.

    Science.gov (United States)

    Gross, Noah B; Duncker, Patrick C; Marshall, John F

    2011-11-01

    Methamphetamine (mAMPH) is an addictive psychostimulant drug that releases monoamines through nonexocytotic mechanisms. In animals, binge mAMPH dosing regimens deplete markers for monoamine nerve terminals, for example, dopamine and serotonin transporters (DAT and SERT), in striatum and cerebral cortex. Although the precise mechanism of mAMPH-induced damage to monoaminergic nerve terminals is uncertain, both dopamine D1 and D2 receptors are known to be important. Systemic administration of dopamine D1 or D2 receptor antagonists to rodents prevents mAMPH-induced damage to striatal dopamine nerve terminals. Because these studies employed systemic antagonist administration, the specific brain regions involved remain to be elucidated. The present study examined the contribution of dopamine D1 and D2 receptors in striatum to mAMPH-induced DAT and SERT neurotoxicities. In this experiment, either the dopamine D1 antagonist, SCH23390, or the dopamine D2 receptor antagonist, sulpiride, was intrastriatally infused during a binge mAMPH regimen. Striatal DAT and cortical, hippocampal, and amygdalar SERT were assessed as markers of mAMPH-induced neurotoxicity 1 week following binge mAMPH administration. Blockade of striatal dopamine D1 or D2 receptors during an otherwise neurotoxic binge mAMPH regimen produced widespread protection against mAMPH-induced striatal DAT loss and cortical, hippocampal, and amygdalar SERT loss. This study demonstrates that (1) dopamine D1 and D2 receptors in striatum, like nigral D1 receptors, are needed for mAMPH-induced striatal DAT reductions, (2) these same receptors are needed for mAMPH-induced SERT loss, and (3) these widespread influences of striatal dopamine receptor antagonists are likely attributable to circuits connecting basal ganglia to thalamus and cortex. Copyright © 2011 Wiley-Liss, Inc.

  17. [Utilization of Occupational Therapy in Children - Results from the KiGGS Basis Survey].

    Science.gov (United States)

    Weber, A; Karch, D; Thyen, U; Rommel, A; Schlack, R; Hölling, H; von Kries, R

    2016-03-01

    A population-based analysis on use of occupational therapy by child's parentally reported health restrictions and socio-demographic determinants is missing. The basis KiGGS survey (2003 to 2006) reports on health in 17 641 children aged 0 to 17 years. The use of occupational therapy in the last 12 months could be ticked as other therapies with a free text field to name occupational therapy or others. Health restrictions potentially relevant for the use of occupational therapy and sociodemographic factors were assessed. The proportion of use of occupational therapy explained by the health restrictions was estimated by the population attributable risk fraction. The average use of occupational therapy for 3 to 13-year-olds was 2.4%. There was no association with the socioeconomic status; Children with immigration background used occupational therapy less often (e. g. age group 3 to 6 years: ORadjusted 0.2 [95-% KI: 0.1-1.0]). The proportion of occupational therapy explainable by the health restrictions considered ranged from 45% (3 to 6 years) to 65% (11 to 13 years). The lower use of occupational therapy in the KiGGS survey compared to health insurance reports may be explained by the ascertainment method. A lower use of occupational therapy related to immigration background matches lower use for physician visits. The causes for the low proportion of explained occupational therapy in young children and the lower use in children with immigration background warrant further research. © Georg Thieme Verlag KG Stuttgart · New York.

  18. Implementation of HACCP system in production of Paški cheese

    Directory of Open Access Journals (Sweden)

    Šime Gligora

    2007-06-01

    Full Text Available Since August 2006 all participants in Republic of Croatia dealing with the food have an obligation to introduce Hazard Analysis of Critical Control Point (HACCP system. Therefore, all producers of dairy products, as well as registered producers of Paški cheese have to implement HACCP system in their facilities. The aim of this work is to describe implementation and use of HACCP system in «Sirena - mala sirana» which is a small-scale cheese factory situated in a place Kolan on the island of Pag. For this reason, EU and Croatian legislative related to HACCP system is firstly described. After that, procedure of certification is presented, as well as prerequisite programsof the system which are the base for successful implementation of the HACCP system. Furthermore, appliance of HACCP in Paški cheese production through system’s documentation is described. Flow diagram is presented, analysis of hazardous and determination of critical control points is described trough defined production processes. Next, control, monitoring and corrective measures for production processes are described. Finally, HACCP plan and Standard Sanitation Operative Procedures (SSOP are presented. Besides that, traceability system and training plan are shown, as well as all required record lists and other documentation for HACCP system. With implementation of the HACCP system in «Sirena» cheese facility, general hygiene was improved as well as hygiene of equipment and personnel. Risk of product contamination is reduced to a minimum level. With effective management of control measures and records, quality of produced Paški cheese was also improved

  19. Hot spot detection for breast cancer in Ki-67 stained slides: image dependent filtering approach

    Science.gov (United States)

    Niazi, M. Khalid Khan; Downs-Kelly, Erinn; Gurcan, Metin N.

    2014-03-01

    We present a new method to detect hot spots from breast cancer slides stained for Ki67 expression. It is common practice to use centroid of a nucleus as a surrogate representation of a cell. This often requires the detection of individual nuclei. Once all the nuclei are detected, the hot spots are detected by clustering the centroids. For large size images, nuclei detection is computationally demanding. Instead of detecting the individual nuclei and treating hot spot detection as a clustering problem, we considered hot spot detection as an image filtering problem where positively stained pixels are used to detect hot spots in breast cancer images. The method first segments the Ki-67 positive pixels using the visually meaningful segmentation (VMS) method that we developed earlier. Then, it automatically generates an image dependent filter to generate a density map from the segmented image. The smoothness of the density image simplifies the detection of local maxima. The number of local maxima directly corresponds to the number of hot spots in the breast cancer image. The method was tested on 23 different regions of interest images extracted from 10 different breast cancer slides stained with Ki67. To determine the intra-reader variability, each image was annotated twice for hot spots by a boardcertified pathologist with a two-week interval in between her two readings. A computer-generated hot spot region was considered a true-positive if it agrees with either one of the two annotation sets provided by the pathologist. While the intra-reader variability was 57%, our proposed method can correctly detect hot spots with 81% precision.

  20. Development of striatal patch/matrix organization in organotypic co-cultures of perinatal striatum, cortex and substantia nigra.

    Science.gov (United States)

    Snyder-Keller, A; Costantini, L C; Graber, D J

    2001-01-01

    Organotypic cultures of fetal or early postnatal striatum were used to assess striatal patch formation and maintenance in the presence or absence of dopaminergic and glutamatergic influences. Vibratome-cut slices of the striatum prepared from embryonic day 19 to postnatal day 4 rat pups were maintained in static culture on clear membrane inserts in Dulbecco's modified Eagle's medium/F12 (1:1) with 20% horse serum. Some were co-cultured with embryonic day 12-16 ventral mesencephalon and/or embryonic day 19 to postnatal day 4 cortex, which produced a dense dopaminergic innervation and a modest cortical innervation. Donors of striatal and cortical tissue were previously injected with bromo-deoxyuridine (BrdU) on embryonic days 13 and 14 in order to label striatal neurons destined to populate the patch compartment of the striatum. Patches of BrdU-immunoreactive cells were maintained in organotypic cultures of late prenatal (embryonic days 20-22) or early postnatal striatum in the absence of nigral dopaminergic or cortical glutamatergic influences. In slices taken from embryonic day 19 fetuses prior to the time of in vivo patch formation, patches were observed to form after 10 days in vitro, in 39% of nigral-striatal co-cultures compared to 6% of striatal slices cultured alone or in the presence of cortex only. Patches of dopaminergic fibers, revealed by tyrosine hydroxylase immunoreactivity, were observed in the majority of nigral-striatal co-cultures. Immunostaining for the AMPA-type glutamate receptor GluR1 revealed a dense patch distribution in nearly all cultures, which developed in embryonic day 19 cultures after at least six days in vitro. These findings indicate that striatal patch/matrix organization is maintained in organotypic culture, and can be induced to form in vitro in striatal slices removed from fetuses prior to the time of in vivo patch formation. Furthermore, dopaminergic innervation from co-cultured pieces of ventral mesencephalon enhances patch

  1. Observations of Young Stellar Objects with Infrared Interferometry: Recent Results from PTI, KI and IOTA

    Science.gov (United States)

    Akeson, Rachel

    Young stellar objects have been one of the favorite targets of infrared interferometers for many years. In this contribution I will briefly review some of the first results and their contributions to the field and then describe some of the recent results from the Keck Interferometer (KI), the Palomar Testbed Interferometer (PTI) and the Infrared-Optical Telescope Array (IOTA). This conference also saw many exciting new results from the VLTI at both near and mid-infrared wavelengths that are covered by other contributions.

  2. Relative validation of the KiGGS Food Frequency Questionnaire among adolescents in Germany

    Directory of Open Access Journals (Sweden)

    Truthmann Julia

    2011-12-01

    Full Text Available Abstract Background The aim of this study was to determine the relative validity of the self-administered Food Frequency Questionnaire (FFQ "What do you eat?", which was used in the German National Health Interview and Examination Survey for Children and Adolescents (KiGGS 2003-2006. Methods The validation was conducted in the EsKiMo Nutrition Module, a subsample of KiGGS. The study population included 1,213 adolescents aged between 12 and 17. A modified diet history interview DISHES (Dietary Interview Software for Health Examination Studies was used as the reference method. In order to compare the food groups, the data assessed with both instruments were aggregated to 40 similar food groups. The statistical analysis included calculating and comparing Spearman's correlation coefficients, calculating the mean difference between both methods, and ranking participants (quartiles according to food group consumption, including weighted kappa coefficients. Correlations were also evaluated for relative body weight and socioeconomic status subgroups. Results In the total study population the Spearman correlation coefficients ranged from 0.22 for pasta/rice to 0.69 for margarine; most values were 0.50 and higher. The mean difference ranged between 1.4% for milk and 100.3% for pasta/rice. The 2.5 percentiles and 97.5 percentiles indicated a wide range of differences. Classifications in the same and adjacent quartile varied between 70.1% for pasta/rice and 90.8% for coffee. For most groups, Cohen's weighted kappa showed values between 0.21 and 0.60. Only for white bread and pasta/rice were values less than 0.20. Most of the 40 food groups showed acceptable to good correlations in all investigated subgroups concerning age, sex, body weight and socio-economic status. Conclusions The KiGGS FFQ showed fair to moderate ranking validity except for pasta/rice and white bread. However, the ability to assess absolute intakes is limited. The correlation coefficients

  3. [Neuroendocrine tumors of digestive system: morphologic spectrum and cell proliferation (Ki67 index)].

    Science.gov (United States)

    Delektorskaia, V V; Kushliskiĭ, N E

    2013-01-01

    This review deals with the analysis of up-to-date concepts ofdiferent types of human neuroendocrine tumors of the digestive system. It summarizes the information on the specifics of recent histological classifications and criteria of morphological diagnosis accounting histological, ultrastructural and immunohistochemical parameters. Current issues of the nomenclature as well as various systems of grading and staging are discussed. In the light of these criteria the results of the own research clinical value of the determination of cell proliferation in primary and metastatic gastroenteropancreatic neuroendocrine neoplasms on the basis of evaluation of the Ki67 antigen expression are also presented.

  4. Prognostic significance of MCM2, Ki-67 and gelsolin in non-small cell lung cancer

    International Nuclear Information System (INIS)

    Yang, Jun; Tan, Dongfeng; Ramnath, Nithya; Moysich, Kirsten B; Asch, Harold L; Swede, Helen; Alrawi, Sadir J; Huberman, Joel; Geradts, Joseph; Brooks, John SJ

    2006-01-01

    Uncontrolled proliferation and increased motility are hallmarks of neoplastic cells, therefore markers of proliferation and motility may be valuable in assessing tumor progression and prognosis. MCM2 is a member of the minichromosome maintenance (MCM) protein family. It plays critical roles in the initiation of DNA replication and in replication fork movement, and is intimately related to cell proliferation. Ki-67 is a proliferation antigen that is expressed during all but G 0 phases of the cell cycle. Gelsolin is an actin-binding protein that regulates the integrity of the actin cytoskeletal structure and facilitates cell motility. In this study, we assessed the prognostic significance of MCM2 and Ki-67, two markers of proliferation, and gelsolin, a marker of motility, in non-small cell lung cancer (NSCLC). 128 patients with pathologically confirmed, resectable NSCLC (stage I-IIIA) were included. Immunohistochemistry was utilized to measure the expressions of these markers in formalin-fixed, paraffin-embedded tumor tissues. Staining and scoring of MCM2, Ki-67 and gelsolin was independently performed. Analyses were performed to evaluate the prognostic significance of single expression of each marker, as well as the prognostic significance of composite expressions of MCM2 and gelsolin. Cox regression and Kaplan-Meier survival analysis were used for statistical analysis. Of the three markers, higher levels of gelsolin were significantly associated with an increased risk of death (adjusted RR = 1.89, 95% CI = 1.17–3.05, p = 0.01), and higher levels of MCM2 were associated with a non-significant increased risk of death (adjusted RR = 1.36, 95% CI = 0.84–2.20, p = 0.22). Combined, adjusted analyses revealed a significantly poor prognostic effect for higher expression of MCM2 and gelsolin compared to low expression of both biomarkers (RR = 2.32, 95% CI = 1.21–4.45, p = 0.01). Ki-67 did not display apparent prognostic effect in this study sample. The results suggest

  5. Macrophytic flora and vegetation of the rivers Svrljiški and Beli Timok (Eastern Serbia

    Directory of Open Access Journals (Sweden)

    Jenačković, D.

    2010-12-01

    Full Text Available Floristic and phytocoenological investigations of macrophytic vegetation of the rivers Svrljiški and Beli Timok in Eastern Serbia were performed. Analysis of the collected plants showed that the hydrophilous flora contains 26 species from 17 families and 21 genuses. Phytocoenological analysis showed 5 different associations from 3 alliances, 3 orders and 3 classis. Aquatic vegetation is represented by the associations Myriophyllo-Potametum and Potametum nodosi, moor vegetation by associations Scirpetum lacustris and Sparganietum erecti, while nitrophilous vegetation is represented by association Polygono-Bidentetum tripartitae. These associations have formed three clear vegetation belts: submerged, floating and emerged vegetation.

  6. Relative validation of the KiGGS Food Frequency Questionnaire among adolescents in Germany

    Science.gov (United States)

    2011-01-01

    Background The aim of this study was to determine the relative validity of the self-administered Food Frequency Questionnaire (FFQ) "What do you eat?", which was used in the German National Health Interview and Examination Survey for Children and Adolescents (KiGGS 2003-2006). Methods The validation was conducted in the EsKiMo Nutrition Module, a subsample of KiGGS. The study population included 1,213 adolescents aged between 12 and 17. A modified diet history interview DISHES (Dietary Interview Software for Health Examination Studies) was used as the reference method. In order to compare the food groups, the data assessed with both instruments were aggregated to 40 similar food groups. The statistical analysis included calculating and comparing Spearman's correlation coefficients, calculating the mean difference between both methods, and ranking participants (quartiles) according to food group consumption, including weighted kappa coefficients. Correlations were also evaluated for relative body weight and socioeconomic status subgroups. Results In the total study population the Spearman correlation coefficients ranged from 0.22 for pasta/rice to 0.69 for margarine; most values were 0.50 and higher. The mean difference ranged between 1.4% for milk and 100.3% for pasta/rice. The 2.5 percentiles and 97.5 percentiles indicated a wide range of differences. Classifications in the same and adjacent quartile varied between 70.1% for pasta/rice and 90.8% for coffee. For most groups, Cohen's weighted kappa showed values between 0.21 and 0.60. Only for white bread and pasta/rice were values less than 0.20. Most of the 40 food groups showed acceptable to good correlations in all investigated subgroups concerning age, sex, body weight and socio-economic status. Conclusions The KiGGS FFQ showed fair to moderate ranking validity except for pasta/rice and white bread. However, the ability to assess absolute intakes is limited. The correlation coefficients for most food items were

  7. Proliferation assessment in breast carcinomas using digital image analysis based on virtual Ki67/cytokeratin double staining.

    Science.gov (United States)

    Røge, Rasmus; Riber-Hansen, Rikke; Nielsen, Søren; Vyberg, Mogens

    2016-07-01

    Manual estimation of Ki67 Proliferation Index (PI) in breast carcinoma classification is labor intensive and prone to intra- and interobserver variation. Standard Digital Image Analysis (DIA) has limitations due to issues with tumor cell identification. Recently, a computer algorithm, DIA based on Virtual Double Staining (VDS), segmenting Ki67-positive and -negative tumor cells using digitally fused parallel cytokeratin (CK) and Ki67-stained slides has been introduced. In this study, we compare VDS with manual stereological counting of Ki67-positive and -negative cells and examine the impact of the physical distance of the parallel slides on the alignment of slides. TMAs, containing 140 cores of consecutively obtained breast carcinomas, were stained for CK and Ki67 using optimized staining protocols. By means of stereological principles, Ki67-positive and -negative cell profiles were counted in sampled areas and used for the estimation of PIs of the whole tissue core. The VDS principle was applied to both the same sampled areas and the whole tissue core. Additionally, five neighboring slides were stained for CK in order to examine the alignment algorithm. Correlation between manual counting and VDS in both sampled areas and whole core was almost perfect (correlation coefficients above 0.97). Bland-Altman plots did not reveal any skewness in any data ranges. There was a good agreement in alignment (>85 %) in neighboring slides, whereas agreement decreased in non-neighboring slides. VDS gave similar results compared with manual counting using stereological principles. Introduction of this method in clinical and research practice may improve accuracy and reproducibility of Ki67 PI.

  8. Interobserver reproducibility and accuracy of p16/Ki-67 dual-stain cytology in cervical cancer screening.

    Science.gov (United States)

    Wentzensen, Nicolas; Fetterman, Barbara; Tokugawa, Diane; Schiffman, Mark; Castle, Philip E; Wood, Shannon N; Stiemerling, Eric; Poitras, Nancy; Lorey, Thomas; Kinney, Walter

    2014-12-01

    Dual-stain cytology for p16 and Ki-67 has been proposed as a biomarker in cervical cancer screening. The authors evaluated the reproducibility and accuracy of dual-stain cytology among 10 newly trained evaluators. In total, 480 p16/Ki-67-stained slides from human papillomavirus-positive women were evaluated in masked fashion by 10 evaluators. None of the evaluators had previous experience with p16 or p16/Ki-67 cytology. All participants underwent p16/Ki-67 training and subsequent proficiency testing. Reproducibility of dual-stain cytology was measured using the percentage agreement, individual and aggregate κ values, as well as McNemar statistics. Clinical performance for the detection of cervical intraepithelial neoplasia grade 2 or greater (CIN2+) was evaluated for each individual evaluator and for all evaluators combined compared with the reference evaluation by a cytotechnologist who had extensive experience with dual-stain cytology. The percentage agreement of individual evaluators with the reference evaluation ranged from 83% to 91%, and the κ values ranged from 0.65 to 0.81. The combined κ value was 0.71 for all evaluators and 0.73 for cytotechnologists. The average sensitivity and specificity for the detection of CIN2+ among novice evaluators was 82% and 64%, respectively; whereas the reference evaluation had 84% sensitivity and 63% specificity, respectively. Agreement on dual-stain positivity increased with greater numbers of p16/Ki-67-positive cells on the slides. Good to excellent reproducibility of p16/Ki-67 dual-stain cytology was observed with almost identical clinical performance of novice evaluators compared with reference evaluations. The current findings suggest that p16/Ki-67 dual-stain evaluation can be implemented in routine cytology practice with limited training. © 2014 American Cancer Society.

  9. Optogenetic approaches to evaluate striatal function in animal models of Parkinson disease.

    Science.gov (United States)

    Parker, Krystal L; Kim, Youngcho; Alberico, Stephanie L; Emmons, Eric B; Narayanan, Nandakumar S

    2016-03-01

    Optogenetics refers to the ability to control cells that have been genetically modified to express light-sensitive ion channels. The introduction of optogenetic approaches has facilitated the dissection of neural circuits. Optogenetics allows for the precise stimulation and inhibition of specific sets of neurons and their projections with fine temporal specificity. These techniques are ideally suited to investigating neural circuitry underlying motor and cognitive dysfunction in animal models of human disease. Here, we focus on how optogenetics has been used over the last decade to probe striatal circuits that are involved in Parkinson disease, a neurodegenerative condition involving motor and cognitive abnormalities resulting from degeneration of midbrain dopaminergic neurons. The precise mechanisms underlying the striatal contribution to both cognitive and motor dysfunction in Parkinson disease are unknown. Although optogenetic approaches are somewhat removed from clinical use, insight from these studies can help identify novel therapeutic targets and may inspire new treatments for Parkinson disease. Elucidating how neuronal and behavioral functions are influenced and potentially rescued by optogenetic manipulation in animal models could prove to be translatable to humans. These insights can be used to guide future brain-stimulation approaches for motor and cognitive abnormalities in Parkinson disease and other neuropsychiatric diseases.

  10. Fast oscillations in cortical-striatal networks switch frequency following rewarding events and stimulant drugs.

    Science.gov (United States)

    Berke, J D

    2009-09-01

    Oscillations may organize communication between components of large-scale brain networks. Although gamma-band oscillations have been repeatedly observed in cortical-basal ganglia circuits, their functional roles are not yet clear. Here I show that, in behaving rats, distinct frequencies of ventral striatal local field potential oscillations show coherence with different cortical inputs. The approximately 50 Hz gamma oscillations that normally predominate in awake ventral striatum are coherent with piriform cortex, whereas approximately 80-100 Hz high-gamma oscillations are coherent with frontal cortex. Within striatum, entrainment to gamma rhythms is selective to fast-spiking interneurons, with distinct fast-spiking interneuron populations entrained to different gamma frequencies. Administration of the psychomotor stimulant amphetamine or the dopamine agonist apomorphine causes a prolonged decrease in approximately 50 Hz power and increase in approximately 80-100 Hz power. The same frequency switch is observed for shorter epochs spontaneously in awake, undrugged animals and is consistently provoked for reward receipt. Individual striatal neurons can participate in these brief high-gamma bursts with, or without, substantial changes in firing rate. Switching between discrete oscillatory states may allow different modes of information processing during decision-making and reinforcement-based learning, and may also be an important systems-level process by which stimulant drugs affect cognition and behavior.

  11. Interaction of structural analogs of dopamine, chlorpromazine and sulpiride with striatal dopamine receptors

    International Nuclear Information System (INIS)

    Wallace, R.A.

    1987-01-01

    The objectives of these studies were to determine if the nitrogen atom of dopaminergic agonists and antagonists drugs is required for interaction with the D-1 and D-2 dopamine receptors and whether the positively charged or uncharged molecular species interacts with these receptors. To address these issues, permanently charged analogs of dopamine, chlorpromazine and sulpiride were synthesized in which a dimethylsulfonium, dimethylselenonium or quaternary ammonium group replaced the amine group. Permanently uncharged analogs which contained a methylsulfide, methylselenide and sulfoxide group instead of an amine group were also synthesized. The interactions of these compounds with striatal dopamine receptors were studied. We found that the permanently charged dopamine analogs bound to the D-2 receptor of striatal membranes like conventional dopaminergic agonists and displayed agonist activity at the D-2 receptor regulating potassium-evoked [ 3 H] acetylcholine release. In contrast, the permanently uncharged analogs bound only to the high affinity state of the D-2 receptor and had neither agonist or antagonist activity

  12. Selective updating of working memory content modulates meso-cortico-striatal activity.

    Science.gov (United States)

    Murty, Vishnu P; Sambataro, Fabio; Radulescu, Eugenia; Altamura, Mario; Iudicello, Jennifer; Zoltick, Bradley; Weinberger, Daniel R; Goldberg, Terry E; Mattay, Venkata S

    2011-08-01

    Accumulating evidence from non-human primates and computational modeling suggests that dopaminergic signals arising from the midbrain (substantia nigra/ventral tegmental area) mediate striatal gating of the prefrontal cortex during the selective updating of working memory. Using event-related functional magnetic resonance imaging, we explored the neural mechanisms underlying the selective updating of information stored in working memory. Participants were scanned during a novel working memory task that parses the neurophysiology underlying working memory maintenance, overwriting, and selective updating. Analyses revealed a functionally coupled network consisting of a midbrain region encompassing the substantia nigra/ventral tegmental area, caudate, and dorsolateral prefrontal cortex that was selectively engaged during working memory updating compared to the overwriting and maintenance of working memory content. Further analysis revealed differential midbrain-dorsolateral prefrontal interactions during selective updating between low-performing and high-performing individuals. These findings highlight the role of this meso-cortico-striatal circuitry during the selective updating of working memory in humans, which complements previous research in behavioral neuroscience and computational modeling. Published by Elsevier Inc.

  13. Abnormal Striatal BOLD Responses to Reward Anticipation and Reward Delivery in ADHD

    Science.gov (United States)

    Furukawa, Emi; Bado, Patricia; Tripp, Gail; Mattos, Paulo; Wickens, Jeff R.; Bramati, Ivanei E.; Alsop, Brent; Ferreira, Fernanda Meireles; Lima, Debora; Tovar-Moll, Fernanda; Sergeant, Joseph A.; Moll, Jorge

    2014-01-01

    Altered reward processing has been proposed to contribute to the symptoms of attention deficit hyperactivity disorder (ADHD). The neurobiological mechanism underlying this alteration remains unclear. We hypothesize that the transfer of dopamine release from reward to reward-predicting cues, as normally observed in animal studies, may be deficient in ADHD. Functional magnetic resonance imaging (fMRI) was used to investigate striatal responses to reward-predicting cues and reward delivery in a classical conditioning paradigm. Data from 14 high-functioning and stimulant-naïve young adults with elevated lifetime symptoms of ADHD (8 males, 6 females) and 15 well-matched controls (8 males, 7 females) were included in the analyses. During reward anticipation, increased blood-oxygen-level-dependent (BOLD) responses in the right ventral and left dorsal striatum were observed in controls, but not in the ADHD group. The opposite pattern was observed in response to reward delivery; the ADHD group demonstrated significantly greater BOLD responses in the ventral striatum bilaterally and the left dorsal striatum relative to controls. In the ADHD group, the number of current hyperactivity/impulsivity symptoms was inversely related to ventral striatal responses during reward anticipation and positively associated with responses to reward. The BOLD response patterns observed in the striatum are consistent with impaired predictive dopamine signaling in ADHD, which may explain altered reward-contingent behaviors and symptoms of ADHD. PMID:24586543

  14. Atrophy of reward-related striatal structures in fatigued MS patients is independent of physical disability.

    Science.gov (United States)

    Damasceno, Alfredo; Damasceno, Benito Pereira; Cendes, Fernando

    2016-05-01

    MRI studies have shown gray-matter abnormalities in fatigued multiple sclerosis (MS) patients. However, given that physical disability is highly correlated to MS fatigue, it is often difficult to disentangle its effect in these MRI findings. The objective of this research paper is to investigate gray-matter damage in mildly disabled MS patients, addressing which variables were better related to fatigue while controlling for physical disability and depression. Forty-nine relapsing-remitting MS (RRMS) patients and 30 controls underwent MRI (3T). Fatigue was assessed using the Fatigue Severity Scale (FSS). Multivariate logistic regression was performed to assess the contribution of clinical and MRI metrics to fatigue. Statistical analyses were performed controlling for disability and depression. Fatigue was present in 22 (44.9%) patients. FSS score was highly correlated with EDSS (p = 0.00001). Patients with fatigue had lower brain cortical and subcortical gray-matter volumes. However, after controlling for EDSS, only the caudate and the accumbens volumes remained statistically significant. Fatigued MS patients have a global cortical and subcortical gray-matter atrophy that seems largely related to higher physical disability. However, striatal structures involved in effort-reward functions exhibited smaller volumes in fatigued patients, independently of physical disability and depressive symptoms, supporting the theory of cortico-striatal network impairment in MS fatigue. © The Author(s), 2015.

  15. Effects of caffeine on striatal neurotransmission: focus on cannabinoid CB1 receptors.

    Science.gov (United States)

    Rossi, Silvia; De Chiara, Valentina; Musella, Alessandra; Mataluni, Giorgia; Sacchetti, Lucia; Siracusano, Alberto; Bernardi, Giorgio; Usiello, Alessandro; Centonze, Diego

    2010-04-01

    Caffeine is the most commonly self-administered psychoactive substance worldwide. At usual doses, the effects of caffeine on vigilance, attention, mood and arousal largely depend on the modulation of central adenosine receptors. The present review article describes the action of caffeine within the striatum, to provide a possible molecular mechanism at the basis of the psychomotor and reinforcing properties of this pharmacological agent. The striatum is in fact a subcortical area involved in sensorimotor, cognitive, and emotional processes, and recent experimental findings showed that chronic caffeine consumption enhances the sensitivity of striatal GABAergic synapses to the stimulation of cannabinoid CB1 receptors. The endocannabinoid system is involved in the psychoactive effects of many compounds, and adenosine A2A receptors (the main receptor target of caffeine) elicit a permissive effect towards CB1 receptors, thus suggesting that A2A-CB1 receptor interaction plays a major role in the generation and maintenance of caffeine reinforcing behavior. Aim of this review is to describe the effects of caffeine on striatal neurotransmission with special reference to the modulation of the endocannabinoid system.

  16. Decreased striatal D2 receptor density associated with severe behavioral abnormality in Alzheimer's disease

    International Nuclear Information System (INIS)

    Tanaka, Yasuhiro; Meguro, Kenichi; Yamaguchi, Satoshi

    2003-01-01

    Since patients manifesting behavioral and psychological symptoms of dementia (BPSD) are a burden for their families and caregivers, the underlying neurobiological mechanism of this condition should be clarified. Using positron emission tomography (PET), we previously reported that wandering behavior in dementia was associated with a disturbed dopaminergic neuron system. We herein investigated the relationship between the severity of BPSD and the striatal D 2 receptor density in Alzheimer's disease (AD). Ten patients with probable AD as per the National Institute of Neurological and Communicative Disorders and Stroke (NINCDS) and the AD and Related Disorders Association (ADRDA) criteria and five normal subjects were examined with PET. The tracer used was [ 11 C]raclopride (D 2 antagonist). The uptake of [ 11 C]raclopride was calculated as the estimation of binding potential (BP) of the striatum to the cerebellum. The AD patients were institutionalized in multiple nursing homes, and their BPSD were evaluated by the Behavioral Pathology in AD Frequency Weighted Severity Scale (BEHAVE-AD-FW) scale (Reisberg). There was a significant inverse Spearman's correlation between BEHAVE-AD-FW score and the BP, especially between the score of the behavioral domain and the BP values. The BP was found to be lower in severer BPSD patients. Patients with AD who manifest severe BPSD may have some dysfunction of striatal dopamine metabolism compared with those without BPSD. (author)

  17. KV7 Channels Regulate Firing during Synaptic Integration in GABAergic Striatal Neurons

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    M. Belén Pérez-Ramírez

    2015-01-01

    Full Text Available Striatal projection neurons (SPNs process motor and cognitive information. Their activity is affected by Parkinson’s disease, in which dopamine concentration is decreased and acetylcholine concentration is increased. Acetylcholine activates muscarinic receptors in SPNs. Its main source is the cholinergic interneuron that responds with a briefer latency than SPNs during a cortical command. Therefore, an important question is whether muscarinic G-protein coupled receptors and their signaling cascades are fast enough to intervene during synaptic responses to regulate synaptic integration and firing. One of the most known voltage dependent channels regulated by muscarinic receptors is the KV7/KCNQ channel. It is not known whether these channels regulate the integration of suprathreshold corticostriatal responses. Here, we study the impact of cholinergic muscarinic modulation on the synaptic response of SPNs by regulating KV7 channels. We found that KV7 channels regulate corticostriatal synaptic integration and that this modulation occurs in the dendritic/spines compartment. In contrast, it is negligible in the somatic compartment. This modulation occurs on sub- and suprathreshold responses and lasts during the whole duration of the responses, hundreds of milliseconds, greatly altering SPNs firing properties. This modulation affected the behavior of the striatal microcircuit.

  18. Impulsivity in Parkinson’s Disease Is Associated With Alterations in Affective and Sensorimotor Striatal Networks

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    Marit F. L. Ruitenberg

    2018-04-01

    Full Text Available A subset of patients with Parkinson’s disease (PD experiences problems with impulse control, characterized by a loss of voluntary control over impulses, drives, or temptations regarding excessive hedonic behavior. The present study aimed to better understand the neural basis of such impulse control disorders (ICDs in PD. We collected resting-state functional connectivity and structural MRI data from 21 PD patients with ICDs and 30 patients without such disorders. To assess impulsivity, all patients completed the Barratt Impulsiveness Scale and performed an information-gathering task. MRI results demonstrated substantial differences in neural characteristics between PD patients with and without ICDs. Results showed that impulsivity was linked to alterations in affective basal ganglia circuitries. Specifically, reduced frontal–striatal connectivity and GPe volume were associated with more impulsivity. We suggest that these changes affect decision making and result in a preference for risky or inappropriate actions. Results further showed that impulsivity was linked to alterations in sensorimotor striatal networks. Enhanced connectivity within this network and larger putamen volume were associated with more impulsivity. We propose that these changes affect sensorimotor processing such that patients have a greater propensity to act. Our findings suggest that the two mechanisms jointly contribute to impulsive behaviors in PD.

  19. Levodopa administration modulates striatal processing of punishment-associated items in healthy participants.

    Science.gov (United States)

    Wittmann, Bianca C; D'Esposito, Mark

    2015-01-01

    Appetitive and aversive processes share a number of features such as their relevance for action and learning. On a neural level, reward and its predictors are associated with increased firing of dopaminergic neurons, whereas punishment processing has been linked to the serotonergic system and to decreases in dopamine transmission. Recent data indicate, however, that the dopaminergic system also responds to aversive stimuli and associated actions. In this pharmacological functional magnetic resonance imaging study, we investigated the contribution of the dopaminergic system to reward and punishment processing in humans. Two groups of participants received either placebo or the dopamine precursor levodopa and were scanned during alternating reward and punishment anticipation blocks. Levodopa administration increased striatal activations for cues presented in punishment blocks. In an interaction with individual personality scores, levodopa also enhanced striatal activation for punishment-predictive compared with neutral cues in participants scoring higher on the novelty-seeking dimension. These data support recent indications that dopamine contributes to punishment processing and suggest that the novelty-seeking trait is a measure of susceptibility to drug effects on motivation. These findings are also consistent with the possibility of an inverted U-shaped response function of dopamine in the striatum, suggesting an optimal level of dopamine release for motivational processing.

  20. Episodic Memory Encoding Interferes with Reward Learning and Decreases Striatal Prediction Errors

    Science.gov (United States)

    Braun, Erin Kendall; Daw, Nathaniel D.

    2014-01-01

    Learning is essential for adaptive decision making. The striatum and its dopaminergic inputs are known to support incremental reward-based learning, while the hippocampus is known to support encoding of single events (episodic memory). Although traditionally studied separately, in even simple experiences, these two types of learning are likely to co-occur and may interact. Here we sought to understand the nature of this interaction by examining how incremental reward learning is related to concurrent episodic memory encoding. During the experiment, human participants made choices between two options (colored squares), each associated with a drifting probability of reward, with the goal of earning as much money as possible. Incidental, trial-unique object pictures, unrelated to the choice, were overlaid on each option. The next day, participants were given a surprise memory test for these pictures. We found that better episodic memory was related to a decreased influence of recent reward experience on choice, both within and across participants. fMRI analyses further revealed that during learning the canonical striatal reward prediction error signal was significantly weaker when episodic memory was stronger. This decrease in reward prediction error signals in the striatum was associated with enhanced functional connectivity between the hippocampus and striatum at the time of choice. Our results suggest a mechanism by which memory encoding may compete for striatal processing and provide insight into how interactions between different forms of learning guide reward-based decision making. PMID:25378157

  1. Phasic dopamine release drives rapid activation of striatal D2-receptors

    Science.gov (United States)

    Marcott, Pamela F; Mamaligas, Aphroditi A; Ford, Christopher P

    2014-01-01

    Summary Striatal dopamine transmission underlies numerous goal-directed behaviors. Medium spiny neurons (MSNs) are a major target of dopamine in the striatum. However, as dopamine does not directly evoke a synaptic event in MSNs, the time course of dopamine signaling in these cells remains unclear. To examine how dopamine release activates D2-receptors on MSNs, G-protein activated inwardly rectifying potassium (GIRK2; Kir 3.2) channels were virally overexpressed in the striatum and the resulting outward currents were used as a sensor of D2-receptor activation. Electrical and optogenetic stimulation of dopamine terminals evoked robust D2-receptor inhibitory post-synaptic currents (IPSCs) in GIRK2-expressing MSNs that occurred in under a second. Evoked D2-IPSCs could be driven by repetitive stimulation and were not occluded by background dopamine tone. Together, the results indicate that D2-receptors on MSNs exhibit functional low affinity and suggest that striatal D2-receptors can encode both tonic and phasic dopamine signals. PMID:25242218

  2. Modulation of acetylcholine release from rat striatal slices by the GABA/benzodiazepine receptor complex

    Energy Technology Data Exchange (ETDEWEB)

    Supavilai, P.; Karobath, M.

    1985-02-04

    GABA, THIP and muscimol enhance spontaneous and inhibit electrically induced release of tritium labelled compounds from rat striatal slices which have been pre-labelled with /sup 3/H-choline. Baclofen is inactive in this model. Muscimol can inhibit electrically induced release of tritiated material by approximately 75% with half maximal effects at 2 ..mu..M. The response to muscimol can be blocked by the GABA antagonists bicuculline methobromide, picrotoxin, anisatin, R 5135 and CPTBO (cyclopentylbicyclophosphate). Drugs which act on the benzodiazepine receptor (BR) require the presence of muscimol to be effective and they modulate the effects of muscimol in a bidirectional manner. Thus BR agonists enhance and inverse BR agonists attenuate the inhibitory effects of muscimol on electrically induced release. Ro15-1788, a BR antagonist, does not modulate the inhibitory effects of muscimol but antagonizes the actions of clonazepam, a BR agonist, and of DMCM, an inverse BR agonist. These results demonstrate that a GABA/benzodiazepine receptor complex can modulate acetylcholine release from rat striatal slices in vitro. 24 references, 3 figures, 5 table.

  3. Altered cingulo-striatal function underlies reward drive deficits in schizophrenia.

    Science.gov (United States)

    Park, Il Ho; Chun, Ji Won; Park, Hae-Jeong; Koo, Min-Seong; Park, Sunyoung; Kim, Seok-Hyeong; Kim, Jae-Jin

    2015-02-01

    Amotivation in schizophrenia is assumed to involve dysfunctional dopaminergic signaling of reward prediction or anticipation. It is unclear, however, whether the translation of neural representation of reward value to behavioral drive is affected in schizophrenia. In order to examine how abnormal neural processing of response valuation and initiation affects incentive motivation in schizophrenia, we conducted functional MRI using a deterministic reinforcement learning task with variable intervals of contingency reversals in 20 clinically stable patients with schizophrenia and 20 healthy controls. Behaviorally, the advantage of positive over negative reinforcer in reinforcement-related responsiveness was not observed in patients. Patients showed altered response valuation and initiation-related striatal activity and deficient rostro-ventral anterior cingulate cortex activation during reward approach initiation. Among these neural abnormalities, rostro-ventral anterior cingulate cortex activation was correlated with positive reinforcement-related responsiveness in controls and social anhedonia and social amotivation subdomain scores in patients. Our findings indicate that the central role of the anterior cingulate cortex is in translating action value into driving force of action, and underscore the role of the cingulo-striatal network in amotivation in schizophrenia. Copyright © 2014 Elsevier B.V. All rights reserved.

  4. Interaction between striatal volume and DAT1 polymorphism predicts working memory development during adolescence

    Directory of Open Access Journals (Sweden)

    F. Nemmi

    2018-04-01

    Full Text Available There is considerable inter-individual variability in the rate at which working memory (WM develops during childhood and adolescence, but the neural and genetic basis for these differences are poorly understood. Dopamine-related genes, striatal activation and morphology have been associated with increased WM capacity after training. Here we tested the hypothesis that these factors would also explain some of the inter-individual differences in the rate of WM development.We measured WM performance in 487 healthy subjects twice: at age 14 and 19. At age 14 subjects underwent a structural MRI scan, and genotyping of five single nucleotide polymorphisms (SNPs in or close to the dopamine genes DRD2, DAT-1 and COMT, which have previously been associated with gains in WM after WM training. We then analyzed which biological factors predicted the rate of increase in WM between ages 14 and 19.We found a significant interaction between putamen size and DAT1/SLC6A3 rs40184 polymorphism, such that TC heterozygotes with a larger putamen at age 14 showed greater WM improvement at age 19.The effect of the DAT1 polymorphism on WM development was exerted in interaction with striatal morphology. These results suggest that development of WM partially share neuro-physiological mechanism with training-induced plasticity. Keywords: Working memory, Development, Dopamine, Striatum, DAT-1, rs40184

  5. Emotion-induced loss aversion and striatal-amygdala coupling in low-anxious individuals.

    Science.gov (United States)

    Charpentier, Caroline J; De Martino, Benedetto; Sim, Alena L; Sharot, Tali; Roiser, Jonathan P

    2016-04-01

    Adapting behavior to changes in the environment is a crucial ability for survival but such adaptation varies widely across individuals. Here, we asked how humans alter their economic decision-making in response to emotional cues, and whether this is related to trait anxiety. Developing an emotional decision-making task for functional magnetic resonance imaging, in which gambling decisions were preceded by emotional and non-emotional primes, we assessed emotional influences on loss aversion, the tendency to overweigh potential monetary losses relative to gains. Our behavioral results revealed that only low-anxious individuals exhibited increased loss aversion under emotional conditions. This emotional modulation of decision-making was accompanied by a corresponding emotion-elicited increase in amygdala-striatal functional connectivity, which correlated with the behavioral effect across participants. Consistent with prior reports of 'neural loss aversion', both amygdala and ventral striatum tracked losses more strongly than gains, and amygdala loss aversion signals were exaggerated by emotion, suggesting a potential role for this structure in integrating value and emotion cues. Increased loss aversion and striatal-amygdala coupling induced by emotional cues may reflect the engagement of adaptive harm-avoidance mechanisms in low-anxious individuals, possibly promoting resilience to psychopathology. © The Author (2015). Published by Oxford University Press.

  6. Regulation of GABA and benzodiazepine receptors following neurotoxin-induced striatal and medial forebrain bundle lesions

    International Nuclear Information System (INIS)

    Pan, H.S.I.

    1985-01-01

    GABA, a major inhibitory transmitter, is used by many projection neurons of the striatum. To investigate the role of GABA in striatal function, the GABA receptor complex was studied after lesions of the striatum or the nigrostriatal neurons. Quantitative receptor autoradiography using thaw-mounted tissue slices was developed for the study of GABA and benzodiazepine (BDZ) receptors. With the technique established, binding to GABA and BDZ receptors after unilateral striatal kainate lesions was examined. Subsequently, changes in GABA and BDZ receptors were studied following the destruction of dopaminergic nigrostriatal cells by unilateral 6-hydroxydopamine lesion of the medial forebrain bundle. In summary, quantitative receptor autoradiography allowed the detection of GABA and BDZ receptor changes in multiple small areas in each lesioned brain. This technique made it feasible to carry out kinetic saturation, and competition studies using less than 1 mg of tissue. The data suggest that dopamine is functionally inhibitory on striatopallidal neurons but is functionally excitatory on striatoentopeduncular and striatonigral cells which in turn inhibit the thalamus. This quantitative autoradiographic technique can be generalized to study other transmitter receptors and can be combined with 2-deoxyglucose uptake studies

  7. Effects of isomers of apomorphines on dopamine receptors in striatal and limbic tissue of rat brain

    Energy Technology Data Exchange (ETDEWEB)

    Kula, N.S.; Baldessarini, R.J.; Bromley, S.; Neumeyer, J.L.

    1985-09-16

    The optical isomers of apomorphine (APO) and N-propylnorapomorphine (NPA) were interacted with three biochemical indices of dopamine (Da) receptors in extrapyramidal and limbic preparations of rat brain tissues. There were consistent isomeric preferences for the R(-) configuration of both DA analogs in stimulation adenylate cyclase (D-1 sites) and in competing for high affinity binding of /sup 3/H-spiroperidol (D-2 sites) and of /sup 3/H-ADTN (DA agonist binding sites) in striatal tissue, with lesser isomeric differences in the limbic tissue. The S(+) apomorphines did not inhibit stimulation of adenylate cyclase by DA. The tendency for greater activity of higher apparent affinity of R(-) apomorphines in striatum may reflect the evidently greater abundance of receptor sites in that region. There were only small regional differences in interactions of the apomorphine isomers with all three receptor sites, except for a strong preference of (-)NPA for striatal D-2 sites. These results do not parallel our recent observations indicating potent and selective antidopaminergic actions of S(+) apomorphines in the rat limbic system. They suggest caution in assuming close parallels between current biochemical functional, especially behavioral, methods of evaluating dopamine receptors of mammalian brain.

  8. Reduced striatal volumes in Parkinson’s disease: a magnetic resonance imaging study

    Directory of Open Access Journals (Sweden)

    Pitcher Toni L

    2012-08-01

    Full Text Available Abstract Background The presence and extent of structural changes in the brain as a consequence of Parkinson’s disease (PD is still poorly understood. Methods High-resolution 3-tesla T1-weighted structural magnetic resonance images in sixty-five PD and 27 age-matched healthy control participants were examined. Putamen, caudate, and intracranial volumes were manually traced in the axial plane of 3D reconstructed images. Striatal nuclei volumes were normalized to intracranial volume for statistical comparison. Disease status was assessed using the Unified Parkinson’s Disease Rating Scale and Hoehn and Yahr scale. Cognitive status was assessed using global status tests and detailed neuropsychological testing. Results Both caudate and putamen volumes were smaller in PD brains compared to controls after adjusting for age and gender. Caudate volumes were reduced by 11% (p = 0.001 and putamen volumes by 8.1% (p = 0.025. PD striatal volumes were not found to be significantly correlated with cognitive or motor decline. Conclusion Small, but significant reductions in the volume of both the caudate and putamen occur in PD brains. These reductions are independent of the effects of age and gender, however the relation of these reductions to the functional loss of dopamine, which is characteristic of PD, remains unclear.

  9. Episodic memory encoding interferes with reward learning and decreases striatal prediction errors.

    Science.gov (United States)

    Wimmer, G Elliott; Braun, Erin Kendall; Daw, Nathaniel D; Shohamy, Daphna

    2014-11-05

    Learning is essential for adaptive decision making. The striatum and its dopaminergic inputs are known to support incremental reward-based learning, while the hippocampus is known to support encoding of single events (episodic memory). Although traditionally studied separately, in even simple experiences, these two types of learning are likely to co-occur and may interact. Here we sought to understand the nature of this interaction by examining how incremental reward learning is related to concurrent episodic memory encoding. During the experiment, human participants made choices between two options (colored squares), each associated with a drifting probability of reward, with the goal of earning as much money as possible. Incidental, trial-unique object pictures, unrelated to the choice, were overlaid on each option. The next day, participants were given a surprise memory test for these pictures. We found that better episodic memory was related to a decreased influence of recent reward experience on choice, both within and across participants. fMRI analyses further revealed that during learning the canonical striatal reward prediction error signal was significantly weaker when episodic memory was stronger. This decrease in reward prediction error signals in the striatum was associated with enhanced functional connectivity between the hippocampus and striatum at the time of choice. Our results suggest a mechanism by which memory encoding may compete for striatal processing and provide insight into how interactions between different forms of learning guide reward-based decision making. Copyright © 2014 the authors 0270-6474/14/3414901-12$15.00/0.

  10. Perineuronal nets play a role in regulating striatal function in the mouse.

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    Hyunchul Lee

    Full Text Available The striatum is the primary input nucleus of the basal ganglia, a collection of nuclei that play important roles in motor control and associative learning. We have previously reported that perineuronal nets (PNNs, aggregations of chondroitin-sulfate proteoglycans (CSPGs, form in the matrix compartment of the mouse striatum during the second postnatal week. This period overlaps with important developmental changes, including the attainment of an adult-like gait. Here, we investigate the identity of the cells encapsulated by PNNs, characterize their topographical distribution and determine their function by assessing the impact of enzymatic digestion of PNNs on two striatum-dependent behaviors: ambulation and goal-directed spatial learning. We show PNNs are more numerous caudally, and that a substantial fraction (41% of these structures surrounds parvalbumin positive (PV+ interneurons, while approximately 51% of PV+ cells are ensheathed by PNNs. The colocalization of these structures is greatest in dorsal, lateral and caudal regions of the striatum. Bilateral digestion of striatal PNNs led to an increase in both the width and variability of hind limb gait. Intriguingly, this also resulted in an improvement in the acquisition rate of the Morris water maze. Together, these data show that PNNs are associated with specific elements of striatal circuits and play a key role in regulating the function of this important structure in the mouse.

  11. Perineuronal nets play a role in regulating striatal function in the mouse.

    Science.gov (United States)

    Lee, Hyunchul; Leamey, Catherine A; Sawatari, Atomu

    2012-01-01

    The striatum is the primary input nucleus of the basal ganglia, a collection of nuclei that play important roles in motor control and associative learning. We have previously reported that perineuronal nets (PNNs), aggregations of chondroitin-sulfate proteoglycans (CSPGs), form in the matrix compartment of the mouse striatum during the second postnatal week. This period overlaps with important developmental changes, including the attainment of an adult-like gait. Here, we investigate the identity of the cells encapsulated by PNNs, characterize their topographical distribution and determine their function by assessing the impact of enzymatic digestion of PNNs on two striatum-dependent behaviors: ambulation and goal-directed spatial learning. We show PNNs are more numerous caudally, and that a substantial fraction (41%) of these structures surrounds parvalbumin positive (PV+) interneurons, while approximately 51% of PV+ cells are ensheathed by PNNs. The colocalization of these structures is greatest in dorsal, lateral and caudal regions of the striatum. Bilateral digestion of striatal PNNs led to an increase in both the width and variability of hind limb gait. Intriguingly, this also resulted in an improvement in the acquisition rate of the Morris water maze. Together, these data show that PNNs are associated with specific elements of striatal circuits and play a key role in regulating the function of this important structure in the mouse.

  12. Remediation of Veliki bački kanal and sustainable use of resources in its surroundings

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    Stojanović Vladimir

    2014-01-01

    Full Text Available Veliki bački kanal is one of the most polluted watercourses in Serbia and it is frequently the central topic of the analysis of huge ecological issues in Serbia. It was dug at the turn of the 19th century with the main purpose to drain the wetland areas in central Bačka and to enhance economic growth of the settlements that had been colonized several times during the 18th century. Although it is being studied mostly from environment protection perspective at present, it has been changing the features of the landscape and the environment in this area. The issue of intensive pollution, predominantly from food industry, has been increasing since the second half of the 20th century. This type of pollution completely diminished the canal functions planned by the project designers. Current and future canal functions are: drainage and flood protection, irrigation, water supply, wastewater recipient, canal traffic, fish farming, tourism (recreation and nature protection. Remediation is crucial and fundamental prerequisite for sustainable use or Veliki bački kanal resources.

  13. Immunohistochemical distribution of Ki67 in epidermis of thick glabrous skin of human digits.

    Science.gov (United States)

    Petrovic, Aleksandar; Petrovic, Vladimir; Milojkovic, Bobana; Nikolic, Ivan; Jovanovic, Dragan; Antovic, Aleksandra; Milic, Miroslav

    2018-01-01

    The glabrous skin on the flexor sides of hands and feet, compared to other integument regions, has thicker epidermis and more complex pattern of epidermal ridges, wherefore in microscopy is denominated as thick skin. The epidermis of this skin type has individually unique and permanent superficial patterns, called dermatoglyphics, which are maintained by regenerative potential of deep epidermal rete ridges, that interdigitate with adjacent dermis. Using light microscopy, we analyzed cadaveric big toes thick skin samples, described histology of deep epidermal ridges (intermediate, limiting, and transverse), and quantitatively evidenced their pattern of proliferation by immunohistochemical assessment of Ki67. Immunohistochemical distribution of Ki67 was confined to basal and suprabasal layers, with pattern of distribution specific for intermediate, limiting and transverse ridges that gradually transform within epidermal height. Deep epidermal ridges, interdigitating with dermal papillae, participate in construction of intricate epidermal base, whose possible role in epidermal regeneration was also discussed. Having a prominent morphology, this type of epidermis offers the best morphological insight in complexities of skin organization, and its understanding could challenge and improve currently accepted models of epidermal organization.

  14. High Rate Performance Nanocomposite Electrode of Mesoporous Manganese Dioxide/Silver Nanowires in KI Electrolytes

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    Yanhua Jiang

    2015-10-01

    Full Text Available In recent years, manganese dioxide has become a research hotspot as an electrode material because of its low price. However, it has also become an obstacle to industrialization due to its low ratio of capacitance and the low rate performance which is caused by the poor electrical conductivity. In this study, a KI solution with electrochemical activity was innovatively applied to the electrolyte, and we systematically investigated the rate performance of the mesoporous manganese dioxide and the composite electrode with silver nanowires in supercapacitors. The results showed that when mesoporous manganese dioxide and mesoporous manganese dioxide/silver nanowires composite were used as electrodes, the strength of the current was amplified five times (from 0.1 to 0.5 A/g, the remaining rates of specific capacitance were 95% (from 205.5 down to 197.1 F/g and 92% (from 208.1 down to 191.7 F/g in the KI electrolyte, and the rate performance was much higher than which in an Na2SO4 electrolyte with a remaining rate of 25% (from 200.3 down to 49.1 F/g and 60% (from 187.2 down to 113.1 F/g. The morphology and detail structure were investigated by Scanning electron microscopy, X-ray diffraction, Fourier transform infrared spectrometry and Nitrogen adsorption-desorption isotherms. The electrochemical performance was assessed by cyclic voltammograms, galvanostatic charge/discharge and electrochemical impedance spectroscopy.

  15. Memories of Serbian victims under Bulgarian occupation in Leskovački glasnik (1915-1918

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    Antić Dejan D.

    2015-01-01

    Full Text Available The Serbian army was forced to retreat towards Metohija and Albania eventually due to the armed aggression and attacks from the north and east in October 1915 by the united forces of the German and Austro-Hungarian units against the Kingdom of Serbia. Together with the army, the monarch, executive and legislative branch, intellectuals and civilians also retreated, not wanting to fall in the hands of the incoming army formations of the Central Powers. Following the retreat of the government and army bodies, the territory of the Kingdom of Serbia found itself under the control of the enemy forces, which started the 3-year period of occupation. The subject of this paper are the texts written by the newspaper called Leskovački glasnik (Leskovac Messenger in the period between World War I and World War II, which dealt with the sufferings of the Serbian civilians in the Bulgarian occupied zone from 1915 to 1918. Special attention is paid to the Leskovački glasnik's reports about marking the anniversary of the Bulgarian terror and killings of Serbs, about opening and consecration of memorials, about the heroic deeds and the tragic destiny of the people in south Serbia.

  16. Nonstoichiometric complex of gramicidin D with KI at 0.80 (angstrom) resolution

    International Nuclear Information System (INIS)

    Olczak, A.; Glowka, M.L.; Szczesio, M.; Bojarsk, J.; Duax, W.L.; Burkhart, B.M.; Wawrzak, Z.

    2007-01-01

    The crystal structure of a nonstoichiometric complex of gramicidin D (gD) with KI has been determined at 100 K using synchrotron radiation. The final R factor was 0.106 for 83 988 observed reflections (Friedel pairs were not merged) collected to 0.80 (angstrom). The structure consists of four independent pentadecapeptides and numerous solvent molecules and salt ions. The general architecture of the antiparallel double-stranded gramicidin dimers in the crystal (a right-handed antiparallel DSβH R form) closely resembles that of previously published cation complexes of gD. However, a significantly different mixture of gramicidin isomers is found in the crystal of the KI complex, including partial occupancy of phenylalanine at position 11. Only three sites in each of the two crystallographically independent channels are partially occupied by potassium cations instead of the commonly observed seven sites. The sum of the partial occupancies of K + (1.10 per two dimers) is consistent with the sum of the iodide occupancies (1.095 over eight sites), which is also confirmed by the anomalous signal of the iodide. There was a significant asymmetry of the distribution and occupancies of cations in the crystallographically independent gramicidin channels, in contrast to the distribution found in the rubidium chloride complex with gD.

  17. Comparison of 5 Ki-67 antibodies regarding reproducibility and capacity to predict prognosis in breast cancer: does the antibody matter?

    Science.gov (United States)

    Ács, Balázs; Kulka, Janina; Kovács, Kristóf Attila; Teleki, Ivett; Tőkés, Anna-Mária; Meczker, Ágnes; Győrffy, Balázs; Madaras, Lilla; Krenács, Tibor; Szász, Attila Marcell

    2017-07-01

    Although several antibodies are available for immunohistochemical detection of Ki-67, even the most commonly used MIB-1 has not been validated yet. Our aim was to compare 5 commercially available antibodies for detection of Ki-67 in terms of agreement and their ability in predicting prognosis of breast cancer. Tissue microarrays were constructed from 378 breast cancer patients' representative formalin-fixed, paraffin-embedded tumor blocks. Five antibodies were used to detect Ki-67 expression: MIB-1 using chromogenic detection and immunofluorescent-labeled MIB-1, SP-6, 30-9, poly, and B56. Semiquantitative assessment was performed by 2 pathologists independently on digitized slides. To compare the 5 antibodies, intraclass correlation and concordance correlation coefficient were used. All the antibodies but immunofluorescent-labeled MIB-1 (at 20% and 30% thresholds, P=.993 and P=.342, respectively) and B56 (at 30% threshold, P=.288) separated high- and low-risk patient groups. However, there were a significant difference (P values for all comparisons≤.005) and a moderate concordance (intraclass correlation, 0.645) between their Ki-67 labeling index scores. The highest concordance was found between MIB-1 and poly (concordance correlation coefficient=0.785) antibodies. None of the antibodies except Ki-67 labeling index as detected by poly (P=.031) at 20% threshold and lymph node status (Pantibodies in their capacity to detect proliferating tumor cells and to separate low- and high-risk breast cancer patient groups. Copyright © 2017 Elsevier Inc. All rights reserved.

  18. [Expression of Ki-67 and P53 protein in oral squamous cell carcinoma and its clinical significance].

    Science.gov (United States)

    He, Wei; Xiao, Yan; Chen, Wei-min

    2015-04-01

    To investigate the clinical and pathological features and its relationship with the expression of Ki-67 and p53 protein in oral squamous cell carcinoma. Immunohistochemical SP staining method was used to quantify the protein expression levels of Ki-67 and p53 protein in 10 cases of normal oral mucosa, 16 cases of oral leukoplakia (OLK) tissue, and 48 cases of oral squamous cell carcinoma. The relationship of the expression of Ki-67 and p53 protein to clinical and pathological data was analyzed, and SPSS17.0 software package was used for statistical analysis. The positive expression rate of Ki-67 protein in normal oral mucosa, oral leukoplakia and oral squamous cell carcinoma was 30%, 56.3% and 79.2%, respectively; The positive expression rate of p53 was 0%, 43.8%, and 70.8%, respectively; Ki-67 and p53 expression had significant difference among normal oral mucosa, oral leukoplakia and oral squamous cell carcinoma (Poral squamous cell carcinoma (Poral squamous cell carcinoma tissues may play an important role in the development of oral squamous cell carcinoma.

  19. HIV Infection Is Associated with Impaired Striatal Function during Inhibition with Normal Cortical Functioning on Functional MRI

    NARCIS (Netherlands)

    du Plessis, Stéfan; Vink, Matthijs; Joska, John A; Koutsilieri, Eleni; Bagadia, Asif; Stein, Dan J; Emsley, Robin

    2015-01-01

    The aim of the present study was to investigate the effect of HIV infection on cortical and subcortical regions of the frontal-striatal system involved in the inhibition of voluntary movement. Functional MRI (fMRI) studies suggest that human immunodeficiency virus (HIV) infection is associated with

  20. A case of Cotard syndrome: (123)I-IBZM SPECT imaging of striatal D(2) receptor binding.

    Science.gov (United States)

    De Risio, Sergio; De Rossi, Giuseppe; Sarchiapone, Marco; Camardese, Giovanni; Carli, Vladimir; Cuomo, Chiara; Satta, Maria Antonietta; Di Giuda, Daniela

    2004-01-15

    A case of 'dèlire de nègation' that suddenly appeared in a 43-year-old male is presented. No alteration in regional cerebral blood, as measured by (99m)Tc-HMPAO-SPECT, was found, but (123)I-IBZM-SPECT analysis showed reduced striatal D(2) receptor binding that further decreased after treatment.

  1. Exercise-induced rescue of tongue function without striatal dopamine sparing in a rat neurotoxin model of Parkinson disease.

    Science.gov (United States)

    Ciucci, Michelle R; Schaser, Allison J; Russell, John A

    2013-09-01

    Unilateral lesions to the medial forebrain bundle with 6-hydroxydopamine (6-OHDA) lead to force and timing deficits during a complex licking task. We hypothesized that training targeting tongue force generation during licking would improve timing and force measures and also lead to striatal dopamine sparing. Nine month-old male Fisher344/Brown Norway rats were used in this experiment. Sixteen rats were in the control condition and received tongue exercise (n=8) or no exercise (n=8). Fourteen rats were in the 6-OHDA lesion condition and underwent tongue exercise (n=7) and or no exercise (n=7). Following 4 weeks of training and post-training measures, all animals underwent bilateral stimulation of the hypoglossal nerves to measure muscle contractile properties and were then transcardially perfused and brain tissues collected for immunohistochemistry to examine striatal dopamine content. Results demonstrated that exercise animals performed better for maximal force, average force, and press rate than their no-exercise counterparts, and the 6-OHDA animals that underwent exercise performed as well as the Control No Exercise group. Interestingly, there were no group differences for tetanic muscle force, despite behavioral recovery of forces. Additionally, behavioral and neurochemical analyses indicate that there were no differences in striatal dopamine. Thus, targeted exercise can improve tongue force and timing deficits related to 6-OHDA lesions and this exercise likely has a central, versus peripheral (muscle strength) mechanism. However, this mechanism is not related to sparing of striatal dopamine content. Copyright © 2013 Elsevier B.V. All rights reserved.

  2. Synthesis and binding to striatal membranes of non carrier added I-123 labeled 4'-iodococaine

    Energy Technology Data Exchange (ETDEWEB)

    Metwally, S.A.M.; Gatley, S.J.; Wolf, A.P.; Yu, D.-W. (Brookhaven National Lab., Upton, NY (United States))

    1992-03-01

    An {sup 123}I labeled cocaine analog, 4'-({sup 123}I)iodococaine, has been prepared by oxidative destannylation of the tributyltin analog and shown to interact with cocaine binding sites in rat brain striatal membranes. It may thus be a suitable SPECT radiotracer for studies of the dopamine reuptake site in neurodegenerative diseases. (Author).

  3. Epothilone D prevents binge methamphetamine-mediated loss of striatal dopaminergic markers.

    Science.gov (United States)

    Killinger, Bryan A; Moszczynska, Anna

    2016-02-01

    Exposure to binge methamphetamine (METH) can result in a permanent or transient loss of dopaminergic (DAergic) markers such as dopamine (DA), dopamine transporter, and tyrosine hydroxylase (TH) in the striatum. We hypothesized that the METH-induced loss of striatal DAergic markers was, in part, due to a destabilization of microtubules (MTs) in the nigrostriatal DA pathway that ultimately impedes anterograde axonal transport of these markers. To test this hypothesis, adult male Sprague-Dawley rats were treated with binge METH or saline in the presence or absence of epothilone D (EpoD), a MT-stabilizing compound, and assessed 3 days after the treatments for the levels of several DAergic markers as well as for the levels of tubulins and their post-translational modifications (PMTs). Binge METH induced a loss of stable long-lived MTs within the striatum but not within the substantia nigra pars compacta (SNpc). Treatment with a low dose of EpoD increased the levels of markers of stable MTs and prevented METH-mediated deficits in several DAergic markers in the striatum. In contrast, administration of a high dose of EpoD appeared to destabilize MTs and potentiated the METH-induced deficits in several DAergic markers. The low-dose EpoD also prevented the METH-induced increase in striatal DA turnover and increased behavioral stereotypy during METH treatment. Together, these results demonstrate that MT dynamics plays a role in the development of METH-induced losses of several DAergic markers in the striatum and may mediate METH-induced degeneration of terminals in the nigrostriatal DA pathway. Our study also demonstrates that MT-stabilizing drugs such as EpoD have a potential to serve as useful therapeutic agents to restore function of DAergic nerve terminals following METH exposure when administered at low doses. Administration of binge methamphetamine (METH) negatively impacts neurotransmission in the nigrostriatal dopamine (DA) system. The effects of METH include

  4. Striatal pre- and postsynaptic profile of adenosine A(2A receptor antagonists.

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    Marco Orru

    2011-01-01

    Full Text Available Striatal adenosine A(2A receptors (A(2ARs are highly expressed in medium spiny neurons (MSNs of the indirect efferent pathway, where they heteromerize with dopamine D(2 receptors (D(2Rs. A(2ARs are also localized presynaptically in cortico-striatal glutamatergic terminals contacting MSNs of the direct efferent pathway, where they heteromerize with adenosine A(1 receptors (A(1Rs. It has been hypothesized that postsynaptic A(2AR antagonists should be useful in Parkinson's disease, while presynaptic A(2AR antagonists could be beneficial in dyskinetic disorders, such as Huntington's disease, obsessive-compulsive disorders and drug addiction. The aim or this work was to determine whether selective A(2AR antagonists may be subdivided according to a preferential pre- versus postsynaptic mechanism of action. The potency at blocking the motor output and striatal glutamate release induced by cortical electrical stimulation and the potency at inducing locomotor activation were used as in vivo measures of pre- and postsynaptic activities, respectively. SCH-442416 and KW-6002 showed a significant preferential pre- and postsynaptic profile, respectively, while the other tested compounds (MSX-2, SCH-420814, ZM-241385 and SCH-58261 showed no clear preference. Radioligand-binding experiments were performed in cells expressing A(2AR-D(2R and A(1R-A(2AR heteromers to determine possible differences in the affinity of these compounds for different A(2AR heteromers. Heteromerization played a key role in the presynaptic profile of SCH-442416, since it bound with much less affinity to A(2AR when co-expressed with D(2R than with A(1R. KW-6002 showed the best relative affinity for A(2AR co-expressed with D(2R than co-expressed with A(1R, which can at least partially explain the postsynaptic profile of this compound. Also, the in vitro pharmacological profile of MSX-2, SCH-420814, ZM-241385 and SCH-58261 was is in accordance with their mixed pre- and postsynaptic profile

  5. The phosphorylation status and cytoskeletal remodeling of striatal astrocytes treated with quinolinic acid

    International Nuclear Information System (INIS)

    Pierozan, Paula; Ferreira, Fernanda; Ortiz de Lima, Bárbara; Gonçalves Fernandes, Carolina; Totarelli Monteforte, Priscila; Castro Medaglia, Natalia de; Bincoletto, Claudia; Soubhi Smaili, Soraya; Pessoa-Pureur, Regina

    2014-01-01

    Quinolinic acid (QUIN) is a glutamate agonist which markedly enhances the vulnerability of neural cells to excitotoxicity. QUIN is produced from the amino acid tryptophan through the kynurenine pathway (KP). Dysregulation of this pathway is associated with neurodegenerative conditions. In this study we treated striatal astrocytes in culture with QUIN and assayed the endogenous phosphorylating system associated with glial fibrillary acidic protein (GFAP) and vimentin as well as cytoskeletal remodeling. After 24 h incubation with 100 µM QUIN, cells were exposed to 32 P-orthophosphate and/or protein kinase A (PKA), protein kinase dependent of Ca 2+ /calmodulin II (PKCaMII) or protein kinase C (PKC) inhibitors, H89 (20 μM), KN93 (10 μM) and staurosporin (10 nM), respectively. Results showed that hyperphosphorylation was abrogated by PKA and PKC inhibitors but not by the PKCaMII inhibitor. The specific antagonists to ionotropic NMDA and non-NMDA (50 µM DL-AP5 and CNQX, respectively) glutamate receptors as well as to metabotropic glutamate receptor (mGLUR; 50 µM MCPG), mGLUR1 (100 µM MPEP) and mGLUR5 (10 µM 4C3HPG) prevented the hyperphosphorylation provoked by QUIN. Also, intra and extracellular Ca 2+ quelators (1 mM EGTA; 10 µM BAPTA-AM, respectively) prevented QUIN-mediated effect, while Ca 2+ influx through voltage-dependent Ca 2+ channel type L (L-VDCC) (blocker: 10 µM verapamil) is not implicated in this effect. Morphological analysis showed dramatically altered actin cytoskeleton with concomitant change of morphology to fusiform and/or flattened cells with retracted cytoplasm and disruption of the GFAP meshwork, supporting misregulation of actin cytoskeleton. Both hyperphosphorylation and cytoskeletal remodeling were reversed 24 h after QUIN removal. Astrocytes are highly plastic cells and the vulnerability of astrocyte cytoskeleton may have important implications for understanding the neurotoxicity of QUIN in neurodegenerative disorders. - Highlights:

  6. Coordinated Ramping of Dorsal Striatal Pathways preceding Food Approach and Consumption.

    Science.gov (United States)

    London, Tanisha D; Licholai, Julia A; Szczot, Ilona; Ali, Mohamed A; LeBlanc, Kimberly H; Fobbs, Wambura C; Kravitz, Alexxai V

    2018-04-04

    The striatum controls food-related actions and consumption and is linked to feeding disorders, including obesity and anorexia nervosa. Two populations of neurons project from the striatum: direct pathway medium spiny neurons and indirect pathway medium spiny neurons. The selective contribution of direct pathway medium spiny neurons and indirect pathway medium spiny neurons to food-related actions and consumption remains unknown. Here, we used in vivo electrophysiology and fiber photometry in mice (of both sexes) to record both spiking activity and pathway-specific calcium activity of dorsal striatal neurons during approach to and consumption of food pellets. While electrophysiology revealed complex task-related dynamics across neurons, population calcium was enhanced during approach and inhibited during consumption in both pathways. We also observed ramping changes in activity that preceded both pellet-directed actions and spontaneous movements. These signals were heterogeneous in the spiking units, with neurons exhibiting either increasing or decreasing ramps. In contrast, the population calcium signals were homogeneous, with both pathways having increasing ramps of activity for several seconds before actions were initiated. An analysis comparing population firing rates to population calcium signals also revealed stronger ramping dynamics in the calcium signals than in the spiking data. In a second experiment, we trained the mice to perform an action sequence to evaluate when the ramping signals terminated. We found that the ramping signals terminated at the beginning of the action sequence, suggesting they may reflect upcoming actions and not preconsumption activity. Plasticity of such mechanisms may underlie disorders that alter action selection, such as drug addiction or obesity. SIGNIFICANCE STATEMENT Alterations in striatal function have been linked to pathological consumption in disorders, such as obesity and drug addiction. We recorded spiking and

  7. The phosphorylation status and cytoskeletal remodeling of striatal astrocytes treated with quinolinic acid

    Energy Technology Data Exchange (ETDEWEB)

    Pierozan, Paula; Ferreira, Fernanda; Ortiz de Lima, Bárbara; Gonçalves Fernandes, Carolina [Departamento de Bioquímica, Instituto de Ciências Básicas da Saúde, Universidade Federal do Rio Grande do Sul, Porto Alegre, RS 90035-003 (Brazil); Totarelli Monteforte, Priscila; Castro Medaglia, Natalia de; Bincoletto, Claudia; Soubhi Smaili, Soraya [Departamento de Farmacologia, Universidade Federal de São Paulo (UNIFESP/EPM), São Paulo, SP (Brazil); Pessoa-Pureur, Regina, E-mail: rpureur@ufrgs.br [Departamento de Bioquímica, Instituto de Ciências Básicas da Saúde, Universidade Federal do Rio Grande do Sul, Porto Alegre, RS 90035-003 (Brazil)

    2014-04-01

    Quinolinic acid (QUIN) is a glutamate agonist which markedly enhances the vulnerability of neural cells to excitotoxicity. QUIN is produced from the amino acid tryptophan through the kynurenine pathway (KP). Dysregulation of this pathway is associated with neurodegenerative conditions. In this study we treated striatal astrocytes in culture with QUIN and assayed the endogenous phosphorylating system associated with glial fibrillary acidic protein (GFAP) and vimentin as well as cytoskeletal remodeling. After 24 h incubation with 100 µM QUIN, cells were exposed to {sup 32}P-orthophosphate and/or protein kinase A (PKA), protein kinase dependent of Ca{sup 2+}/calmodulin II (PKCaMII) or protein kinase C (PKC) inhibitors, H89 (20 μM), KN93 (10 μM) and staurosporin (10 nM), respectively. Results showed that hyperphosphorylation was abrogated by PKA and PKC inhibitors but not by the PKCaMII inhibitor. The specific antagonists to ionotropic NMDA and non-NMDA (50 µM DL-AP5 and CNQX, respectively) glutamate receptors as well as to metabotropic glutamate receptor (mGLUR; 50 µM MCPG), mGLUR1 (100 µM MPEP) and mGLUR5 (10 µM 4C3HPG) prevented the hyperphosphorylation provoked by QUIN. Also, intra and extracellular Ca{sup 2+} quelators (1 mM EGTA; 10 µM BAPTA-AM, respectively) prevented QUIN-mediated effect, while Ca{sup 2+} influx through voltage-dependent Ca{sup 2+} channel type L (L-VDCC) (blocker: 10 µM verapamil) is not implicated in this effect. Morphological analysis showed dramatically altered actin cytoskeleton with concomitant change of morphology to fusiform and/or flattened cells with retracted cytoplasm and disruption of the GFAP meshwork, supporting misregulation of actin cytoskeleton. Both hyperphosphorylation and cytoskeletal remodeling were reversed 24 h after QUIN removal. Astrocytes are highly plastic cells and the vulnerability of astrocyte cytoskeleton may have important implications for understanding the neurotoxicity of QUIN in neurodegenerative

  8. Inflammation alters AMPA-stimulated calcium responses in dorsal striatal D2 but not D1 spiny projection neurons.

    Science.gov (United States)

    Winland, Carissa D; Welsh, Nora; Sepulveda-Rodriguez, Alberto; Vicini, Stefano; Maguire-Zeiss, Kathleen A

    2017-11-01

    Neuroinflammation precedes neuronal loss in striatal neurodegenerative diseases and can be exacerbated by the release of proinflammatory molecules by microglia. These molecules can affect trafficking of AMPARs. The preferential trafficking of calcium-permeable versus impermeable AMPARs can result in disruptions of [Ca 2+ ] i and alter cellular functions. In striatal neurodegenerative diseases, changes in [Ca 2+ ] i and L-type voltage-gated calcium channels (VGCCs) have been reported. Therefore, this study sought to determine whether a proinflammatory environment alters AMPA-stimulated [Ca 2+ ] i through calcium-permeable AMPARs and/or L-type VGCCs in dopamine-2- and dopamine-1-expressing striatal spiny projection neurons (D2 and D1 SPNs) in the dorsal striatum. Mice expressing the calcium indicator protein, GCaMP in D2 or D1 SPNs, were utilized for calcium imaging. Microglial activation was assessed by morphology analyses. To induce inflammation, acute mouse striatal slices were incubated with lipopolysaccharide (LPS). Here we report that LPS treatment potentiated AMPA responses only in D2 SPNs. When a nonspecific VGCC blocker was included, we observed a decrease of AMPA-stimulated calcium fluorescence in D2 but not D1 SPNs. The remaining agonist-induced [Ca 2+ ] i was mediated by calcium-permeable AMPARs because the responses were completely blocked by a selective calcium-permeable AMPAR antagonist. We used isradipine, the highly selective L-type VGCC antagonist to determine the role of L-type VGCCs in SPNs treated with LPS. Isradipine decreased AMPA-stimulated responses selectively in D2 SPNs after LPS treatment. Our findings suggest that dorsal striatal D2 SPNs are specifically targeted in proinflammatory conditions and that L-type VGCCs and calcium-permeable AMPARs are important mediators of this effect. © 2017 Federation of European Neuroscience Societies and John Wiley & Sons Ltd.

  9. The bioenergetic status relates to dopamine neuron loss in familial PD with PINK1 mutations.

    Directory of Open Access Journals (Sweden)

    Rüediger Hilker

    Full Text Available Mutations in the PINK1 gene cause autosomal recessive familial Parkinson's disease (PD. The gene encodes a mitochondrial protein kinase that plays an important role in maintaining mitochondrial function and integrity. However, the pathophysiological link between mutation-related bioenergetic deficits and the degenerative process in dopaminergic neurons remains to be elucidated. We performed phosphorous ((31P and proton ((1H 3-T magnetic resonance spectroscopic imaging (MRSI in 11 members of a German family with hereditary PD due to PINK1 mutations (PARK6 compared to 23 age-matched controls. All family members had prior 18-Fluorodopa (FDOPA positron emission tomography (PET. The striatal FDOPA uptake was correlated with quantified metabolic brain mapping in MRSI. At group level, the heterozygous PINK1 mutation carriers did not show any MRSI abnormalities relative to controls. In contrast, homozygous individuals with manifest PD had putaminal GPC, PCr, HEP and β-ATP levels well above the 2SD range of controls. Across all subjects, the FDOPA K(i values correlated positively with MI (r = 0.879, p<0.001 and inversely with β-ATP (r = -0.784, p = 0.008 and GPC concentrations (r = -0.651, p = 0.030 in the putamen. Our combined imaging data suggest that the dopaminergic deficit in this family with PD due to PINK1 mutations relates to osmolyte dysregulation, while the delivery of high energy phosphates was preserved. Our results corroborate the hypothesis that PINK1 mutations result in reduced neuronal survival, most likely due to impaired cellular stress resistance.

  10. Differences in number and distribution of striatal calbindin medium spiny neurons between a vocal-learner (Melopsittacus undulatus and a non-vocal learner bird (Colinus virginianus

    Directory of Open Access Journals (Sweden)

    Elena eGarcia-Calero

    2013-12-01

    Full Text Available Striatal projecting neurons, known as medium spiny neurons (MSNs, segregate into two compartments called matrix and striosome in the mammalian striatum. The matrix domain is characterized by the presence of calbindin immunopositive (CB+ MSNs, not observed in the striosome subdivision. The existence of a similar CB+ MSN population has recently been described in two striatal structures in male zebra finch (a vocal learner bird: the striatal capsule and the Area X, a nucleus implicated in song learning. Female zebra finches show a similar pattern of CB+ MSNs than males in the developing striatum but loose these cells in juveniles and adult stages. In the present work we analyzed the existence and allocation of CB+MSNs in the striatal domain of the vocal learner bird budgerigar (representative of psittaciformes order and the non-vocal learner bird quail (representative of galliformes order. We studied the co-localization of CB protein with FoxP1, a transcription factor expressed in vertebrate striatal MSNs. We observed CB+ MSNs in the medial striatal domain of adult male and female budgerigars, although this cell type was missing in the potentially homologous nucleus for Area X in budgerigar. In quail, we observed CB+ cells in the striatal domain at developmental and adult stages but they did not co-localize with the MSN marker FoxP1. We also described the existence of the CB+ striatal capsule in budgerigar and quail and compared these results with the CB+ striatal capsule observed in juvenile zebra finches. Together, these results point out important differences in CB+MSN distribution between two representative species of vocal learner and non-vocal learner avian orders (respectively the budgerigar and the quail, but also between close vocal learner bird families.

  11. Current Status and Future Prospect of K-NET and KiK-net

    Science.gov (United States)

    Aoi, S.; Kunugi, T.; Suzuki, W.; Nakamura, H.; Fujiwara, H.

    2014-12-01

    During 18 years since the deployment of K-NET following the Kobe earthquake, our attention has mainly focused on rapidity of the data collection and an unfailing and reliable observation. In this presentation, we review three generations of the instruments employed by K-NET and KiK-net from these two points of view.At beginning of the 2000's, we newly developed the second generation instruments (K-NET02, K-NET02A, KiK-net06) to replace the first generation instruments (K-NET95, SMAC-MDK) employed when the networks were constructed in the 1990's. These instruments have an automatic dial-out function. It takes typically 2-5 s to establish communication and a few seconds to send the pre-trigger data. After that, data is available typically within a 1.5 s delay. Not only waveform data but also strong motion indexes such as real-time intensity, PGA, PGV, PGD, and response spectra are continuously sent once a second.After the 2011 Tohoku earthquake, we have developed the third generation instruments (K-NET11, KiK-net11) and have replaced almost half of the all stations country wide. Main improvement of this instrument is more unfailing and reliable observation. Because we have often experienced very large ground motions (e.g. 45 records exceeding gravity), the maximum measureable range was expanded from 2000 gal to 4000 gal for the second generation instrument, and to 8000 gal for the third. For the third generation instrument, in case of power failure, observation (including transmission of data) works for seven days thanks to the backup battery, while for the second generation instruments it works only for one day. By adding an oblique component to the three-component accelerometers, we could automatically distinguish shaking data from noise such as electric pulses which may cause a false alarm in EEW. Implementation to guarantee the continuity of observation under severe conditions such as during the Tohoku earthquake is very important, as well as a highly efficient

  12. Evaluation of Ki-67 Staining Levels as an Independent Biomarker of Biochemical Recurrence After Salvage Radiation Therapy for Prostate Cancer

    International Nuclear Information System (INIS)

    Parker, Alexander S.; Heckman, Michael G.; Wu, Kevin J.; Crook, Julia E.; Hilton, Tracy W.; Pisansky, Thomas M.; Bernard, Johnny R.; Schild, Steven E.; Khor, Li Yan; Hammond, Elizabeth H.; Pollack, Alan; Buskirk, Steven J.

    2009-01-01

    Purpose: We recently published a scoring algorithm to predict biochemical recurrence (BCR) after salvage radiation therapy (SRT) for prostate cancer. Currently, this algorithm is based on clinicopathologic features and does not incorporate information from tumor-based biomarkers. Herein, we evaluate the ability of Ki-67 staining in primary prostate cancer to independently aid in the prediction of BCR among men undergoing SRT. Methods and Materials: We identified 147 patients who were treated with SRT between July 1987 and July 2003 at Mayo Clinic (Rochester, MN; Jacksonville, FL; Scottsdale, AZ). Staining levels of Ki-67 in primary tumor samples were detected by use of a monoclonal antibody and quantified by use of a computer-assisted method. We used Cox proportional hazards models to examine the association of Ki-67 staining and BCR in single-variable models and after multivariable adjustment. Results: The risk of BCR for men with tumors in the highest tertile of Ki-67 staining is approximately two times that for men with tumors in the lower two tertiles (relative risk, 2.02; 95% confidence interval, 1.23-3.32; p = 0.005) after adjustment for the features in our original scoring algorithm. Further adjustment for additional covariates did not attenuate this association. Evidence from concordance index values supports that Ki-67 staining adds to the predictive ability of our existing scoring algorithm. Conclusions: Our data suggest that higher levels of Ki-67 staining are associated with increased risk of BCR after SRT, independent of existing clinicopathologic covariates. Future studies involving larger numbers of patients are required to validate these results and also explore possible means of combining this biomarker with existing prognostic tools.

  13. KiVa Anti-Bullying Program in Italy: Evidence of Effectiveness in a Randomized Control Trial.

    Science.gov (United States)

    Nocentini, Annalaura; Menesini, Ersilia

    2016-11-01

    The present study aims to evaluate the effectiveness of the KiVa anti-bullying program in Italy through a randomized control trial of students in grades 4 and 6. The sample involved 2042 students (51 % female; grade 4, mean age = 8.85; ds = 0.43; grade 6, mean age = 10.93; ds = 0.50); 13 comprehensive schools were randomly assigned into intervention (KiVa) or control (usual school provision) conditions. Different outcomes (bullying, victimization, pro-bullying attitudes, pro-victim attitudes, empathy toward victims), analyses (longitudinal mixed model with multiple-item scales; longitudinal prevalence of bullies and victims using Olweus' single question), and estimates of effectiveness (Cohen's d; odds ratios) were considered in order to compare the Italian results with those from other countries. Multilevel models showed that KiVa reduced bullying and victimization and increased pro-victim attitudes and empathy toward the victim in grade 4, with effect sizes from 0.24 to 0.40. In grade 6, KiVa reduced bullying, victimization, and pro-bullying attitudes; the effects were smaller as compared to grade 4, yet significant (d ≥ 0.20). Finally, using Olweus dichotomous definition of bullies and victims, results showed that the odds of being a victim were 1.93 times higher for a control student than for a KiVa student in grade 4. Overall, the findings provide evidence of the effectiveness of the program in Italy; the discussion will focus on factors that influenced successfully the transportability of the KiVa program in Italy.

  14. Neoplasias astrocitárias e correlação com as proteínas p53 mutada e Ki-67 Astrocytic neoplasms and correlation with mutate p53 and Ki-67 proteins

    Directory of Open Access Journals (Sweden)

    Gustavo Rassier Isolan

    2005-12-01

    Full Text Available As neoplasias astrocitárias correspondem a 60% dos tumores do sistema nervoso central, sendo o estudo da biologia molecular um importante passo para a compreensão da gênese e comportamento biológico destas doenças. As proteínas Ki-67, que é um marcador de proliferação celular, e p53, que é o produto do gene supressor de tumor de mesmo nome, são importantes marcadores tumorais. O objetivo deste estudo foi identificar e quantificar as proteínas Ki-67 e produto do gene supressor de tumor TP53 em diferentes graus de malignidade das neoplasias astrocitárias, bem como analisar suas relações com idade e sexo. Foram estudadas por imuno-histoquímica as proteínas Ki-67 e p53 em 47 pacientes com neoplasias astrocitárias ressecadas cirurgicamente, classificadas previamente e revisadas quanto ao grau de malignidade, de acordo com o proposto pela Organização Mundial da Saúde. Os núcleos celulares imunomarcados foram quantificados no programa Imagelab-softium pela razão paramétrica absoluta entre os núcleos de células positivas e o número total de células tumorais, sendo contadas 1000 células. O delineamento utilizado foi transversal não controlado. Para análise estatística as variáveis foram divididas em grupos, que para a Ki-67 foram ausente, 5% e para a p53 foram ausente (0, The astrocytic neoplasms respond by 60% of the central nervous system tumors, being the study of the molecular biology an important step for the understanding of the genesis and biological behavior of these diseases. The Ki-67 proteins, which are markers of the cellular proliferation, and p53, which is the product of the tumor suppressor gene TP53, are both important tumoral markers. This study intends to identify and quantify the Ki-67 and p53 proteins in astrocytic tumors of different grades of malignancy, as well as to analyze their relations with age and gender. Ki-67 and p53 proteins in 47 patients with surgically resected astrocytic neoplasms were

  15. Mobbing in vrste agresij, ki so jim izpostavljeni zaposleni v zdravstveni negi ter ukrepi za preprečevanje

    OpenAIRE

    Lorbek, Tanja

    2013-01-01

    Največjo grožnjo zaposlenim danes predstavlja čustveno in psihično nasilje, spolno ter drugo nadlegovanje na delovnem mestu, pogosto imenovano mobbing. Prilagajanje novim družbenim razmeram in novim vrednotam, malikovanje kapitala in konkurenčnosti, ki v resnici pomeni tekmovalnost, je v odnose na delovnem mestu vneslo občutek negotovosti. Temu se je pridružil tudi pojav prostega pretoka blaga, storitev in oseb, ki poleg kopičenja dobička povzroča tudi negotovost pri zaposlovanju in brezposel...

  16. Striatal FP-CIT uptake differs in the subtypes of early Parkinson's disease

    International Nuclear Information System (INIS)

    Spiegel, J.; Fassbender, K.; Dillmann, U.; Hellwig, D.; Samnick, S.; Moellers, M.-O.; Kirsch, C.-M.; Jost, W.

    2007-01-01

    In idiopathic Parkinson's disease (PD), a tremor-dominant type (TDT), an akinetic-rigid type (ART), and a mixed type (MT) are distinguished. We compared cerebral [I- 123 ]FP-CIT SPECT in the PD subtypes (67 patients Hoehn and Yahr stage 1:26 with ART, 19 with MT, 22 with TDT). We measured the ratios putamen/occipital lobe binding and caudate nucleus/occipital lobe binding. Parkinsonian motor symptoms were quantified by UPDRS motor scale. In both putamen and caudate nucleus contralateral to the clinically affected body side TDT patients showed a significantly higher FP-CIT uptake than ART or MT patients (ANOVA; p 0.05). The missing correlation between striatal FP-CIT uptake and tremor suggests, that further systems besides the nigrostriatal dopaminergic system may contribute to generation of parkinsonian tremor. (author)

  17. Striatal fast-spiking interneurons selectively modulate circuit output and are required for habitual behavior.

    Science.gov (United States)

    O'Hare, Justin K; Li, Haofang; Kim, Namsoo; Gaidis, Erin; Ade, Kristen; Beck, Jeff; Yin, Henry; Calakos, Nicole

    2017-09-05

    Habit formation is a behavioral adaptation that automates routine actions. Habitual behavior correlates with broad reconfigurations of dorsolateral striatal (DLS) circuit properties that increase gain and shift pathway timing. The mechanism(s) for these circuit adaptations are unknown and could be responsible for habitual behavior. Here we find that a single class of interneuron, fast-spiking interneurons (FSIs), modulates all of these habit-predictive properties. Consistent with a role in habits, FSIs are more excitable in habitual mice compared to goal-directed and acute chemogenetic inhibition of FSIs in DLS prevents the expression of habitual lever pressing. In vivo recordings further reveal a previously unappreciated selective modulation of SPNs based on their firing patterns; FSIs inhibit most SPNs but paradoxically promote the activity of a subset displaying high fractions of gamma-frequency spiking. These results establish a microcircuit mechanism for habits and provide a new example of how interneurons mediate experience-dependent behavior.

  18. Secretory phospholipase A2 potentiates glutamate-induced rat striatal neuronal cell death in vivo

    DEFF Research Database (Denmark)

    Kolko, M; Bruhn, T; Christensen, Thomas

    1999-01-01

    The secretory phospholipases A2 (sPLA2) OS2 (10, 20 and 50 pmol) or OS1, (50 pmol) purified from taipan snake Oxyuranus scutellatus scutellatus venom, and the excitatory amino acid glutamate (Glu) (2.5 and 5.0 micromol) were injected into the right striatum of male Wistar rats. Injection of 10...... no tissue damage or neurological abnormality. After injection of 5.0 micromol Glu, the animals initially circled towards the side of injection, and gradually developed generalized clonic convulsions. These animals showed a well demarcated striatal infarct. When non-toxic concentrations of 20 pmol OS2 and 2.......5 micromol Glu were co-injected, a synergistic neurotoxicity was observed. Extensive histological damage occurred in the entire right hemisphere, and in several rats comprising part of the contralateral hemisphere. These animals were apathetic in the immediate hours following injection, with circling towards...

  19. Dopamine D2 receptors in striatal output neurons enable the psychomotor effects of cocaine.

    Science.gov (United States)

    Kharkwal, Geetika; Radl, Daniela; Lewis, Robert; Borrelli, Emiliana

    2016-10-11

    The psychomotor effects of cocaine are mediated by dopamine (DA) through stimulation of striatal circuits. Gabaergic striatal medium spiny neurons (MSNs) are the only output of this pivotal structure in the control of movements. The majority of MSNs express either the DA D1 or D2 receptors (D1R, D2R). Studies have shown that the motor effect of cocaine depends on the DA-mediated stimulation of D1R-expressing MSNs (dMSNs), which is mirrored at the cellular level by stimulation of signaling pathways leading to phosphorylation of ERKs and induction of c-fos Nevertheless, activation of dMSNs by cocaine is necessary but not sufficient, and D2R signaling is required for the behavioral and cellular effects of cocaine. Indeed, cocaine motor effects and activation of signaling in dMSNs are blunted in mice with the constitutive knockout of D2R (D2RKO). Using mouse lines with a cell-specific knockout of D2R either in MSNs (MSN-D2RKO) or in dopaminergic neurons (DA-D2RKO), we show that D2R signaling in MSNs is required and permissive for the motor stimulant effects of cocaine and the activation of signaling in dMSNs. MSN-D2RKO mice show the same phenotype as constitutive D2RKO mice both at the behavioral and cellular levels. Importantly, activation of signaling in dMSNs by cocaine is rescued by intrastriatal injection of the GABA antagonist, bicuculline. These results are in support of intrastriatal connections of D2R + -MSNs (iMSNs) with dMSNs and indicate that D2R signaling in MSNs is critical for the function of intrastriatal circuits.

  20. Recruitment of prefrontal-striatal circuit in response to skilled motor challenge.

    Science.gov (United States)

    Guo, Yumei; Wang, Zhuo; Prathap, Sandhya; Holschneider, Daniel P

    2017-12-13

    A variety of physical fitness regimens have been shown to improve cognition, including executive function, yet our understanding of which parameters of motor training are important in optimizing outcomes remains limited. We used functional brain mapping to compare the ability of two motor challenges to acutely recruit the prefrontal-striatal circuit. The two motor tasks - walking in a complex running wheel with irregularly spaced rungs or walking in a running wheel with a smooth internal surface - differed only in the extent of skill required for their execution. Cerebral perfusion was mapped in rats by intravenous injection of [C]-iodoantipyrine during walking in either a motorized complex wheel or in a simple wheel. Regional cerebral blood flow (rCBF) was quantified by whole-brain autoradiography and analyzed in three-dimensional reconstructed brains by statistical parametric mapping and seed-based functional connectivity. Skilled or simple walking compared with rest, increased rCBF in regions of the motor circuit, somatosensory and visual cortex, as well as the hippocampus. Significantly greater rCBF increases were noted during skilled walking than for simple walking. Skilled walking, unlike simple walking or the resting condition, was associated with a significant positive functional connectivity in the prefrontal-striatal circuit (prelimbic cortex-dorsomedial striatum) and greater negative functional connectivity in the prefrontal-hippocampal circuit. Our findings suggest tha