Frontal lobe syndrome from bilateral globus pallidus lesions a complication of Wernicke's encephalopathy

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Arruda, Walter Oleschko

1991-01-01

A 38 year-old man developed the classical clinical picture of Wernicke's encephalopathy as a consequence of prolonged total parenteral nutrition. As a late complication he developed a frontal lobe syndrome. Bilateral globus pallidus lesions were observed in the CT-scan examination. Some aspects related to the cortical syndromes caused by subcortical lesions are discussed. Relata-se um caso de encefalopatia de Wernicke que ocorreu em paciente masculino de 38 anos, como complicação de alimen...

High Signal Intensity in the Dentate Nucleus and Globus Pallidus on Unenhanced T1-Weighted MR Images: Comparison between Gadobutrol and Linear Gadolinium-Based Contrast Agents.

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Moser, F G; Watterson, C T; Weiss, S; Austin, M; Mirocha, J; Prasad, R; Wang, J

2018-02-01

In view of the recent observations that gadolinium deposits in brain tissue after intravenous injection, our aim of this study was to compare signal changes in the globus pallidus and dentate nucleus on unenhanced T1-weighted MR images in patients receiving serial doses of gadobutrol, a macrocyclic gadolinium-based contrast agent, with those seen in patients receiving linear gadolinium-based contrast agents. This was a retrospective analysis of on-site patients with brain tumors. Fifty-nine patients received only gadobutrol, and 60 patients received only linear gadolinium-based contrast agents. Linear gadolinium-based contrast agents included gadoversetamide, gadobenate dimeglumine, and gadodiamide. T1 signal intensity in the globus pallidus, dentate nucleus, and pons was measured on the precontrast portions of patients' first and seventh brain MRIs. Ratios of signal intensity comparing the globus pallidus with the pons (globus pallidus/pons) and dentate nucleus with the pons (dentate nucleus/pons) were calculated. Changes in the above signal intensity ratios were compared within the gadobutrol and linear agent groups, as well as between groups. The dentate nucleus/pons signal ratio increased in the linear gadolinium-based contrast agent group ( t = 4.215, P linear gadolinium-based contrast agent group ( t = 2.931, P linear gadolinium-based contrast agents. © 2018 by American Journal of Neuroradiology.

Globus Pallidus Interna Deep Brain Stimulation in a Patient with Medically Intractable Meige Syndrome

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Dae-Woong Bae

2014-10-01

Full Text Available Medical therapies in patients with Meige syndrome, including botulinum toxin injection, have been limited because of incomplete response or adverse side effects. We evaluated a patient with Meige syndrome who was successfully treated with deep brain stimulation (DBS in the globus pallidus interna (GPi. This case report and other previous reports suggest that bilateral GPi DBS may be an effective treatment for medically refractory Meige syndrome, without significant adverse effects.

T1 Shortening in the Globus Pallidus after Multiple Administrations of Gadobutrol: Assessment with a Multidynamic Multiecho Sequence.

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Kang, Koung Mi; Choi, Seung Hong; Hwang, Moonjung; Yun, Tae Jin; Kim, Ji-Hoon; Sohn, Chul-Ho

2018-04-01

Purpose To determine the association between the administration of the macrocyclic contrast medium gadobutrol and T1 relaxation time in the brains of patients with normal renal function by using multidynamic multiecho (MDME) magnetic resonance (MR) imaging sequences. Materials and Methods The institutional review board approved this retrospective study, and the need to obtain written informed consent was waived. This study included 46 patients (revealed by an electronic medical record search) who had received one or more gadobutrol injections and a maximum of one MR imaging contrast medium injection other than gadobutrol before MDME sequence acquisition. One radiologist performed quantitative analyses of regions of interest on quantitative T1 maps twice to cover the normal-appearing globus pallidus (GP), frontal white matter, frontal cortex, and thalamus. The number of administrations and the cumulative dose of gadobutrol, age, intervals between administrations, sex, and treatment were investigated. Univariable and multivariable linear regression analyses of the T1 values in four brain regions and the GP-to-thalamus signal intensity (SI) ratio were performed. P values of less than the Bonferroni-corrected value of .01 were considered to indicate significant differences. Results Intraobserver reproducibility was good to excellent (intraclass correlation coefficients, 0.62-0.81). Because of high multicollinearity between the number of gadobutrol administrations and accumulated dose (r = 0.96, P .01). Conclusion Multiple exposures to gadobutrol are associated with T1 shortening in the GP. © RSNA, 2017 Online supplemental material is available for this article.

Left globus pallidus abnormality in never-medicated patients with schizophrenia

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Early, T.S.; Reiman, E.M.; Raichle, M.E.; Spitznagel, E.L.

1987-01-01

Schizophrenia is a severe psychiatric disorder characterized by onset in young adulthood, the occurrence of hallucinations and delusions, and the development of enduring psychosocial disability. The pathophysiology of this disorder remains unknown. Studies of cerebral blood flow and metabolism designed to identify brain abnormalities in schizophrenia have been limited by inadequate methods of anatomical localization and the possibility of persistent medication effects. The authors have now used positron emission tomography and a validated method of anatomical localization in an attempt to identify abnormalities of regional cerebral blood flow in newly diagnosed never-medicated patients with schizophrenia. An exploratory study of 5 patients and 10 normal control subjects identified abnormally high blood flow in the left globus pallidus of patients with schizophrenia. A replication study of 5 additional patients and 10 additional control subjects confirmed this finding. No other abnormalities were found

Adenosine A2A Receptor Modulates the Activity of Globus Pallidus Neurons in Rats

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Hui-Ling Diao

2017-11-01

Full Text Available The globus pallidus is a central nucleus in the basal ganglia motor control circuit. Morphological studies have revealed the expression of adenosine A2A receptors in the globus pallidus. To determine the modulation of adenosine A2A receptors on the activity of pallidal neurons in both normal and parkinsonian rats, in vivo electrophysiological and behavioral tests were performed in the present study. The extracellular single unit recordings showed that micro-pressure administration of adenosine A2A receptor agonist, CGS21680, regulated the pallidal firing activity. GABAergic neurotransmission was involved in CGS21680-induced modulation of pallidal neurons via a PKA pathway. Furthermore, application of two adenosine A2A receptor antagonists, KW6002 or SCH442416, mainly increased the spontaneous firing of pallidal neurons, suggesting that endogenous adenosine system modulates the activity of pallidal neurons through adenosine A2A receptors. Finally, elevated body swing test (EBST showed that intrapallidal microinjection of adenosine A2A receptor agonist/antagonist induced ipsilateral/contralateral-biased swing, respectively. In addition, the electrophysiological and behavioral findings also revealed that activation of dopamine D2 receptors by quinpirole strengthened KW6002/SCH442416-induced excitation of pallidal activity. Co-application of quinpirole with KW6002 or SCH442416 alleviated biased swing in hemi-parkinsonian rats. Based on the present findings, we concluded that pallidal adenosine A2A receptors may be potentially useful in the treatment of Parkinson's disease.

Systemic blockade of dopamine D2-like receptors increases high-voltage spindles in the globus pallidus and motor cortex of freely moving rats.

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Chen Yang

Full Text Available High-voltage spindles (HVSs have been reported to appear spontaneously and widely in the cortical-basal ganglia networks of rats. Our previous study showed that dopamine depletion can significantly increase the power and coherence of HVSs in the globus pallidus (GP and motor cortex of freely moving rats. However, it is unclear whether dopamine regulates HVS activity by acting on dopamine D₁-like receptors or D₂-like receptors. We employed local-field potential and electrocorticogram methods to simultaneously record the oscillatory activities in the GP and primary motor cortex (M1 in freely moving rats following systemic administration of dopamine receptor antagonists or saline. The results showed that the dopamine D₂-like receptor antagonists, raclopride and haloperidol, significantly increased the number and duration of HVSs, and the relative power associated with HVS activity in the GP and M1 cortex. Coherence values for HVS activity between the GP and M1 cortex area were also significantly increased by dopamine D₂-like receptor antagonists. On the contrary, the selective dopamine D₁-like receptor antagonist, SCH23390, had no significant effect on the number, duration, or relative power of HVSs, or HVS-related coherence between M1 and GP. In conclusion, dopamine D₂-like receptors, but not D₁-like receptors, were involved in HVS regulation. This supports the important role of dopamine D₂-like receptors in the regulation of HVSs. An siRNA knock-down experiment on the striatum confirmed our conclusion.

Systemic blockade of dopamine D2-like receptors increases high-voltage spindles in the globus pallidus and motor cortex of freely moving rats.

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Yang, Chen; Ge, Shun-Nan; Zhang, Jia-Rui; Chen, Lei; Yan, Zhi-Qiang; Heng, Li-Jun; Zhao, Tian-Zhi; Li, Wei-Xin; Jia, Dong; Zhu, Jun-Ling; Gao, Guo-Dong

2013-01-01

High-voltage spindles (HVSs) have been reported to appear spontaneously and widely in the cortical-basal ganglia networks of rats. Our previous study showed that dopamine depletion can significantly increase the power and coherence of HVSs in the globus pallidus (GP) and motor cortex of freely moving rats. However, it is unclear whether dopamine regulates HVS activity by acting on dopamine D₁-like receptors or D₂-like receptors. We employed local-field potential and electrocorticogram methods to simultaneously record the oscillatory activities in the GP and primary motor cortex (M1) in freely moving rats following systemic administration of dopamine receptor antagonists or saline. The results showed that the dopamine D₂-like receptor antagonists, raclopride and haloperidol, significantly increased the number and duration of HVSs, and the relative power associated with HVS activity in the GP and M1 cortex. Coherence values for HVS activity between the GP and M1 cortex area were also significantly increased by dopamine D₂-like receptor antagonists. On the contrary, the selective dopamine D₁-like receptor antagonist, SCH23390, had no significant effect on the number, duration, or relative power of HVSs, or HVS-related coherence between M1 and GP. In conclusion, dopamine D₂-like receptors, but not D₁-like receptors, were involved in HVS regulation. This supports the important role of dopamine D₂-like receptors in the regulation of HVSs. An siRNA knock-down experiment on the striatum confirmed our conclusion.

Seizure-induced damage to substantia nigra and globus pallidus is accompanied by pronounced intra- and extracellular acidosis

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Inamura, K.; Smith, M.L.; Hansen, A.J.; Siesjoe, B.K.

1989-01-01

Status epilepticus of greater than 30-min duration in rats gives rise to a conspicuous lesion in the substantia nigra pars reticulata (SNPR) and globus pallidus (GP). The objective of the present study was to explore whether the lesion, which encompasses necrosis of both neurons and glial cells, is related to intra- and extracellular acidosis. Using the flurothyl model previously described to produce seizures, we assessed regional pH values with the autoradiographic 5,5-dimethyl[2-14C]oxazolidine-2,4-dione technique. Regional pH values were assessed in animals with continuous seizures for 20 and 60 min, as well as in those allowed to recover for 30 and 120 min after seizure periods of 20 or 60 min. In additional animals, changes in extracellular fluid pH (pHe) were measured with ion-selective microelectrodes, and extracellular fluid (ECF) volume was calculated from the diffusion profile for electrophoretically administered tetramethylammonium. In structures such as the neocortex and the hippocampus, which show intense metabolic activation during seizures, status epilepticus of 20- and 60-min duration was accompanied by a reduction of the composite tissue pH (pHt) of 0.2-0.3 unit. Recovery of pHt was observed upon termination of seizures. In SNPR and in GP, the acidosis was marked to excessive after 20 and 60 min of seizures (delta pHt approximately 0.6 after 60 min)

Signal intensity change on unenhanced T1-weighted images in dentate nucleus and globus pallidus after multiple administrations of gadoxetate disodium: an intraindividual comparative study

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Conte, Giorgio; Minotti, Marta; De Piano, Francesca [Universita degli Studi di Milano, Postgraduation School in Radiodiagnostics, Milan (Italy); Preda, Lorenzo [Universita degli Studi di Pavia, Department of Clinical-Surgical Diagnostic and Pediatric Sciences, Pavia (Italy); National Center of Oncological Hadrontherapy (CNAO Foundation), Division of Radiology, Pavia (Italy); Cocorocchio, Emilia; Ferrucci, Pier Francesco [European Institute of Oncology, Melanoma and Sarcoma Medical Oncology Division, Milan (Italy); Raimondi, Sara [European Institute of Oncology, Division of Epidemiology and Biostatistics, Milan (Italy); Giannitto, Caterina; Petralia, Giuseppe [European Institute of Oncology, Division of Radiology, Milan (Italy); Bellomi, Massimo [European Institute of Oncology, Division of Radiology, Milan (Italy); Universita degli Studi di Milano, Oncology and Haematology/Oncology Department, Milan (Italy)

2017-10-15

To investigate whether there is an increased signal intensity (SI) of dentate nucleus (DN) and globus pallidus (GP) on unenhanced T1-weighted magnetic resonance imaging (MRI), in patients who had undergone multiple administrations of gadoxetate disodium. We retrospectively included stage III melanoma patients, who had been previously enrolled in a trial of adjuvant therapy and who had undergone whole-body contrast-enhanced MRIs with gadoxetate disodium every three months for their follow-up. The SI ratios of DN-to-pons and GP-to-thalamus on unenhanced T1-weighted images were calculated. The difference in SI ratios between the first and the last MRI examinations was assessed and a linear mixed model was performed to detect how SI ratios varied with the number of administrations. Eighteen patients were included in our study. The number of gadoxetate disodium administrations ranged from 2 to 18. Paired t-test did not show any significant difference in DN-to-pons (p=0.21) and GP-to-thalamus (p=0.09) SI ratios by the end of the study. DN-to-pons SI ratio and GP-to-thalamus SI ratio did not significantly increase with increasing the number of administrations (p=0.14 and p=0.06, respectively). Multiple administrations of gadoxetate disodium are not associated with increased SI in DN and GP in the brain. (orig.)

New MRI findings in Creutzfeldt-Jakob disease: high signal in the globus pallidus on T 1-weighted images

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Priester, J.A. de; Wilmink, J.T.; Jansen, G.H.; Kruijk, J.R. de

1999-01-01

We report a 49-year-old woman with Creutzfeldt-Jakob disease (CJD). In addition to typical high-signal lesions on proton-density and T 2-weighted images there was high signal in the globus pallidus bilaterally on T 1-weighted images. The latter feature has not been described previously and probably due to deposition of prion protein, as found at autopsy. (orig.)

Dopamine depletion increases the power and coherence of high-voltage spindles in the globus pallidus and motor cortex of freely moving rats.

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Ge, Shunnan; Yang, Chen; Li, Min; Li, Jiang; Chang, Xiaozan; Fu, Jian; Chen, Lei; Chang, Chongwang; Wang, Xuelian; Zhu, Junling; Gao, Guodong

2012-07-17

Studies on patients with Parkinson's disease and in animal models have observed enhanced synchronization of oscillations in several frequency bands within and between the cortical-basal ganglia (BG) structures. Recent research has also shown that synchronization of high-voltage spindles (HVSs) in the cortex, striatum and substantia nigra pars reticulate is increased by dopamine depletion. However, more evidence is needed to determine whether HVS activity in the whole cortex-BG network represents homologous alteration following dopamine depletion. As the globus pallidus (GP) is in a central position to propagate and synchronize oscillations in the cortical-BG circuits, we employed local-field potentials and electrocorticogram to simultaneously record oscillations in the GP and primary (M1) and secondary (M2) motor cortices on freely moving 6-hydroxydopamine (6-OHDA) lesioned and control rats. Results showed that HVS episodes recorded from GP, and M2 and M1 cortex areas were more numerous and longer in 6-OHDA lesioned rats compared to controls. Relative power associated with HVS activity in the GP, and M2 and M1 cortices of 6-OHDA lesioned rats was significantly greater than that for control rats. Coherence values for HVS activity between the GP, and M2 and M1 cortex areas were significantly increased by dopamine depletion. Time lag between the M1 cortex HVS and GP HVS was significantly shorter for dopamine depleted than normal rats. Findings indicate a crucial rule for dopamine in the regulation of HVS activity in the whole cortical-BG circuit, and suggest a close relationship between abnormally synchronized HVS oscillations in the cortex-BG network and Parkinson's disease. Copyright © 2012 Elsevier B.V. All rights reserved.

New MRI findings in Creutzfeldt-Jakob disease: high signal in the globus pallidus on T 1-weighted images

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Priester, J.A. de; Wilmink, J.T. [Dept. of Radiology, University Hospital Maastricht (Netherlands); Jansen, G.H. [Department of Neuropathology, University Hospital Utrecht (Netherlands); Kruijk, J.R. de [Department of Neurology, University Hospital Maastricht (Netherlands)

1999-04-01

We report a 49-year-old woman with Creutzfeldt-Jakob disease (CJD). In addition to typical high-signal lesions on proton-density and T 2-weighted images there was high signal in the globus pallidus bilaterally on T 1-weighted images. The latter feature has not been described previously and probably due to deposition of prion protein, as found at autopsy. (orig.) With 3 figs., 11 refs.

Signal intensity at unenhanced T1-weighted magnetic resonance in the globus pallidus and dentate nucleus after serial administrations of a macrocyclic gadolinium-based contrast agent in children

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Rossi Espagnet, Maria Camilla; Bernardi, Bruno; Figa-Talamanca, Lorenzo [Ospedale Pediatrico Bambino Gesu, IRCCS, Neuroradiology Unit, Imaging Department, Rome (Italy); Pasquini, Luca [Ospedale Pediatrico Bambino Gesu, IRCCS, Neuroradiology Unit, Imaging Department, Rome (Italy); University Sapienza, Neuroradiology Unit, Azienda Ospedaliera Sant' Andrea, Rome (Italy); Toma, Paolo [Ospedale Pediatrico Bambino Gesu, IRCCS, Department of Imaging, Rome (Italy); Napolitano, Antonio [Ospedale Pediatrico Bambino Gesu, IRCCS, Enterprise Risk Management, Medical Physics Department, Rome (Italy)

2017-09-15

Few studies have been conducted on the relations between T1-weighted signal intensity changes in the pediatric brain following gadolinium-based contrast agent (GBCA) exposure. The purpose of this study is to investigate the effect of multiple administrations of a macrocyclic GBCA on signal intensity in the globus pallidus and dentate nucleus of the pediatric brain on unenhanced T1-weighted MR images. This retrospective study included 50 patients, mean age: 8 years (standard deviation: 4.8 years), with normal renal function exposed to ≥6 administrations of the same macrocyclic GBCA (gadoterate meglumine) and a control group of 59 age-matched GBCA-naive patients. The globus pallidus-to-thalamus signal intensity ratio and dentate nucleus-to-pons signal intensity ratio were calculated from unenhanced T1-weighted images for both patients and controls. A mixed linear model was used to evaluate the effects on signal intensity ratios of the number of GBCA administrations, the time interval between administrations, age, radiotherapy and chemotherapy. T-test analyses were performed to compare signal intensity ratio differences between successive administrations and baseline MR signal intensity ratios in patients compared to controls. P-values were considered significant if <0.05. A significant effect of the number of GBCA administrations on relative signal intensities globus pallidus-to-thalamus (F[8]=3.09; P=0.002) and dentate nucleus-to-pons (F[8]=2.36; P=0.021) was found. The relative signal intensities were higher at last MR examination than at baseline (P<0.001). Quantitative analysis evaluation of globus pallidus:thalamus and dentate nucleus:pons of the pediatric brain demonstrated an increase after serial administrations of macrocyclic GBCA. Further research is necessary to fully understand GBCA pharmacokinetic in children. (orig.)

The globus pallidus sends reward-related signals to the lateral habenula.

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Hong, Simon; Hikosaka, Okihide

2008-11-26

As a major output station of the basal ganglia, the globus pallidus internal segment (GPi) projects to the thalamus and brainstem nuclei thereby controlling motor behavior. A less well known fact is that the GPi also projects to the lateral habenula (LHb) which is often associated with the limbic system. Using the monkey performing a saccade task with positionally biased reward outcomes, we found that antidromically identified LHb-projecting neurons were distributed mainly in the dorsal and ventral borders of the GPi and that their activity was strongly modulated by expected reward outcomes. A majority of them were excited by the no-reward-predicting target and inhibited by the reward-predicting target. These reward-dependent modulations were similar to those in LHb neurons but started earlier than those in LHb neurons. These results suggest that GPi may initiate reward-related signals through its effects on the LHb, which then influences the dopaminergic and serotonergic systems.

Reversibility of hyperintense globus pallidus on T 1-weighted MRI following surgery for a portosystemic shunt in an 8-year-old girl

International Nuclear Information System (INIS)

Ikeda, Shinji; Sera, Yoshihisa; Yoshida, Mituhiro; Ohshiro, Hajime; Uchino, Shinichiro; Seguchi, Sasa; Endo, Fumio

1999-01-01

An 8-year-old Japanese girl with a portosystemic shunt had shown hyperammonaemia since she was 3 years of age. MRI of her brain showed bilateral hyperintense globus pallidus. A portosystemic shunt was evident on US and angiography. She underwent surgical banding of the shunt, after which the lesion and clinical symptoms disappeared. (orig.)

Increasing signal intensity within the dentate nucleus and globus pallidus on unenhanced T1W magnetic resonance images in patients with relapsing-remitting multiple sclerosis: correlation with cumulative dose of a macrocyclic gadolinium-based contrast agent, gadobutrol

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Stojanov, Dragan A. [University of Nis, Faculty of Medicine, Nis (Serbia); Clinical Center Nis, Center for Radiology, Nis (Serbia); Aracki-Trenkic, Aleksandra [Clinical Center Nis, Center for Radiology, Nis (Serbia); Vojinovic, Slobodan; Ljubisavljevic, Srdjan [University of Nis, Faculty of Medicine, Nis (Serbia); Clinical Center Nis, Clinic for Neurology, Nis (Serbia); Benedeto-Stojanov, Daniela [University of Nis, Faculty of Medicine, Nis (Serbia)

2016-03-15

To evaluate correlation between cumulative dose of gadobutrol and signal intensity (SI) within dentate nucleus and globus pallidus on unenhanced T1-weighted images in patients with relapsing-remitting multiple sclerosis (RRMS). Dentate nucleus-to-pons and globus pallidus-to-thalamus SI ratios, and renal and liver functions, were evaluated after multiple intravenous administrations of 0.1 mmol/kg gadobutrol at 27, 96-98, and 168 weeks. We compared SI ratios based on the number of administrations, total amount of gadobutrol administered, and time between injections. Globus pallidus-to-thalamus (p = 0.025) and dentate nucleus-to-pons (p < 0.001) SI ratios increased after multiple gadobutrol administrations, correlated with the number of administrations (ρ = 0.263, p = 0.046, respectively) and depended on the length of administration (p = 0.017, p = 0.037, respectively). Patients receiving gadobutrol at 27 weeks showed the greatest increase in both SI ratios (p = 0.006; p = 0.014, respectively, versus 96-98 weeks). GGT increased at the end of the study (p = 0.004). In patients with RRMS, SI within the dentate nucleus and globus pallidus increased on unenhanced T1-weighted images after multiple gadobutrol injections. Administration of the same total amount of gadobutrol over a shorter period caused greater SI increase. (orig.)

Aberrant resting-state corticostriatal functional connectivity in cirrhotic patients with hyperintense globus pallidus on T1-weighted MR imaging.

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Xi-Qi Zhu

Full Text Available Neurobiological and neuroimaging studies have emphasized the structural and functional alterations in the striatum of cirrhotic patients, but alterations in the functional connections between the striatum and other brain regions have not yet been explored. Of note, manganese accumulation in the nervous system, frequently reflected by hyperintensity at the bilateral globus pallidus (GP on T1-weighted imaging, has been considered a factor affecting the striatal and cortical functions in hepatic decompensation. We employed resting-state functional magnetic resonance imaging to analyze the temporal correlation between the striatum and the remaining brain regions using seed-based correlation analyses. The two-sample t-test was conducted to detect the differences in corticostriatal connectivity between 44 cirrhotic patients with hyperintensity at the bilateral GP and 20 healthy controls. Decreased connectivity of the caudate was detected in the anterior/middle cingulate gyrus, and increased connectivity of the caudate was found in the left motor cortex. A reduction in functional connectivity was found between the putamen and several regions, including the anterior cingulate gyrus, right insular lobe, inferior frontal gyrus, left parahippocampal gyrus, and anterior lobe of the right cerebellum; increased connectivity was detected between the putamen and right middle temporal gyrus. There were significant correlations between the corticostriatal connectivity and neuropsychological performances in the patient group, but not between the striatal connectivity and GP signal intensity. These alterations in the corticostriatal functional connectivity suggested the abnormalities in the intrinsic brain functional organiztion among the cirrhotic patients with manganese deposition, and may be associated with development of metabolic encephalopathy. The manganese deposition in nervous system, however, can not be an independent factor predicting the resting

Globus pallidus high-signal lesions: A predominant MRI finding in children with neurofibromatosis type 1

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Arif Khan

2013-01-01

Full Text Available Introduction: Lesions of the brain, recognized as unidentified bright objects (UBOs, are commonly observed as areas of increased T2-weighted signal intensity on magnetic resonance imaging (MRI in children with neurofibromatosis type 1 (NF1. Identification of these lesions is not currently encompassed in the National Institute of Health (NIH diagnostic criteria for NF1. Objective: We aimed to determine the prevalence of UBOs in children with NF1 and identify areas of the brain that are commonly affected by these lesions, allowing us to evaluate whether UBOs should be included in the diagnostic criteria for the diagnosis of NF1. Materials and Methods: We reviewed the cranial MRI scans of 22 children who had been diagnosed with sporadic or familial NF1 in accordance with the criteria established by NIH. UBOs were present in 81% of the children with NF1. Results: These lesions have a predilection for specific areas of the brain, including the globus pallidus (72%, cerebellum (66%, brainstem (27% and cerebral hemispheres (16%. The prevalence of UBOs identified varied significantly with age and sex; they were infrequent in children less than 4 years of age but were common in those aged between 4 and 12 years of age. UBOs were more commonly seen in males (66.6% compared with females (33.3%. Repeat MRI scan on a subset of these patients with UBOs did not show any significant changes despite a worsening in clinical symptoms. Conclusion and Discussion: We have shown that UBOs are a common finding in children with NF1, and are most prevalent between the ages of 4 and 12 years. Many sites of the brain are affected by these lesions, most notably the globus pallidus and the cerebellum. Further research must be conducted to elucidate the significance of UBOs in patients with NF1 and whether these lesions have any utility in the clinical detection of NF1.

Parvalbumin+ Neurons and Npas1+ Neurons Are Distinct Neuron Classes in the Mouse External Globus Pallidus.

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Hernández, Vivian M; Hegeman, Daniel J; Cui, Qiaoling; Kelver, Daniel A; Fiske, Michael P; Glajch, Kelly E; Pitt, Jason E; Huang, Tina Y; Justice, Nicholas J; Chan, C Savio

2015-08-26

Compelling evidence suggests that pathological activity of the external globus pallidus (GPe), a nucleus in the basal ganglia, contributes to the motor symptoms of a variety of movement disorders such as Parkinson's disease. Recent studies have challenged the idea that the GPe comprises a single, homogenous population of neurons that serves as a simple relay in the indirect pathway. However, we still lack a full understanding of the diversity of the neurons that make up the GPe. Specifically, a more precise classification scheme is needed to better describe the fundamental biology and function of different GPe neuron classes. To this end, we generated a novel multicistronic BAC (bacterial artificial chromosome) transgenic mouse line under the regulatory elements of the Npas1 gene. Using a combinatorial transgenic and immunohistochemical approach, we discovered that parvalbumin-expressing neurons and Npas1-expressing neurons in the GPe represent two nonoverlapping cell classes, amounting to 55% and 27% of the total GPe neuron population, respectively. These two genetically identified cell classes projected primarily to the subthalamic nucleus and to the striatum, respectively. Additionally, parvalbumin-expressing neurons and Npas1-expressing neurons were distinct in their autonomous and driven firing characteristics, their expression of intrinsic ion conductances, and their responsiveness to chronic 6-hydroxydopamine lesion. In summary, our data argue that parvalbumin-expressing neurons and Npas1-expressing neurons are two distinct functional classes of GPe neurons. This work revises our understanding of the GPe, and provides the foundation for future studies of its function and dysfunction. Until recently, the heterogeneity of the constituent neurons within the external globus pallidus (GPe) was not fully appreciated. We addressed this knowledge gap by discovering two principal GPe neuron classes, which were identified by their nonoverlapping expression of the

Parvalbumin+ Neurons and Npas1+ Neurons Are Distinct Neuron Classes in the Mouse External Globus Pallidus

Science.gov (United States)

Hernández, Vivian M.; Hegeman, Daniel J.; Cui, Qiaoling; Kelver, Daniel A.; Fiske, Michael P.; Glajch, Kelly E.; Pitt, Jason E.; Huang, Tina Y.; Justice, Nicholas J.

2015-01-01

Compelling evidence suggests that pathological activity of the external globus pallidus (GPe), a nucleus in the basal ganglia, contributes to the motor symptoms of a variety of movement disorders such as Parkinson's disease. Recent studies have challenged the idea that the GPe comprises a single, homogenous population of neurons that serves as a simple relay in the indirect pathway. However, we still lack a full understanding of the diversity of the neurons that make up the GPe. Specifically, a more precise classification scheme is needed to better describe the fundamental biology and function of different GPe neuron classes. To this end, we generated a novel multicistronic BAC (bacterial artificial chromosome) transgenic mouse line under the regulatory elements of the Npas1 gene. Using a combinatorial transgenic and immunohistochemical approach, we discovered that parvalbumin-expressing neurons and Npas1-expressing neurons in the GPe represent two nonoverlapping cell classes, amounting to 55% and 27% of the total GPe neuron population, respectively. These two genetically identified cell classes projected primarily to the subthalamic nucleus and to the striatum, respectively. Additionally, parvalbumin-expressing neurons and Npas1-expressing neurons were distinct in their autonomous and driven firing characteristics, their expression of intrinsic ion conductances, and their responsiveness to chronic 6-hydroxydopamine lesion. In summary, our data argue that parvalbumin-expressing neurons and Npas1-expressing neurons are two distinct functional classes of GPe neurons. This work revises our understanding of the GPe, and provides the foundation for future studies of its function and dysfunction. SIGNIFICANCE STATEMENT Until recently, the heterogeneity of the constituent neurons within the external globus pallidus (GPe) was not fully appreciated. We addressed this knowledge gap by discovering two principal GPe neuron classes, which were identified by their nonoverlapping

Studies on the clinical significance of pallidal high intensity of T1-weighted MR imaging in patients with liver cirrhosis

International Nuclear Information System (INIS)

Morino, Koutaro

1997-01-01

We investigated the clinical significances of signals in cirrhotic patients with special relation to subclinical hepatic encephalopathy. MRI was carried out in 30 patients with liver cirrhosis in the abscence of hepatic encephalopathy greater than grade II, and in 20 healthy subjects. Signal intensity of the globus pallidus was standardized to GP index. GP index=100 x (signal intensity of the globus pallidus - signal intensity of the putamen)/(signal intensity of the globus pallidus + signal intensity of the putamen). Normal value of GP index obtained in healthy subjects was -0.66∼4.70. Twenty seven of 30 cirrhotic patients showed GP index higher than the normal range. GP index correlated significantly with the blood manganese concentration. This observation suggested that the pallidal high intensity signals were brought about by the deposition of Mn in the globus pallidus. GP index correlated significantly with the central conduction time (CCT) measured by somatosensory evoked potentials. GP index and CCT may reflect the similar pathophysiological changes of the brain in patients with liver cirrhosis. Multivariate analysis revealed that GP index was explained well by the presence of portal systemic shunts and by preceding histories of hepatic encephalopathy but not by the present grade of the liver parenchymal damage. For the earlier diagnosis of subclinical hepatic encephalopathy, GP index showed an excellent parameter similar to those of somatosensory evoked potentials and psychometric tests. GP index is favorable than electrophysiological methods in terms of its non-invasiveness to the patients and simplicity of the examination technique. (K.H.)

Studies on the clinical significance of pallidal high intensity of T{sub 1}-weighted MR imaging in patients with liver cirrhosis

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Morino, Koutaro [Gifu Univ. (Japan). School of Medicine

1997-03-01

We investigated the clinical significances of signals in cirrhotic patients with special relation to subclinical hepatic encephalopathy. MRI was carried out in 30 patients with liver cirrhosis in the abscence of hepatic encephalopathy greater than grade II, and in 20 healthy subjects. Signal intensity of the globus pallidus was standardized to GP index. GP index=100 x (signal intensity of the globus pallidus - signal intensity of the putamen)/(signal intensity of the globus pallidus + signal intensity of the putamen). Normal value of GP index obtained in healthy subjects was -0.66{approx}4.70. Twenty seven of 30 cirrhotic patients showed GP index higher than the normal range. GP index correlated significantly with the blood manganese concentration. This observation suggested that the pallidal high intensity signals were brought about by the deposition of Mn in the globus pallidus. GP index correlated significantly with the central conduction time (CCT) measured by somatosensory evoked potentials. GP index and CCT may reflect the similar pathophysiological changes of the brain in patients with liver cirrhosis. Multivariate analysis revealed that GP index was explained well by the presence of portal systemic shunts and by preceding histories of hepatic encephalopathy but not by the present grade of the liver parenchymal damage. For the earlier diagnosis of subclinical hepatic encephalopathy, GP index showed an excellent parameter similar to those of somatosensory evoked potentials and psychometric tests. GP index is favorable than electrophysiological methods in terms of its non-invasiveness to the patients and simplicity of the examination technique. (K.H.)

Modeling Laterality of the Globus Pallidus Internus in Patients With Parkinson's Disease.

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Sharim, Justin; Yazdi, Daniel; Baohan, Amy; Behnke, Eric; Pouratian, Nader

2017-04-01

Neurosurgical interventions such as deep brain stimulation surgery of the globus pallidus internus (GPi) play an important role in the treatment of medically refractory Parkinson's disease (PD), and require high targeting accuracy. Variability in the laterality of the GPi across patients with PD has not been well characterized. The aim of this report is to identify factors that may contribute to differences in position of the motor region of GPi. The charts and operative reports of 101 PD patients following deep brain stimulation surgery (70 males, aged 11-78 years) representing 201 GPi were retrospectively reviewed. Data extracted for each subject include age, gender, anterior and posterior commissures (AC-PC) distance, and third ventricular width. Multiple linear regression, stepwise regression, and relative importance of regressors analysis were performed to assess the predictive ability of these variables on GPi laterality. Multiple linear regression for target vs. third ventricular width, gender, AC-PC distance, and age were significant for normalized linear regression coefficients of 0.333 (p laterality of 0.19 mm per mm of ventricular width, 0.11 mm per mm of AC-PC distance, 0.017 mm per year in age, and 0.54 mm increase for male gender. This variability highlights the limitations of indirect targeting alone, and argues for the continued use of MRI as well as intraoperative physiological testing to account for such factors that contribute to patient-specific variability in GPi localization. © 2016 International Neuromodulation Society.

Properties of Neurons in External Globus Pallidus Can Support Optimal Action Selection

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Bogacz, Rafal; Martin Moraud, Eduardo; Abdi, Azzedine; Magill, Peter J.; Baufreton, Jérôme

2016-01-01

The external globus pallidus (GPe) is a key nucleus within basal ganglia circuits that are thought to be involved in action selection. A class of computational models assumes that, during action selection, the basal ganglia compute for all actions available in a given context the probabilities that they should be selected. These models suggest that a network of GPe and subthalamic nucleus (STN) neurons computes the normalization term in Bayes’ equation. In order to perform such computation, the GPe needs to send feedback to the STN equal to a particular function of the activity of STN neurons. However, the complex form of this function makes it unlikely that individual GPe neurons, or even a single GPe cell type, could compute it. Here, we demonstrate how this function could be computed within a network containing two types of GABAergic GPe projection neuron, so-called ‘prototypic’ and ‘arkypallidal’ neurons, that have different response properties in vivo and distinct connections. We compare our model predictions with the experimentally-reported connectivity and input-output functions (f-I curves) of the two populations of GPe neurons. We show that, together, these dichotomous cell types fulfil the requirements necessary to compute the function needed for optimal action selection. We conclude that, by virtue of their distinct response properties and connectivities, a network of arkypallidal and prototypic GPe neurons comprises a neural substrate capable of supporting the computation of the posterior probabilities of actions. PMID:27389780

Childhood Laryngeal Dystonia Following Bilateral Globus Pallidus Abnormality: A Case Study and Review of Literature

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Mohammad Javad Saeedi Borujeni

2017-01-01

Full Text Available Introduction:Dystonia is a disorder of movement caused by various etiologies. Laryngeal dystonia is caused by the spasm of laryngeal muscles. It is a disorder caused by vocal fold movement in which excessive adduction or abduction of the vocal folds occurs during speech. The pathophysiology of this type of dystonia is not fully known. Some researchers have suggested that basal ganglia structures and their connections with cortical areas have been involved in the pathogenesis of dystonia. Case Report:In this paper a 7.5-year-old boy suffering from laryngeal dystonia with bilateral lesions in Globus Pallidus is presented. The patient also suffered from swallowing problems, monotone voice, vocal tremor, hypersensitivity of gag reflex, and stuttering. Drug treatment failed to cure him; therefore, he was referred to rehabilitation therapy.  Conclusion:In conclusion, special attention should be brought upon laryngeal dystonia, especially in patients showing Extra-pyramidal symptoms and/or abnormalities of the basal ganglia. In children, laryngeal dystonia may be potentially fatal. Lack of consideration for this condition during rehabilitation therapy can lead to serious consequences for a child.

Optimal MRI methods for direct stereotactic targeting of the subthalamic nucleus and globus pallidus

International Nuclear Information System (INIS)

O'Gorman, Ruth L.; Shmueli, Karin; Ashkan, Keyoumars; Selway, Richard P.; Samuel, Michael; Lythgoe, David J.; Shahidiani, Asal; Wastling, Stephen J.; Footman, Michelle; Jarosz, Jozef

2011-01-01

Reliable identification of the subthalamic nucleus (STN) and globus pallidus interna (GPi) is critical for deep brain stimulation (DBS) of these structures. The purpose of this study was to compare the visibility of the STN and GPi with various MRI techniques and to assess the suitability of each technique for direct stereotactic targeting. MR images were acquired from nine volunteers with T2- and proton density-weighted (PD-W) fast spin echo, susceptibility-weighted imaging (SWI), phase-sensitive inversion recovery and quantitative T1, T2 and T2 * mapping sequences. Contrast-to-noise ratios (CNR) for the STN and GPi were calculated for all sequences. Targeting errors on SWI were evaluated on magnetic susceptibility maps. The sequences demonstrating the best conspicuity of DBS target structures (SWI and T2*) were then applied to ten patients with movement disorders, and the CNRs for these techniques were assessed. SWI offers the highest CNR for the STN, but standard PD-W images provide the best CNR for the pallidum. Susceptibility maps indicated that the GPi margins may be shifted slightly on SWI, although no shifts were seen for the STN. SWI may improve the visibility of the STN on pre-operative MRI, potentially improving the accuracy of direct stereotactic targeting. (orig.)

Prototypic and Arkypallidal Neurons in the Dopamine-Intact External Globus Pallidus

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Abdi, Azzedine; Mallet, Nicolas; Mohamed, Foad Y.; Sharott, Andrew; Dodson, Paul D.; Nakamura, Kouichi C.; Suri, Sana; Avery, Sophie V.; Larvin, Joseph T.; Garas, Farid N.; Garas, Shady N.; Vinciati, Federica; Morin, Stéphanie; Bezard, Erwan

2015-01-01

Studies in dopamine-depleted rats indicate that the external globus pallidus (GPe) contains two main types of GABAergic projection cell; so-called “prototypic” and “arkypallidal” neurons. Here, we used correlative anatomical and electrophysiological approaches in rats to determine whether and how this dichotomous organization applies to the dopamine-intact GPe. Prototypic neurons coexpressed the transcription factors Nkx2-1 and Lhx6, comprised approximately two-thirds of all GPe neurons, and were the major GPe cell type innervating the subthalamic nucleus (STN). In contrast, arkypallidal neurons expressed the transcription factor FoxP2, constituted just over one-fourth of GPe neurons, and innervated the striatum but not STN. In anesthetized dopamine-intact rats, molecularly identified prototypic neurons fired at relatively high rates and with high regularity, regardless of brain state (slow-wave activity or spontaneous activation). On average, arkypallidal neurons fired at lower rates and regularities than prototypic neurons, and the two cell types could be further distinguished by the temporal coupling of their firing to ongoing cortical oscillations. Complementing the activity differences observed in vivo, the autonomous firing of identified arkypallidal neurons in vitro was slower and more variable than that of prototypic neurons, which tallied with arkypallidal neurons displaying lower amplitudes of a “persistent” sodium current important for such pacemaking. Arkypallidal neurons also exhibited weaker driven and rebound firing compared with prototypic neurons. In conclusion, our data support the concept that a dichotomous functional organization, as actioned by arkypallidal and prototypic neurons with specialized molecular, structural, and physiological properties, is fundamental to the operations of the dopamine-intact GPe. PMID:25926446

Distinct Developmental Origins Manifest in the Specialized Encoding of Movement by Adult Neurons of the External Globus Pallidus

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Dodson, Paul D.; Larvin, Joseph T.; Duffell, James M.; Garas, Farid N.; Doig, Natalie M.; Kessaris, Nicoletta; Duguid, Ian C.; Bogacz, Rafal; Butt, Simon J.B.; Magill, Peter J.

2015-01-01

Summary Transcriptional codes initiated during brain development are ultimately realized in adulthood as distinct cell types performing specialized roles in behavior. Focusing on the mouse external globus pallidus (GPe), we demonstrate that the potential contributions of two GABAergic GPe cell types to voluntary action are fated from early life to be distinct. Prototypic GPe neurons derive from the medial ganglionic eminence of the embryonic subpallium and express the transcription factor Nkx2-1. These neurons fire at high rates during alert rest, and encode movements through heterogeneous firing rate changes, with many neurons decreasing their activity. In contrast, arkypallidal GPe neurons originate from lateral/caudal ganglionic eminences, express the transcription factor FoxP2, fire at low rates during rest, and encode movements with robust increases in firing. We conclude that developmental diversity positions prototypic and arkypallidal neurons to fulfil distinct roles in behavior via their disparate regulation of GABA release onto different basal ganglia targets. PMID:25843402

Increased signal intensities in the dentate nucleus and globus pallidus on unenhanced T1-weighted images: evidence in children undergoing multiple gadolinium MRI exams

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Hu, Houchun H.; Pokorney, Amber; Towbin, Richard B.; Miller, Jeffrey H. [Phoenix Children' s Hospital, Department of Medical Imaging and Radiology, Phoenix, AZ (United States)

2016-10-15

Recent reports have suggested residual gadolinium deposition in the brain in subjects undergoing multiple contrast-enhanced MRI exams. These findings have raised some concerns regarding gadolinium-based contrast agent (GBCA) usage and retention in brain tissues. To summarize findings of hyperintense brain structures on precontrast T1-weighted images in 21 children undergoing multiple GBCA MRI exams. This retrospective study involved 21 patients, each of whom received multiple MRI examinations (range: 5-37 exams) with GBCA over the course of their medical treatment (duration from first to most recent exam: 1.2-12.9 years). The patients were between 0.9 and 14.4 years of age at the time of their first GBCA exam. Regions of interest were drawn in the dentate nucleus and the globus pallidus on 2-D fast spin echo images acquired at 1.5 T. The signal intensities of these two structures were normalized by that of the corpus callosum genu. Signal intensity ratios from these patients were compared to control patients of similar ages who have never received GBCA. Signal intensity ratios increased between the first and the most recent MRI exam in all 21 patients receiving GBCA, with an increase of 18.6%±12.7% (range: 0.5% to 47.5%) for the dentate nucleus and 12.4%±7.4% (range: -1.2% to 33.7%) for the globus pallidus (P<0.0001). Signal intensity ratios were also higher in GBCA patients than in controls (P<0.01). The degree of signal intensity enhancement did not correlate with statistical significance to the cumulative number or volume of GBCA administrations each patient received, the patient's age or the elapsed time between the first and most recent GBCA MRI exams. These results in children are consistent with recent findings in adults, suggesting possible gadolinium deposition in the brain. (orig.)

Immediate recovery of neurological function in response to deep brain stimulation of the globus pallidus internus in a patient with idiopathic camptocormia

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I. Madrazo

2016-04-01

Full Text Available Camptocormia is a major disabling abnormality characterized by severe forward flexion of the thoracolumbar spine. We report here on the effectiveness of deep brain stimulation (DBS for the management of a case of untreatable idiopathic camptocormia. The patient, a 51-year-old male, with an 11-year-long history of radicular pain. Camptocormia symptomatology initiated 4 years ago. Preoperative muscle electrodiagnostic testing was within normal limits. Myopathy was ruled out. In the standing position myokymic discharges were recorded. Under local anesthesia and stereotactic control, electrodes for DBS were placed bilaterally in the globus pallidus internus. Patient's symptoms disappeared immediately following DBS. This response cannot be attributed to the surgical procedure itself. When stimulators were turned “off” accidentally, the patient returned immediately to his pre-surgery condition. Erect posture and walking were restored when stimulators were back “on”.

Long-Term Clinical Outcome of Internal Globus Pallidus Deep Brain Stimulation for Dystonia.

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Hye Ran Park

Full Text Available GPi (Internal globus pallidus DBS (deep brain stimulation is recognized as a safe, reliable, reversible and adjustable treatment in patients with medically refractory dystonia.This report describes the long-term clinical outcome of 36 patients implanted with GPi DBS at the Neurosurgery Department of Seoul National University Hospital.Nine patients with a known genetic cause, 12 patients with acquired dystonia, and 15 patients with isolated dystonia without a known genetic cause were included. When categorized by phenomenology, 29 patients had generalized, 5 patients had segmental, and 2 patients had multifocal dystonia. Patients were assessed preoperatively and at defined follow-up examinations postoperatively, using the Burke-Fahn-Marsden dystonia rating scale (BFMDRS for movement and functional disability assessment. The mean follow-up duration was 47 months (range, 12-84.The mean movement scores significantly decreased from 44.88 points preoperatively to 26.45 points at 60-month follow up (N = 19, P = 0.006. The mean disability score was also decreased over time, from 11.54 points preoperatively to 8.26 points at 60-month follow up, despite no statistical significance (N = 19, P = 0.073. When analyzed the movement and disability improvement rates at 12-month follow up point, no significant difference was noted according to etiology, disease duration, age at surgery, age of onset, and phenomenology. However, the patients with DYT-1 dystonia and isolated dystonia without a known genetic cause showed marked improvement.GPi DBS is a safe and efficient therapeutic method for treatment of dystonia patients to improve both movement and disability. However, this study has some limitations caused by the retrospective design with small sample size in a single-center.

Deep brain stimulation of the antero-medial globus pallidus interna for Tourette syndrome.

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Perminder S Sachdev

Full Text Available BACKGROUND: We have previously reported the results of Deep Brain Stimulation (DBS of the antero-medial globus pallidus interna (GPi for severe Tourette Syndrome (TS in 11 patients. We extend this case series to 17 patients and a longer follow-up to a maximum of 46 months. METHODS: 17 patients (14 male; mean age 29.1 years, range 17-51 years with severe and medically intractable TS were implanted with Medtronic quadripolar electrodes bilaterally in the antero-medial GPi. The primary outcome measure was the Yale Global Tic Severity Scale (YGTSS. Secondary outcome measures included the Yale-Brown Obsessive Compulsive Scale, Hamilton Depression Rating Scale, Gilles de la Tourette Quality of Life Scale and Global Assessment of Functioning. Follow up was at one month, three months and finally at a mean 24.1 months (range 8-46 months following surgery. RESULTS: Overall, there was a 48.3% reduction in motor tics and a 41.3% reduction in phonic tics at one month, and this improvement was maintained at final follow-up. 12 out of 17 (70.6% patients had a>50% reduction in YGTSS score at final follow up. Only 8 patients required ongoing pharmacotherapy for tics post-surgery. Patients improved significantly on all secondary measures. Adverse consequences included lead breakage in 4 patients, infection (1, transient anxiety (2, dizziness (1, poor balance (1 and worsening of stuttering (1. CONCLUSIONS: This case series provides further support that antero-medial GPi DBS is an effective and well tolerated treatment for a subgroup of severe TS, with benefits sustained up to 4 years.

Effect of subthalamic nucleus or globus pallidus interna stimulation on oculomotor function in patients with Parkinson's disease.

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Fridley, Jared; Adams, Gareth; Sun, Ping; York, Michelle; Atassi, Farah; Lai, Eugene; Simpson, Richard; Viswanathan, Ashwin; Yoshor, Daniel

2013-01-01

Deep brain stimulation (DBS) of either the globus pallidus interna (GPi) or subthalamic nucleus (STN) is similarly effective for treating somatomotor manifestations of Parkinson's disease (PD), but differences in how stimulation of each target affects oculomotor function are poorly understood. We sought to determine if stimulation of the STN, but not the GPi, affects oculomotor function in PD patients. Nineteen PD patients with DBS implants (8 bilateral GPi, 9 bilateral STN and 2 unilateral STN) were studied. Testing was performed with stimulation on, then off. Somatomotor function was tested using the Unified Parkinson's Disease Rating Scale (UPDRS) motor exam. For oculomotor testing, patients performed pro- and antisaccade tasks while monitored with an infrared eye tracker. Saccadic latency, saccadic intrusions, and square-wave jerks (SWJs) were measured for each trial. As expected, UPDRS motor scores improved with both GPi and STN stimulation. With GPi stimulation, there was no significant difference in oculomotor function with stimulation on or off. However, with STN stimulation on, there was a significant increase in the mean number of SWJs/s, as well as a significant decrease in latency for both pro- and antisaccade tasks. Stimulation of either GPi or STN had similar effects on somatomotor function, but only STN stimulation significantly altered oculomotor function. Copyright © 2013 S. Karger AG, Basel.

Gadolinium Accumulation in the Deep Cerebellar Nuclei and Globus Pallidus After Exposure to Linear but Not Macrocyclic Gadolinium-Based Contrast Agents in a Retrospective Pig Study With High Similarity to Clinical Conditions.

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Boyken, Janina; Frenzel, Thomas; Lohrke, Jessica; Jost, Gregor; Pietsch, Hubertus

2018-05-01

The aim of this retrospective study was to determine the gadolinium (Gd) concentration in different brain areas in a pig cohort that received repeated administration of Gd-based contrast agents (GBCAs) at standard doses over several years, comparable with a clinical setting. Brain tissue was collected from 13 Göttingen mini pigs that had received repeated intravenous injections of gadopentetate dimeglumine (Gd-DTPA; Magnevist) and/or gadobutrol (Gadovist). The animals have been included in several preclinical imaging studies since 2008 and received cumulative Gd doses ranging from 7 to 129 mmol per animal over an extended period. Two animals with no history of administration of GBCA were included as controls. Brain autopsies were performed not earlier than 8 and not later than 38 months after the last GBCA application. Tissues from multiple brain areas including cerebellar and cerebral deep nuclei, cerebellar and cerebral cortex, and pons were analyzed for Gd using inductively coupled plasma mass spectrometry. Of the 13 animals, 8 received up to 48 injections of gadobutrol and Gd-DTPA and 5 received up to 29 injections of gadobutrol only. In animals that had received both Gd-DTPA and gadobutrol, a median (interquartile range) Gd concentration of 1.0 nmol/g tissue (0.44-1.42) was measured in the cerebellar nuclei and 0.53 nmol/g (0.29-0.62) in the globus pallidus. The Gd concentration in these areas in gadobutrol-only animals was 50-fold lower with median concentrations of 0.02 nmol/g (0.01-0.02) for cerebellar nuclei and 0.01 nmol/g (0.01-0.01) for globus pallidus and was comparable with control animals with no GBCA history. Accordingly, in animals that received both GBCAs, the amount of residual Gd correlated with the administered dose of Gd-DTPA (P ≤ 0.002) but not with the total Gd dose, consisting of Gd-DTPA and gadobutrol. The Gd concentration in cortical tissue and in the pons was very low (≤0.07 nmol/g tissue) in all animals analyzed. Multiple exposure

Serial 1H-MRS of thalamus during deep brain stimulation of bilateral globus pallidus internus for primary generalized dystonia

International Nuclear Information System (INIS)

Chernov, Mikhail F.; Iseki, Hiroshi; Takakura, Kintomo; Ochiai, Taku; Taira, Takaomi; Hori, Tomokatsu; Ono, Yuko; Nakamura, Ryoichi; Muragaki, Yoshihiro

2008-01-01

The physiological mechanisms of deep brain stimulation (DBS) are not completely clear. Our understanding of them may be facilitated with the use of proton magnetic resonance spectroscopy ( 1 H-MRS). Serial 1 H-MRS of both thalami was performed during the course of DBS of bilateral globus pallidus internus in a patient with primary generalized dystonia. Two days after microelectrode implantation, a pulse frequency of 185 Hz was applied for stimulation. It resulted in relief of symptoms and a decrease of Burke-Fahn-Marsden dystonia rating scale (BFMDRS) scores, and was accompanied by a prominent increase of N-acetylaspartate (NAA)/choline-containing compounds (Cho) ratio, a mild increase of NAA/creatine (Cr) ratio, and a moderate decrease of Cho/Cr ratio. Two weeks later, for a search of the optimal stimulation mode, the pulse frequency was switched to 60 Hz, which resulted in clinical deterioration and significant increase of BFMDRS scores. At that time, all investigated 1 H-MRS-detected metabolic parameters had nearly returned to the pretreatment levels. Use of serial 1 H-MRS investigations of various brain structures during DBS in cases of movement disorders permits detailed evaluation of the treatment response, has a potential for its possible prediction, and may facilitate understanding of the physiological mechanisms of stimulation. (orig.)

Comparison of Globus Pallidus Interna and Subthalamic Nucleus in Deep Brain Stimulation for Parkinson Disease: An Institutional Experience and Review

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Shazia Mirza

2017-01-01

Full Text Available Deep Brain Stimulation (DBS has revolutionized the lives of patients of Parkinson disease, offering therapeutic options to those not benefiting entirely from medications alone. With its proven track record of outperforming the best medical management, the goal is to unlock the full potential of this therapy. Currently, the Globus Pallidus Interna (GPi and Subthalamic Nucleus (STN are both viable targets for DBS, and the choice of site should focus on the constellation of symptoms, both motor and nonmotor, which are key determinants to quality of life. Our article sheds light on the specific advantages and drawbacks of the two sites, highlighting the need for matching the inherent properties of a target with specific desired effects in patients. UT Southwestern Medical Center has a robust and constantly evolving DBS program and the narrative from our center provides invaluable insight into the practical realities of DBS. The ultimate decision in selecting a DBS target is complex, ideally made by a multidisciplinary team, tailored towards each patient’s profile and their expectations, by drawing upon scientific evidence coupled with experience. Ongoing research is expanding our knowledge base, which should be dynamically incorporated into an institute’s DBS paradigm to ensure that patients receive the optimal therapy.

Gadolinium deposition within the dentate nucleus and globus pallidus after repeated administrations of gadolinium-based contrast agents - current status

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Stojanov, Dragan [University of Nis, Faculty of Medicine, Nis (Serbia); Center for Radiology, Nis (Serbia); Aracki-Trenkic, Aleksandra [Center for Radiology, Nis (Serbia); Benedeto-Stojanov, Daniela [University of Nis, Faculty of Medicine, Nis (Serbia)

2016-05-15

Gadolinium-based contrast agents (GBCAs) have been used clinically since 1988 for contrast-enhanced magnetic resonance imaging (CE-MRI). Generally, GBCAs are considered to have an excellent safety profile. However, GBCA administration has been associated with increased occurrence of nephrogenic systemic fibrosis (NSF) in patients with severely compromised renal function, and several studies have shown evidence of gadolinium deposition in specific brain structures, the globus pallidus and dentate nucleus, in patients with normal renal function. Gadolinium deposition in the brain following repeated CE-MRI scans has been demonstrated in patients using T1-weighted unenhanced MRI and inductively coupled plasma mass spectroscopy. Additionally, rodent studies with controlled GBCA administration also resulted in neural gadolinium deposits. Repeated GBCA use is associated with gadolinium deposition in the brain. This is especially true with the use of less-stable, linear GBCAs. In spite of increasing evidence of gadolinium deposits in the brains of patients after multiple GBCA administrations, the clinical significance of these deposits continues to be unclear. Here, we discuss the current state of scientific evidence surrounding gadolinium deposition in the brain following GBCA use, and the potential clinical significance of gadolinium deposition. There is considerable need for further research, both to understand the mechanism by which gadolinium deposition in the brain occurs and how it affects the patients in which it occurs. (orig.)

Transgenic Mouse Lines Subdivide External Segment of the Globus Pallidus (GPe) Neurons and Reveal Distinct GPe Output Pathways

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Mastro, Kevin J.; Bouchard, Rachel S.; Holt, Hiromi A. K.

2014-01-01

Cell-type diversity in the brain enables the assembly of complex neural circuits, whose organization and patterns of activity give rise to brain function. However, the identification of distinct neuronal populations within a given brain region is often complicated by a lack of objective criteria to distinguish one neuronal population from another. In the external segment of the globus pallidus (GPe), neuronal populations have been defined using molecular, anatomical, and electrophysiological criteria, but these classification schemes are often not generalizable across preparations and lack consistency even within the same preparation. Here, we present a novel use of existing transgenic mouse lines, Lim homeobox 6 (Lhx6)–Cre and parvalbumin (PV)–Cre, to define genetically distinct cell populations in the GPe that differ molecularly, anatomically, and electrophysiologically. Lhx6–GPe neurons, which do not express PV, are concentrated in the medial portion of the GPe. They have lower spontaneous firing rates, narrower dynamic ranges, and make stronger projections to the striatum and substantia nigra pars compacta compared with PV–GPe neurons. In contrast, PV–GPe neurons are more concentrated in the lateral portions of the GPe. They have narrower action potentials, deeper afterhyperpolarizations, and make stronger projections to the subthalamic nucleus and parafascicular nucleus of the thalamus. These electrophysiological and anatomical differences suggest that Lhx6–GPe and PV–GPe neurons participate in different circuits with the potential to contribute to different aspects of motor function and dysfunction in disease. PMID:24501350

Altered neuronal activity in the primary motor cortex and globus pallidus after dopamine depletion in rats.

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Wang, Min; Li, Min; Geng, Xiwen; Song, Zhimin; Albers, H Elliott; Yang, Maoquan; Zhang, Xiao; Xie, Jinlu; Qu, Qingyang; He, Tingting

2015-01-15

The involvement of dopamine (DA) neuron loss in the etiology of Parkinson's disease has been well documented. The neural mechanisms underlying the effects of DA loss and the resultant motor dysfunction remain unknown. To gain insights into how loss of DA disrupts the electrical processes in the cortico-subcortical network, the present study explores the effects of DA neuron depletion on electrical activity in the primary motor cortex (M1), on the external and the internal segment of the globus pallidus (GPe and GPi respectively), and on their temporal relationships. Comparison of local field potentials (LFPs) in these brain regions from unilateral hemispheric DA neuron depleted rats and neurologically intact rats revealed that the spectrum power of LFPs in 12-70Hz (for M1, and GPe) and in 25-40Hz (for GPi) was significantly greater in the DA depleted rats than that in the control group. These changes were associated with a shortening of latency in LFP activities between M1 and GPe, from several hundred milliseconds in the intact animals to close to zero in the DA depleted animals. LFP oscillations in M1 were significantly more synchronized with those in GPe in the DA depleted rats compared with those in the control rats. By contrast, the synchronization of oscillation in LFP activities between M1 and GPi did not differ between the DA depleted and intact rats. Not surprisingly, rats that had DA neuron depletion spent more time along the ladder compared with the control rats. These data suggest that enhanced oscillatory activity and increased synchronization of LFPs may contribute to movement impairment in the rat model of Parkinson's disease. Copyright © 2014 Elsevier B.V. All rights reserved.

High-frequency stimulation of the globus pallidus interna nucleus modulates GFRα1 gene expression in the basal ganglia.

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Ho, Duncun Xun Kiat; Tan, Yong Chee; Tan, Jiayi; Too, Heng Phon; Ng, Wai Hoe

2014-04-01

Deep brain stimulation (DBS) is an established therapy for movement disorders such as Parkinson's disease (PD). Although the efficacy of DBS is clear, its precise molecular mechanism remains unknown. The glial cell line derived factor (GDNF) family of ligands has been shown to confer neuroprotective effects on dopaminergic neurons, and putaminal infusion of GDNF have been investigated in PD patients with promising results. Despite the potential therapeutic role of GDNF in alleviating motor symptoms, there is no data on the effects of electrical stimulation on GDNF-family receptor (GFR) expression in the basal ganglia structures. Here, we report the effects of electrical stimulation on GFRα1 isoforms, particularly GFRα1a and GFRα1b. Wistar rats underwent 2 hours of high frequency stimulation (HFS) at the globus pallidus interna nucleus. A control group was subjected to a similar procedure but without stimulation. The HFS group, sacrificed 24 hours after treatment, had a threefold decrease in mRNA expression level of GFRα1b (p=0.037), but the expression level reverted to normal 72 hours after stimulation. Our preliminary data reveal the acute effects of HFS on splice isoforms of GFRα1, and suggest that HFS may modulate the splice isoforms of GFRα1a and GFRα1b to varying degrees. Going forward, elucidating the interactions between HFS and GFR may shed new insights into the complexity of GDNF signaling in the nervous system and lead to better design of clinical trials using these signaling pathways to halt disease progression in PD and other neurodegenerative diseases. Copyright © 2013 Elsevier Ltd. All rights reserved.

Deep Brain Stimulation of the Internal Globus Pallidus Improves Response Initiation and Proactive Inhibition in Patients With Parkinson’s Disease

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Yixin Pan

2018-04-01

Full Text Available Background: Impulse control disorder is not uncommon in patients with Parkinson’s disease (PD who are treated with dopamine replacement therapy and subthalamic deep brain stimulation (DBS. Internal globus pallidus (GPi-DBS is increasingly used, but its role in inhibitory control has rarely been explored. In this study, we evaluated the effect of GPi-DBS on inhibitory control in PD patients.Methods: A stop-signal paradigm was used to test response initiation, proactive inhibition, and reactive inhibition. The subjects enrolled in the experiment were 27 patients with PD, of whom 13 had received only drug treatment and 14 had received bilateral GPi-DBS in addition to conventional medical treatment and 15 healthy individuals.Results: Our results revealed that with GPi-DBS on, patients with PD showed significantly faster responses than the other groups in trials where it was certain that no stop signal would be presented. Proactive inhibition was significantly different in the surgical patients with GPi-DBS on versus when GPi-DBS was off, in surgical patients with GPi-DBS on versus drug-treated patients, and in healthy controls versus drug-treated patients. Correlation analyses revealed that when GPi-DBS was on, there was a statistically significant moderate positive relationship between proactive inhibition and dopaminergic medication.Conclusion: GPi-DBS may lead to an increase in response initiation speed and improve the dysfunctional proactive inhibitory control observed in PD patients. Our results may help us to understand the role of the GPi in cortical-basal ganglia circuits.

Meta-analysis comparing deep brain stimulation of the globus pallidus and subthalamic nucleus to treat advanced Parkinson disease.

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Liu, Yi; Li, Weina; Tan, Changhong; Liu, Xi; Wang, Xin; Gui, Yuejiang; Qin, Lu; Deng, Fen; Hu, Changlin; Chen, Lifen

2014-09-01

Deep brain stimulation (DBS) is the surgical procedure of choice for patients with advanced Parkinson disease (PD). The globus pallidus internus (GPi) and the subthalamic nucleus (STN) are commonly targeted by this procedure. The purpose of this meta-analysis was to compare the efficacy of DBS in each region. MEDLINE/PubMed, EMBASE, Web of Knowledge, and the Cochrane Library were searched for English-language studies published before April 2013. of studies investigating the efficacy and clinical outcomes of DBS of the GPi and STN for PD were analyzed. Six eligible trials containing a total of 563 patients were included in the analysis. Deep brain stimulation of the GPi or STN equally improved motor function, measured by the Unified Parkinson's Disease Rating Scale Section III (UPDRSIII) (motor section, for patients in on- and off-medication phases), within 1 year postsurgery. The change score for the on-medication phase was 0.68 (95% CI - 2.12 to 3.47, p > 0.05; 5 studies, 518 patients) and for the off-medication phase was 1.83 (95% CI - 3.12 to 6.77, p > 0.05; 5 studies, 518 patients). The UPDRS Section II (activities of daily living) scores for patients on medication improved equally in both DBS groups (p = 0.97). STN DBS allowed medication dosages to be reduced more than GPi DBS (95% CI 129.27-316.64, p < 0.00001; 5 studies, 540 patients). Psychiatric symptoms, measured by Beck Depression Inventory, 2nd edition scores, showed greater improvement from baseline after GPi DBS than after STN DBS (standardized mean difference -2.28, 95% CI -3.73 to -0.84, p = 0.002; 3 studies, 382 patients). GPi and STN DBS improve motor function and activities of daily living for PD patients. Differences in therapeutic efficacy for PD were not observed between the 2 procedures. STN DBS allowed greater reduction in medication for patients, whereas GPi DBS provided greater relief from psychiatric symptoms. An understanding of other symptomatic aspects of targeting each region and long

Localization of Basal Ganglia and Thalamic Damage in Dyskinetic Cerebral Palsy.

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Aravamuthan, Bhooma R; Waugh, Jeff L

2016-01-01

Dyskinetic cerebral palsy affects 15%-20% of patients with cerebral palsy. Basal ganglia injury is associated with dyskinetic cerebral palsy, but the patterns of injury within the basal ganglia predisposing to dyskinetic cerebral palsy are unknown, making treatment difficult. For example, deep brain stimulation of the globus pallidus interna improves dystonia in only 40% of patients with dyskinetic cerebral palsy. Basal ganglia injury heterogeneity may explain this variability. To investigate this, we conducted a qualitative systematic review of basal ganglia and thalamic damage in dyskinetic cerebral palsy. Reviews and articles primarily addressing genetic or toxic causes of cerebral palsy were excluded yielding 22 studies (304 subjects). Thirteen studies specified the involved basal ganglia nuclei (subthalamic nucleus, caudate, putamen, globus pallidus, or lentiform nuclei, comprised by the putamen and globus pallidus). Studies investigating the lentiform nuclei (without distinguishing between the putamen and globus pallidus) showed that all subjects (19 of 19) had lentiform nuclei damage. Studies simultaneously but independently investigating the putamen and globus pallidus also showed that all subjects (35 of 35) had lentiform nuclei damage (i.e., putamen or globus pallidus damage); this was followed in frequency by damage to the putamen alone (70 of 101, 69%), the subthalamic nucleus (17 of 25, 68%), the thalamus (88 of 142, 62%), the globus pallidus (7/35, 20%), and the caudate (6 of 47, 13%). Globus pallidus damage was almost always coincident with putaminal damage. Noting consistent involvement of the lentiform nuclei in dyskinetic cerebral palsy, these results could suggest two groups of patients with dyskinetic cerebral palsy: those with putamen-predominant damage and those with panlenticular damage involving both the putamen and the globus pallidus. Differentiating between these groups could help predict response to therapies such as deep brain

Neuronal firing in the globus pallidus internus and the ventrolateral thalamus related to parkinsonian motor symptoms

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CHEN Hai; ZHUANG Ping; ZHANG Yu-qing; LI Jian-yu; LI Yong-jie

2009-01-01

Background It has been proposed that parkinsonian motor signs result from hyperactivity in the output nucleus of the basal ganglia, which suppress the motor thalamus and cortical areas. This study aimed to explore the neuronal activity in the globus pallidus internus (GPi) and the ventrolateral thalamic nuclear group (ventral oral posterior/ventral intermediate, Vop/Vim) in patients with Parkinson's disease (PD).Methods Twenty patients with PD who underwent neurosurgery were studied. Microelectrode recording was performed in the GPi (n=10) and the Vop/Vim (n=10) intraoperatively. Electromyography (EMG) contralateral to the surgery was simultaneously performed. Single unit analysis was carried out. The interspike intervals (ISI) and coefficient of variation (CV) of ISI were calculated. Histograms of ISI were constructed. A unified Parkinson's disease rating scale (UPDRS) was used to assess the clinical outcome of surgery.Results Three hundred and sixty-three neurons were obtained from 20 trajectories. Of 175 GPi neurons, there were 15.4% with tremor frequency, 69.2% with tonic firing, and 15.4% with irregular discharge. Of 188 thalamic neurons, there were 46.8% with tremor frequency, 22.9% with tonic firing, and 30.3% with irregular discharge. The numbers of three patterns of neuron in GPi and Vop/Vim were significantly different (P <0.001). ISI analysis revealed that mean firing rate of the three patterns of GPi neurons was (80.9±63.9) Hz (n=78), which was higher than similar neurons with 62.9 Hz in a normal primate. For the Vop/Vim group, ISI revealed that mean firing rate of the three patterns of neurons (n=95) was (23.2±17.1) Hz which was lower than similar neurons with 30 Hz in the motor thalamus of normal primates. UPDRS indicated that the clinical outcome of pallidotomy was (64.3±9.5)%, (83.4±19.1)% and (63.4±36.3)%, and clinical outcome of thalamotomy was (92.2±12.9)%, (68.0±25.2)% and (44.3±27.2)% for tremor, rigidity and bradykinesia, respectively

Cognition and Depression Following Deep Brain Stimulation of the Subthalamic Nucleus and Globus Pallidus Pars Internus in Parkinson's Disease: A Meta-Analysis.

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Combs, Hannah L; Folley, Bradley S; Berry, David T R; Segerstrom, Suzanne C; Han, Dong Y; Anderson-Mooney, Amelia J; Walls, Brittany D; van Horne, Craig

2015-12-01

Parkinson's disease (PD) is a common, degenerative disorder of the central nervous system. Individuals experience predominantly extrapyramidal symptoms including resting tremor, rigidity, bradykinesia, gait abnormalities, cognitive impairment, depression, and neurobehavioral concerns. Cognitive impairments associated with PD are diverse, including difficulty with attention, processing speed, executive functioning, memory recall, visuospatial functions, word-retrieval, and naming. Deep brain stimulation (DBS) of the subthalamic nucleus (STN) or globus pallidus internus (GPi) is FDA approved and has been shown to be effective in reducing motor symptoms of PD. Studies have found that stimulating STN and GPi are equally effective at improving motor symptoms and dyskinesias; however, there has been discrepancy as to whether the cognitive, behavioral, and mood symptoms are affected differently between the two targets. The present study used random-effects meta-analytic models along with a novel p-curve analytic procedure to compare the potential cognitive and emotional impairments associated with STN-DBS in the current literature to those associated with GPi-DBS. Forty-one articles were reviewed with an aggregated sample size of 1622 patients. Following STN-DBS, small declines were found in psychomotor speed, memory, attention, executive functions, and overall cognition; and moderate declines were found in both semantic and phonemic fluency. However, GPi-DBS resulted in fewer neurocognitive declines than STN-DBS (small declines in attention and small-moderate declines in verbal fluency). With regards to its effect on depression symptomatology, both GPi-DBS and STN-DBS resulted in lower levels of depressive symptoms post-surgery. From a neurocognitive standpoint, both GPi-DBS and STN-DBS produce subtle cognitive declines but appears to be relatively well tolerated.

Tonic and phasic changes in anteromedial globus pallidus activity in Tourette syndrome.

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Israelashvili, Michal; Smeets, Anouk Y J M; Bronfeld, Maya; Zeef, Dagmar H; Leentjens, Albert F G; van Kranen-Mastenbroek, Vivianne; Janssen, Marcus L F; Temel, Yasin; Ackermans, Linda; Bar-Gad, Izhar

2017-07-01

Tourette syndrome is a hyperkinetic neurodevelopmental disorder characterized by tics. Assess the neuronal changes in the associative/limbic GP associated with Tourette syndrome. Neurophysiological recordings were performed from the anterior (associative/limbic) GPe and GPi of 8 awake patients during DBS electrode implantation surgeries. The baseline firing rate of the neurons was low in a state-dependent manner in both segments of the GP. Tic-dependent transient rate changes were found in the activity of individual neurons of both segments around the time of the tic. Neither oscillatory activity of individual neurons nor correlations in their interactions were observed. The results demonstrate the involvement of the associative/limbic pathway in the underlying pathophysiology of Tourette syndrome and point to tonic and phasic modulations of basal ganglia output as a key mechanisms underlying the abnormal state of the disorder and the expression of individual tics, respectively. © 2017 International Parkinson and Movement Disorder Society. © 2017 International Parkinson and Movement Disorder Society.

Supersensitivity of GABAergic systems induced within rat substantia nigra and globus pallidus by haloperidol

International Nuclear Information System (INIS)

Frey, J.J.M.

1986-01-01

The supersensitivity was demonstrated by an increase in the responsiveness of individual neurons within these brain regions to microiontophoretically-applied GABA and by an up regulation of GABA binding sites. Rates received haloperidol for 30 days in their feed and were then withdrawn from treatment for 48 hrs. 3 H-GABA binding was found to be significantly elevated with the SN R (55%) and GP (42%). Scatchard analysis of 3 H-muscimol binding isotherms indicated that the number (B max ) of high affinity binding sites within the GP was significantly increased (32%); within the SN R , significant increases were detected in the B max of both high (23%) and low (58%) affinity 3 H-muscimol binding sites. After CHAL treatment, signs of dopaminergic supersensitivity within the basal ganglia were also observed. Spontaneous locomotor activity and apomorphine-induced stereotyped behavior were increased and specific 3 H-spiroperidol binding was elevated within the striatum (60%) and GP (236%)

Altered effective connectivity network of the basal ganglia in low-grade hepatic encephalopathy: a resting-state fMRI study with Granger causality analysis.

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Rongfeng Qi

Full Text Available BACKGROUND: The basal ganglia often show abnormal metabolism and intracranial hemodynamics in cirrhotic patients with hepatic encephalopathy (HE. Little is known about how the basal ganglia affect other brain system and is affected by other brain regions in HE. The purpose of this study was to investigate whether the effective connectivity network associated with the basal ganglia is disturbed in HE patients by using resting-state functional magnetic resonance imaging (rs-fMRI. METHODOLOGY/PRINCIPAL FINDINGS: Thirty five low-grade HE patients and thirty five age- and gender- matched healthy controls participated in the rs-fMRI scans. The effective connectivity networks associated with the globus pallidus, the primarily affected region within basal ganglia in HE, were characterized by using the Granger causality analysis and compared between HE patients and healthy controls. Pearson correlation analysis was performed between the abnormal effective connectivity and venous blood ammonia levels and neuropsychological performances of all HE patients. Compared with the healthy controls, patients with low-grade HE demonstrated mutually decreased influence between the globus pallidus and the anterior cingulate cortex (ACC, cuneus, bi-directionally increased influence between the globus pallidus and the precuneus, and either decreased or increased influence from and to the globus pallidus in many other frontal, temporal, parietal gyri, and cerebellum. Pearson correlation analyses revealed that the blood ammonia levels in HE patients negatively correlated with effective connectivity from the globus pallidus to ACC, and positively correlated with that from the globus pallidus to precuneus; and the number connectivity test scores in patients negatively correlated with the effective connectivity from the globus pallidus to ACC, and from superior frontal gyrus to globus pallidus. CONCLUSIONS/SIGNIFICANCE: Low-grade HE patients had disrupted effective

Management of Globus Pharyngeus

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S. Kortequee

2013-01-01

Full Text Available Globus pharyngeus is a common ENT condition. This paper reviews the current evidence on globus and gives a rational guide to the management of patients with globus. The aetiology of globus is still unclear though most ENT surgeons believe that reflux whether acidic or not plays a significant role. Though proton pump inhibitors are used extensively in practice, there is little evidence to support their efficacy. Most patients with globus can be discharged after simple office investigations. The role of pepsin-induced laryngeal injury is an exciting concept that needs further study. Given the benign nature of globus pharyngeus, in most cases, reassurance rather than treatment or extensive investigation with rigid oesophagoscopy or contrast swallows is all that is needed. We need more research into the aetiology of globus.

Deep Brain Stimulation of the Globus Pallidus Internus in Patients with Intractable Tourette Syndrome: A 1-year Follow-up Study

Institute of Scientific and Technical Information of China (English)

Xiao-Hua Zhang; Jian-Yu Li; Yu-Qing Zhang; Yong-Jie Li

2016-01-01

Background:Deep brain stimulation (DBS) has been a promising treatment for patients with refractory Tourette syndrome (TS) for more than a decade.Despite successful DBS treatment of TS in more than 100 patients worldwide,studies with a large patient sample and long-term follow-up assessments are still scarce.Accordingly,we investigated the clinical efficacy and safety of globus pallidus internus (GPi) DBS in the treatment of intractable TS in 24 patients with a l-year follow-up assessment.Methods:Bilateral/unilateral GPi-DBS was performed in 24 patients with TS.We evaluated symptoms of tics and obsessive-compulsive disorder (OCD) through the Yale Global Tic Severity Scale (YGTSS) and Yale-Brown Obsessive-compulsive Scale (Y-BOCS).We used the Wechsler Adult Intelligence Scale-Revised in China (WAIS-RC) to evaluate the safety of the treatment.We conducted follow-up assessments of all patients for at least 12 months (12-99 months).Results:Symptoms of tics and OCD were significantly relieved at a 12-month follow-up assessment.The mean YGTSS score was 74.04 ± 11.52,49.83 ± 10.91,32.58 ± 7.97,and 31.21 ± 8.87 at baseline,3,6,and 12 months,respectively.The mean YGTSS scores obtained at the follow-up assessments were significantly different from the baseline (P ＜ 0.05).The improvement in motor tics was superior to that in phonic tics.The mean Y-BOCS scores were 21.61 ± 4.97,18 ± 4.58,14.39 ± 3.99,and 13.78 ± 4.56 at baseline,3,6,and 12 months,respectively (P ＜ 0.05).We observed a remarkable improvement in psychiatric comorbidities,such as OCD and attention-deficit hyperactivity disorder,after the procedure.WAIS-RC scores were comparable before and after the operation.There were no severe postoperative complications.Conclusion:GPi-DBS appears to comprehensively alleviate tic symptoms and psychiatric comorbidities in patients with TS,thus significantly improving patients' quality of life.

Visualization of the internal globus pallidus: sequence and orientation for deep brain stimulation using a standard installation protocol at 3.0 Tesla.

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Nölte, Ingo S; Gerigk, Lars; Al-Zghloul, Mansour; Groden, Christoph; Kerl, Hans U

2012-03-01

Deep-brain stimulation (DBS) of the internal globus pallidus (GPi) has shown remarkable therapeutic benefits for treatment-resistant neurological disorders including dystonia and Parkinson's disease (PD). The success of the DBS is critically dependent on the reliable visualization of the GPi. The aim of the study was to evaluate promising 3.0 Tesla magnetic resonance imaging (MRI) methods for pre-stereotactic visualization of the GPi using a standard installation protocol. MRI at 3.0 T of nine healthy individuals and of one patient with PD was acquired (FLAIR, T1-MPRAGE, T2-SPACE, T2*-FLASH2D, susceptibility-weighted imaging mapping (SWI)). Image quality and visualization of the GPi for each sequence were assessed by two neuroradiologists independently using a 6-point scale. Axial, coronal, and sagittal planes of the T2*-FLASH2D images were compared. Inter-rater reliability, contrast-to-noise ratios (CNR) and signal-to-noise ratios (SNR) for the GPi were determined. For illustration, axial T2*-FLASH2D images were fused with a section schema of the Schaltenbrand-Wahren stereotactic atlas. The GPi was best and reliably visualized in axial and to a lesser degree on coronal T2*-FLASH2D images. No major artifacts in the GPi were observed in any of the sequences. SWI offered a significantly higher CNR for the GPi compared to standard T2-weighted imaging using the standard parameters. The fusion of the axial T2*-FLASH2D images and the atlas projected the GPi clearly in the boundaries of the section schema. Using a standard installation protocol at 3.0 T T2*-FLASH2D imaging (particularly axial view) provides optimal and reliable delineation of the GPi.

Brain MR imaging in patients with hepatic cirrhosis: relationship between high intensity signal in basal ganglia on T1-weighted images and elemental concentrations in brain

International Nuclear Information System (INIS)

Maeda, H.; Sato, M.; Yoshikawa, A.; Kimura, M.; Sonomura, T.; Terada, M.; Kishi, K.

1997-01-01

In patients with hepatic cirrhosis, the globus pallidus and putamen show high intensity on T1-weighted MRI. While the causes of this high signal have been thought to include paramagnetic substances, especially manganese, no evidence for this has been presented. Autopsy in four cases of hepatic cirrhosis permitted measurement of metal concentrations in brain and histopathological examination. In three cases the globus pallidus showed high intensity on T1-weighted images. Mean manganese concentrations in globus pallidus, putamen and frontal white matter were 3.03 ± 0.38, 2.12 ± 0.37, and 1.38 ± 0.24 (μg/g wet weight), respectively, being approximately four- to almost ten-fold the normal values. Copper concentrations in globus pallidus and putamen were also high, 50 % more than normal. Calcium, iron, zinc and magnesium concentrations were all normal. The fourth case showed no abnormal intensity in the basal ganglia and brain metal concentrations were all normal. Histopathologically, cases with showing high signal remarkable atrophy, necrosis, and deciduation of nerve cells and proliferation of glial cells and microglia in globus pallidus. These findings were similar to those in chronic manganese poisoning. On T1-weighted images, copper deposition shows no abnormal intensity. It is therefore inferred that deposition of highly concentrations of manganese may caused high signal on T1-weighted images and nerve cell death in the globus pallidus. (orig.). With 2 figs., 2 tabs

MRI findings of the brain after gas explosion and its relationship with post-traumatic stress disorder

International Nuclear Information System (INIS)

Zhao Ruifeng; Jin Yilong; Li Huabing; Li Shufeng; Tian Shuwen; Li Haixue; Chen Yanhui; Wang Tianliang; Ma Lin; Ren Zijing; Ma Lin

2008-01-01

Objective: To investigate MR findings and dynamic changes of the brain after gas explosion, and to evaluate the relationship between MR findings and post-traumatic stress disorder (PTSD). Methods: Forty-nine survivors of a gas explosion (group A) were examined with brain MRI within 1 to 3 days, and serial MR follow-up examinations were also performed. Forty miners not under the ground that day were assigned as group B, and 40 staff working on the ground as group C. The signal intensity values of hippocampus and globus pallidus on T 2 WI were measured in the three groups and F test was performed by using SPSS 13.0. The relationship between signal intensity values of hippocampus/globus pallidus and PTSD was explored, and the relationship between ADC values of hippocampus and PTSD was also investigated. Results: In group A, slight low signal on T 1 WI and high signal on T 2 WI were detected on initial MRI in hippocarnpus (33 cases), globus pallidus (12 cases), cortex (10 cases), and midbrain (2 cases), respectively. On follow-up MRI at 2 months, lesions in hippocampus disappeared (25 cases) or remained slight high signal on T 2 WI (8 cases), lesions in globus pallidus disappeared (3 cases, 5 sides) or showed shrinkage and encephalomalacia (9 cases), cortical lesions resulted in encephalomalacia in 2 cases and returned normal in the others, and lesions in the midbrain showed encephalomalacia. For comparison of T 2 signal intensity values in hippocampus and globus pallidus, there was significant difference between group A and group B (P 0.05). In group A, the T 2 signal intensities of PTSD and non- PTSD were 455 ± 37 and 462 ± 53 in the left hippocampus, and 458 ± 36 and 460 ± 43 in the right hippocampus on 1 to 3 days, and the T 2 signal intensities of PTSD and non-PTSD were 438 ± 29 and 424 ± 37 in the left hippocampus, and 442 ± 31 and 430 ± 32 in the right hippocampus at 2 months. The T 2 signal intensities of PTSD and non-PTSD were 361 ± 35 and 366 ± 63

Brain CT scan in acute carbon monoxide poisoning

International Nuclear Information System (INIS)

We, En-Huei

1986-01-01

The brain CT findings in 19 patients with acute carbon monoxide poisoning was analysed and the emphasis was placed on the relationship between CT findings and prognosis. Five had a normal manifestation in CT ; eight had the findings of ovoid or patchy low density area in globus pallidus, bilateral or unlateral, during the second day to fifth week after poisoning, and the low density areas were decreasing and blurring in edge in follow up and at last disappeared during 3 - 14 weeks in three cases of them ; nine showed the appearance of diffuse low density of white matter and of globus pallidus in some of them ; two had an appearance of brain atrophy. The pathology of CT findings mentioned above may be brain edema, necrosis, malacia and degeneration in gray matter and globus pallidus. The result suggested the cases with normal CT manifestation, cerebral edema and decreasing and disappearing low density area had a good prognosis, in contrary, the cases with persistant low density in globus pallidus had a poorer prognosis. (author)

Globus File Transfer Services | High-Performance Computing | NREL

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installed on the systems at both ends of the data transfer. The NREL endpoint is nrel#globus. Click Login on the Globus web site. On the login page select "Globus ID" as the login method and click Login to the Globus website. From the Manage Data drop down menu, select Transfer Files. Then click Get

Reclassification of Geobacillus pallidus (Scholz et al. 1988) Banat et al. 2004 as Aeribacillus pallidus gen. nov., comb. nov.

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Miñana-Galbis, David; Pinzón, Dora L; Lorén, J Gaspar; Manresa, Angels; Oliart-Ros, Rosa M

2010-07-01

Although Anoxybacillus and Geobacillus, two genera of thermophilic bacteria close to the genus Bacillus, have only been described recently, the number of species in these genera has increased rapidly. Four thermophilic, lipolytic strains (DR01, DR02, DR03 and DR04) isolated from a hot spring in Veracruz (Mexico), which could not be identified phenotypically, were subjected to 16S rRNA gene sequence analysis. Three strains were identified as belonging to the genus Anoxybacillus, but strain DR03 was identified as Geobacillus pallidus. This result led us to perform a phylogenetic analysis of the genera Anoxybacillus and Geobacillus based on 16S rRNA gene sequences from all the type strains of these genera. Phylogenetic trees showed three major clusters, Anoxybacillus-Geobacillus tepidamans, Geobacillus sensu stricto and Geobacillus pallidus, while the 16S rRNA gene sequences of G. pallidus (DR03 and the type strain) showed low similarity to sequences of Anoxybacillus (92.5-95.1 %) and Geobacillus (92.8-94.5 %) species, as well as to Bacillus subtilis (92.2-92.4 %). In addition, G. pallidus could be differentiated from Anoxybacillus and Geobacillus on the basis of DNA G+C content and fatty acid and polar lipid profiles. From these results, it is proposed that Geobacillus pallidus should be classified in a novel genus, for which we propose the name Aeribacillus, as Aeribacillus pallidus gen. nov., comb. nov. The type strain of Aeribacillus pallidus is H12(T) (=ATCC 51176(T) =DSM 3670(T) =LMG 19006(T)).

Simultaneous Activation of Multiple Memory Systems during Learning: Insights from Electrophysiology and Modeling

Science.gov (United States)

2010-06-01

autonomic and pain functions, and facilitating/inhibiting voluntary movements. The external segment of the globus pallidus (globus pallidus externa, GPe...or less responsive to pain stimuli. 1.2.4. Other cortico-basal ganglia loops Alexander, Strick and colleagues have additionally defined a number of... orofacial loop and loops through inferotemporal and posterior parietal cortical areas have also been defined. 1.2.5. Interactions between loops Once

Gastropharyngeal and gastroesophageal reflux in globus and hoarseness

NARCIS (Netherlands)

Smit, C. F.; van Leeuwen, J. A.; Mathus-Vliegen, L. M.; Devriese, P. P.; Semin, A.; Tan, J.; Schouwenburg, P. F.

2000-01-01

The role of gastropharyngeal reflux in patients with globus pharyngeus and hoarseness remains unclear. To evaluate patients with complaints of globus, hoarseness, or globus and hoarseness combined for the presence of gastropharyngeal and gastroesophageal reflux. Prospective clinical cohort study of

MRI of bilirubin encephalopathy (kernicterus: A case series of 4 patients from Sub-Saharan Africa, May 2017

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Getachew Assefa Neknek, MD

2018-06-01

Full Text Available Characteristic magnetic resonance imaging (MRI findings in patients with chronic kernicterus are bilateral and symmetric T2-weighted hyperintensities in the globus pallidus. We report 4 cases of infants with clinical, laboratory, and MRI findings of kernicterus in this case series. This is the first MRI report of kernicterus in Ethiopia. Awareness of the disease is raised in this report, and the role of magnetic resonance in detecting signal abnormalities associated with kernicterus in the globus pallidi is underscored. We recommend MRI to be part of the investigation in neonates with jaundice. Keywords: Kernicterus, Globus pallidus, MRI

Cranial MRI in hepatic disease; Relationship between MR imaging and clinical symptoms and laboratory analysis of liver function

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Iijima, Masakazu; Kamitani, Toshiaki; Kamakura, Keiko; Nagata, Naokazu; Tsuchiya, Kazuhiro (National Defense Medical Coll., Tokorozawa, Saitama (Japan))

1993-10-01

Magnetic resonance imaging studies on 12 cases with hepatic disease were performed. In 11 adult patients with chronic hepatic failure, T[sub 1]-weighted images demonstrated increased signal in the globus pallidus in 7 patients (63.6%) and in some parts of the cerebral peduncles in 6 patients (54.5%), in the substantia innominata in 4 patients (36.3%). There might be some correlation between the abnormality of MR imaging and clinical symptoms of hepatic encephalopathy. There was a significant correlation between the intensity of the signal and Fischer's ratio of amino acid analysis. In one patient with Wilson's disease, who developed symptoms of central nervous system, T[sub 1]-weighted images demonstrated increased signal in the globus pallidus. After treatment of D-penicillamine, the signal of the globus pallidus decreased. (author).

Diagnostic value of conventional MRI combined with DTI for neonatal hyperbilirubinemia

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Ruifang Yan

2018-04-01

Full Text Available Background: Neonatal hyperbilirubinemia (NHB is a common clinical disease and can cause bilirubin encephalopathy in severe cases. It is now widely accepted that increased signal intensity in the globus pallidus on MR T1WI is an important sign of neonatal bilirubin encephalopathy. And brain diffusion tensor imaging (DTI has not been used extensively to study hyperbilirubinemia (HB. So we compared newborns with different hyperbilirubinemia of different severities and healthy newborns in order to determine the relationships among MRI signal intensities, serum bilirubin levels, and the molecular changes in brain water diffusion in hyperbilirubinemia. Methods: Seventy-three newborns with hyperbilirubinemia were grouped into three groups: the mild increase group (M, 27 cases, the moderate increase group (O, 28 cases, and the severe group (S, 18 cases. The groups were based on serum bilirubin levels. We performed cranial MRI in these newborns, as well as 29 healthy full-term infants (group N. We compared and analyzed the mean signal values for the globus pallidus and the relationship between the bilirubin level and the score on the neonatal behavioral neurological assessment. Fifteen, 10, and 10 patients in groups M, O + S, and N were successfully examined using diffusion tensor imaging (DTI. We assessed the relationships among the signal from the globus pallidus, fractional anisotropy (FA, and average diffusion coefficient (DCav of the posterior limb of the internal capsule (PLIC. Results: There were significant differences in the mean signal value of bilateral globus pallidus between group O/S and group N [p = 0.029 and 0.000 (left, 0.038 and 0.000 (right]. There were no significant differences in bilateral FA or DCav values between the patient groups and group N. The bilateral PLIC-FA and DCav values were significantly different between the patient groups and group N (P = 0.014 and 0.047, respectively. Conclusions: Increased signal intensity

Globus Identity, Access, and Data Management: Platform Services for Collaborative Science

Science.gov (United States)

Ananthakrishnan, R.; Foster, I.; Wagner, R.

2016-12-01

Globus is software-as-a-service for research data management, developed at, and operated by, the University of Chicago. Globus, accessible at www.globus.org, provides high speed, secure file transfer; file sharing directly from existing storage systems; and data publication to institutional repositories. 40,000 registered users have used Globus to transfer tens of billions of files totaling hundreds of petabytes between more than 10,000 storage systems within campuses and national laboratories in the US and internationally. Web, command line, and REST interfaces support both interactive use and integration into applications and infrastructures. An important component of the Globus system is its foundational identity and access management (IAM) platform service, Globus Auth. Both Globus research data management and other applications use Globus Auth for brokering authentication and authorization interactions between end-users, identity providers, resource servers (services), and a range of clients, including web, mobile, and desktop applications, and other services. Compliant with important standards such as OAuth, OpenID, and SAML, Globus Auth provides mechanisms required for an extensible, integrated ecosystem of services and clients for the research and education community. It underpins projects such as the US National Science Foundation's XSEDE system, NCAR's Research Data Archive, and the DOE Systems Biology Knowledge Base. Current work is extending Globus services to be compliant with FEDRAMP standards for security assessment, authorization, and monitoring for cloud services. We will present Globus IAM solutions and give examples of Globus use in various projects for federated access to resources. We will also describe how Globus Auth and Globus research data management capabilities enable rapid development and low-cost operations of secure data sharing platforms that leverage Globus services and integrate them with local policy and security.

Epiglottic cyst as an etiological factor of globus sensation.

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Polat, Bahtiyar; Karahatay, Serdar; Gerek, Mustafa

2015-09-01

Globus is a subjective complaint that describes a sensation of a lump or a foreign body in the throat. Despite being a well-known and common clinical condition, the etiological factors have not been definitely elucidated yet. The study was set up to ascertain the relationship between epiglottic cysts and globus sensation. All patients undergoing investigation and treatments for globus sensation were included in the study. Patients with epiglottic cysts but no other possible causes of globus sensation were constituted the series of patients. Patients were asked to assess the levels of complaint before and after the carbon dioxide (CO2) laser excisions of the cysts. Epiglottic cysts were found in 10 (5.4%) of the 182 patients. Three of these 10 patients who had concomitant diseases or conditions that may cause globus sensation and one patient who refused the surgery were excluded from the study. All the remaining six patients reported relief of the globus sensation after the CO2 laser excisions of the cysts. Our results, obtained from this limited series, indicated that epiglottic cysts may be considered as one of the etiological factors of globus sensation.

A single-neuron tracing study of arkypallidal and prototypic neurons in healthy rats.

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Fujiyama, Fumino; Nakano, Takashi; Matsuda, Wakoto; Furuta, Takahiro; Udagawa, Jun; Kaneko, Takeshi

2016-12-01

The external globus pallidus (GP) is known as a relay nucleus of the indirect pathway of the basal ganglia. Recent studies in dopamine-depleted and healthy rats indicate that the GP comprises two main types of pallidofugal neurons: the so-called "prototypic" and "arkypallidal" neurons. However, the reconstruction of complete arkypallidal neurons in healthy rats has not been reported. Here we visualized the entire axonal arborization of four single arkypallidal neurons and six single prototypic neurons in rat brain using labeling with a viral vector expressing membrane-targeted green fluorescent protein and examined the distribution of axon boutons in the target nuclei. Results revealed that not only the arkypallidal neurons but nearly all of the prototypic neurons projected to the striatum with numerous axon varicosities. Thus, the striatum is a major target nucleus for pallidal neurons. Arkypallidal and prototypic GP neurons located in the calbindin-positive and calbindin-negative regions mainly projected to the corresponding positive and negative regions in the striatum. Because the GP and striatum calbindin staining patterns reflect the topographic organization of the striatopallidal projection, the striatal neurons in the sensorimotor and associative regions constitute the reciprocal connection with the GP neurons in the corresponding regions.

Application experiences with the Globus toolkit.

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Brunett, S.

1998-06-09

The Globus grid toolkit is a collection of software components designed to support the development of applications for high-performance distributed computing environments, or ''computational grids'' [14]. The Globus toolkit is an implementation of a ''bag of services'' architecture, which provides application and tool developers not with a monolithic system but rather with a set of stand-alone services. Each Globus component provides a basic service, such as authentication, resource allocation, information, communication, fault detection, and remote data access. Different applications and tools can combine these services in different ways to construct ''grid-enabled'' systems. The Globus toolkit has been used to construct the Globus Ubiquitous Supercomputing Testbed, or GUSTO: a large-scale testbed spanning 20 sites and included over 4000 compute nodes for a total compute power of over 2 TFLOPS. Over the past six months, we and others have used this testbed to conduct a variety of application experiments, including multi-user collaborative environments (tele-immersion), computational steering, distributed supercomputing, and high throughput computing. The goal of this paper is to review what has been learned from these experiments regarding the effectiveness of the toolkit approach. To this end, we describe two of the application experiments in detail, noting what worked well and what worked less well. The two applications are a distributed supercomputing application, SF-Express, in which multiple supercomputers are harnessed to perform large distributed interactive simulations; and a tele-immersion application, CAVERNsoft, in which the focus is on connecting multiple people to a distributed simulated world.

Radiologic evaluation of the globus symptom using videotape recorder

International Nuclear Information System (INIS)

Kim, Myeong Jin; Chung, Tae Sub; Lee, Jong Tae; Yoo, Hyung Sik; Suh, Jung Ho; Chang, Tae Young; Park, In Yong

1988-01-01

The authors examined barium swallow in 213 patients with globus symptom and 79 patients with vague gastric problems without globus symptom. Abnormal findings were more frequently detected on videorecording than on conventional esophagogram. Radiologic findings were transient cricopharyngeal indentation (CPI), residual barium collection and delayed clearing from hypopharynx (RB), laryngeal penetration of barium, barium retention in vallecula and or pyriform sinuses. Among them residual barium in hypopharynx was more frequently detected in patients with globus symptom than in patients without globus symptom. Globus symptom was more frequent in adult women, but age and sex difference did not affect the incidence of the abnormal radiologic findings. Cricopharyngeal indentation was most frequently seen at the level of C5-6 interspace and had a tendency of moving upward gradually during the indentation in about half of the cases. Most of the CPI was seen in early phase of swallowing and was visible within 1 sec. Residual barium collection was mostly seen in C6 or C6-7 level. RB had no cause and effect relationship with CPI, and it was not secondary result of obstructive effect of CPI. The authors think that videotape recording can be a useful method for evaluation of globus symptom. The residual barium collection in hypopharynx can be a significant finding in globus symptom

Microstructural Changes within the Basal Ganglia Differ between Parkinson Disease Subtypes.

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Nagae, Lidia M; Honce, Justin M; Tanabe, Jody; Shelton, Erika; Sillau, Stefan H; Berman, Brian D

2016-01-01

Diffusion tensor imaging (DTI) of the substantia nigra has shown promise in detecting and quantifying neurodegeneration in Parkinson disease (PD). It remains unknown, however, whether differences in microstructural changes within the basal ganglia underlie PD motor subtypes. We investigated microstructural changes within the basal ganglia of mild to moderately affected PD patients using DTI and sought to determine if microstructural changes differ between the tremor dominant (TD) and postural instability/gait difficulty (PIGD) subtypes. Fractional anisotropy, mean diffusivity, radial, and axial diffusivity were obtained from bilateral caudate, putamen, globus pallidus, and substantia nigra of 21 PD patients (12 TD and 9 PIGD) and 20 age-matched healthy controls. T-tests and ANOVA methods were used to compare PD patients, subtypes, and controls, and Spearman correlations tested for relationships between DTI and clinical measures. We found our cohort of PD patients had reduced fractional anisotropy within the substantia nigra and increased mean and radial diffusivity within the substantia nigra and globus pallidus compared to controls, and that changes within those structures were largely driven by the PIGD subtype. Across all PD patients fractional anisotropy within the substantia nigra correlated with disease stage, while in PIGD patients increased diffusivity within the globus pallidus correlated with disease stage and motor severity. We conclude that PIGD patients have more severely affected microstructural changes within the substantia nigra compared to TD, and that microstructural changes within the globus pallidus may be particularly relevant for the manifestation of the PIGD subtype.

Holmes’ Tremor with Shoulder Pain Treated by Deep Brain Stimulation of Unilateral Ventral Intermediate Thalamic Nucleus and Globus Pallidus Internus

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Sabri Aydın

2017-05-01

Full Text Available A 21-year-old male was admitted with severe right arm and hand tremors after a thalamic hemorrhage caused by a traffic accident. He was also suffering from agonizing pain in his right shoulder that manifested after the tremor. Neurologic examination revealed a disabling, severe, and irregular kinetic and postural tremor in the right arm during target-directed movements. There was also an irregular ipsilateral rest tremor and dystonic movements in the distal part of the right arm. The amplitude was moderate at rest and extremely high during kinetic and intentional movements. The patient underwent left globus pallidum internus and ventral intermediate thalamic nucleus deep brain stimulation. The patient improved by more than 80% as rated by the Fahn-Tolosa-Marin Tremor Rating Scale and Visual Analog Scale six months after surgery.

Exposure to the cytokine EGF leads to abnormal hyperactivity of pallidal GABA neurons: implications for schizophrenia and its modeling.

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Sotoyama, Hidekazu; Namba, Hisaaki; Chiken, Satomi; Nambu, Atsushi; Nawa, Hiroyuki

2013-08-01

Previous studies on a cytokine model for schizophrenia reveal that the hyperdopaminergic innervation and neurotransmission in the globus pallidus (GP) is involved in its behavioral impairments. Here, we further explored the physiological consequences of the GP abnormality in the indirect pathway, using the same schizophrenia model established by perinatal exposure to epidermal growth factor (EGF). Single-unit recordings revealed that the neural activity from the lateral GP was elevated in EGF-treated rats in vivo and in vitro (i.e., slice preparations), whereas the central area of the GP exhibited no significant differences. The increase in the pallidal activity was normalized by subchronic treatment with risperidone, which is known to ameliorate their behavioral deficits. We also monitored extracellular GABA concentrations in the substantia nigra, one of the targets of pallidal efferents. There was a significant increase in basal GABA levels in EGF-treated rats, whereas high potassium-evoked GABA effluxes and glutamate levels were not affected. A neurotoxic lesion in the GP of EGF-treated rats normalized GABA concentrations to control levels. Corroborating our in vivo results, GABA release from GP slices was elevated in EGF-treated animals. These findings suggest that the hyperactivity and enhanced GABA release of GP neurons represent the key pathophysiological features of this cytokine-exposure model for schizophrenia. © 2013 International Society for Neurochemistry.

The influence of puberty on subcortical brain development.

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Goddings, Anne-Lise; Mills, Kathryn L; Clasen, Liv S; Giedd, Jay N; Viner, Russell M; Blakemore, Sarah-Jayne

2014-03-01

Puberty is characterized by hormonal, physical and psychological transformation. The human brain undergoes significant changes between childhood and adulthood, but little is known about how puberty influences its structural development. Using a longitudinal sample of 711 magnetic resonance imaging scans from 275 individuals aged 7-20years, we examined how subcortical brain regions change in relation to puberty. Our regions of interest included the amygdala, hippocampus and corpus striatum including the nucleus accumbens (NA), caudate, putamen and globus pallidus (GP). Pubertal development was significantly related to structural volume in all six regions in both sexes. Pubertal development and age had both independent and interactive influences on volume for the amygdala, hippocampus and putamen in both sexes, and the caudate in females. There was an interactive puberty-by-age effect on volume for the NA and GP in both sexes, and the caudate in males. These findings suggest a significant role for puberty in structural brain development. © 2013. Published by Elsevier Inc. All rights reserved.

Endorphin mediation of post-ictal effects of kindled seizures in rats.

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Kelsey, J E; Belluzzi, J D

1982-12-16

Brief electrical stimulation of the enkephalin-rich globus pallidus at 1-h intervals produced kindled, clonic seizures in rats as rapidly as similar stimulation of the amygdala. Massing the kindling trials at 10-min intervals inhibited the occurrence of subsequent seizures, especially following globus pallidus stimulation. Naloxone (20 mg/kg), an opiate receptor antagonist, reversed this post-ictal inhibition of seizures following massed trials, but had no effect on seizures kindled at 1-h intervals. Thus, endorphin-released during seizures do not appear to mediate the production of kindled seizures, but do appear to mediate the transient posts ictal inhibition of seizures.

A GridFTP transport driver for Globus XIO

International Nuclear Information System (INIS)

Kettimuthu, R.; Wantao, L.; Link, J.; Bresnahan, J.

2008-01-01

GridFTP is a high-performance, reliable data transfer protocol optimized for high-bandwidth wide-area networks. Based on the Internet FTP protocol, it defines extensions for high-performance operation and security. The Globus implementation of GridFTP provides a modular and extensible data transfer system architecture suitable for wide area and high-performance environments. GridFTP is the de facto standard in projects requiring secure, robust, high-speed bulk data transport. For example, the high energy physics community is basing its entire tiered data movement infrastructure for the Large Hadron Collider computing Grid on GridFTP; the Laser Interferometer Gravitational Wave Observatory routinely uses GridFTP to move 1 TB a day during production runs; and GridFTP is the recommended data transfer mechanism to maximize data transfer rates on the TeraGrid. Commonly used GridFTP clients include globus-url-copy, uberftp, and the Globus Reliable File Transfer service. In this paper, we present a Globus XIO based client to GridFTP that provides a simple Open/Close/Read/Write (OCRW) interface to the users. Such a client greatly eases the addition of GridFTP support to third-party programs, such as SRB and MPICH-G2. Further, this client provides an easier and familiar interface for applications to efficiently access remote files. We compare the performance of this client with that of globus-url-copy on multiple endpoints in the TeraGrid infrastructure. We perform both memory-to-memory and disk-to-disk transfers and show that the performance of this OCRW client is comparable to that of globus-url-copy. We also show that our GridFTP client significantly outperforms the GPFS WAN on the TeraGrid.

Efficient digital implementation of a conductance-based globus pallidus neuron and the dynamics analysis

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Yang, Shuangming; Wei, Xile; Deng, Bin; Liu, Chen; Li, Huiyan; Wang, Jiang

2018-03-01

Balance between biological plausibility of dynamical activities and computational efficiency is one of challenging problems in computational neuroscience and neural system engineering. This paper proposes a set of efficient methods for the hardware realization of the conductance-based neuron model with relevant dynamics, targeting reproducing the biological behaviors with low-cost implementation on digital programmable platform, which can be applied in wide range of conductance-based neuron models. Modified GP neuron models for efficient hardware implementation are presented to reproduce reliable pallidal dynamics, which decode the information of basal ganglia and regulate the movement disorder related voluntary activities. Implementation results on a field-programmable gate array (FPGA) demonstrate that the proposed techniques and models can reduce the resource cost significantly and reproduce the biological dynamics accurately. Besides, the biological behaviors with weak network coupling are explored on the proposed platform, and theoretical analysis is also made for the investigation of biological characteristics of the structured pallidal oscillator and network. The implementation techniques provide an essential step towards the large-scale neural network to explore the dynamical mechanisms in real time. Furthermore, the proposed methodology enables the FPGA-based system a powerful platform for the investigation on neurodegenerative diseases and real-time control of bio-inspired neuro-robotics.

MR measurement of the basal ganglia volume in the tourette syndrome

International Nuclear Information System (INIS)

Liao Kaibing; Li Guiping; Yang Bo; Feng Gansheng

2014-01-01

Objective: To compare the volume of the basal ganglia in patients with Tourette syndrome (TS) and the normal volunteers and to explore the underlying anatomical basis of TS. Methods: Thirty-one cases of TS (TS subjects), 31 gender and age-matched subjects (the control subjects) were examined on a 3.0 T MRI system. The volume of the caudate nucleus, globus pallidus, putamen of the two sides and the brain volume were measured with volume analysis software, and the data were normalized according to the individual brain volume. Statistical analysis was performed using t test to compare between the TS subjects and the controls. Results: The volume of the both sides of the caudate nucleus, putamen and globus pallidus of TS subjects were (4.11 ±0.12) and (3.76 ±0.11), (2.28 ±0.12) and (2.35 ±0.28), (4.98 ±0.20) and (4.89 ±0.31) cm 3 , while they were (4.88 ±0.19) and (4.30 ±0.12), (2.28 ±0.12) and (2.35 ±0.28), (4.98 ±0.20) and (4.89 ±0.31) cm 3 in the controls, respectively. There were significant differences in the bilateral caudate nucleus and globus pallidus between the TS subjects and control subjects (t=2.97, 1.74, 3.72, 3.93, P<0.05), but there were no significant differences of the volume in the bilateral putamen between the TS and control subjects (t=0.47, 1.31, P>0.05). The volume was not significantly different between the left and right caudate nucleus in the TS subjects (t=1.81, P>0.05), but the left volume of the caudate nucleus was bigger in the control subjects compared with the right volume, however, there was significant difference between the bilateral caudate nucleus in the control subjects (t=2.34, P<0.05). There were no differences of volume between the bilateral globus pallidus and putamen in both the TS and control subjects (t=1.12, 1.44, 1.68, 0.38, P>0.05). Conclusion: The abnormal volume of caudate nucleus, putamen, and the globus pallidus may be involved in the pathogenesis of TS. (authors)

Magnetic resonance imaging of functional connectivity in Parkinson disease in the resting brain

International Nuclear Information System (INIS)

Liu Xian; Liu Bo; Luo Xiaodong; Li Ningna; Chen Zhiguang; Chen Jun

2009-01-01

Objective: To investigate functional connectivity changes in Parkinson disease in the resting brain using functional magnetic resonance imaging. Methods: Nine patients with Parkinson disease and eight age-matched healthy volunteers were entered into the study. The bilateral globus pallidus were chosen as seed points, the functional MR data acquired in the resting state were processed to investigate functional connectivity in PD patients and the results were compared with those of the controls. Results: In age-matched healthy controls, there are regions which had functional connectivity with bilateral globus pallidus, including bilateral temporal poles, bilateral hippocampus, bilateral thalami, posterior cingulate cortex, right middle occipital gyms and right superior parietal gyms. In PD patients, brain regions including bilateral cerebellum, left hippocampus, bilateral superior temporal gyri, left inferior frontal gyrus, left middle frontal gyrus, left precentral gyrus, left inferior parietal gyrus and left superior parietal gyrus, had functional connectivity with bilateral globus pallidus. Compared to healthy controls, increased functional connectivity in bilateral cerebellum, bilateral temporal lobes, left frontal lobe and left parietal lobe, and decreased functional connectivity in bilateral thalami were observed in PD patients. Conclusion: Abnormal changes of brain functional connectivity exists in Parkinson's disease in the resting state. (authors)

FDG-PET study of the bilateral subthalamic nucleus stimulation effects on the regional cerebral metabolism in advanced Parkinson disease

International Nuclear Information System (INIS)

Li, D.; Shen, J.; Zan, S.; Sun, B.; Zuo, C.; Guan, Y.; Zhao, Y.

2006-01-01

The aim of the study was to evaluate the changes in regional cerebral metabolic rate of glucose (rCMRGIu) induced by bilateral subthalamic nucleus (STN) stimulation in advanced Parkinson's disease (PD). 18 F-Fluorodeoxyglucose (FDG) PET data obtained before and one month after stimulation were analyzed with statistical parametric mapping (SPM). As a result of clinically effective bilateral STN stimulation, rCMRGIu increased in lateral globus pallidus (GP), upper brain stem, dorsolateral prefrontal cortex (DLPFC) and posterior parietal-occipital cortex, and decreased in the orbital frontal cortex and parahippocampus gyrus (p <0.001). We conclude that the alleviation of clinical symptoms in advanced PD by bilateral STN stimulation may be the result of activation of both ascending and descending pathways from STN and of restoration of the impaired higher-order cortex functions. (author)

Diagnostic value of low-field MRI for acute poisoning brain injury

International Nuclear Information System (INIS)

Dang Lianrong; He Qinyi

2012-01-01

Objective: To investigate the value of low-field MIR in diagnosis of acute CO poisoning brain injury. Methods: The brain MIR and clinical data of 110 patients with acute CO poisoning brain injury confirmed by clinical examination were retrospectively analyzed. Results: Long T1 and T2 signal intensity was showed on MRI in cerebral hemispheres and globus pallidus symmetrically. There were three basic types of MIR manifestations, white matter of brain type, globus pallidus type and brain mixed type. Conclusions: MRI could be used for confirming the degree and range of acute CO poisoning brain injury. It has important clinical value in the diagnosis, staging and prognosis of patients with acute CO poisoning brain injury. (authors)

Neurotensin effects on N-type calcium currents among rat pallidal neurons: an electrophysiological and immunohistochemical study.

Science.gov (United States)

Martorana, Alessandro; Martella, Giuseppina; D'Angelo, Vincenza; Fusco, Francesca Romana; Spadoni, Francesca; Bernardi, Giorgio; Stefani, Alessandro

2006-10-01

The tridecapeptide neurotensin (NT) is involved in the modulation of dopamine (DA)-mediated functions in the nigrostriatal and mesocorticolimbic pathways. Its relevance in mammalian globus pallidus (GP) is questioned. A recent electrophysiological study on GP slices described NT-mediated robust membrane depolarization, depending upon the suppression of potassium conductance and/or the activation of cation current. Here, we have studied whether NT also affected high-voltage-activated calcium (Ca(2+)) currents, by means of whole-cell recordings on isolated GP neurons. In our hands, the full peptide and the segment NT8-13 reversibly inhibited N-like Ca(2+) current in about 60% of the recorded dissociated neurons, irrespective of their capacitance. The NT-mediated modulation showed no desensitization and was antagonized by the NT1 antagonists SR48692 and SR142948. These results imply an abundant expression of NTS(1) on GP cell somata. Then, we performed a light and immunofluorescence-confocal microscopy study of NTS(1) localization among GP neurons. We found that NTS(1) is localized in about 56% of GP neurons in both subpopulations of neurons, namely parvalbumin positive and negative. We conclude that NT, likely released from the striatal terminals in GP, acts through the postsynaptic NTS(1) preferentially localized in the lateral aspects of the GP. These data suggest a new implication (neither merely presynaptic nor simply "excitatory") for NT in the modulation of GP firing pattern. In addition, NT might have a role in affecting the interplay among the endogenous release of GABA/glutamate and DA. This hypothesis might have implications on both sensori-motor and associative functions of the GP and should be tested in DA-denervated disease models.

Characterization of Thermophilic Halotolerant Aeribacillus pallidus TD1 from Tao Dam Hot Spring, Thailand

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Somchai Santiwatanakul

2011-08-01

Full Text Available The bacterial strain TD1 was isolated from Tao Dam hot spring in Thailand. Strain TD1 was Gram positive, rod-shaped, aerobic, motile, and endospore forming. The cell was 2.0–40 mm in length and about 0.4 mm in diameter. The optimum growth occurred at 55–60 °C and at pH 7–8. Strain TD1 was able to grow on medium containing up to 10% NaCl. The DNA G+C content was 38.9 mol%. The cellular fatty acid content was mainly C16:0, which comprised 25.04% of the total amount of cellular fatty acid. 16S rDNA showed 99% identity to Aeribacillus pallidus DSM 3670T. Bayesian tree analysis strongly supported the idea that strain TD1 is affiliated with genus Aeribacillus, as Aeribacillus pallidus strain TD1. Although the 16S rDNA of A. pallidus strain TD1 is similar to that of A. pallidus DSM 3670T, some physiological properties and the cellular fatty acid profiles differ significantly. A. pallidus strain TD1 can produce extracellular pectate lyase, which has not been reported elsewhere for other bacterial strains in the genus Aeribacillus. A. pallidus strain TD1 may be a good candidate as a pectate lyase producer, which may have useful industrial applications.

Characterization of thermophilic halotolerant Aeribacillus pallidus TD1 from Tao Dam Hot Spring, Thailand.

Science.gov (United States)

Yasawong, Montri; Areekit, Supatra; Pakpitchareon, Arda; Santiwatanakul, Somchai; Chansiri, Kosum

2011-01-01

The bacterial strain TD1 was isolated from Tao Dam hot spring in Thailand. Strain TD1 was Gram positive, rod-shaped, aerobic, motile, and endospore forming. The cell was 2.0-40 μm in length and about 0.4 μm in diameter. The optimum growth occurred at 55-60 °C and at pH 7-8. Strain TD1 was able to grow on medium containing up to 10% NaCl. The DNA G+C content was 38.9 mol%. The cellular fatty acid content was mainly C(16:0), which comprised 25.04% of the total amount of cellular fatty acid. 16S rDNA showed 99% identity to Aeribacillus pallidus DSM 3670(T). Bayesian tree analysis strongly supported the idea that strain TD1 is affiliated with genus Aeribacillus, as Aeribacillus pallidus strain TD1. Although the 16S rDNA of A. pallidus strain TD1 is similar to that of A. pallidus DSM 3670(T), some physiological properties and the cellular fatty acid profiles differ significantly. A. pallidus strain TD1 can produce extracellular pectate lyase, which has not been reported elsewhere for other bacterial strains in the genus Aeribacillus. A. pallidus strain TD1 may be a good candidate as a pectate lyase producer, which may have useful industrial applications.

Globus Online: Climate Data Management for Small Teams

Science.gov (United States)

Ananthakrishnan, R.; Foster, I.

2013-12-01

Large and highly distributed climate data demands new approaches to data organization and lifecycle management. We need, in particular, catalogs that can allow researchers to track the location and properties of large numbers of data files, and management tools that can allow researchers to update data properties and organization during their research, move data among different locations, and invoke analysis computations on data--all as easily as if they were working with small numbers of files on their desktop computer. Both catalogs and management tools often need to be able to scale to extremely large quantities of data. When developing solutions to these problems, it is important to distinguish between the needs of (a) large communities, for whom the ability to organize published data is crucial (e.g., by implementing formal data publication processes, assigning DOIs, recording definitive metadata, providing for versioning), and (b) individual researchers and small teams, who are more frequently concerned with tracking the diverse data and computations involved in what highly dynamic and iterative research processes. Key requirements in the latter case include automated data registration and metadata extraction, ease of update, close-to-zero management overheads (e.g., no local software install); and flexible, user-managed sharing support, allowing read and write privileges within small groups. We describe here how new capabilities provided by the Globus Online system address the needs of the latter group of climate scientists, providing for the rapid creation and establishment of lightweight individual- or team-specific catalogs; the definition of logical groupings of data elements, called datasets; the evolution of catalogs, dataset definitions, and associated metadata over time, to track changes in data properties and organization as a result of research processes; and the manipulation of data referenced by catalog entries (e.g., replication of a dataset to

Optogenetic Activation of the Sensorimotor Cortex Reveals "Local Inhibitory and Global Excitatory" Inputs to the Basal Ganglia.

Science.gov (United States)

Ozaki, Mitsunori; Sano, Hiromi; Sato, Shigeki; Ogura, Mitsuhiro; Mushiake, Hajime; Chiken, Satomi; Nakao, Naoyuki; Nambu, Atsushi

2017-12-01

To understand how information from different cortical areas is integrated and processed through the cortico-basal ganglia pathways, we used optogenetics to systematically stimulate the sensorimotor cortex and examined basal ganglia activity. We utilized Thy1-ChR2-YFP transgenic mice, in which channelrhodopsin 2 is robustly expressed in layer V pyramidal neurons. We applied light spots to the sensorimotor cortex in a grid pattern and examined neuronal responses in the globus pallidus (GP) and entopeduncular nucleus (EPN), which are the relay and output nuclei of the basal ganglia, respectively. Light stimulation typically induced a triphasic response composed of early excitation, inhibition, and late excitation in GP/EPN neurons. Other response patterns lacking 1 or 2 of the components were also observed. The distribution of the cortical sites whose stimulation induced a triphasic response was confined, whereas stimulation of the large surrounding areas induced early and late excitation without inhibition. Our results suggest that cortical inputs to the GP/EPN are organized in a "local inhibitory and global excitatory" manner. Such organization seems to be the neuronal basis for information processing through the cortico-basal ganglia pathways, that is, releasing and terminating necessary information at an appropriate timing, while simultaneously suppressing other unnecessary information. © The Author 2017. Published by Oxford University Press.

Acute carbon monoxide intoxication : the relation between MR findings and clinical outcome

International Nuclear Information System (INIS)

Chang, Jin Bae; Jeong, Hae Woong; Kim, Ki Nam; Kim, Dong Wook; Kim, Chang Soo

1999-01-01

To analyse MR findings of various involving sites and the relation between such findings and clinical outcome, the authors retrospectively reviewed MR images of acute carbon monoxide intoxication. In 12 patients, MR images obtained from several hours to 12 days after acute carbon monoxide intoxication were reviewed. The images were analysed with regard to involved sites, symmetricity, signal intensity, and the presence or absence of hemorrhage, and the relationship between MR findings and clinical outcome; the presence of delayed encephalopathy was then determined. The globus pallidus(n=9), white matter(n=3), [centrum semiovale(n=2), periventricular white matter(n=1)] and gyrus(n=6) [inferior temporal gyrus(n=2), cingulate gyrus(n=1), precentral gyrus(n=1), hippocampal gyrus(n=1), parahippocampal gyrus(n=1)] were typically involved, and there was also involvenent of the corpus callosum(n=3), thalamus(n=2) and midbrain(n=2). All lesions of the globus pallidus, thalamus, midbrain and temporal lobe were bilaterally symmetric. In all these cases, subtle or prominent low signal intensity was seen on spin-echo T1WI, and high signal intensity on PDWI and T2WI. Some lesions of the globus pallidus(n=1), thalamus(n=1) and midbrain(n=1) were associated with hemorrhage, which occurred during the early subacute stage and was seen on high/low signal intensity T1/T2WI images. Acute cerebral(n=1) and cerebellar(n=1) infarctions were also seen. Cerebral white matter involvement correlated with poor clinical outcome, and in two cases, delayed encephalopathy developed. In these cases of acute carbon monoxide intoxication, the globus pallidus, white matter, cortex and hippocampus were frequently involved, and there was also involvement of various sites such as the corpus callosum, thalamus and midbrain. Lesions of the temporal lobe, thalamus and midbrain were bilaterally symmetric. The involvement of cerebral white matter and the presence of delayed encephalopathy can influence

Esophageal Sensorimotor Function and Psychological Factors Each Contribute to Symptom Severity in Globus Patients.

Science.gov (United States)

Rommel, Nathalie; Van Oudenhove, Lukas; Arts, Joris; Caenepeel, Philip; Tack, Jan; Pauwels, Ans

2016-10-01

Altered upper esophageal sphincter (UES) and esophageal body (EB) sensorimotor function and psychosocial factors may both be involved in symptom generation in globus, but their common impact is not yet assessed. The aim of the study is (1) to compare UES and EB sensitivity and compliance of globus patients with healthy controls (HC); (2) to study the association of globus symptom severity (GSS) with UES and EB sensitivity and compliance, UES motor function and psychosocial factors. In 58 globus patients, GSS, somatization, and anxiety disorders were determined using validated questionnaires. In 26 HC and 42/58 patients, UES and EB sensitivity and compliance were assessed twice using barostat measurements. UES function of 27 globus patients was evaluated using high-resolution manometry. Bivariate correlations and a general linear model tested the association of these factors with GSS. UES and EB compliance did not differ between globus patients and HC. Upon repeated distension, UES habituation was seen in both groups, whereas EB sensitization (23.3±1.3 vs. 19.5±1.5 mm Hg, Pdisorder (t=3.04, P=0.004), and post-traumatic stress severity (ρ=0.40, P=0.005) were associated with GSS. UES compliance and somatization were independently associated with GSS. A trend (P=0.061) was found for the association of GSS with change in EB compliance. UES compliance, change in EB compliance, and somatization explain 40% of the variance in GSS. This indicates that globus is a complex disorder of the brain-gut axis rather than a "psychosomatic" disorder or a peripheral esophageal disorder.

Iron as a risk factor in neurological diseases

Science.gov (United States)

Galazka-Friedman, Jolanta

2008-02-01

In this review the properties of iron in various human brain structures (e.g. Substantia nigra, globus pallidus, hippocampus) were analyzed to assess the possibility of initiation of oxidative stress leading to such diseases as Parkinson’s and Alzheimer’s disease, and progressive supranuclear palsy. Our own studies with the use of Mössbauer spectroscopy, electron microscopy and enzyme-linked immuno-absorbent assay (ELISA) were confronted with other methods used in other laboratories. Our results suggest that hippocampus is the most fragile for oxidative stress structure in human brain (the death of nervous cells in hippocampus leads to Alzheimer’s disease). Changes in iron metabolism were also found in substantia nigra (the death of nervous cells of this structure produces Parkinson’s disease) and in globus pallidus (neurodegeneration of this structure causes progressive supranuclear palsy).

Iron as a risk factor in neurological diseases

International Nuclear Information System (INIS)

Galazka-Friedman, Jolanta

2008-01-01

In this review the properties of iron in various human brain structures (e.g. Substantia nigra, globus pallidus, hippocampus) were analyzed to assess the possibility of initiation of oxidative stress leading to such diseases as Parkinson's and Alzheimer's disease, and progressive supranuclear palsy. Our own studies with the use of Moessbauer spectroscopy, electron microscopy and enzyme-linked immuno-absorbent assay (ELISA) were confronted with other methods used in other laboratories. Our results suggest that hippocampus is the most fragile for oxidative stress structure in human brain (the death of nervous cells in hippocampus leads to Alzheimer's disease). Changes in iron metabolism were also found in substantia nigra (the death of nervous cells of this structure produces Parkinson's disease) and in globus pallidus (neurodegeneration of this structure causes progressive supranuclear palsy).

Globus Platform-as-a-Service for Collaborative Science Applications.

Science.gov (United States)

Ananthakrishnan, Rachana; Chard, Kyle; Foster, Ian; Tuecke, Steven

2015-02-01

Globus, developed as Software-as-a-Service (SaaS) for research data management, also provides APIs that constitute a flexible and powerful Platform-as-a-Service (PaaS) to which developers can outsource data management activities such as transfer and sharing, as well as identity, profile and group management. By providing these frequently important but always challenging capabilities as a service, accessible over the network, Globus PaaS streamlines web application development and makes it easy for individuals, teams, and institutions to create collaborative applications such as science gateways for science communities. We introduce the capabilities of this platform and review representative applications.

New results from Globus-M spherical tokamak

International Nuclear Information System (INIS)

Gusev, V.K.

2002-01-01

New results from Globus-M spherical tokamak (ST) are presented. Reported are the achievements of high plasma current of 0.36 MA and high toroidal magnetic field of 0.55 T. Plasma column stability in Globus-M is conserved at low edge safety factors and high plasma densities. Achieved lowest safety factor was q(cyl) 19 m -3 . New methods of density increase are discussed. Low-density boarder of operational space is investigated. Runaway electrons properties and conditions of their generation are investigated. Results look promising for STs. Plasma-wall interaction study was performed. Silicon probes were installed into vacuum vessel. They were exposed to boronization, first, and then deposited film interacted with plasma. Discussed are film properties. Briefly described are new diagnostic tools installed on tokamak. Status and preliminary results obtained with auxiliary heating systems are shown. (author)

The increased risk of globus pharyngeus in patients with chronic thyroiditis: a case control study.

Science.gov (United States)

Karahatay, S; Ayan, A; Aydin, U; Ince, S; Emer, O; Alagoz, E

2015-12-01

A correlation between globus pharyngeus and thyroid gland inflammation has been mentioned in previous studies. However, the potential risk of globus pharyngeus in chronic thyroiditis patients has not been shown so far. The aim of this study is to investigate a possible association between chronic thyroiditis and globus pharyngeus. The study was performed in an ultrasound (US) center of a tertiary health care institution. Ninety-two patients who were under examination for suspected thyroid pathologies or undergoing follow-up for a previously diagnosed thyroid disease were enrolled in the study. The patients were divided into two groups according to the existence of globus symptoms. Subsequently, all patients underwent high-resolution thyroid ultrasounds. The patients whose ultrasound findings were suggestive of chronic thyroiditis constituted the second subgroup. The demographic data of the patients and other ultrasound findings including the volume of the thyroid glands and nodules, if any, were noted as well. Sixty-seven female (73%) and 25 male (27%) patients were enrolled in the study. Thirty-two (35%) of the 92 patients constituted the globus pharyngeus group according to their responses to the questionnaire and the US findings were concordant with chronic thyroiditis in 36 (39%) patients. The correlation between chronic thyroiditis and globus sensation was significant (p = 0.004), and the odds ratio was calculated as 3.7 (95% CI = 1.5-9.11). Other parameters including age, sex, thyroid volume and nodule status were not significantly related to globus pharyngeus in this particular patient series. In the presented study, the risk of globus pharyngeus occurrence was calculated as 3.7-fold higher in patients with chronic thyroiditis. Being a preliminary report, it is necessary to confirm this finding and understand the pathophysiological mechanism via further investigations with a larger patient series.

Thalamic involvement in a patient with kernicterus

Energy Technology Data Exchange (ETDEWEB)

Yilmaz, Yueksel [Department of Pediatrics, Marmara University School of Medicine, Istanbul (Turkey); Ekinci, Gazanfer [Department of Radiology, Marmara University School of Medicine, Istanbul (Turkey)

2002-07-01

We report the MR imaging findings of a 16-month-old boy with dyskinetic cerebral palsy resulting from kernicterus. T2-weighted images showed symmetric bilateral hyperintensity in the thalamus in addition to the globus pallidus. (orig.)

Gadolinium-based Contrast Agent Accumulates in the Brain Even in Subjects without Severe Renal Dysfunction: Evaluation of Autopsy Brain Specimens with Inductively Coupled Plasma Mass Spectroscopy.

Science.gov (United States)

Kanda, Tomonori; Fukusato, Toshio; Matsuda, Megumi; Toyoda, Keiko; Oba, Hiroshi; Kotoku, Jun'ichi; Haruyama, Takahiro; Kitajima, Kazuhiro; Furui, Shigeru

2015-07-01

To use inductively coupled plasma mass spectroscopy (ICP-MS) to evaluate gadolinium accumulation in brain tissues, including the dentate nucleus (DN) and globus pallidus (GP), in subjects who received a gadolinium-based contrast agent (GBCA). Institutional review board approval was obtained for this study. Written informed consent for postmortem investigation was obtained either from the subject prior to his or her death or afterward from the subject's relatives. Brain tissues obtained at autopsy in five subjects who received a linear GBCA (GBCA group) and five subjects with no history of GBCA administration (non-GBCA group) were examined with ICP-MS. Formalin-fixed DN tissue, the inner segment of the GP, cerebellar white matter, the frontal lobe cortex, and frontal lobe white matter were obtained, and their gadolinium concentrations were measured. None of the subjects had received a diagnosis of severely compromised renal function (estimated glomerular filtration rate brain regions. Gadolinium was detected in all specimens in the GBCA agent group (mean, 0.25 µg per gram of brain tissue ± 0.44 [standard deviation]), with significantly higher concentrations in each region (P = .004 vs the non-GBCA group for all regions). In the GBCA group, the DN and GP showed significantly higher gadolinium concentrations (mean, 0.44 µg/g ± 0.63) than other regions (0.12 µg/g ± 0.16) (P = .029). Even in subjects without severe renal dysfunction, GBCA administration causes gadolinium accumulation in the brain, especially in the DN and GP.

Sex Commonalities and Differences in Obesity-Related Alterations in Intrinsic Brain Activity and Connectivity.

Science.gov (United States)

Gupta, Arpana; Mayer, Emeran A; Labus, Jennifer S; Bhatt, Ravi R; Ju, Tiffany; Love, Aubrey; Bal, Amanat; Tillisch, Kirsten; Naliboff, Bruce; Sanmiguel, Claudia P; Kilpatrick, Lisa A

2018-02-01

This study aimed to characterize obesity-related sex differences in the intrinsic activity and connectivity of the brain's reward networks. Eighty-six women (n = 43) and men (n = 43) completed a 10-minute resting functional magnetic resonance imaging scan. Sex differences and commonalities in BMI-related frequency power distribution and reward seed-based connectivity were investigated by using partial least squares analysis. For whole-brain activity in both men and women, increased BMI was associated with increased slow-5 activity in the left globus pallidus (GP) and substantia nigra. In women only, increased BMI was associated with increased slow-4 activity in the right GP and bilateral putamen. For seed-based connectivity in women, increased BMI was associated with reduced slow-5 connectivity between the left GP and putamen and the emotion and cortical regulation regions, but in men, increased BMI was associated with increased connectivity with the medial frontal cortex. In both men and women, increased BMI was associated with increased slow-4 connectivity between the right GP and bilateral putamen and the emotion regulation and sensorimotor-related regions. The stronger relationship between increased BMI and decreased connectivity of core reward network components with cortical and emotion regulation regions in women may be related to the greater prevalence of emotional eating. The present findings suggest the importance of personalized treatments for obesity that consider the sex of the affected individual. © 2017 The Obesity Society.

Infantile neuroaxonal dystrophy: neuroradiological studies in 11 patients

International Nuclear Information System (INIS)

Farina, L.; Bruzzone, M.G.; D'Incerti, L.; Savoiardo, M.; Nardocci, N.; Zorzi, G.; Verga, L.; Morbin, M.

1999-01-01

We report the imaging findings in 11 patients with infantile neuroaxonal dystrophy. Ten patients underwent 15 MRI examinations; one patient had only CT. Of the ten patients who underwent MRI, eight had cerebellar atrophy and mildly increased signal from the cerebellar cortex on T2-weighted images. With T2 weighting there was slightly increased signal from the dentate nuclei in two patients and from the posterior periventricular white matter in three. We saw four patients with a thin optic chiasm. The only two brothers in the series had markedly low signal from the globus pallidus and substantia nigra on 1.5 T T2-weighted images, as seen in Hallervorden-Spatz disease (HSD). Abnormalities of the globus pallidus may be related to a protracted course of the disease. However, an overlap with HSD should be considered. (orig.)

Selective peripheral denervation: comparison with pallidal stimulation and literature review

NARCIS (Netherlands)

Contarino, Maria Fiorella; van den Munckhof, Pepijn; Tijssen, Marina A. J.; de Bie, Rob M. A.; Bosch, D. Andries; Schuurman, P. Richard; Speelman, Johannes D.

2014-01-01

Patients with cervical dystonia who are non-responders to Botulinum toxin qualify for surgery. Selective peripheral denervation (Bertrand's procedure, SPD) and deep brain stimulation of the globus pallidus (GPi-DBS) are available surgical options. Although peripheral denervation has potential

Monitoring the grid with the Globus Toolkit MDS4

International Nuclear Information System (INIS)

Schopf, Jennifer M; Pearlman, Laura; Miller, Neill; Kesselman, Carl; Foster, Ian; D'Arcy, Mike; Chervenak, Ann

2006-01-01

The Globus Toolkit Monitoring and Discovery System (MDS4) defines and implements mechanisms for service and resource discovery and monitoring in distributed environments. MDS4 is distinguished from previous similar systems by its extensive use of interfaces and behaviors defined in the WS-Resource Framework and WS-Notification specifications, and by its deep integration into essentially every component of the Globus Toolkit. We describe the MDS4 architecture and the Web service interfaces and behaviors that allow users to discover resources and services, monitor resource and service states, receive updates on current status, and visualize monitoring results. We present two current deployments to provide insights into the functionality that can be achieved via the use of these mechanisms

Gadolinium deposition in the brain: association with various GBCAs using a generalized additive model

Energy Technology Data Exchange (ETDEWEB)

Bae, Sohi; Lee, Ho-Joon; Han, Kyunghwa; Park, Yae-Won; Choi, Yoon Seong; Ahn, Sung Soo; Kim, Jinna; Lee, Seung-Koo [Yonsei University College of Medicine, Department of Radiology, Severance Hospital, Research Institute of Radiological Science, Seoul (Korea, Republic of)

2017-08-15

To determine the relationship between the number of administrations of various gadolinium-based contrast agents (GBCAs) and increased T1 signal intensity in the globus pallidus (GP) and dentate nucleus (DN). This retrospective study included 122 patients who underwent double-dose GBCA-enhanced magnetic resonance imaging. Two radiologists calculated GP-to-thalamus (TH) signal intensity ratio, DN-to-pons signal intensity ratio and relative change (R{sub change}) between the baseline and final examinations. Interobserver agreement was evaluated. The relationships between R{sub change} and several factors, including number of each GBCA administrations, were analysed using a generalized additive model. Six patients (4.9%) received linear GBCAs (mean 20.8 number of administration; range 15-30), 44 patients (36.1%) received macrocyclic GBCAs (mean 26.1; range 14-51) and 72 patients (59.0%) received both types of GBCAs (mean 31.5; range 12-65). Interobserver agreement was almost perfect (0.99; 95% CI: 0.99-0.99). R{sub change} (DN:pons) was associated with gadodiamide (p = 0.006) and gadopentetate dimeglumine (p < 0.001), but not with other GBCAs. R{sub change} (GP:TH) was not associated with GBCA administration. Previous administration of linear agents gadoiamide and gadopentetate dimeglumine is associated with increased T1 signal intensity in the DN, whereas macrocyclic GBCAs do not show an association. (orig.)

Frequency-selectivity of a thalamocortical relay neuron during Parkinson's disease and deep brain stimulation: a computational study

NARCIS (Netherlands)

Cagnan, Hayriye; Cagnan, H.; Meijer, Hil Gaétan Ellart; van Gils, Stephanus A.; Krupa, M.; Heida, Tjitske; Rudolph, Michelle; Wadman, Wyse J.; Martens, Hubert C.F.

2009-01-01

In this computational study, we investigated (i) the functional importance of correlated basal ganglia (BG) activity associated with Parkinson's disease (PD) motor symptoms by analysing the effects of globus pallidus internum (GPi) bursting frequency and synchrony on a thalamocortical (TC) relay

Structural Findings in the Brain MRI of Patients with Acute Carbon Monoxide Poisoning

Directory of Open Access Journals (Sweden)

Yasmin Davoudi

2014-09-01

Conclusion: The white matter and globus pallidus were the most common affected regions in brain following acute CO poisoning. Signal abnormalities and restricted diffusion in MRI were correlated with duration of exposure to CO but not with the carboxyhemoglobin levels.

Association between swallow perception and esophageal bolus clearance in patients with globus sensation.

Science.gov (United States)

Chen, Chien-Lin; Yi, Chih-Hsun; Liu, Tso-Tsai

2013-04-01

Globus sensation is common, but its pathogenesis is not yet clear. Our purpose was to investigate subjective perception of swallowing and esophageal motility by combined multichannel intraluminal impedance and manometry (MII-EM) for patients with globus sensation. Combined MII-EM was performed for 25 globus patients and 15 healthy controls. Swallows were abnormal if hypocontractivity or simultaneous contractions occurred. Esophageal bolus transit was incomplete if bolus exit was not found at one or more of all measurement sites. Perception of each swallow was assessed by use of a standardized scoring system, and was enhanced if the score was >1. Few globus patients reported enhanced perception during viscous or solid swallows. Incomplete bolus transit and enhanced perception occurred similarly between viscous and solid boluses. Agreement between enhanced perception and proximal bolus clearance was greater during solid swallows (κ = 0.45, 95 % CI: 0.32-0.58) than during viscous swallows (κ = 0.13, 95 % CI: 0-0.25) (P perception and total bolus clearance was greater during solid swallows (κ = 0.46, 95 % CI: 0.34-0.58) than during viscous swallows (κ = 0.11, 95 % CI: 0-0.22) (P perception is uncommon in patients with globus sensation, although there is a significant association between enhanced esophageal perception and solid bolus clearance. Application of a solid bolus may help better delineation of the interrelationship between the subjective perception of bolus passage and the objective measurement of bolus clearance.

Study of MRI characteristics of newborn bilirubin encephalopathy

International Nuclear Information System (INIS)

Wu Wulin; Wang Xiaoyi; Liao Weihua; Liu Fan; Zhang Ping

2008-01-01

Objective: To explore routine magnetic resonance imaging characteristics of newborn bilirubin encephalopathy (NBE). Methods: MRI features and clinical data of 17 patients with Newborn bilirubin encephalopathy were retrospectively analyzed, globus pallidus (GP)and subthalamic signal intensity was evaluated. The increase of GP signal intensity and serum total bilirubin peak value were analyzed using pearson correlation analysis. Serum total bilirubin peak value between patients with high signal in the subthalamic nuclei on T 1 WI and patients without high signal in the subthalamic nuclei were compared statistically. Results: The main MRI presentation in the NBE group was abnormally increased signal intensity in the GP on T 1 WI, which was not apparent on T 2 WI. One patient showed abnormal high signal intensity in the posteromedial part of GP. Nine patients had high signal in the subthalamic nuclei on T 1 WI and normal signal on T 2 WI. Four patients showed high signal in the brainstem with sparing of dorsal pontine. The increase in value of GP signal intensity was 249.0-423.8 in 12 patients and their serum total bilirubin peak values were 366.0-983.3 μmol/L. A positive correlation was found between increase of GP signal intensity and serum total bilirubin peak value. The serum total bilirubin level of abnormal subthalamic group and normal subthalamic group were 660.7±192.4 μmol/L and 513.3±107.51 μmol/L respectively. The difference between the two groups was not statistically significant (t=1.914, P>0.05). Conclusion: The routine MRI has some characteristics and is useful in the diagnosis of newborn bilirubin encephalopathy. (authors)

Pathophysiology and treatment of patients with globus sensation ―from the viewpoint of esophageal motility dysfunction―

Science.gov (United States)

Manabe, Noriaki; Tsutsui, Hideaki; Kusunoki, Hiroaki; Hata, Jiro; Haruma, Ken

2014-01-01

"Globus sensation" is often described as the sensation of a lump in the throat associated with dry swallowing or the need for dry swallowing, which disappears completely during eating or drinking and for which no organic cause can be established. Due to the uncertain etiology of "globus sensation", it remains difficult to establish standard treatment strategies for affected patients. Lately most attention has been focused on gastroesophageal reflux disease and several reports have indicated that there is a close relationship between esophageal acid reflux and globus sensation. Nowadays, empirical therapy with a high dose of a proton pump inhibitor (PPI) is considered to be indicated for patients with globus sensation, after excluding organic diseases such as pharyngeal cancer, Zenker's diverticulum, or thyroid enlargement. If patients are nonresponsive to PPI therapy, evaluation of esophageal motility should be done. In our recent study, 47.9% had abnormal esophageal motility, with the most common esophageal motility abnormality being an ineffective esophageal motility in PPI-resistant patients with globus sensation. This suggests that prokinetics alone or adding prokinetics to PPI should be the treatment to be considered, although few studies have investigated the efficacy of prokinetics in the treatment of patients with globus sensation. If patients without any esophageal motility dysfunctions are nonresponsive to PPI therapy, either cognitive-behavioral therapy, anti-depressants, or gabapentin could be helpful, although further well-designed, randomized controlled large-scale studies will be necessary to determine the effectiveness of each treatment strategy on patients with globus sensation. PMID:26081369

Congress of Neurological Surgeons Systematic Review and Evidence-Based Guideline on Subthalamic Nucleus and Globus Pallidus Internus Deep Brain Stimulation for the Treatment of Patients With Parkinson's Disease: Executive Summary.

Science.gov (United States)

Rughani, Anand; Schwalb, Jason M; Sidiropoulos, Christos; Pilitsis, Julie; Ramirez-Zamora, Adolfo; Sweet, Jennifer A; Mittal, Sandeep; Espay, Alberto J; Martinez, Jorge Gonzalez; Abosch, Aviva; Eskandar, Emad; Gross, Robert; Alterman, Ron; Hamani, Clement

2018-06-01

Is bilateral subthalamic nucleus deep brain stimulation (STN DBS) more, less, or as effective as bilateral globus pallidus internus deep brain stimulation (GPi DBS) in treating motor symptoms of Parkinson's disease, as measured by improvements in Unified Parkinson's Disease Rating Scale, part III (UPDRS-III) scores? Given that bilateral STN DBS is at least as effective as bilateral GPi DBS in treating motor symptoms of Parkinson's disease (as measured by improvements in UPDRS-III scores), consideration can be given to the selection of either target in patients undergoing surgery to treat motor symptoms. (Level I). Is bilateral STN DBS more, less, or as effective as bilateral GPi DBS in allowing reduction of dopaminergic medication in Parkinson's disease? When the main goal of surgery is reduction of dopaminergic medications in a patient with Parkinson's disease, then bilateral STN DBS should be performed instead of GPi DBS. (Level I). Is bilateral STN DBS more, less, or as effective as bilateral GPi DBS in treating dyskinesias associated with Parkinson's disease? There is insufficient evidence to make a generalizable recommendation regarding the target selection for reduction of dyskinesias. However, when the reduction of medication is not anticipated and there is a goal to reduce the severity of "on" medication dyskinesias, the GPi should be targeted. (Level I). Is bilateral STN DBS more, less, or as effective as bilateral GPi DBS in improving quality of life measures in Parkinson's disease? When considering improvements in quality of life in a patient undergoing DBS for Parkinson's disease, there is no basis to recommend bilateral DBS in 1 target over the other. (Level I). Is bilateral STN DBS associated with greater, lesser, or a similar impact on neurocognitive function than bilateral GPi DBS in Parkinson disease? If there is significant concern about cognitive decline, particularly in regards to processing speed and working memory in a patient undergoing DBS

[Use of high frequency cinematography in diagnosis of globus sensation].

Science.gov (United States)

Alberty, J; Oelerich, M

1996-09-01

Globus pharyngis is a frequent symptom in patients who consult an otolaryngologist. In many cases, routine diagnostic work-up including history, clinical examination, and barium swallow fail to revealing the underlying pathogenesis. In a retrospective study, we present 51 selected patients suffering from globus pharyngis of unknown origin who were investigated by high-speed cineradiography in a standardized manner. Twenty-four of the patients enrolled in the study (47.1%) showed functional and/or structural swallowing disorders. In 13 cases (25.5%) dyskinesias of the superior esophagus sphincter muscle were found. Five of these patients (9.8%) also had an inconstant hypopharyngeal diverticulum. Six cases (11.8%) showed laryngeal penetration or tracheal aspiration. In four cases (7.8%) functional disorders of pharyngeal, and in three cases (5.9%) functional disorders of oral bolus transport were found. Furthermore one hypopharyngeal web (1.9%) and two benign tumors (3.9%) were detected. In many cases, varying combinations of these findings occurred. Using high-speed cineradiography for evaluation of globus pharyngis results in an increased incidence of pathologic findings, and thus is an important method for interdisciplinary diagnostic work up of patients suffering from this symptom.

Effects of stereotactic neurosurgery on postural instability and gait in Parkinson's disease

NARCIS (Netherlands)

Bakker, Maaike; Esselink, Rianne A. J.; Munneke, Marten; Limousin-Dowsey, Patricia; Speelman, Hans D.; Bloem, Bastiaan R.

2004-01-01

Postural instability and gait disability (PIGD) are disabling signs of Parkinson's disease. Stereotactic surgery aimed at the internal globus pallidus (GPi) or subthalamic nucleus (STN) might improve PIGD, but the precise effects remain unclear. We performed a systematic review of studies that

A randomized double-blind crossover trial comparing subthalamic and pallidal deep brain stimulation for dystonia

DEFF Research Database (Denmark)

Schjerling, Lisbeth; Hjermind, Lena E; Jespersen, Bo

2013-01-01

Object The authors' aim was to compare the subthalamic nucleus (STN) with the globus pallidus internus (GPi) as a stimulation target for deep brain stimulation (DBS) for medically refractory dystonia. Methods In a prospective double-blind crossover study, electrodes were bilaterally implanted in ...

Infantile neuroaxonal dystrophy: neuroradiological studies in 11 patients

Energy Technology Data Exchange (ETDEWEB)

Farina, L.; Bruzzone, M.G.; D`Incerti, L.; Savoiardo, M. [Department of Neuroradiology, Istituto Nazionale Neurologico C. Besta, Milan (Italy); Nardocci, N.; Zorzi, G. [Department of Child Neurology, Istituto Nazionale Neurologico C. Besta, Milan (Italy); Verga, L.; Morbin, M. [Department of Neuropathology, Istituto Nazionale, Neurologico C. Besta, Milan (Italy)

1999-05-01

We report the imaging findings in 11 patients with infantile neuroaxonal dystrophy. Ten patients underwent 15 MRI examinations; one patient had only CT. Of the ten patients who underwent MRI, eight had cerebellar atrophy and mildly increased signal from the cerebellar cortex on T2-weighted images. With T2 weighting there was slightly increased signal from the dentate nuclei in two patients and from the posterior periventricular white matter in three. We saw four patients with a thin optic chiasm. The only two brothers in the series had markedly low signal from the globus pallidus and substantia nigra on 1.5 T T2-weighted images, as seen in Hallervorden-Spatz disease (HSD). Abnormalities of the globus pallidus may be related to a protracted course of the disease. However, an overlap with HSD should be considered. (orig.) With 3 figs., 1 tab., 28 refs.

Brain MRI changes in chronic liver disease

Energy Technology Data Exchange (ETDEWEB)

Skehan, S. [Department of Diagnostic Imaging, St. Vincent`s Hospital, Elm Park, Dublin 4 (Ireland); Norris, S. [Liver Unit, St. Vincent`s Hospital, Elm Park, Dublin 4 (Ireland); Hegarty, J. [Liver Unit, St. Vincent`s Hospital, Elm Park, Dublin 4 (Ireland); Owens, A. [Department of Diagnostic Imaging, St. Vincent`s Hospital, Elm Park, Dublin 4 (Ireland); MacErlaine, D. [Department of Diagnostic Imaging, St. Vincent`s Hospital, Elm Park, Dublin 4 (Ireland)

1997-08-01

Cirrhotic patients are known to have abnormally high signal principally in the globus pallidus on non-contrast T1-weighted MRI. The purpose of this study was to relate MR changes to clinical and pathological features of chronic liver disease. We confirmed abnormally high signal in the globus pallidus on T1-weighted images in 25 of 28 patients with chronic liver disease, showing that it also occurs in patients who have not yet progressed to cirrhosis. Changes were seen in patients both with and without clinical portosystemic shunting. This abnormality is not responsible for hepatic encephalopathy. Cholestatic disease was more likely to produce marked changes than non-cholestatic disease. No statistically significant correlation was demonstrated between the severity of liver disease and the degree of MR abnormality. However, marked improvement in MR appearances was seen after successful liver transplantation. (orig.). With 3 figs., 4 tabs.

Brain MRI changes in chronic liver disease

International Nuclear Information System (INIS)

Skehan, S.; Norris, S.; Hegarty, J.; Owens, A.; MacErlaine, D.

1997-01-01

Cirrhotic patients are known to have abnormally high signal principally in the globus pallidus on non-contrast T1-weighted MRI. The purpose of this study was to relate MR changes to clinical and pathological features of chronic liver disease. We confirmed abnormally high signal in the globus pallidus on T1-weighted images in 25 of 28 patients with chronic liver disease, showing that it also occurs in patients who have not yet progressed to cirrhosis. Changes were seen in patients both with and without clinical portosystemic shunting. This abnormality is not responsible for hepatic encephalopathy. Cholestatic disease was more likely to produce marked changes than non-cholestatic disease. No statistically significant correlation was demonstrated between the severity of liver disease and the degree of MR abnormality. However, marked improvement in MR appearances was seen after successful liver transplantation. (orig.). With 3 figs., 4 tabs

A prospective cohort-study of 122 adult patients presenting to an otolaryngologist's office with globus pharyngeus

DEFF Research Database (Denmark)

Rasmussen, Eva Rye; Schnack, Didde Traerup; Ravn, Andreas Tomaas

2018-01-01

OBJECTIVES: To investigate the epidemiology of globus pharyngeus in adult patients presenting to the otolaryngologist's office. Also the predictors of persisting symptoms, prevalence of anxiety and the effect of clinical assessment were analyzed. DESIGN: This was a prospective cohort study. Follow......-up was done using a postal questionnaire. SETTING: One otolaryngologists' office comprising three medical doctors. PARTICIPANTS: 122 consecutive globus patients presenting to one otolaryngology office in a one-year period. MAIN OUTCOME MEASURES: Globus incidence, gender- and age-distribution, predictors...... of persisting symptoms and the patient's health related concerns. RESULTS: 3.8% of first-time visits were regarding globus. The mean age was 48 years [range 20-88 y] and a female predominance was found (ratio 1.49). 84% experienced anxiety, mainly due to fear of cancer. The most common pathological findings...

Hyperintensity of basal ganglia on T{sub 1}-weighted images in patients with liver cirrhosis. Correlation with hepatic encephalopathy and liver function

Energy Technology Data Exchange (ETDEWEB)

Maeda, Hiroko; Kita, Keisuke; Mizobata, Toshiharu; Kimura, Masashi; Sonomura, Tetsuo; Kishi, Kazushi; Tanaka, Kayo; Sato, Morio; Yamada, Ryosaku [Wakayama Medical Coll. (Japan)

1995-04-01

Brain MR imaging was performed in 38 liver cirrhosis (LC) patients and 9 normal volunteers. On T{sub 1}-weighted images, the signal intensity of globus pallidus (S1) and frontal white matter (S2) was measured and S1/S2 ratio was explored. We examined the relationship between S1/S2 ratio and liver function parameters. High signal intensity in bilateral globus pallidus was noted on T{sub 1} W1 in 28 of 38 LC patients. The S1/S2 ratio of 1.186{+-}0.097 in the 38 LC patients was significantly higher than 0.987{+-}0.062 in the 9 normal volunteers (p<0.001), while T{sub 2}-weighted images showed no abnormal intensity. Compared with the LC patients with hepatic encephalopathy (HE) (n=7) and without HE (n=31), the former S1/S2 ratio (1.239{+-}0.057) was significantly higher than the latter (1.174{+-}0.097) (p<0.05). There was a significant correlation between the value of the S1/S2 ratio and deterioration of ICG R{sub 15} (r=0.501, p<0.005), prolongation of prothrombine time (r=-0.392, p<0.05) and decrease of choline esterase (r=-0.336, p<0.05). There was, however, little correlation between the value of the S1/S2 ratio and ammonia and Fisher ratio. In conclusion, there is a significant relationship between high intensity of globus pallidus on T{sub 1}-WI and the degree of liver dysfunction. (author).

Envenomation by neotropical Opisthoglyphous colubrid Thamnodynastes cf. pallidus Linné, 1758 (Serpentes:Colubridae in Venezuela Envenenamiento por la colubrida opistoglifa Thamnodynastes cf. pallidus Linné, 1758 (Serpentes:Colubridae en Venezuela

Directory of Open Access Journals (Sweden)

Fresnel Diaz

2004-10-01

Full Text Available This is a case report of a "non-venomous" snake bite in a herpetologist observed at the Sciences Faculty of the Universidad de los Andes (Mérida, Venezuela. The patient was bitten on the middle finger of the left hand, and shows signs of pronounced local manifestations of envenomation such as bleeding from the tooth imprint, swelling and warmth. He was treated with local care, analgesics, and steroids. He was dismissed from the hospital and observed at home during five days with marked improvement of envenomation. The snake was brought to the medical consult and identified as a Thamnodynastes cf. pallidus specimen. This report represents the first T. pallidus accident described in a human.Se reporta un caso de una mordedura de serpiente "no venenosa", en un herpetólogo observado en la Facultad de Ciencias de la Universidad de los Andes (Mérida, Venezuela. El paciente fue mordido en el dedo medio de la mano izquierda, mostrando pronunciados signos locales de sangramiento por la impronta ocasionada por los dientes de la serpiente, edema y calor local. El paciente fue tratado con cuidados locales, analgésicos y esteroides. Fue dado de alta del hospital y observado en el hogar durante 5 días, con marcada mejoría del envenenamiento. La serpiente fue traída a la consulta médica e identificada como un espécimen de Thamnodynastes cf. pallidus. Este es el primer caso humano descrito, ocasionado por un T. pallidus.

Psychiatric and social outcome after deep brain stimulation for advanced Parkinson's disease

NARCIS (Netherlands)

Boel, J.A.; Odekerken, V.J.J.; Geurtsen, G.J.; Schmand, B.A.; Cath, D.C.; Figee, M.; van den Munckhof, P.; de Haan, R.J.; Schuurman, P.R.; de Bie, R.M.A.

BACKGROUND: The aim of this study was to assess psychiatric and social outcome 12 months after bilateral deep brain stimulation (DBS) of the globus pallidus pars interna (GPi) and subthalamic nucleus (STN) for advanced Parkinson's disease (PD). METHODS: We randomly assigned patients to receive GPi

Psychiatric and social outcome after deep brain stimulation for advanced Parkinson's disease

NARCIS (Netherlands)

Boel, Judith A; Odekerken, Vincent J J; Geurtsen, Gert J; Schmand, Ben A; Cath, Danielle C; Figee, Martijn; van den Munckhof, Pepijn; de Haan, Rob J; Schuurman, P Richard; de Bie, Rob M A

2016-01-01

BACKGROUND: The aim of this study was to assess psychiatric and social outcome 12 months after bilateral deep brain stimulation (DBS) of the globus pallidus pars interna (GPi) and subthalamic nucleus (STN) for advanced Parkinson's disease (PD). METHODS: We randomly assigned patients to receive GPi

Integration of Globus Online with the ATLAS PanDA Workload Management System

CERN Document Server

Contreras, C; The ATLAS collaboration; Maeno, T; Nilsson, P; Potekhin, M

2012-01-01

The PanDA Workload Management System is the basis for distributed production and analysis for the ATLAS experiment at the LHC. In this role, it relies on sophisticated dynamic data movement facilities developed in ATLAS. In certain scenarios, such as small research teams in ATLAS Tier-3 sites and non-ATLAS Virtual Organizations, the overhead of installation and operation of these components makes their use not very cost effective. Globus Online is an emerging new tool from the Globus Alliance, which already proved popular within the research community. It provides the users with fast and robust file transfer capabilities that can also be managed from a Web interface, and in addition to grid sites, can have individual workstations and laptops serving as data transmission endpoints. We will describe the integration of the Globus Online functionality into the PanDA suite of software, in order to give more flexibility in choosing the method of data transfer to ATLAS Tier-3 and OSG users.

Integration of Globus Online with the ATLAS PanDA Workload Management System

International Nuclear Information System (INIS)

Contreras, C; Deng, W; Maeno, T; Potekhin, M; Nilsson, P

2012-01-01

The PanDA Workload Management System is the basis for distributed production and analysis for the ATLAS experiment at the LHC. In this role, it relies on sophisticated dynamic data movement facilities developed in ATLAS. In certain scenarios, such as small research teams in ATLAS Tier-3 sites and non-ATLAS Virtual Organizations, the overhead of installation and operation of these components makes their use not very cost effective. Globus Online is an emerging new tool from the Globus Alliance, which already proved popular within the research community. It provides the users with fast and robust file transfer capabilities that can also be managed from a Web interface, and in addition to grid sites, can have individual workstations and laptops serving as data transmission endpoints. We will describe the integration of the Globus Online functionality into the PanDA suite of software, in order to give more flexibility in choosing the method of data transfer to ATLAS Tier-3 and Open Science Grid (OSG) users.

Deploying HEP applications using Xen and Globus Virtual Workspaces

International Nuclear Information System (INIS)

Agarwal, A; Desmarais, R; Gable, I; Grundy, D; P-Brown, D; Seuster, R; Vanderster, D C; Sobie, R; Charbonneau, A; Enge, R

2008-01-01

The deployment of HEP applications in heterogeneous grid environments can be challenging because many of the applications are dependent on specific OS versions and have a large number of complex software dependencies. Virtual machine monitors such as Xen could be used to package HEP applications, complete with their execution environments, to run on resources that do not meet their operating system requirements. Our previous work has shown HEP applications running within Xen suffer little or no performance penalty as a result of virtualization. However, a practical strategy is required for remotely deploying, booting, and controlling virtual machines on a remote cluster. One tool that promises to overcome the deployment hurdles using standard grid technology is the Globus Virtual Workspaces project. We describe strategies for the deployment of Xen virtual machines using Globus Virtual Workspace middleware that simplify the deployment of HEP applications

Deep brain stimulation for dystonia: patient selection and outcomes

NARCIS (Netherlands)

Speelman, J. D.; Contarino, M. F.; Schuurman, P. R.; Tijssen, M. A. J.; de Bie, R. M. A.

2010-01-01

In a literature survey, 341 patients with primary and 109 with secondary dystonias treated with deep brain stimulation (DBS) of the internal segment of the globus pallidus (GPi) were identified. In general, the outcomes for primary dystonias were more favourable compared to the secondary forms. For

Deep brain stimulation for dystonia : Patient selection and outcomes

NARCIS (Netherlands)

Speelman, J. D.; Contarino, M. F.; Schuurman, P. R.; Tijssen, M. A. J.; de Bie, R. M. A.

In a literature survey, 341 patients with primary and 109 with secondary dystonias treated with deep brain stimulation (DBS) of the internal segment of the globus pallidus (GPi) were identified. In general, the outcomes for primary dystonias were more favourable compared to the secondary forms. For

Psychiatric and social outcome after deep brain stimulation for advanced Parkinson's disease

NARCIS (Netherlands)

Boel, Judith A.; Odekerken, Vincent J. J.; Geurtsen, Gert J.; Schmand, Ben A.; Cath, Danielle C.; Figee, Martijn; van den Munckhof, Pepijn; de Haan, Rob J.; Schuurman, P. Richard; de Bie, Rob M. A.; van Dijk, J. Marc C.; Staal, Michael

BackgroundThe aim of this study was to assess psychiatric and social outcome 12 months after bilateral deep brain stimulation (DBS) of the globus pallidus pars interna (GPi) and subthalamic nucleus (STN) for advanced Parkinson's disease (PD). MethodsWe randomly assigned patients to receive GPi DBS

Iron in typical and atypical parkinsonism – Mössbauer spectroscopy and MRI studies

Energy Technology Data Exchange (ETDEWEB)

Kuliński, R. [Bródno Hospital, MRI Lab (Poland); Bauminger, E. R. [Hebrew University, Racah Institute of Physics (Israel); Friedman, A. [Medical University of Warsaw, Department of Neurology (Poland); Duda, P.; Gałązka-Friedman, J., E-mail: jgfrie@if.pw.edu.pl [Warsaw University of Technology, Faculty of Physics (Poland)

2016-12-15

Iron may play important role in neurodegeneration. The results of comparative studies of human brain areas (control and pathological) performed by Mössbauer spectroscopy (MS) and magnetic resonance imaging (MRI) techniques are presented. Mössbauer spectroscopy demonstrated a higher concentration of iron in atypical parkinsonism (progressive supranuclear palsy PSP) in the brain areas Substantia Nigra (SN) and Globus Pallidus (GP) involved in this pathological process, compared to control, while the concentration of iron in pathological tissues in typical parkinsonism (Parkinson’s disease - PD) did not differ from that in control. These results were compared with the changes in 1/T1 and 1/T2 (T1 and T2 being the relaxation times determined by MRI). A good linear correlation curve was found between the concentration of iron as determined by MS in different areas of control human brains and between 1/T1 and 1/T2. Whereas the finding in PSP-GP (the brain area involved in PSP) also fitted to such a correlation, this was not so for the correlation between pathological SN – the brain area involved in both diseases – and 1/T2, indicating a dependence of T2 on other factors than just the concentration of iron.

Reduced topological efficiency in cortical-basal Ganglia motor network of Parkinson's disease: a resting state fMRI study.

Science.gov (United States)

Wei, Luqing; Zhang, Jiuquan; Long, Zhiliang; Wu, Guo-Rong; Hu, Xiaofei; Zhang, Yanling; Wang, Jian

2014-01-01

Parkinson's disease (PD) is mainly characterized by dopamine depletion of the cortico-basal ganglia (CBG) motor circuit. Given that dopamine dysfunction could affect functional brain network efficiency, the present study utilized resting-state fMRI (rs-fMRI) and graph theoretical approach to investigate the topological efficiency changes of the CBG motor network in patients with PD during a relatively hypodopaminergic state (12 hours after a last dose of dopamimetic treatment). We found that PD compared with controls had remarkable decreased efficiency in the CBG motor network, with the most pronounced changes observed in rostral supplementary motor area (pre-SMA), caudal SMA (SMA-proper), primary motor cortex (M1), primary somatosensory cortex (S1), thalamus (THA), globus pallidus (GP), and putamen (PUT). Furthermore, reduced efficiency in pre-SMA, M1, THA and GP was significantly correlated with Unified Parkinson's Disease Rating Scale (UPDRS) motor scores in PD patients. Together, our results demonstrate that individuals with PD appear to be less effective at information transfer within the CBG motor pathway, which provides a novel perspective on neurobiological explanation for the motor symptoms in patients. These findings are in line with the pathophysiology of PD, suggesting that network efficiency metrics may be used to identify and track the pathology of PD.

Hemiballismus: Study of a case using positron emission tomography with 18fluoro-2-deoxyglucose

International Nuclear Information System (INIS)

Dubinsky, R.M.; Greenberg, M.; Di Chiro, G.; Baker, M.; Hallett, M.

1989-01-01

A 64-year-old man had right-sided persistent hemiballismus. Cerebral computed tomography (CT) and 0.5-T magnetic resonance imaging (MRI) showed no abnormalities, but 1.5-T MRI showed decreased signal intensity of the putamina, greater on the left than on the right. The subthalamic area was normal on CT and MRI. Positron emission tomography with 18fluoro2-deoxyglucose showed marked hypometabolism of the left putamen (60% of the right) and hypermetabolism of the left parietal lobe (138% of the right). The decreased metabolism of the left putamen may indicate a reduction in neuronal firing. The pathophysiology of the hemiballismus in this case may be loss of tonic inhibition of the lateral globus pallidus from the putamen, leading in turn to greater inhibition of the subthalamic nucleus, less excitation of the medial globus pallidus, and less inhibition of the thalamus and motor cortex, and thus allowing expression of the ballistic movements

Functional neuroanatomy of the basal ganglia as studied by dual-probe microdialysis

International Nuclear Information System (INIS)

O'Connor, William T.

1998-01-01

Dual probe microdialysis was employed in intact rat brain to investigate the effect of intrastriatal perfusion with selective dopamine D 1 and D 2 receptor agonists and with c-fos antisense oligonucleotide on (a) local GABA release in the striatum; (b) the internal segment of the globus pallidus and the substantia nigra pars reticulata, which is the output site of the strionigral GABA pathway; and (c) the external segment of the globus pallidus, which is the output site of the striopallidal GABA pathway. The data provide functional in vivo evidence for a selective dopamine D 1 receptor-mediated activation of the direct strionigral GABA pathway and a selective dopamine D 2 receptor inhibition of the indirect striopallidal GABA pathway and provides a neuronal substrate for parallel processing in the basal ganglia regulation of motor function. Taken together, these findings offer new therapeutic strategies for the treatment of dopamine-linked disorders such as Parkinson's disease, Huntington's disease, and schizophrenia

Functional neuroanatomy of the basal ganglia as studied by dual-probe microdialysis

Energy Technology Data Exchange (ETDEWEB)

O' Connor, William T. E-mail: woconn@iveagh.ucd.ie

1998-11-01

Dual probe microdialysis was employed in intact rat brain to investigate the effect of intrastriatal perfusion with selective dopamine D{sub 1} and D{sub 2} receptor agonists and with c-fos antisense oligonucleotide on (a) local GABA release in the striatum; (b) the internal segment of the globus pallidus and the substantia nigra pars reticulata, which is the output site of the strionigral GABA pathway; and (c) the external segment of the globus pallidus, which is the output site of the striopallidal GABA pathway. The data provide functional in vivo evidence for a selective dopamine D{sub 1} receptor-mediated activation of the direct strionigral GABA pathway and a selective dopamine D{sub 2} receptor inhibition of the indirect striopallidal GABA pathway and provides a neuronal substrate for parallel processing in the basal ganglia regulation of motor function. Taken together, these findings offer new therapeutic strategies for the treatment of dopamine-linked disorders such as Parkinson's disease, Huntington's disease, and schizophrenia.

Structures of Ebola virus GP and sGP in complex with therapeutic antibodies.

Science.gov (United States)

Pallesen, Jesper; Murin, Charles D; de Val, Natalia; Cottrell, Christopher A; Hastie, Kathryn M; Turner, Hannah L; Fusco, Marnie L; Flyak, Andrew I; Zeitlin, Larry; Crowe, James E; Andersen, Kristian G; Saphire, Erica Ollmann; Ward, Andrew B

2016-08-08

The Ebola virus (EBOV) GP gene encodes two glycoproteins. The major product is a soluble, dimeric glycoprotein (sGP) that is secreted abundantly. Despite the abundance of sGP during infection, little is known regarding its structure or functional role. A minor product, resulting from transcriptional editing, is the transmembrane-anchored, trimeric viral surface glycoprotein (GP). GP mediates attachment to and entry into host cells, and is the intended target of antibody therapeutics. Because large portions of sequence are shared between GP and sGP, it has been hypothesized that sGP may potentially subvert the immune response or may contribute to pathogenicity. In this study, we present cryo-electron microscopy structures of GP and sGP in complex with GP-specific and GP/sGP cross-reactive antibodies undergoing human clinical trials. The structure of the sGP dimer presented here, in complex with both an sGP-specific antibody and a GP/sGP cross-reactive antibody, permits us to unambiguously assign the oligomeric arrangement of sGP and compare its structure and epitope presentation to those of GP. We also provide biophysical evaluation of naturally occurring GP/sGP mutations that fall within the footprints identified by our high-resolution structures. Taken together, our data provide a detailed and more complete picture of the accessible Ebolavirus glycoprotein landscape and a structural basis to evaluate patient and vaccine antibody responses towards differently structured products of the GP gene.

Hallervorden-Spatz disease: 2 cases of siblings

International Nuclear Information System (INIS)

Song, Jong Gi; Kim, In One; Kim, Woo Sun; Yeon, Kyung Mo

1994-01-01

We report two patients with Hallervorden-Spatz disease, who were diagnosed by same MR findings of marked low signal intensity in the globus and substantia nigra. They presented with ataxic and spastic gait, intention tremor, delayed mental development, and dysarthria. They were 7 year-old male and 8 year-old female siblings, who were healthy until 3 years of age when they suffered from progressive symptoms. T2-weighted images showed marked low signal intensity in the globus pallidus and substantia nigra indicating an increased iron deposition, and it might suggest Hallervorden-Spatz disease

Improvement of both dystonia and tics with 60 Hz pallidal deep brain stimulation.

Science.gov (United States)

Hwynn, Nelson; Tagliati, Michele; Alterman, Ron L; Limotai, Natlada; Zeilman, Pamela; Malaty, Irene A; Foote, Kelly D; Morishita, Takashi; Okun, Michael S

2012-09-01

Deep brain stimulation has been utilized in both dystonia and in medication refractory Tourette syndrome. We present an interesting case of a patient with a mixture of disabling dystonia and Tourette syndrome whose coexistent dystonia and tics were successfully treated with 60 Hz-stimulation of the globus pallidus region.

Psychiatric and social outcome after deep brain stimulation for advanced Parkinson's disease

NARCIS (Netherlands)

Boel, Judith A.; Odekerken, Vincent J. J.; Geurtsen, Gert J.; Schmand, Ben A.; Cath, Danielle C.; Figee, Martijn; van den Munckhof, Pepijn; de Haan, Rob J.; Schuurman, P. Richard; de Bie, Rob M. A.; van Laar, Teus; van Dijk, J. Marc C.; Mosch, Arne; Hoffmann, Carel F. E.; Nijssen, Peter C. G.; Beute, Guus N.; van Vugt, Jeroen P. P.; Lenders, Mathieu W. P. M.; Contarino, M. Fiorella; Bour, Lo J.

2016-01-01

The aim of this study was to assess psychiatric and social outcome 12 months after bilateral deep brain stimulation (DBS) of the globus pallidus pars interna (GPi) and subthalamic nucleus (STN) for advanced Parkinson's disease (PD). We randomly assigned patients to receive GPi DBS (n = 65) or STN

Demyelination of subcortical nuclei in multiple sclerosis

Science.gov (United States)

Krutenkova, E.; Aitmagambetova, G.; Khodanovich, M.; Bowen, J.; Gangadharan, B.; Henson, L.; Mayadev, A.; Repovic, P.; Qian, P.; Yarnykh, V.

2016-02-01

Myelin containing in basal ganglia in multiple sclerosis patients was evaluated using new noninvasive quantitative MRI method fast whole brain macromolecular proton fraction mapping. Myelin level in globus pallidus and putamen significantly decreased in multiple sclerosis patients as compared with healthy control subjects but not in substantia nigra and caudate nucleus.

Globus Nexus: A Platform-as-a-Service Provider of Research Identity, Profile, and Group Management.

Science.gov (United States)

Chard, Kyle; Lidman, Mattias; McCollam, Brendan; Bryan, Josh; Ananthakrishnan, Rachana; Tuecke, Steven; Foster, Ian

2016-03-01

Globus Nexus is a professionally hosted Platform-as-a-Service that provides identity, profile and group management functionality for the research community. Many collaborative e-Science applications need to manage large numbers of user identities, profiles, and groups. However, developing and maintaining such capabilities is often challenging given the complexity of modern security protocols and requirements for scalable, robust, and highly available implementations. By outsourcing this functionality to Globus Nexus, developers can leverage best-practice implementations without incurring development and operations overhead. Users benefit from enhanced capabilities such as identity federation, flexible profile management, and user-oriented group management. In this paper we present Globus Nexus, describe its capabilities and architecture, summarize how several e-Science applications leverage these capabilities, and present results that characterize its scalability, reliability, and availability.

Globus Nexus: A Platform-as-a-Service provider of research identity, profile, and group management

Energy Technology Data Exchange (ETDEWEB)

Chard, Kyle; Lidman, Mattias; McCollam, Brendan; Bryan, Josh; Ananthakrishnan, Rachana; Tuecke, Steven; Foster, Ian

2016-03-01

Globus Nexus is a professionally hosted Platform-as-a-Service that provides identity, profile and group management functionality for the research community. Many collaborative e-Science applications need to manage large numbers of user identities, profiles, and groups. However, developing and maintaining such capabilities is often challenging given the complexity of modern security protocols and requirements for scalable, robust, and highly available implementations. By outsourcing this functionality to Globus Nexus, developers can leverage best-practice implementations without incurring development and operations overhead. Users benefit from enhanced capabilities such as identity federation, flexible profile management, and user-oriented group management. In this paper we present Globus Nexus, describe its capabilities and architecture, summarize how several e-Science applications leverage these capabilities, and present results that characterize its scalability, reliability, and availability.

Demyelination of subcortical nuclei in multiple sclerosis

International Nuclear Information System (INIS)

Krutenkova, E; Aitmagambetova, G; Khodanovich, M; Yarnykh, V; Bowen, J; Gangadharan, B; Henson, L; Mayadev, A; Repovic, P; Qian, P

2016-01-01

Myelin containing in basal ganglia in multiple sclerosis patients was evaluated using new noninvasive quantitative MRI method fast whole brain macromolecular proton fraction mapping. Myelin level in globus pallidus and putamen significantly decreased in multiple sclerosis patients as compared with healthy control subjects but not in substantia nigra and caudate nucleus. (paper)

Biofilm characteristics and evaluation of the sanitation procedures of thermophilic Aeribacillus pallidus E334 biofilms.

Science.gov (United States)

Kilic, Tugba; Karaca, Basar; Ozel, Beste Piril; Ozcan, Birgul; Cokmus, Cumhur; Coleri Cihan, Arzu

2017-04-01

The ability of Aeribacillus pallidus E334 to produce pellicle and form a biofilm was studied. Optimal biofilm formation occurred at 60 °C, pH 7.5 and 1.5% NaCl. Extra polymeric substances (EPS) were composed of proteins and eDNA (21.4 kb). E334 formed biofilm on many surfaces, but mostly preferred polypropylene and glass. Using CLSM analysis, the network-like structure of the EPS was observed. The A. pallidus biofilm had a novel eDNA content. DNaseI susceptibility (86.8% removal) of eDNA revealed its importance in mature biofilms, but the purified eDNA was resistant to DNaseI, probably due to its extended folding outside the matrix. Among 15 cleaning agents, biofilms could be removed with alkaline protease and sodium dodecyl sulphate (SDS). The removal of cells from polypropylene and biomass on glass was achieved with combined SDS/alkaline protease treatment. Strong A. pallidus biofilms could cause risks for industrial processes and abiotic surfaces must be taken into consideration in terms of sanitation procedures.

Plasma heating and fuelling in the Globus-M spherical tokamak

International Nuclear Information System (INIS)

Gusev, V.K.; Barsukov, A.G.; Belyakov, V.A.

2005-01-01

The results of the last two years of plasma investigations at Globus-M are presented. Described are improvements helping to achieve high performance OH plasmas, which are used as the target for auxiliary heating and fuelling experiments. Increased energy content, high beta poloidal and good confinement are reported. Experiments on NBI plasma heating with a wide range of plasma parameters were performed. Some results are presented and analyzed. Experiments on RF plasma heating in the frequency range of fundamental ion cyclotron harmonics are described. In some experiments which were performed for the first time in spherical tokamaks, promising results were achieved. Noticeable ion heating was recorded at low launched power and a high concentration of hydrogen minority in deuterium plasmas. Simulations of RF wave absorption are briefly discussed. Described also are modification of the plasma gun and test-stand experiments. Fuelling experiments performed at Globus-M are discussed. (author)

Comparative imaging study on monkeys with hemi-parkinsonism

International Nuclear Information System (INIS)

Wang Wei; Yu Xiaoping; Mao Jun; Liu Sheng; Wang Xiaoyi; Peng Guangchun; Wang Ruiwen

2003-01-01

Objective: To study the imaging appearance of experimental Parkinson's disease (PD) and to evaluate the different medical imaging exams on PD. Methods: CT, MRI, SPECT (dopamine transporter imaging and regional cerebral blood flow imaging, DAT imaging and rCBF imaging), and PET (glucose metabolism imaging) were performed on 8 monkeys before and after the infusion of MPTP into unilateral internal carotid artery to develop hemi-Parkinsonism models. Results: Hemi-Parkinsonism models were successfully induced on all 8 monkeys. On DAT imaging, the uptake values of the lesioned striatums decreased obviously after the MPTP treatment and were lower than that of the contralateral ones. The glucose metabolic rates of the lesioned striatums and thalamus in PD models were lower, compared to that of the healthy monkeys and that of the contralateral sides of themselves. Neither DAT nor glucose metabolism abnormalities was found on both the contralateral sides of the healthy and PD monkeys. On MRI images before MPTP treatment, only 4 of 8 PD models showed hypointense in bilateral globus pallidus. No abnormal MRI findings occurred in the first 2 months after injection of MPTP. At tile third month, hypointense appeared in globus pallidus of three monkeys. Enlarged hyposignal region in globus pallidus were found in three models. Of the above 6 monkeys, two appeared hypointense in putamina. Substantia nigra demonstrated no abnormalities before and after MPTP treatment. All rCBF and CT images were normal. Conclusion: The decreased density of DAT and decreased glucose metabolism on experimental PD can be showed early by DAT imaging and glucose metabolism imaging, MRI can show abnormal signal in the basal ganglia of PD but it is later than DAT and glucose metabolism imaging. CT and rCBF find no abnormality on PD

Characterization and emulsifying property of a novel bioemulsifier by Aeribacillus pallidus YM-1.

Science.gov (United States)

Zheng, C; Li, Z; Su, J; Zhang, R; Liu, C; Zhao, M

2012-07-01

  Biosurfactants and bioemulsifiers commonly have the advantages of biodegradability, low toxicity, selectivity and biocompatibility over chemically synthesized surfactants. The goal of the study is to present a novel bioemulsifier with great application potential.   Aeribacillus pallidus YM-1, isolated from crude oil contaminated soil, was found to produce a novel high molecular bioemulsifier with an emulsification index of 60 ± 1% without remarkable surface tension reduction (45·7 ± 0·1 mN m(-1) ). The number-average molecular weight was determined as 526 369 Da by gel permeation chromatography analysis. Bioemulsifier was subjected to FT-IR and a complex of carbohydrates (41·1%), lipids (47·6%) and proteins (11·3%) was determined.   The bioemulsifier of A. pallidus YM-1 was isolated from the glucose-based culture medium and characterized with the help of chemical analytical techniques. The bioemulsifier exhibited a promising emulsifying property for biotechnology application potential in bioremediation and microbial enhanced oil recovery.   This is the first report of the bioemulsifier production by A. pallidus. The potential emulsifying activity of the bioemulsifier in the present study may be explored in various biotechnological and industrial applications. © 2012 The Authors. Journal of Applied Microbiology © 2012 The Society for Applied Microbiology.

Hyperintensity of basal ganglia on T1-weighted images in patients with liver cirrhosis. Correlation with hepatic encephalopathy and liver function

International Nuclear Information System (INIS)

Maeda, Hiroko; Kita, Keisuke; Mizobata, Toshiharu; Kimura, Masashi; Sonomura, Tetsuo; Kishi, Kazushi; Tanaka, Kayo; Sato, Morio; Yamada, Ryosaku

1995-01-01

Brain MR imaging was performed in 38 liver cirrhosis (LC) patients and 9 normal volunteers. On T 1 -weighted images, the signal intensity of globus pallidus (S1) and frontal white matter (S2) was measured and S1/S2 ratio was explored. We examined the relationship between S1/S2 ratio and liver function parameters. High signal intensity in bilateral globus pallidus was noted on T 1 W1 in 28 of 38 LC patients. The S1/S2 ratio of 1.186±0.097 in the 38 LC patients was significantly higher than 0.987±0.062 in the 9 normal volunteers (p 2 -weighted images showed no abnormal intensity. Compared with the LC patients with hepatic encephalopathy (HE) (n=7) and without HE (n=31), the former S1/S2 ratio (1.239±0.057) was significantly higher than the latter (1.174±0.097) (p 15 (r=0.501, p 1 -WI and the degree of liver dysfunction. (author)

CT of the brain in acute carbon monoxide poisoning

International Nuclear Information System (INIS)

Ohno, Masato; Uchino, Akira; Hayashi, Kazuji; Nakata, Hajime.

1988-01-01

Cerebral computed tomographic (CT) findings of acute carbon monoxide (Co) poisoning were analized in thirty-six cases treated with hyperbraric oxygen therapy and their relationship with prognosis was evaluated. The cases were classified into there groups, early stage, interval form, and non-interval form groups. In all groups, the initial abnormality was low density areas presumably due to edema, demyelination and/or softening. It was seen in the globus pallidus and/or white matter. Following these initial changes, cerebral hemorrhage, ventricular dilatation, and cerebral atrophy developed in a few cases. The frequency of abnormal CT findings was higher in the interval form group (85 %) or non-interval group (83 %) than the early stage group (41 %). The prognosis was good in most cases with normal CT findings. The possibility of recovery diminished in the patients with abnormal CT findings. The prognosis was particularly poor in cases showing abnormality both in globus pallidus and white matter. We conclude that CT is useful not only for detecting the pathologic change but also for predicting the prognosis of the patient with acute Co poisoning. (author)

Role of transnasal flexible laryngo-oesophagoscopy (TNFLO) in investigating patients with globus symptoms.

Science.gov (United States)

Mohammed, H; Coates, M; Masterson, L; Chan, W Y; Hassan, Y; Nassif, R

2017-12-01

To explore the rationale for investigating patients presenting with globus symptoms. In this regard, we also assess the efficacy and safety of transnasal flexible laryngo-oesophagoscopy (TNFLO). A prospective study in a head and neck cancer centre of patients with persistent globus symptoms with normal flexible nasoendoscopy/indirect mirror laryngoscopy and failure of first-line medical treatment. The role of TNFLO in investigating these patients was assessed. A total of 218 patients were recruited in this study. Positive findings included upper aerodigestive cancers in two patients, other pathologies included reflux (four patients), cricopharyngeus-related pathologies (19 patients), candida (five patients). There were only five re-referrals of patients who were discharged following normal examination with TNFLO. In nine patients, TNFLO could not be completed and they went on to have other diagnostic procedures CONCLUSION: This article is the largest to date in the UK to assess the role of TNFLO in investigating patients with globus symptoms. TNFLO is equal to rigid endoscopy as a diagnostic tool. However, it is superior in terms of image clarity, ability to record video images and safety. © 2017 John Wiley & Sons Ltd.

The role of transnasal oesophagoscopy in the management of globus pharyngeus and non-progressive dysphagia.

Science.gov (United States)

Sanyaolu, L N; Jemah, A; Stew, B; Ingrams, D R

2016-01-01

Introduction Transnasal oesophagoscopy is a relatively new method of examining the upper aerodigestive tract via the nasal passage as an outpatient procedure without the need for sedation. It has been shown to be a well tolerated, safe and accurate technique, that can therefore be used in the investigation of patients thought to have globus pharyngeus and other non sinister causes of dysphagia. Methods A total of 150 consecutive patients undergoing transnasal oesophagoscopy were analysed retrospectively. Results The main indications for this procedure were non-progressive dysphagia (n=68, 45%) and globus pharyngeus (n=60, 40%). Transnasal oesophagoscopy was normal in 65% of patients and 42% of patients were discharged from clinic at the same appointment with no further investigation. The most common positive findings were laryngeal erythema (13%) and oesophagitis (10%). Conclusions Transnasal oesophagoscopy is a useful adjunct to the management of patients with the symptoms of globus pharyngeus and non-progressive dysphagia.

Neural correlates of long-term intense romantic love.

Science.gov (United States)

Acevedo, Bianca P; Aron, Arthur; Fisher, Helen E; Brown, Lucy L

2012-02-01

The present study examined the neural correlates of long-term intense romantic love using functional magnetic resonance imaging (fMRI). Ten women and 7 men married an average of 21.4 years underwent fMRI while viewing facial images of their partner. Control images included a highly familiar acquaintance; a close, long-term friend; and a low-familiar person. Effects specific to the intensely loved, long-term partner were found in: (i) areas of the dopamine-rich reward and basal ganglia system, such as the ventral tegmental area (VTA) and dorsal striatum, consistent with results from early-stage romantic love studies; and (ii) several regions implicated in maternal attachment, such as the globus pallidus (GP), substantia nigra, Raphe nucleus, thalamus, insular cortex, anterior cingulate and posterior cingulate. Correlations of neural activity in regions of interest with widely used questionnaires showed: (i) VTA and caudate responses correlated with romantic love scores and inclusion of other in the self; (ii) GP responses correlated with friendship-based love scores; (iii) hypothalamus and posterior hippocampus responses correlated with sexual frequency; and (iv) caudate, septum/fornix, posterior cingulate and posterior hippocampus responses correlated with obsession. Overall, results suggest that for some individuals the reward-value associated with a long-term partner may be sustained, similar to new love, but also involves brain systems implicated in attachment and pair-bonding.

Neural correlates of long-term intense romantic love

Science.gov (United States)

Aron, Arthur; Fisher, Helen E.; Brown, Lucy L.

2012-01-01

The present study examined the neural correlates of long-term intense romantic love using functional magnetic resonance imaging (fMRI). Ten women and 7 men married an average of 21.4 years underwent fMRI while viewing facial images of their partner. Control images included a highly familiar acquaintance; a close, long-term friend; and a low-familiar person. Effects specific to the intensely loved, long-term partner were found in: (i) areas of the dopamine-rich reward and basal ganglia system, such as the ventral tegmental area (VTA) and dorsal striatum, consistent with results from early-stage romantic love studies; and (ii) several regions implicated in maternal attachment, such as the globus pallidus (GP), substantia nigra, Raphe nucleus, thalamus, insular cortex, anterior cingulate and posterior cingulate. Correlations of neural activity in regions of interest with widely used questionnaires showed: (i) VTA and caudate responses correlated with romantic love scores and inclusion of other in the self; (ii) GP responses correlated with friendship-based love scores; (iii) hypothalamus and posterior hippocampus responses correlated with sexual frequency; and (iv) caudate, septum/fornix, posterior cingulate and posterior hippocampus responses correlated with obsession. Overall, results suggest that for some individuals the reward-value associated with a long-term partner may be sustained, similar to new love, but also involves brain systems implicated in attachment and pair-bonding. PMID:21208991

Psychosocial factors in GP work: the effects of taking a GP position or leaving GP work.

Science.gov (United States)

Heponiemi, Tarja; Kouvonen, Anne; Aalto, Anna-Mari; Elovainio, Marko

2013-06-01

We examined the effects of leaving public sector general practitioner (GP) work and of taking a GP position on changes in work-related psychosocial factors, such as time pressure, patient-related stress, distress and work interference with family. In addition, we examined whether changes in time pressure and patient-related stress mediated the association of employment change with changes of distress and work interference with family. Participants were 1705 Finnish physicians (60% women) who responded to surveys in 2006 and 2010. Analyses of covariance were conducted to examine the effect of employment change to outcome changes adjusted for gender, age and response format. Mediational effects were tested following the procedures outlined by Baron and Kenny. Employment change was significantly associated with all the outcomes. Leaving public sector GP work was associated with substantially decreased time pressure, patient-related stress, distress and work interference with family. In contrast, taking a position as a public sector GP was associated with an increase in these factors. Mediation tests suggested that the associations of employment change with distress change and work interference with family change were partially explained by the changes in time pressure and patient-related stress. Our results showed that leaving public sector GP work is associated with favourable outcomes, whereas taking a GP position in the public sector is associated with adverse effects. Primary health-care organizations should pay more attention to the working conditions of their GPs, in particular, to time pressure and patient-related stress.

Plasma jet source parameter optimisation and experiments on injection into Globus-M spherical tokamak

International Nuclear Information System (INIS)

Gusev, V.K.; Petrov, Yu.V.; Sakharov, N.V.; Semenov, A.A.; Voronin, A.V.

2005-01-01

Results of theoretical and experimental research on the plasma sources and injection of plasma and gas jet produced by the modified source into tokamak Globus-M are presented. An experimental test stand was developed for investigation of intense plasma jet generation. Optimisation of pulsed coaxial accelerator parameters by means of analytical calculations is performed with the aim of achieving the highest flow velocity at limited coaxial electrode length and discharge current. The optimal parameters of power supply to generate a plasma jet with minimal impurity contamination and maximum flow velocity were determined. A comparison of experimental and calculation results is made. Plasma jet parameters are measured, such as: impurity species content, pressure distribution across the jet, flow velocity, plasma density, etc. Experiments on the interaction of a higher kinetic energy plasma jet with the magnetic field and plasma of the Globus-M tokamak were performed. Experimental results on plasma and gas jet injection into different Globus-M discharge phases are presented and discussed. Results are presented on the investigation of plasma jet injection as the source for discharge breakdown, plasma current startup and initial density rise. (author)

Pattern approach to MR imaging in patients with end-stage hepatic failure: a proposal for a new disease entity 'hepatic encephalopathy continuum'

Energy Technology Data Exchange (ETDEWEB)

Kim, Ho Kyun [Catholic University of Daegu, Department of Radiology, School of Medicine, Daegu (Korea); Lee, Hui Joong; Lee, Wonho; Kim, Yong Sun [Kyungpook National University Hospital, Department of Radiology, Daegu (Korea); Jang, Han Won [Yeungnam University College of Medicine, Department of Radiology, Daegu (Korea); Byun, Kyung Hwan [Pochon CHA University, Department of Radiology, School of Medicine, Kumi CHA Hospital, Kumi (Korea)

2008-08-15

The purpose of this study was to evaluate the clinical features and the characteristics of MR images of patients with end-stage hepatic failure. We reviewed the MR findings and clinical features of 31 consecutive patients (20 men, 11 women=31, mean age 58.7 years) who had been diagnosed with clinical hepatic encephalopathy. Associations between the lesion locations on each MR sequence were analyzed using a binominal test. The clinical and MR findings were compared in relation to the etiology and clinical status. The most frequently involved site, seen as high signal intensity on T2-W images, was the corpus callosum (20 patients), followed by the dentate nucleus (16 patients) and the globus pallidus (13 patients). Significant associations were seen between the pallidus and the crus cerebri, between the crus cerebri and the red nucleus, between the crus cerebri and the dentate nucleus, and between the red nucleus and the dentate nucleus on the T2-W and DW images (P<0.004). The crus cerebri, red nucleus, and dentate nucleus were involved concurrently with the corpus callosum more frequently in hepatic encephalopathy grades 3 and 4. Concurrent involvement of the globus pallidus-crus cerebri-red nucleus-dentate nucleus axis was the main MR pattern in end-stage hepatic encephalopathy, which connected with various areas of the brain. We hypothesize that these overlapping MR features could be regarded as an entity denoted as the 'hepatic encephalopathy continuum'. (orig.)

Pattern approach to MR imaging in patients with end-stage hepatic failure: a proposal for a new disease entity ''hepatic encephalopathy continuum''

International Nuclear Information System (INIS)

Kim, Ho Kyun; Lee, Hui Joong; Lee, Wonho; Kim, Yong Sun; Jang, Han Won; Byun, Kyung Hwan

2008-01-01

The purpose of this study was to evaluate the clinical features and the characteristics of MR images of patients with end-stage hepatic failure. We reviewed the MR findings and clinical features of 31 consecutive patients (20 men, 11 women=31, mean age 58.7 years) who had been diagnosed with clinical hepatic encephalopathy. Associations between the lesion locations on each MR sequence were analyzed using a binominal test. The clinical and MR findings were compared in relation to the etiology and clinical status. The most frequently involved site, seen as high signal intensity on T2-W images, was the corpus callosum (20 patients), followed by the dentate nucleus (16 patients) and the globus pallidus (13 patients). Significant associations were seen between the pallidus and the crus cerebri, between the crus cerebri and the red nucleus, between the crus cerebri and the dentate nucleus, and between the red nucleus and the dentate nucleus on the T2-W and DW images (P<0.004). The crus cerebri, red nucleus, and dentate nucleus were involved concurrently with the corpus callosum more frequently in hepatic encephalopathy grades 3 and 4. Concurrent involvement of the globus pallidus-crus cerebri-red nucleus-dentate nucleus axis was the main MR pattern in end-stage hepatic encephalopathy, which connected with various areas of the brain. We hypothesize that these overlapping MR features could be regarded as an entity denoted as the ''hepatic encephalopathy continuum''. (orig.)

[Detection of a higher incidence of pathologic somatic findings in globus sensation by use of high frequency cinematography].

Science.gov (United States)

Hannig, C; Wuttge-Hannig, A; Bockmeyer, M

1987-07-01

Since December 1984 303 patients have undergone examination in our Multidisciplinary Consultation Service for Swallowing Disorders; 117 of them were suffering from typical globus symptoms. We were able to increase the yield of detection of organic lesions by use of the technique of 35 mm film cineradiography with a rate of 50 frames/s. Frame-by-frame analysis and computer-assisted evaluation showed that 80% of the patients with globus symptoms suffered from one or more underlying organic diseases, which could often be treated later with success. We found an increased incidence of early hypopharyngeal diverticula, webs, and motility disorders of the upper esophageal sphincter often associated with gastro-esophageal reflux or weakness of the pharyngeal wall. Cineradiography proved to be a very important tool in the analysis of the pharyngeal swallow in globus pharyngis.

CD73 is a major regulator of adenosinergic signalling in mouse brain.

Directory of Open Access Journals (Sweden)

Natalia Kulesskaya

Full Text Available CD73 (ecto-5'-nucleotidase is a cell surface enzyme that regulates purinergic signalling by desphosphorylating extracellular AMP to adenosine. 5'-nucleotidases are known to be expressed in brain, but the expression of CD73 and its putative physiological functions at this location remain elusive. Here we found, using immunohistochemistry of wild-type and CD73 deficient mice, that CD73 is prominently expressed in the basal ganglia core comprised of striatum (caudate nucleus and putamen and globus pallidus. Furthermore, meninges and the olfactory tubercle were found to specifically express CD73. Analysis of wild type (wt and CD73 deficient mice revealed that CD73 confers the majority of 5'-nucleotidase activity in several areas of the brain. In a battery of behavioural tests and in IntelliCage studies, the CD73 deficient mice demonstrated significantly enhanced exploratory locomotor activity, which probably reflects the prominent expression of CD73 in striatum and globus pallidus that are known to control locomotion. Furthermore, the CD73 deficient mice displayed altered social behaviour. Overall, our data provide a novel mechanistic insight into adenosinergic signalling in brain, which is implicated in the regulation of normal and pathological behaviour.

Correlation of computed tomography, magnetic resonance imaging and clinical outcome in acute carbon monoxide poisoning.

Science.gov (United States)

Ozcan, Namik; Ozcam, Giray; Kosar, Pinar; Ozcan, Ayse; Basar, Hulya; Kaymak, Cetin

2016-01-01

Carbon monoxide is a toxic gas for humans and is still a silent killer in both developed and developing countries. The aim of this case series was to evaluate early radiological images as a predictor of subsequent neuropsychological sequelae, following carbon monoxide poisoning. After carbon monoxide exposure, early computed tomography scans and magnetic resonance imaging findings of a 52-year-old woman showed bilateral lesions in the globus pallidus. This patient was discharged and followed for 90 days. The patient recovered without any neurological sequela. In a 58-year-old woman exposed to carbon monoxide, computed tomography showed lesions in bilateral globus pallidus and periventricular white matter. Early magnetic resonance imaging revealed changes similar to that like in early tomography images. The patient recovered and was discharged from hospital. On the 27th day of exposure, the patient developed disorientation and memory impairment. Late magnetic resonance imaging showed diffuse hyperintensity in the cerebral white matter. White matter lesions which progress to demyelination and end up in neuropsychological sequelae cannot always be diagnosed by early computed tomography and magnetic resonance imaging in carbon monoxide poisoning. Copyright © 2014 Sociedade Brasileira de Anestesiologia. Published by Elsevier Editora Ltda. All rights reserved.

Microsoft Dynamics GP 2013 implementation

CERN Document Server

Yudin, Victoria

2013-01-01

A step-by-step guide for planning and carrying out your Microsoft Dynamics GP 2013 implementation. Detailed descriptions and illustrations of setup screens and practical examples and advice are included for the Dynamics GP system and core modules.If you are a new or existing Microsoft Dynamics GP consultant or an end user who wants to implement, install, and set up core modules of Dynamics GP 2013, then this book is for you. A basic understanding of business management systems and either Dynamics GP or a similar application is recommended.

OGSA Globus Toolkits evaluation activity at CERN

CERN Document Server

Chen, D; Foster, D; Kalyaev, V; Kryukov, A; Lamanna, M; Pose, V; Rocha, R; Wang, C

2004-01-01

An Open Grid Service Architecture (OGSA) Globus Toolkit 3 (GT3) evaluation group is active at CERN since GT3 was available in early beta version (Spring 2003). This activity focuses on the evaluation of the technology as promised by the OGSA/OGSI paradigm and on GT3 in particular. The goal is to study this new technology and its implications with the goal to provide useful input for the large grid initiatives active in the LHC Computing Grid (LCG) project. A particular effort has been devoted to investigate performance and deployment issues, having in mind the LCG requirements, in particular scalability and robustness.

Gp96 Peptide Antagonist gp96-II Confers Therapeutic Effects in Murine Intestinal Inflammation

Directory of Open Access Journals (Sweden)

Claudia A. Nold-Petry

2017-12-01

Full Text Available BackgroundThe expression of heat shock protein gp96 is strongly correlated with the degree of tissue inflammation in ulcerative colitis and Crohn’s disease, thereby leading us to the hypothesis that inhibition of expression via gp96-II peptide prevents intestinal inflammation.MethodsWe employed daily injections of gp96-II peptide in two murine models of intestinal inflammation, the first resulting from five daily injections of IL-12/IL-18, the second via a single intrarectal application of TNBS (2,4,6-trinitrobenzenesulfonic acid. We also assessed the effectiveness of gp96-II peptide in murine and human primary cell culture.ResultsIn the IL-12/IL-18 model, all gp96-II peptide-treated animals survived until day 5, whereas 80% of placebo-injected animals died. gp96-II peptide reduced IL-12/IL-18-induced plasma IFNγ by 89%, IL-1β by 63%, IL-6 by 43% and tumor necrosis factor (TNF by 70% compared to controls. The clinical assessment Disease Activity Index of intestinal inflammation severity was found to be significantly lower in the gp96-II-treated animals when compared to vehicle-injected mice. gp96-II peptide treatment in the TNBS model limited weight loss to 5% on day 7 compared with prednisolone treatment, whereas placebo-treated animals suffered a 20% weight loss. Histological disease severity was reduced equally by prednisolone (by 40% and gp96-II peptide (35%. Mice treated with either gp96-II peptide or prednisolone exhibited improved endoscopic scores compared with vehicle-treated control mice: vascularity, fibrin, granularity, and translucency scores were reduced by up to 49% by prednisolone and by up to 30% by gp96-II peptide. In vitro, gp96-II peptide reduced TLR2-, TLR4- and IL-12/IL-18-induced cytokine expression in murine splenocytes, with declines in constitutive IL-6 (54%, lipopolysaccharide-induced TNF (48%, IL-6 (81% and in Staphylococcus epidermidis-induced TNF (67% and IL-6 (81%, as well as IL-12/IL-18-induced IFNγ (75%. gp

Computation of an MRI brain atlas from a population of Parkinson’s disease patients

Science.gov (United States)

Angelidakis, L.; Papageorgiou, I. E.; Damianou, C.; Psychogios, M. N.; Lingor, P.; von Eckardstein, K.; Hadjidemetriou, S.

2017-11-01

Parkinson’s Disease (PD) is a degenerative disorder of the brain. This study presents an MRI-based brain atlas of PD to characterize associated alterations for diagnostic and interventional purposes. The atlas standardizes primarily the implicated subcortical regions such as the globus pallidus (GP), substantia nigra (SN), subthalamic nucleus (STN), caudate nucleus (CN), thalamus (TH), putamen (PUT), and red nucleus (RN). The data were 3.0 T MRI brain images from 16 PD patients and 10 matched controls. The images used were T1-weighted (T 1 w), T2-weighted (T 2 w) images, and Susceptibility Weighted Images (SWI). The T1w images were the reference for the inter-subject non-rigid registration available from 3DSlicer. Anatomic labeling was achieved with BrainSuite and regions were refined with the level sets segmentation of ITK-Snap. The subcortical centers were analyzed for their volume and signal intensity. Comparison with an age-matched control group unravels a significant PD-related T1w signal loss in the striatum (CN and PUT) centers, but approximately a constant volume. The results in this study improve MRI based PD localization and can lead to the development of novel biomarkers.

Structural and biochemical characterization of a nitrilase from the thermophilic bacterium, Geobacillus pallidus RAPc8

CSIR Research Space (South Africa)

Williamson, DS

2010-09-01

Full Text Available . In common with the plant nitrilases, the recombinant G. pallidus RAPc8 enzyme produced both acid and amide products from nitrile substrates. Electron microscopy and image classification showed complexes having crescentlike, “c-shaped”, circular and “figure...

Involvement of the subthalamic nucleus and globus pallidus internus in attention

Czech Academy of Sciences Publication Activity Database

Bocková, M.; Chládek, Jan; Jurák, Pavel; Halámek, Josef; Baláž, M.; Rektor, I.

2011-01-01

Roč. 118, č. 8 (2011), s. 1235-1245 ISSN 0300-9564 R&D Projects: GA AV ČR IAA200650801; GA MŠk ED0017/01/01 Institutional research plan: CEZ:AV0Z20650511 Keywords : basal ganglia * ERP * ERD/S * attention * DBS Subject RIV: FH - Neurology Impact factor: 2.730, year: 2011

Idiopathic Basal Ganglia Calcification Presented with Impulse Control Disorder

OpenAIRE

Sahin, Cem; Levent, Mustafa; Akbaba, Gulhan; Kara, Bilge; Yeniceri, Emine Nese; Inanc, Betul Battaloglu

2015-01-01

Primary familial brain calcification (PFBC), also referred to as Idiopathic Basal Ganglia Calcification (IBGC) or “Fahr’s disease,” is a clinical condition characterized by symmetric and bilateral calcification of globus pallidus and also basal ganglions, cerebellar nuclei, and other deep cortical structures. It could be accompanied by parathyroid disorder and other metabolic disturbances. The clinical features are dysfunction of the calcified anatomic localization. IBGC most commonly present...

Anaesthesia for a patient with Deep Brain Stimulator: Case Report and Review of Literature

Directory of Open Access Journals (Sweden)

Raj mala

2014-07-01

Full Text Available Deep brain stimulator (DBS devices are used for unilateral or bilateral stimulation of thalamus, subthalamus and globus pallidus to treat movement disorders. DBS can interfere with domestic and medical equipment such as electrocardiography (ECG, slow wave diathermy, electrocautery, peripheral nerve stimulators, pacemakers, external and implantable cardioverters and defibrillators. This case report describes a patient with such a device who presented for bilateral (B/L cataract surgery.

A comparative immunogenicity study in rabbits of disulfide-stabilized, proteolytically cleaved, soluble trimeric human immunodeficiency virus type 1 gp140, trimeric cleavage-defective gp140 and monomeric gp120

International Nuclear Information System (INIS)

Beddows, Simon; Franti, Michael; Dey, Antu K.; Kirschner, Marc; Iyer, Sai Prasad N.; Fisch, Danielle C.; Ketas, Thomas; Yuste, Eloisa; Desrosiers, Ronald C.; Klasse, Per Johan; Maddon, Paul J.; Olson, William C.; Moore, John P.

2007-01-01

The human immunodeficiency virus type 1 (HIV-1) surface envelope glycoprotein (Env) complex, a homotrimer containing gp120 surface glycoprotein and gp41 transmembrane glycoprotein subunits, mediates the binding and fusion of the virus with susceptible target cells. The Env complex is the target for neutralizing antibodies (NAbs) and is the basis for vaccines intended to induce NAbs. Early generation vaccines based on monomeric gp120 subunits did not confer protection from infection; one alternative approach is therefore to make and evaluate soluble forms of the trimeric Env complex. We have directly compared the immunogenicity in rabbits of two forms of soluble trimeric Env and monomeric gp120 based on the sequence of HIV-1 JR-FL . Both protein-only and DNA-prime, protein-boost immunization formats were evaluated, DNA-priming having little or no influence on the outcome. One form of trimeric Env was made by disrupting the gp120-gp41 cleavage site by mutagenesis (gp140 UNC ), the other contains an intramolecular disulfide bond to stabilize the cleaved gp120 and gp41 moieties (SOSIP.R6 gp140). Among the three immunogens, SOSIP.R6 gp140 most frequently elicited neutralizing antibodies against the homologous, neutralization-resistant strain, HIV-1 JR-FL . All three proteins induced NAbs against more sensitive strains, but the breadth of activity against heterologous primary isolates was limited. When antibodies able to neutralize HIV-1 JR-FL were detected, antigen depletion studies showed they were not directed at the V3 region but were targeted at other, undefined gp120 and also non-gp120 epitopes

Identification of Novel Compound Mutations in PLA2G6-Associated Neurodegeneration Patient with Characteristic MRI Imaging.

Science.gov (United States)

Guo, Sen; Yang, Liu; Liu, Huijie; Chen, Wei; Li, Jinchen; Yu, Ping; Sun, Zhong Sheng; Chen, Xiang; Du, Jie; Cai, Tao

2017-08-01

Neurodegeneration with brain iron accumulation comprises a heterogeneous group of disorders characterized clinically by progressive motor dysfunction. Accurate identification of de novo and rare inherited mutations is important for determining causative genes of undiagnosed neurological diseases. In the present study, we report a unique case with cerebellar ataxia symptoms and social communication difficulties in an intermarriage family. MRI showed a marked cerebellar atrophy and the "eye-of-the-tiger"-like sign in the medial globus pallidus. Potential genetic defects were screened by whole-exome sequencing (WES) for the patient and four additional family members. A previously undescribed de novo missense mutation (c.1634A>G, p.K545R) in the exon 12 of the PLA2G6 gene was identified. A second rare variant c.1077G>A at the end of exon 7 was also identified, which was inherited from the mother, and resulted in a frame-shift mutation (c.1074_1077del.GTCG) due to an alternative splicing. In conclusion, the identification of the "eye-of-the-tiger"-like sign in the globus pallidus of the patient expands the phenotypic spectrum of PLA2G6-associated disorders and reveals its value in differential diagnosis of PLA2G6-associated disorders.

Biochemical mechanisms of pallidal deep brain stimulation in X-linked dystonia parkinsonism.

Science.gov (United States)

Tronnier, V M; Domingo, A; Moll, C K; Rasche, D; Mohr, C; Rosales, R; Capetian, P; Jamora, R D; Lee, L V; Münchau, A; Diesta, C C; Tadic, V; Klein, C; Brüggemann, N; Moser, A

2015-08-01

Invasive techniques such as in-vivo microdialysis provide the opportunity to directly assess neurotransmitter levels in subcortical brain areas. Five male Filipino patients (mean age 42.4, range 34-52 years) with severe X-linked dystonia-parkinsonism underwent bilateral implantation of deep brain leads into the internal part of the globus pallidus (GPi). Intraoperative microdialysis and measurement of gamma aminobutyric acid and glutamate was performed in the GPi in three patients and globus pallidus externus (GPe) in two patients at baseline for 25/30 min and during 25/30 min of high-frequency GPi stimulation. While the gamma-aminobutyric acid concentration increased in the GPi during high frequency stimulation (231 ± 102% in comparison to baseline values), a decrease was observed in the GPe (22 ± 10%). Extracellular glutamate levels largely remained unchanged. Pallidal microdialysis is a promising intraoperative monitoring tool to better understand pathophysiological implications in movement disorders and therapeutic mechanisms of high frequency stimulation. The increased inhibitory tone of GPi neurons and the subsequent thalamic inhibition could be one of the key mechanisms of GPi deep brain stimulation in dystonia. Such a mechanism may explain how competing (dystonic) movements can be suppressed in GPi/thalamic circuits in favour of desired motor programs. Copyright © 2015 Elsevier Ltd. All rights reserved.

Multiplicative multifractal modeling and discrimination of human neuronal activity

International Nuclear Information System (INIS)

Zheng Yi; Gao Jianbo; Sanchez, Justin C.; Principe, Jose C.; Okun, Michael S.

2005-01-01

Understanding neuronal firing patterns is one of the most important problems in theoretical neuroscience. It is also very important for clinical neurosurgery. In this Letter, we introduce a computational procedure to examine whether neuronal firing recordings could be characterized by cascade multiplicative multifractals. By analyzing raw recording data as well as generated spike train data from 3 patients collected in two brain areas, the globus pallidus externa (GPe) and the globus pallidus interna (GPi), we show that the neural firings are consistent with a multifractal process over certain time scale range (t 1 ,t 2 ), where t 1 is argued to be not smaller than the mean inter-spike-interval of neuronal firings, while t 2 may be related to the time that neuronal signals propagate in the major neural branching structures pertinent to GPi and GPe. The generalized dimension spectrum D q effectively differentiates the two brain areas, both intra- and inter-patients. For distinguishing between GPe and GPi, it is further shown that the cascade model is more effective than the methods recently examined by Schiff et al. as well as the Fano factor analysis. Therefore, the methodology may be useful in developing computer aided tools to help clinicians perform precision neurosurgery in the operating room

Effects of aging on nitrergic system in human basal nuclei

Directory of Open Access Journals (Sweden)

Bruno Lopes dos Santos

2014-10-01

Full Text Available Nitric oxide (NO is a gaseous molecule that plays a role in a number of physiologic processes. The available evidence suggests that NO is a major neurotransmitter involved in motor control and emotion/behavior modulation. To investigate the distribution and morphology of the nitrergic system in human basal nuclei, we studied samples from the striatum, globus pallidus, subthalamic nucleus, substantia nigra and pedunculopontine nucleus of 20 human brains from subjects without neurologic/psychiatric diseases. The samples were stained for NADPH-diaphorase using histochemistry and for neuronal NO synthase using immunohistochemistry. We then analyzed the nitrergic neuronal density and its morphometric parameters. Our data demonstrated that: (I the most posterior regions of the striatum exhibit a higher neuronal density; (II the limbic cortex-associated areas of the striatum exhibit higher neuronal density than other functional subdivisions; (III approximately 90% of the neurons in the subthalamic nucleus express NO; (IV the pedunculopontine nucleus exhibits a massive nitrergic neuronal density; (V in the globus pallidus, there is a marked presence of NO neurons in the medial medullary lamina; and (VI nitrergic neurons were not detected in the substantia nigra. Aging did not change the neuronal density or the morphometric parameters of nitrergic neurons in the analyzed nuclei.

Cognitive dysfunction, MRI findings and manganese levels in alcoholics

Energy Technology Data Exchange (ETDEWEB)

Itoh, Tsutomu; Nakane, Yoshibumi [Nagasaki Univ. (Japan). School of Medicine; Takahashi, Katsurou; Shimanaga, Masaki [National Nagasaki Medical Center, Omura (Japan)

2002-12-01

Alcoholic patients have been known to have brain atrophy and cognitive dysfunction. However, recent studies have reported bilateral signal hyperintensities of the globus pallidus on T1-weighted magnetic resonance imaging (MRI) in liver failure, findings that are typically associated with manganese intoxication. The present study compared brain atrophy on T1-weighted MRI, signal intensity ratios of the globus pallidus on T1-weighted MRI, whole blood manganese levels, and Wechsler Adult Intelligence Scale-Revised (WAIS-R) IQ parameters between alcoholics with and without liver cirrhosis, to investigate cognitive dysfunction, MRI findings and manganese levels in alcoholics. Pallidal hyperintensity was visually identified in 80% of alcoholic patients with liver cirrhosis. In addition, a significant correlation was seen between pallidal signal intensity (P.S.I.) ratio and blood manganese level. However, no significant correlations were found between pallidal signal intensity ratio and any of the WAIS-R parameters. These findings suggest that no direct connection exists between cognitive dysfunction and pallidal hyperintensity in alcoholic patients with liver cirrhosis. We confirmed that brain MRI in alcoholics could detect pallidal signal hyperintensity, suggesting severe liver dysfunction. In addition to diagnosis, brain MRI is useful for therapeutic psychoeducation to alcoholic patients with liver cirrhosis, visualizing the severe liver dysfunction. (author)

Anatomical brain difference of subthreshold depression in young and middle-aged individuals.

Science.gov (United States)

Li, Jing; Wang, Zengjian; Hwang, JiWon; Zhao, Bingcong; Yang, Xinjing; Xin, Suicheng; Wang, Yu; Jiang, Huili; Shi, Peng; Zhang, Ye; Wang, Xu; Lang, Courtney; Park, Joel; Bao, Tuya; Kong, Jian

2017-01-01

Subthreshold depression (StD) is associated with substantial functional impairments due to depressive symptoms that do not fully meet the diagnosis of major depressive disorder (MDD). Its high incidence in the general population and debilitating symptoms has recently put it at the forefront of mood disorder research. In this study we investigated common volumetric brain changes in both young and middle-aged StD patients. Two cohorts of StD patients, young and middle-aged, ( n  = 57) and matched controls ( n  = 76) underwent voxel-based morphometry (VBM). VBM analysis found that: 1) compared with healthy controls, StD patients showed decreased gray matter volume (GMV) in the bilateral globus pallidus and precentral gyrus, as well as increased GMV in the left thalamus and right rostral anterior cingulate cortex/medial prefrontal cortex; 2) there is a significant association between Center for Epidemiological Studies Depression Scale scores and the bilateral globus pallidus (negative) and left thalamus (positive); 3) there is no interaction between age (young vs. middle-age) and group (StD vs. controls). Our findings indicate significant VBM brain changes in both young and middle-aged individuals with StD. Individuals with StD, regardless of age, may share common neural characteristics.

Cognitive dysfunction, MRI findings and manganese levels in alcoholics

International Nuclear Information System (INIS)

Itoh, Tsutomu; Nakane, Yoshibumi

2002-01-01

Alcoholic patients have been known to have brain atrophy and cognitive dysfunction. However, recent studies have reported bilateral signal hyperintensities of the globus pallidus on T1-weighted magnetic resonance imaging (MRI) in liver failure, findings that are typically associated with manganese intoxication. The present study compared brain atrophy on T1-weighted MRI, signal intensity ratios of the globus pallidus on T1-weighted MRI, whole blood manganese levels, and Wechsler Adult Intelligence Scale-Revised (WAIS-R) IQ parameters between alcoholics with and without liver cirrhosis, to investigate cognitive dysfunction, MRI findings and manganese levels in alcoholics. Pallidal hyperintensity was visually identified in 80% of alcoholic patients with liver cirrhosis. In addition, a significant correlation was seen between pallidal signal intensity (P.S.I.) ratio and blood manganese level. However, no significant correlations were found between pallidal signal intensity ratio and any of the WAIS-R parameters. These findings suggest that no direct connection exists between cognitive dysfunction and pallidal hyperintensity in alcoholic patients with liver cirrhosis. We confirmed that brain MRI in alcoholics could detect pallidal signal hyperintensity, suggesting severe liver dysfunction. In addition to diagnosis, brain MRI is useful for therapeutic psychoeducation to alcoholic patients with liver cirrhosis, visualizing the severe liver dysfunction. (author)

Videofluoroscopy of the pharynx and esophagus in patients with globus pharyngis. Comparison with static radiography

International Nuclear Information System (INIS)

Schober, E.; Schima, W.; Pokieser, P.

1995-01-01

The symptom is associated with a multitude of pharyngoesophageal abnormalities. Our study compares the diagnostic yield of videofluoroscopy to that of static radiography in patients suffering from globus pharnygis. A total of 150 consecutive patients complaining of a lump in the throat, but without evidence of dysphagia, were studied in a standardized fashion with both methods. Videofluoroscopy combined with static radiography revealed morphological or functional abnormalities in 75% of our patients. The combination of the two methods yielded significantly more abnormalities in the pharynx and esophagus than videofluoroscopy or static radiography alone. Esophageal motor disorders, pharyngoesophageal sphincter dysfunction and pharyngeal residue of contrast material proved to be the most common abnormalities. In conclusion, videofluoroscopy combined with static radiography is mandatory in the radiological assessment of patients suffering from the globus sensation. (orig.) [de

Association between patients' recommendation of their GP and their evaluation of the GP.

Science.gov (United States)

Vedsted, Peter; Heje, Hanne N

2008-01-01

Patient priorities and patient evaluations indicate that accessibility should receive more attention to increase quality in general practice. The definition of family medicine emphasizes the patient-centred approach, communication skills, continuity, and clinical skills. We aimed to explore the associations between the 23 items in the Europep questionnaire measuring patient evaluation of general practice and the patients' recommendation of their general practitioner (GP) to friends and to study the relationship of these items with the core competences of family medicine. Cross-sectional study where patients aged 18 years and over attending the practice were included. Patients completed the Danish version of the 23 item Europep questionnaire and an additional item about the degree to which they could recommend their GP to friends. Danish general practice (the DanPEP study). A total of 50 191 patients and 690 GPs were included in the analyses. For each item, associations were calculated between a positive answer and the degree to which the patient could recommend the GP. Analyses were made at patient and GP levels. We found 12 items that covered the 10 most strongly associated items from both analyses: four of six items from the "doctor-patient relationship", two of five items from "medical care", and all items from "information and support" and "organization of services". No items from "accessibility" were among the 12 items. Recommending the GP to others was most strongly associated with the "emphatic", "patient-oriented", "informative and coordinating", and "competent/skilled" GP and to a lesser degree with accessibility to general practice.

Potential of Diffusion Tensor Imaging and Relaxometry for the Detection of Specific Pathological Alterations in Parkinson's Disease (PD.

Directory of Open Access Journals (Sweden)

Regina Esterhammer

Full Text Available The purpose of the present study was to evaluate the potential of multimodal MR imaging including mean diffusivity (MD, fractional anisotropy (FA, relaxation rates R2 and R2* to detect disease specific alterations in Parkinson's Disease (PD. We enrolled 82 PD patients (PD-all with varying disease durations (≤5 years: PD≤5, n = 43; >5 years: PD>5, n = 39 and 38 matched healthy controls (HC, receiving diffusion tensor imaging as well as R2 and R2* relaxometry calculated from multi-echo T2*-weighted and dual-echo TSE imaging, respectively. ROIs were drawn to delineate caudate nucleus (CN, putamen (PU, globus pallidus (GP and substantia nigra (SN on the co-registered maps. The SN was divided in 3 descending levels (SL 1-3. The most significant parameters were used for a flexible discrimination analysis (FDA in a training collective consisting of 25 randomized subjects from each group in order to predict the classification of remaining subjects. PD-all showed significant increases in MD, R2 and R2* within SN and its subregions as well as in MD and R2* within different basal ganglia regions. Compared to the HC group, the PD≤5 and the PD>5 group showed significant MD increases within the SN and its lower two subregions, while the PD≤5 group exhibited significant increases in R2 and R2* within SN and its subregions, and tended to elevation within the basal ganglia. The PD>5 group had significantly increased MD in PU and GP, whereas the PD≤5 group presented normal MD within the basal ganglia. FDA achieved right classification in 84% of study participants. Micro-structural damage affects primarily the SN of PD patients and in later disease stages the basal ganglia. Iron contents of PU, GP and SN are increased at early disease stages of PD.

Using Globus GridFTP to Transfer and Share Big Data | Poster

Science.gov (United States)

By Ashley DeVine, Staff Writer, and Mark Wance, Guest Writer; photo by Richard Frederickson, Staff Photographer Transferring big data, such as the genomics data delivered to customers from the Center for Cancer Research Sequencing Facility (CCR SF), has been difficult in the past because the transfer systems have not kept pace with the size of the data. However, the situation is changing as a result of the Globus GridFTP project.

Structure of HIV-1 gp120 with gp41-interactive region reveals layered envelope architecture and basis of conformational mobility.

Science.gov (United States)

Pancera, Marie; Majeed, Shahzad; Ban, Yih-En Andrew; Chen, Lei; Huang, Chih-chin; Kong, Leopold; Kwon, Young Do; Stuckey, Jonathan; Zhou, Tongqing; Robinson, James E; Schief, William R; Sodroski, Joseph; Wyatt, Richard; Kwong, Peter D

2010-01-19

The viral spike of HIV-1 is composed of three gp120 envelope glycoproteins attached noncovalently to three gp41 transmembrane molecules. Viral entry is initiated by binding to the CD4 receptor on the cell surface, which induces large conformational changes in gp120. These changes not only provide a model for receptor-triggered entry, but affect spike sensitivity to drug- and antibody-mediated neutralization. Although some of the details of the CD4-induced conformational change have been visualized by crystal structures and cryoelectron tomograms, the critical gp41-interactive region of gp120 was missing from previous atomic-level characterizations. Here we determine the crystal structure of an HIV-1 gp120 core with intact gp41-interactive region in its CD4-bound state, compare this structure to unliganded and antibody-bound forms to identify structurally invariant and plastic components, and use ligand-oriented cryoelectron tomograms to define component mobility in the viral spike context. Newly defined gp120 elements proximal to the gp41 interface complete a 7-stranded beta-sandwich, which appeared invariant in conformation. Loop excursions emanating from the sandwich form three topologically separate--and structurally plastic--layers, topped off by the highly glycosylated gp120 outer domain. Crystal structures, cryoelectron tomograms, and interlayer chemistry were consistent with a mechanism in which the layers act as a shape-changing spacer, facilitating movement between outer domain and gp41-associated beta-sandwich and providing for conformational diversity used in immune evasion. A "layered" gp120 architecture thus allows movement among alternative glycoprotein conformations required for virus entry and immune evasion, whereas a beta-sandwich clamp maintains gp120-gp41 interaction and regulates gp41 transitions.

Microsoft Dynamics GP 2013 financial management

CERN Document Server

Grieve, Ian

2013-01-01

A standard tutorial-based approach covering Microsoft Dynamics GP 2013 and its six financial modules. The book is intended to allow users to improve their system use and workflow by introducing new modules to assist in financial management.This book is for you if you're a Dynamics GP partner, or Dynamics GP user, primarily focused on delivering application optimizations. This book assumes that you have a working knowledge of Microsoft Dynamics GP and have an understanding of the requirements of financial management.

New results from the Globus-M spherical tokamak

International Nuclear Information System (INIS)

Gusev, V.K.; Ananiev, A.S.; Amoskov, V.M.

2003-01-01

New results from the Globus-M spherical tokamak are presented. High plasma current of 0.36 MA, high toroidal magnetic field of 0.55 T and other important plasma characteristics were achieved. Described are the operational space and plasma stability limits in the OH regime. The factors limiting operational space (MHD instabilities, runaway electrons, etc.) are discussed. New experiments on plasma fuelling are described. First results of experiments with a coaxial plasma gun injector are presented. Initial results of a plasma - wall interaction study are outlined. First results obtained with new diagnostic tools installed on the tokamak are presented. An auxiliary heating system test was performed. Preliminary results of simulations and experiments are given. (author)

Suitability of the alkalistable carbonic anhydrase from a polyextremophilic bacterium Aeribacillus pallidus TSHB1 in biomimetic carbon sequestration.

Science.gov (United States)

Bose, Himadri; Satyanarayana, T

2016-10-01

Carbonic anhydrase (CA) was produced from the polyextremophilic (halotolerant, moderately thermophilic and alkaliphilic) bacterium Aeribacillus pallidus TSHB1 isolated from water and sediment samples of Choti Anhoni hot spring of Pipariya, Madhya Pradesh (India), is being reported to be suitable for carbon sequestration. Growth and CA production were inhibited at higher CO2 concentration (5-10 %). Under optimized culture variables (tryptone 0.8 %, yeast extract 0.08 %, glucose 1 %, micronutrient solution 1 %, inoculums size 1.10 %, agitation 200 at pH 8, and temperature 55 °C), 3.7-fold higher CA production was attained than that under unoptimized conditions. The zymogram analysis of the partially purified CA revealed an activity band corresponding to 32 kDa. The enzyme is stable in the pH range between 8.0 and 11.0 with T 1/2 of 40, 15, and 8 min at 60, 70, and 80 °C, respectively. The CA of A. pallidus displayed a marked enhancement in the rate of CaCO3 precipitation from aqueous CO2. The CA-aided formation of CaCO3 was 42.5 mg mg(-1) protein. Scanning electron microscopy revealed the formation of rhomboid calcite crystals. This is the first report on the production and applicability of CA from the polyextremophilic A. pallidus in carbon sequestration.

Pathological bolus exposure may define gastro-esophageal reflux better than pathological acid exposure in patients with globus.

Science.gov (United States)

Sinn, Dong Hyun; Kim, Beom Jin; Son, Hee Jung; Kim, Jae J; Rhee, Jong Chul; Rhee, Poong-Lyul

2012-01-01

Conventionally, pathological acid exposure (PAE), defined by acid reflux only, is used to identify gastro-esophageal reflux disease (GERD). However, weak acid reflux or non-acid reflux also induces reflux symptoms. Defining abnormal reflux based on all reflux episodes may better identify GERD and would be more useful among patients with atypical GERD symptoms, such as globus. Impedance-pHmetry results of 31 globus patients, off acid suppressants, were analysed. A median of 24 episodes of reflux were observed. Of the reflux episodes, 54% were non-acid reflux and 50% reached the proximal extent. PAE was observed in 6 patients (19%). For 5 patients (16%) without PAE, there was evidence of increased bolus exposure compared to normal controls (an intraesophageal bolus exposure for more than 1.4% of the recording time, defined as pathological bolus exposure, PBE). When GERD was defined by PAE or esophagitis, the prevalence of GERD was 29%. When GERD was defined by PBE, PAE or esophagitis, the prevalence was 42%. PBE identified 13% of the patients who otherwise would have been missed. A significant proportion of patients without PAE had evidence of PBE. PBE may be a more useful definition for identifying patients with abnormal increase in reflux in patients with globus. Further studies are warranted.

On πgp-continuous functions in topological spaces

International Nuclear Information System (INIS)

Park, Jin Han; Park, Jin Keun

2004-01-01

The concept of πgp-closed sets was introduced by Park [On πgp-closed sets in topological spaces, Indian J. Pure Appl. Math., in press]. The aim of this paper is to consider and characterize πgp-irresolute and πgp-continuous functions via the concept of πgp-closed sets and to relate these concepts to the classes of πGPO-compact spaces and πGP-connected spaces

Homologous Basal Ganglia Network Models in Physiological and Parkinsonian Conditions

Directory of Open Access Journals (Sweden)

Jyotika Bahuguna

2017-08-01

Full Text Available The classical model of basal ganglia has been refined in recent years with discoveries of subpopulations within a nucleus and previously unknown projections. One such discovery is the presence of subpopulations of arkypallidal and prototypical neurons in external globus pallidus, which was previously considered to be a primarily homogeneous nucleus. Developing a computational model of these multiple interconnected nuclei is challenging, because the strengths of the connections are largely unknown. We therefore use a genetic algorithm to search for the unknown connectivity parameters in a firing rate model. We apply a binary cost function derived from empirical firing rate and phase relationship data for the physiological and Parkinsonian conditions. Our approach generates ensembles of over 1,000 configurations, or homologies, for each condition, with broad distributions for many of the parameter values and overlap between the two conditions. However, the resulting effective weights of connections from or to prototypical and arkypallidal neurons are consistent with the experimental data. We investigate the significance of the weight variability by manipulating the parameters individually and cumulatively, and conclude that the correlation observed between the parameters is necessary for generating the dynamics of the two conditions. We then investigate the response of the networks to a transient cortical stimulus, and demonstrate that networks classified as physiological effectively suppress activity in the internal globus pallidus, and are not susceptible to oscillations, whereas parkinsonian networks show the opposite tendency. Thus, we conclude that the rates and phase relationships observed in the globus pallidus are predictive of experimentally observed higher level dynamical features of the physiological and parkinsonian basal ganglia, and that the multiplicity of solutions generated by our method may well be indicative of a natural

MRI and MR spectroscopy study on basal ganglia alterations in patients with liver cirrhosis

International Nuclear Information System (INIS)

Wu Haibo; Ma Lin; Cai Youquan; Li Tao; Li Dejun; Liang Li

2007-01-01

Objective: To study the signal changes and metabolic alterations in the basal ganglia (BG) by using magnetic resonance imaging (MRI) and proton magnetic resonance spectroscopy (MRS) in patients with hepatic encephalopathy with and without parkinsonism. Methods: MRI and MRS in the basal ganglia were performed in 27 patients (22 males, 5 females, age ranging from 29 to 62 years) with liver cirrhosis and hepatic encephalopathy. 14 of the 27 patients were classified as having parkinsonian signs evaluated by Unified Parkinson's Disease Rating Scale (UPDRS) test. 18 age-matched healthy volunteers (13 males, 5 females, age ranging from 24 to 51 years) underwent MRI and MRS as a control group. Results: NAA/Cr levels (average numbers are 1.40±0.03, 1.35±0.03 respectively) showed no statistical difference between cirrhotic patients with hepatic encephalopathy and the control group (t=1.16, t=0.87, P>0.05). Values of signal hyperintensities (average numbers are 1.03±0.002, 1.04± 0.003 respectively) in globus pallidus and ratios of mI/Cr(average numbers are 0.63±0.01, 0.61± 0.02 respectively) and Cho/Cr (average numbers are 0.82±0.03, 0.80±0.02 respectively) showed no statistically significant differences between the control group and the 13 patients without parkinsonism (t=0.63, t=-0.52, t=-0.54, P>0.05), whereas values of signal hyperintensities (average numbers are 1.18±0.001, 1.04±0.003 respectively) in globus pallidus and ratios of mI/Cr (average numbers are 0.39±0.02, 0.63±0.01 respectively) and Cho/Cr(average numbers are 0.68±0.01, 0.82±0.03 respectively) shows statistically significant difference in patients without and with parkinsonism (t=-5.16, t=7.61, t=4.12, P<0.05). In patients with cirrhosis, the values of signal hyperintensities in globus pallidus were inversely correlated with the ratio for mI/Cr(r=-0.764, P<0.05) and Cho/Cr (r=-0.553, P<0.05), respectively. Conclusion: MRI and MRS may be useful tools in the evaluation of extrapyramidal

Quantitative evaluation of hyperintensity on T1-weighted MRI in liver cirrhosis : correlation with child-pugh classification and hepatic encephalopathy

International Nuclear Information System (INIS)

Eun, Hyo Won; Choi, Hye Young; Lee, Sun Wha; Yi, Sun Young

1999-01-01

To investigate the differences in signal changes in the globus pallidus and white matter, as seen on T1-weighted MR brain images, and to determine whether these differences can be used as an indicator of subclinical hepatic encephalopathy. A total of 25 cases of liver cirrhosis were evaluated and as a control group, 20 subjects were also studied. Using a 1.5T MRI scannet, brain MR images were obtained, and the differences in signal intensity in both the globus pallidus and thalamus and in both white and gray matter were then quantified using the contrast to noise ratio(CNR). On the basis of the Child-Pugh classification, 25patients with liver cirrhosis were divided into three groups, with eight in group A, eight in B, and nine in C. Using clinical criteria, hepatic encephalopathy was diagnosed in seven of the 25 patients. There after, CNRs(CNR1 and CNR2) were conpared between the control and cirrhotic groups and between cirrhotic groups with or without hepatic encephalopathy. In the control group, mean values were 3.2±5.9 for CNR1 and 8.4±8.0 for CNR2. In the cirrhotic group, these values were 10.6±9.0 for CNR1 and 9.8±6.4 for CNR2. A statistically significant difference was noted between normal and cirrhotic groups only for CNR1(p<0.05). CNR values in patients with liver cirrhosis were 8.5±11.5 for CNR1 and 11.7±8.7 for CNR2 in the Child A group, 10.4±5.1 for CNR1 and 9.3±3.2 for CNR2 in the B group, and 12.8±9.7 for CNR1 and 8.7±6.5 for CNR2 in the C group. There was no significant difference in mean CNRI values between patients with or without hepatic encephalopathy. Differences in signal intensities in the globus pallidus and white matter, as seen on T1-weighted MR brain images, cannot be used as an indicator of hepatic encephalopathy in patients with liver cirrhosis

Quantitative evaluation of hyperintensity on T1-weighted MRI in liver cirrhosis : correlation with child-pugh classification and hepatic encephalopathy

Energy Technology Data Exchange (ETDEWEB)

Eun, Hyo Won; Choi, Hye Young; Lee, Sun Wha; Yi, Sun Young [Ewha Womans Univ. College of Medicine, Seoul (Korea, Republic of)

1999-11-01

To investigate the differences in signal changes in the globus pallidus and white matter, as seen on T1-weighted MR brain images, and to determine whether these differences can be used as an indicator of subclinical hepatic encephalopathy. A total of 25 cases of liver cirrhosis were evaluated and as a control group, 20 subjects were also studied. Using a 1.5T MRI scannet, brain MR images were obtained, and the differences in signal intensity in both the globus pallidus and thalamus and in both white and gray matter were then quantified using the contrast to noise ratio(CNR). On the basis of the Child-Pugh classification, 25patients with liver cirrhosis were divided into three groups, with eight in group A, eight in B, and nine in C. Using clinical criteria, hepatic encephalopathy was diagnosed in seven of the 25 patients. There after, CNRs(CNR1 and CNR2) were conpared between the control and cirrhotic groups and between cirrhotic groups with or without hepatic encephalopathy. In the control group, mean values were 3.2{+-}5.9 for CNR1 and 8.4{+-}8.0 for CNR2. In the cirrhotic group, these values were 10.6{+-}9.0 for CNR1 and 9.8{+-}6.4 for CNR2. A statistically significant difference was noted between normal and cirrhotic groups only for CNR1(p<0.05). CNR values in patients with liver cirrhosis were 8.5{+-}11.5 for CNR1 and 11.7{+-}8.7 for CNR2 in the Child A group, 10.4{+-}5.1 for CNR1 and 9.3{+-}3.2 for CNR2 in the B group, and 12.8{+-}9.7 for CNR1 and 8.7{+-}6.5 for CNR2 in the C group. There was no significant difference in mean CNRI values between patients with or without hepatic encephalopathy. Differences in signal intensities in the globus pallidus and white matter, as seen on T1-weighted MR brain images, cannot be used as an indicator of hepatic encephalopathy in patients with liver cirrhosis.

DNA-binding properties of the Bacillus subtilis and Aeribacillus pallidus AC6 σ(D) proteins.

Science.gov (United States)

Sevim, Elif; Gaballa, Ahmed; Beldüz, A Osman; Helmann, John D

2011-01-01

σ(D) proteins from Aeribacillus pallidus AC6 and Bacillus subtilis bound specifically, albeit weakly, to promoter DNA even in the absence of core RNA polymerase. Binding required a conserved CG motif within the -10 element, and this motif is known to be recognized by σ region 2.4 and critical for promoter activity.

DNA-Binding Properties of the Bacillus subtilis and Aeribacillus pallidus AC6 σD Proteins▿

OpenAIRE

Sevim, Elif; Gaballa, Ahmed; Beldüz, A. Osman; Helmann, John D.

2010-01-01

σD proteins from Aeribacillus pallidus AC6 and Bacillus subtilis bound specifically, albeit weakly, to promoter DNA even in the absence of core RNA polymerase. Binding required a conserved CG motif within the −10 element, and this motif is known to be recognized by σ region 2.4 and critical for promoter activity.

More than Just Fun and Games: BSG and Glo-Bus as Strategic Education Instruments

Science.gov (United States)

Karriker, Joy H.; Aaron, Joshua R.

2014-01-01

Simulations like the BSG and Glo-Bus allow students the opportunity to practice their integrated, strategic management skills in a relatively risk-free environment or "live case." We review these games and address their strengths, along with the challenges associated with their classroom application. Because of their sound designs and…

DNA-Binding Properties of the Bacillus subtilis and Aeribacillus pallidus AC6 σD Proteins▿

Science.gov (United States)

Sevim, Elif; Gaballa, Ahmed; Beldüz, A. Osman; Helmann, John D.

2011-01-01

σD proteins from Aeribacillus pallidus AC6 and Bacillus subtilis bound specifically, albeit weakly, to promoter DNA even in the absence of core RNA polymerase. Binding required a conserved CG motif within the −10 element, and this motif is known to be recognized by σ region 2.4 and critical for promoter activity. PMID:21097624

Optional part-time and longer GP training modules in GP practices associated with more trainees becoming GPs - a cohort study in Switzerland.

Science.gov (United States)

Studerus, Lara; Ahrens, Regina; Häuptle, Christian; Goeldlin, Adrian; Streit, Sven

2018-01-05

Switzerland, like many other countries, has a shortage of General Practitioners (GPs). Optional GP training modules in GP practices were offered during the at least 5-year GP training program to increase student and trainee interest in becoming a GP. The training modules had not yet been evaluated. We determined how many Swiss GP trainees became practicing GPs after they completed optional training modules, and if longer modules were associated with higher rates of GP specialization. In this population-based cohort study, we included GP trainees who chose an optional GP training module in GP practice, provided by the Foundation to Promote Training in General Practice (WHM) between 2006 and 2015. GP trainees were invited to complete an online survey to assess the primary outcome (becoming a practicing GP by 2016). Data on non-responders was collected via an internet search. We calculated univariate time-to-event curves to become a practicing GP, stratified by trainee's gender, length, part-time training, and number of years after graduation until training modules were completed. We used a multivariate model to adjust for characteristics of participants, training, and satisfaction with training modules. We assessed primary outcome for 351 (92.1%) of 381 former GP trainees who participated in a WHM program between 2006 and 2015. Of these 218 (57%) were practicing GPs by 2016. When focusing on the trainees who had completed training between 2006 and 2010, the rate of practicing GPs was even 73%. Longer (p = 0.018) and part-time training modules (p = 0.003) were associated with higher rates of being a practicing GP. Most (81%) practicing GPs thought their optional GP training module was (very) important in their choice of specialty. GP trainees who spent more time training in a GP practice, or who trained part-time were more likely to become practicing GPs. Most (80%) rated their training module as (very) important in their choice of career, highlighting that

stableGP

Data.gov (United States)

National Aeronautics and Space Administration — The code in the stableGP package implements Gaussian process calculations using efficient and numerically stable algorithms. Description of the algorithms is in the...

Rikkunshito improves globus sensation in patients with proton-pump inhibitor-refractory laryngopharyngeal reflux.

Science.gov (United States)

Tokashiki, Ryoji; Okamoto, Isaku; Funato, Nobutoshi; Suzuki, Mamoru

2013-08-21

To investigate the effect of rikkunshito on laryngopharyngeal reflux (LPR) symptoms and gastric emptying in patients with proton-pump inhibitor (PPI)-refractory LPR. In total, 22 patients with LPR were enrolled. Following a 2-wk treatment with PPI monotherapy, PPI-refractory LPR patients were randomly divided into two treatment groups (rikkunshito alone or rikkunshito plus the PPI, lansoprazole). LPR symptoms were assessed using a visual analog scale (VAS) score, gastrointestinal symptoms were assessed using the gastrointestinal symptom rating scale (GSRS), and gastric emptying was assessed using the radio-opaque marker method prior to and 4 wk following treatments. The 4-wk treatment with rikkunshito alone and with rikkunshito plus the PPI significantly decreased the globus sensation VAS scores. The VAS score for sore throat was significantly decreased following treatment with rikkunshito plus PPI but not by rikkunshito alone. Neither treatment significantly changed the GSRS scores. Rikkunshito improved delayed gastric emptying. We found a significant positive correlation between improvements in globus sensation and in gastric emptying (r² = 0.4582, P sensation in patients with PPI-refractory LPR, in part, because of stimulation of gastric emptying. Thus, rikkunshito is an effective treatment for PPI-refractory LPR.

Structural differences in basal ganglia of elite running versus martial arts athletes: a diffusion tensor imaging study.

Science.gov (United States)

Chang, Yu-Kai; Tsai, Jack Han-Chao; Wang, Chun-Chih; Chang, Erik Chihhung

2015-07-01

The aim of this study was to use diffusion tensor imaging (DTI) to characterize and compare microscopic differences in white matter integrity in the basal ganglia between elite professional athletes specializing in running and martial arts. Thirty-three young adults with sport-related skills as elite professional runners (n = 11) or elite professional martial artists (n = 11) were recruited and compared with non-athletic and healthy controls (n = 11). All participants underwent health- and skill-related physical fitness assessments. Fractional anisotropy (FA) and mean diffusivity (MD), the primary indices derived from DTI, were computed for five regions of interest in the bilateral basal ganglia, including the caudate nucleus, putamen, globus pallidus internal segment (GPi), globus pallidus external segment (GPe), and subthalamic nucleus. Results revealed that both athletic groups demonstrated better physical fitness indices compared with their control counterparts, with the running group exhibiting the highest cardiovascular fitness and the martial arts group exhibiting the highest muscular endurance and flexibility. With respect to the basal ganglia, both athletic groups showed significantly lower FA and marginally higher MD values in the GPi compared with the healthy control group. These findings suggest that professional sport or motor skill training is associated with changes in white matter integrity in specific regions of the basal ganglia, although these positive changes did not appear to depend on the type of sport-related motor skill being practiced.

Neural correlates of enhanced visual short-term memory for angry faces: an FMRI study.

Directory of Open Access Journals (Sweden)

Margaret C Jackson

Full Text Available Fluid and effective social communication requires that both face identity and emotional expression information are encoded and maintained in visual short-term memory (VSTM to enable a coherent, ongoing picture of the world and its players. This appears to be of particular evolutionary importance when confronted with potentially threatening displays of emotion - previous research has shown better VSTM for angry versus happy or neutral face identities.Using functional magnetic resonance imaging, here we investigated the neural correlates of this angry face benefit in VSTM. Participants were shown between one and four to-be-remembered angry, happy, or neutral faces, and after a short retention delay they stated whether a single probe face had been present or not in the previous display. All faces in any one display expressed the same emotion, and the task required memory for face identity. We find enhanced VSTM for angry face identities and describe the right hemisphere brain network underpinning this effect, which involves the globus pallidus, superior temporal sulcus, and frontal lobe. Increased activity in the globus pallidus was significantly correlated with the angry benefit in VSTM. Areas modulated by emotion were distinct from those modulated by memory load.Our results provide evidence for a key role of the basal ganglia as an interface between emotion and cognition, supported by a frontal, temporal, and occipital network.

Benzodiazepine effect of {sup 125}I-iomazenil-benzodiazepine receptor binding and serum corticosterone level in a rat model

Energy Technology Data Exchange (ETDEWEB)

Fukumitsu, Nobuyoshi [Proton Medical Research Center, University of Tsukuba, Ibaragi, 305-8575 (Japan)]. E-mail: gzl13162@nifty.ne.jp; Ogi, Shigeyuki [Department of Radiology, Jikei University School of Medicine, Tokyo, 105-8461 (Japan); Uchiyama, Mayuki [Department of Radiology, Jikei University School of Medicine, Tokyo, 105-8461 (Japan); Mori, Yutaka [Department of Radiology, Jikei University School of Medicine, Tokyo, 105-8461 (Japan)

2005-01-01

To test the change in free or unoccupied benzodiazepine receptor (BZR) density in response to diazepam, we investigated {sup 125}I-iomazenil ({sup 125}I-IMZ) binding and serum corticosterone levels in a rat model. Wistar male rats, which received psychological stress using a communication box for 5 days, were divided into two groups according to the amount of administered diazepam: no diazepam [D (0)] group and 10 mg/kg per day [D (10)] group of 12 rats each. The standardized uptake value (SUV) of {sup 125}I-IMZ of the D (10) group were significantly lower (P<.05) than those of the D (0) group in the frontal, parietal and temporal cortices, globus pallidus, hippocampus, amygdala and hypothalamus. The serum corticosterone level ratio in the D (10) group was significantly lower than that in the D (0) group (P<.05). From the change in serum corticosterone levels, diazepam attenuated the psychological stress produced by the physical stress to animals in adjacent compartments. From the reduced binding of {sup 125}I-IMZ, it is clear that diazepam competed with endogenous ligand for the free BZR sites, and the frontal, parietal and temporal cortices, globus pallidus, hippocampus, amygdala and hypothalamus are important areas in which {sup 125}I-IMZ binding is strongly affected by administration of diazepam.

Quantitative analysis of diffusion tensor imaging (DTI) using statistical parametric mapping (SPM) for brain disorders

Science.gov (United States)

Lee, Jae-Seung; Im, In-Chul; Kang, Su-Man; Goo, Eun-Hoe; Kwak, Byung-Joon

2013-07-01

This study aimed to quantitatively analyze data from diffusion tensor imaging (DTI) using statistical parametric mapping (SPM) in patients with brain disorders and to assess its potential utility for analyzing brain function. DTI was obtained by performing 3.0-T magnetic resonance imaging for patients with Alzheimer's disease (AD) and vascular dementia (VD), and the data were analyzed using Matlab-based SPM software. The two-sample t-test was used for error analysis of the location of the activated pixels. We compared regions of white matter where the fractional anisotropy (FA) values were low and the apparent diffusion coefficients (ADCs) were increased. In the AD group, the FA values were low in the right superior temporal gyrus, right inferior temporal gyrus, right sub-lobar insula, and right occipital lingual gyrus whereas the ADCs were significantly increased in the right inferior frontal gyrus and right middle frontal gyrus. In the VD group, the FA values were low in the right superior temporal gyrus, right inferior temporal gyrus, right limbic cingulate gyrus, and right sub-lobar caudate tail whereas the ADCs were significantly increased in the left lateral globus pallidus and left medial globus pallidus. In conclusion by using DTI and SPM analysis, we were able to not only determine the structural state of the regions affected by brain disorders but also quantitatively analyze and assess brain function.

Basal ganglia neuronal activity during scanning eye movements in Parkinson's disease.

Directory of Open Access Journals (Sweden)

Tomáš Sieger

Full Text Available The oculomotor role of the basal ganglia has been supported by extensive evidence, although their role in scanning eye movements is poorly understood. Nineteen Parkinsońs disease patients, which underwent implantation of deep brain stimulation electrodes, were investigated with simultaneous intraoperative microelectrode recordings and single channel electrooculography in a scanning eye movement task by viewing a series of colored pictures selected from the International Affective Picture System. Four patients additionally underwent a visually guided saccade task. Microelectrode recordings were analyzed selectively from the subthalamic nucleus, substantia nigra pars reticulata and from the globus pallidus by the WaveClus program which allowed for detection and sorting of individual neurons. The relationship between neuronal firing rate and eye movements was studied by crosscorrelation analysis. Out of 183 neurons that were detected, 130 were found in the subthalamic nucleus, 30 in the substantia nigra and 23 in the globus pallidus. Twenty percent of the neurons in each of these structures showed eye movement-related activity. Neurons related to scanning eye movements were mostly unrelated to the visually guided saccades. We conclude that a relatively large number of basal ganglia neurons are involved in eye motion control. Surprisingly, neurons related to scanning eye movements differed from neurons activated during saccades suggesting functional specialization and segregation of both systems for eye movement control.

Basal ganglia neuronal activity during scanning eye movements in Parkinson's disease.

Science.gov (United States)

Sieger, Tomáš; Bonnet, Cecilia; Serranová, Tereza; Wild, Jiří; Novák, Daniel; Růžička, Filip; Urgošík, Dušan; Růžička, Evžen; Gaymard, Bertrand; Jech, Robert

2013-01-01

The oculomotor role of the basal ganglia has been supported by extensive evidence, although their role in scanning eye movements is poorly understood. Nineteen Parkinsońs disease patients, which underwent implantation of deep brain stimulation electrodes, were investigated with simultaneous intraoperative microelectrode recordings and single channel electrooculography in a scanning eye movement task by viewing a series of colored pictures selected from the International Affective Picture System. Four patients additionally underwent a visually guided saccade task. Microelectrode recordings were analyzed selectively from the subthalamic nucleus, substantia nigra pars reticulata and from the globus pallidus by the WaveClus program which allowed for detection and sorting of individual neurons. The relationship between neuronal firing rate and eye movements was studied by crosscorrelation analysis. Out of 183 neurons that were detected, 130 were found in the subthalamic nucleus, 30 in the substantia nigra and 23 in the globus pallidus. Twenty percent of the neurons in each of these structures showed eye movement-related activity. Neurons related to scanning eye movements were mostly unrelated to the visually guided saccades. We conclude that a relatively large number of basal ganglia neurons are involved in eye motion control. Surprisingly, neurons related to scanning eye movements differed from neurons activated during saccades suggesting functional specialization and segregation of both systems for eye movement control.

Image-guided preoperative prediction of pyramidal tract side effect in deep brain stimulation

Science.gov (United States)

Baumgarten, C.; Zhao, Y.; Sauleau, P.; Malrain, C.; Jannin, P.; Haegelen, C.

2016-03-01

Deep brain stimulation of the medial globus pallidus is a surgical procedure for treating patients suffering from Parkinson's disease. Its therapeutic effect may be limited by the presence of pyramidal tract side effect (PTSE). PTSE is a contraction time-locked to the stimulation when the current spreading reaches the motor fibers of the pyramidal tract within the internal capsule. The lack of side-effect predictive model leads the neurologist to secure an optimal electrode placement by iterating clinical testing on an awake patient during the surgical procedure. The objective of the study was to propose a preoperative predictive model of PTSE. A machine learning based method called PyMAN (for Pyramidal tract side effect Model based on Artificial Neural network) that accounted for the current of the stimulation, the 3D electrode coordinates and the angle of the trajectory, was designed to predict the occurrence of PTSE. Ten patients implanted in the medial globus pallidus have been tested by a clinician to create a labeled dataset of the stimulation parameters that trigger PTSE. The kappa index value between the data predicted by PyMAN and the labeled data was .78. Further evaluation studies are desirable to confirm whether PyMAN could be a reliable tool for assisting the surgeon to prevent PTSE during the preoperative planning.

Bilateral hyperintense basal ganglia on T1-weighted image

International Nuclear Information System (INIS)

Baik, Seung Kug; Ahn, Woo Hyun; Choi, Han Yong; Kim, Bong Gi

1994-01-01

Bilateral high signal intensity in basal ganglia on T1-weighted images is unusual, the purpose of this study is to describe the pattern of high signal intensity and underlying disease. During the last three years, 8 patients showed bilateral high signal intensity in basal ganglia on T1-weighted image, as compared with cerebral white matter. Authors analyzed the images and underlying causes retrospectively. Of 8 patients, 5 were male and 3 were female. The age ranged from 15 days to 79 years. All patient were examined by a 0.5T superconductive MRI. Images were obtained by spin echo multislice technique. Underlying causes were 4 cases of hepatopathy, 2 cases of calcium metabolism disorder, and one case each of neurofibromatosis and hypoxic brain injury. These process were bilateral in all cases and usually symmetric. In all cases the hyperintense areas were generally homogenous without mass effect or edema, although somewhat nodular appearance was seen in neurofibromatosis. Lesions were located in the globus pallidus and internal capsule in hepatopathy and neurofibromatosis, head of the caudate nucleus in disorder of calcum metabolism, and the globus pallidus in hypoxic brain injury. Although this study is limited by its patient population, bilateral hyperintense basal ganglia is associated with various disease entities. On analysis of hyperintense basal ganglia lesion, the knowledge of clinical information improved diagnostic accuracy

Grey matter alterations in patients with Pantothenate Kinase-Associated Neurodegeneration (PKAN).

Science.gov (United States)

Rodriguez-Raecke, Rea; Roa-Sanchez, Pedro; Speckter, Herwin; Fermin-Delgado, Rafael; Perez-Then, Eddy; Oviedo, Jairo; Stoeter, Peter

2014-09-01

Pantothenate Kinase-Associated Neurodegeneration (PKAN) is a rare heritable disease marked by dystonia and loss of movement control. In contrast to the well-known "Eye-of-the-Tiger" sign affecting the globus pallidus, little is known about other deviations of brain morphology, especially about grey matter changes. We investigated 29 patients with PKAN and 29 age-matched healthy controls using Magnet Resonance Imaging and Voxel-Based Morphometry. As compared to controls, children with PKAN showed increased grey matter density in the putamen and nucleus caudatus and adults with PKAN showed increased grey matter density in the ventral part of the anterior cingulate cortex. A multiple regression analysis with dystonia score as predictor showed grey matter reduction in the cerebellum, posterior cingulate cortex, superior parietal lobule, pars triangularis and small frontal and temporal areas and an analysis with age as predictor showed grey matter decreases in the putamen, nucleus caudatus, supplementary motor area and anterior cingulate cortex. The grey matter increases may be regarded as a secondary phenomenon compensating the increased activity of the motor system due to a reduced inhibitory output of the globus pallidus. With increasing age, the grey matter reduction of cortical midline structures however might contribute to the progression of dystonic symptoms due to loss of this compensatory control. Copyright © 2014 Elsevier Ltd. All rights reserved.

Bilingualism at the core of the brain. Structural differences between bilinguals and monolinguals revealed by subcortical shape analysis.

Science.gov (United States)

Burgaleta, Miguel; Sanjuán, Ana; Ventura-Campos, Noelia; Sebastian-Galles, Núria; Ávila, César

2016-01-15

Naturally acquiring a language shapes the human brain through a long-lasting learning and practice process. This is supported by previous studies showing that managing more than one language from early childhood has an impact on brain structure and function. However, to what extent bilingual individuals present neuroanatomical peculiarities at the subcortical level with respect to monolinguals is yet not well understood, despite the key role of subcortical gray matter for a number of language functions, including monitoring of speech production and language control - two processes especially solicited by bilinguals. Here we addressed this issue by performing a subcortical surface-based analysis in a sample of monolinguals and simultaneous bilinguals (N=88) that only differed in their language experience from birth. This analysis allowed us to study with great anatomical precision the potential differences in morphology of key subcortical structures, namely, the caudate, accumbens, putamen, globus pallidus and thalamus. Vertexwise analyses revealed significantly expanded subcortical structures for bilinguals compared to monolinguals, localized in bilateral putamen and thalamus, as well as in the left globus pallidus and right caudate nucleus. A topographical interpretation of our results suggests that a more complex phonological system in bilinguals may lead to a greater development of a subcortical brain network involved in monitoring articulatory processes. Copyright © 2015 Elsevier Inc. All rights reserved.

Production and characterization of a new antibacterial peptide obtained from Aeribacillus pallidus SAT4

OpenAIRE

Muhammad, Syed Aun; Ahmed, Safia

2015-01-01

A novel thermophilic bacterial strain of the genus Aeribacillus was isolated from Thar Dessert Pakistan. This strain showed significant antibacterial activity against Micrococcus luteus, Staphylococcus aureus, and Pseudomonas aeruginosa. The strain coded as ‘SAT4’ resembled with Aeribacillus pallidus in the morphological, biochemical and molecular tests. The production of antibacterial metabolites by SAT4 was optimized. These active metabolites were precipitated by 50% ammonium sulphate and p...

Image-guided preoperative prediction of pyramidal tract side effect in deep brain stimulation: proof of concept and application to the pyramidal tract side effect induced by pallidal stimulation

OpenAIRE

Baumgarten, Clement; Zhao, Yulong; Sauleau, Paul; Malrain, Cecile; Jannin, Pierre; Haegelen, Claire

2016-01-01

Deep brain stimulation of the medial globus pallidus (GPm) is a surgical procedure for treating patients suffering from Parkinson���s disease. Its therapeutic effect may be limited by the presence of pyramidal tract side effect (PTSE). PTSE is a contraction time-locked to the stimulation when the current spreading reaches the motor fibers of the pyramidal tract within the internal capsule. The objective of the study was to propose a preoperative predictive model of PTSE. A machine learning-ba...

Regional distribution of enkephalinase in rat brain by autoradiography

International Nuclear Information System (INIS)

Waksman, G.; Hamel, E.; Besselievre, R.; Fournie-Zaluski, M.C.; Roques, B.P.; Bouboutou, R.

1984-01-01

The first visualization of enkephalinase (neutral metalloendopeptidase, E.C.3.4.24.11) in rat brain was obtained by autoradiography, using a new tritiated inhibitor: [ 3 H]N-[(R, S) 3-(N-hydroxy) carboxamido-2-benzyl propanoyl]-glycine ( 3 H-HCBP-Gly). The preliminary analysis of sections clearly showed a discrete localization of enkephalinase in enkephalin enriched regions, such as caudate nucleus, putamen, globus pallidus, and substantia nigra. Moreover 3 H-HCBP-Gly binding also occured in choroid plexus and spinal cord [fr

Hypothalamic projections to the ventral medulla oblongata in the rat, with special reference to the nucleus raphe pallidus: a study using autoradiographic and HRP techniques

Energy Technology Data Exchange (ETDEWEB)

Hosoya, Yasuhiko

1985-10-07

Hypothalamic descending projections to the medullary ventral surface were studied autoradiographically in the rat. A small amount of (/sup 3/H)leucine was injected unilaterally into various parts of the hypothalamus by air pressure. Abundant and characteristic terminal labelings were observed bilaterally in the nucleus raphe pallidus, the ventral surface to the pyramidal tract and the nucleus interfascicularis hypoglossi, after injections into the dorsal posterior hypothalamic area caudal to the paraventricular hypothalamic nucleus. Conspicuous, but less numerous labelings were observed in the nucleus raphe obscurus and the ipsilateral raphe magnus. After an injection of (/sup 3/H)leucine into the hypothalamus and injections of horseradish peroxidase (HRP) into the spinal cord in the same animal, silver grains were densely distributed around HRP-labeled neurons in the nucleus raphe pallidus including the nucleus interfascicularis hypoglossi. The present results suggest that the dorsal posterior hypothalamic area projects directly to the spinal-projecting neurons of the nucleus raphe pallidus. 53 refs.; 9 figs.

End-To-End Solution for Integrated Workload and Data Management using GlideinWMS and Globus Online

International Nuclear Information System (INIS)

Mhashilkar, Parag; Miller, Zachary; Weiss, Cathrin; Kettimuthu, Rajkumar; Garzoglio, Gabriele; Holzman, Burt; Duan, Xi; Lacinski, Lukasz

2012-01-01

Grid computing has enabled scientific communities to effectively share computing resources distributed over many independent sites. Several such communities, or Virtual Organizations (VO), in the Open Science Grid and the European Grid Infrastructure use the GlideinWMS system to run complex application work-flows. GlideinWMS is a pilot-based workload management system (WMS) that creates an on-demand, dynamically-sized overlay Condor batch system on Grid resources. While the WMS addresses the management of compute resources, however, data management in the Grid is still the responsibility of the VO. In general, large VOs have resources to develop complex custom solutions, while small VOs would rather push this responsibility to the infrastructure. The latter requires a tight integration of the WMS and the data management layers, an approach still not common in modern Grids. In this paper we describe a solution developed to address this shortcoming in the context of Center for Enabling Distributed Peta-scale Science (CEDPS) by integrating GlideinWMS with Globus Online (GO). Globus Online is a fast, reliable file transfer service that makes it easy for any user to move data. The solution eliminates the need for the users to provide custom data transfer solutions in the application by making this functionality part of the GlideinWMS infrastructure. To achieve this, GlideinWMS uses the file transfer plug-in architecture of Condor. The paper describes the system architecture and how this solution can be extended to support data transfer services other than Globus Online when used with Condor or GlideinWMS.

Yellow fever 17D-vectored vaccines expressing Lassa virus GP1 and GP2 glycoproteins provide protection against fatal disease in guinea pigs.

Science.gov (United States)

Jiang, Xiaohong; Dalebout, Tim J; Bredenbeek, Peter J; Carrion, Ricardo; Brasky, Kathleen; Patterson, Jean; Goicochea, Marco; Bryant, Joseph; Salvato, Maria S; Lukashevich, Igor S

2011-02-01

Yellow Fever (YF) and Lassa Fever (LF) are two prevalent hemorrhagic fevers co-circulating in West Africa and responsible for thousands of deaths annually. The YF vaccine 17D has been used as a vector for the Lassa virus glycoprotein precursor (LASV-GPC) or their subunits, GP1 (attachment glycoprotein) and GP2 (fusion glycoprotein). Cloning shorter inserts, LASV-GP1 and -GP2, between YF17D E and NS1 genes enhanced genetic stability of recombinant viruses, YF17D/LASV-GP1 and -GP2, in comparison with YF17D/LASV-GPC recombinant. The recombinant viruses were replication competent and properly processed YF proteins and LASV GP antigens in infected cells. YF17D/LASV-GP1 and -GP2 induced specific CD8+ T cell responses in mice and protected strain 13 guinea pigs against fatal LF. Unlike immunization with live attenuated reassortant vaccine ML29, immunization with YF17D/LASV-GP1 and -GP2 did not provide sterilizing immunity. This study demonstrates the feasibility of YF17D-based vaccine to control LF in West Africa. Copyright © 2010 Elsevier Ltd. All rights reserved.

Yellow fever 17D-vectored vaccines expressing Lassa virus GP1 and GP2 glycoproteins provide protection against fatal disease in guinea pigs

Science.gov (United States)

Jiang, Xiaohong; Dalebout, Tim J.; Bredenbeek, Peter J.; Carrion, Ricardo; Brasky, Kathleen; Patterson, Jean; Goicochea, Marco; Bryant, Joseph; Salvato, Maria S.; Lukashevich, Igor S.

2010-01-01

Yellow Fever (YF) and Lassa Fever (LF) are two prevalent hemorrhagic fevers co-circulating in West Africa and responsible for thousands of deaths annually. The YF vaccine 17D has been used as a vector for the Lassa virus glycoprotein precursor (LASV-GPC) or their subunits, GP1 (attachment glycoprotein) and GP2 (fusion glycoprotein). Cloning shorter inserts, LASV GP1 and GP2, between YF17D E and NS1 genes enhanced genetic stability of recombinant viruses, YF17D/LASV-GP1 and –GP2, in comparison with YF17D/LASV-GPC recombinant. The recombinant viruses were replication competent and properly processed YF and LASV GP proteins in infected cells. YF17D/LASV-GP1&GP2 induced specific CD8+ T cell responses in mice and protected strain 13 guinea pigs against fatal LF. Unlike immunization with live attenuated reassortant vaccine ML29, immunization with YF17D/LASV-GP1&GP2 did not provide sterilizing immunity. This study demonstrates the feasibility of YF17D-based vaccine to control LF in West Africa. PMID:21145373

Genome Sequence of Aeribacillus pallidus Strain GS3372, an Endospore-Forming Bacterium Isolated in a Deep Geothermal Reservoir

OpenAIRE

Sevasti Filippidou; Marion Jaussi; Thomas Junier; Tina Wunderlin; Nicole Jeanneret; Simona Regenspurg; Po-E Li; Chien-Chi Lo; Shannon Johnson; Kim McMurry; Cheryl D. Gleasner; Momchilo Vuyisich; Patrick S. Chain; Pilar Junier

2015-01-01

The genome of strain GS3372 is the first publicly available strain of Aeribacillus pallidus. This endospore-forming thermophilic strain was isolated from a deep geothermal reservoir. The availability of this genome can contribute to the clarification of the taxonomy of the closely related Anoxybacillus, Geobacillus, and Aeribacillus genera.

A case study for cloud based high throughput analysis of NGS data using the globus genomics system

Directory of Open Access Journals (Sweden)

Krithika Bhuvaneshwar

2015-01-01

Full Text Available Next generation sequencing (NGS technologies produce massive amounts of data requiring a powerful computational infrastructure, high quality bioinformatics software, and skilled personnel to operate the tools. We present a case study of a practical solution to this data management and analysis challenge that simplifies terabyte scale data handling and provides advanced tools for NGS data analysis. These capabilities are implemented using the “Globus Genomics” system, which is an enhanced Galaxy workflow system made available as a service that offers users the capability to process and transfer data easily, reliably and quickly to address end-to-endNGS analysis requirements. The Globus Genomics system is built on Amazon's cloud computing infrastructure. The system takes advantage of elastic scaling of compute resources to run multiple workflows in parallel and it also helps meet the scale-out analysis needs of modern translational genomics research.

1H MR spectroscopy of gray and white matter in carbon monoxide poisoning

DEFF Research Database (Denmark)

Kondziella, D.; Danielsen, E.R.; Hansen, K.

2009-01-01

Carbon monoxide (CO) intoxication leads to acute and chronic neurological deficits, but little is known about the specific noxious mechanisms. (1)H magnetic resonance spectroscopy (MRS) may allow insight into the pathophysiology of CO poisoning by monitoring neurochemical disturbances, yet only......, magnetic resonance imaging (MRI) and neuropsychological testing. Five patients suffered from acute high-dose CO intoxication and were in coma for 1-6 days. In these patients, MRI revealed hyperintensities of the white matter and globus pallidus and also showed increased choline (Cho) and decreased N...

Neuroradiologiske forandringer ved undertrykkelse af tics

DEFF Research Database (Denmark)

Larsen, Sara Bohn; Sørensen, Camilla Birgitte; Skov, Liselotte

2017-01-01

Neuroradiological changes by suppression of tics Tourette’s syndrome is characterized by involuntary tics. First choice of treatment has been pharmacological, but recently, behavioural therapy teaching patients to suppress their tics has been introduced. Neuroimaging studies have shown an increased...... activity in the prefrontal cortex, temporal lobes and caudate nucleus, and a decreased activity in globus pallidus and putamen during inhibition of tics. The activity in the frontal lobes changes with age, probably caused by a lack of compensatory hypertrophy. In order to fully understand the mechanism...

Dopamine response to psychosocial stress in humans and its relationship to individual differences in personality traits.

Science.gov (United States)

Suridjan, Ivonne; Boileau, Isabelle; Bagby, Michael; Rusjan, Pablo M; Wilson, Alan A; Houle, Sylvain; Mizrahi, Romina

2012-07-01

Previous studies have reported inter-individual variability in the dopamine (DA) response to stress. This variability might be related to individual differences in the vulnerability to experience the negative effect of stress. To investigate whether personality traits as measured by the revised NEO personality inventory explain variability in DA response to a psychosocial stress task. Eleven healthy adults, mean age of 26 ± 3.87 underwent two positron emission tomography (PET) scans using the dopamine D(2/3) agonist, [11C]-(+)-PHNO under a control and stress condition. The simplified reference tissue model (SRTM) was used to obtain [11C]-(+)-PHNO binding potential (BP(ND)). Stress-induced DA response was indexed as a percent change in [11C]-(+)-PHNO BP(ND) between control and stress conditions. The regions of interest were defined into D2-rich regions, which included the Associative and Sensorimotor Striatum (AST and SMST); D(2/3) mixed regions, which included the limbic striatum (LST) and globus pallidus (GP); and D3-rich region, which included the Substantia Nigra (SN). Several personality traits within the Neuroticism and Openness to Experience domain were significantly correlated with blunted DA response to stress. Specifically, the Angry-Hostility, Vulnerability, and Depression trait were associated with blunted DA stress response in the AST (r = -0.645, p = 0.032), LST (r = -0.677, p = 0.022) and GP (r = -0.736, p = 0.010), respectively. The Openness to Values was correlated with a decreased DA release in the SN (r = -0.706, p = 0.015). Variability in DA stress response might be related to individual differences in personality. Crown Copyright © 2012. Published by Elsevier Ltd. All rights reserved.

The histamine system in human brain. Changes in neurological and psychiatric disorders

Energy Technology Data Exchange (ETDEWEB)

Goodchild, R.E

1999-09-01

Autoradiographical examination of the distribution of H{sub 1}- and H{sub 3}- histamine receptor subtypes, using [{sup 3}H]-mepyramine and [{sup 3}H]-R-({alpha}) methylhistamine respectively, found high H{sub 1}-receptor binding densities in neocortex, dentate gyrus and basolateral amygdala, with low binding in all subdivisions of the thalamus and other subcortical areas. H{sub 3}-receptor binding was enriched within the nucleus accumbens, globus pallidus and substantia nigra, whilst was low in the hippocampus, subthalamic nucleus, temporal cortex, motor and somatosensory thalamic areas and basolateral amygdala. In situ hybridisation found H{sub 2}-receptor mRNA located in the striatum, thalamus, hippocampal pyramidal cell layer and dentate gyrus, and specific laminae of neocortex. Comparison of autoradiographically determined H{sub 1}-, H{sub 2}- and H{sub 3}-receptor binding densities between normal and pathological cases found significantly decreased (p < 0.005, ANOVA) striatal and pallidal H{sub 3}-receptor binding in Huntington's disease (HD), with unaltered binding in the insular cortex. A significant correlation (p < 0.01) was present between binding in the internal globus pallidus and HD grade. Binding to the striatal H{sub 1}-receptor was increased (p < 0.05, ANOVA) in Parkinson's disease (PD), whilst H{sub 2}- (measured using [{sup 125}I]-iodoaminopotentidine) and H{sub 3}-receptor binding densities were normal in all areas examined. H{sub 1}-receptor binding was also increased in the hippocampus of Lewy-body dementia (DLB) cases (p < 0.05, Students two-tailed T-Test), whilst hippocampal and cortical H{sub 2}-receptor binding densities were decreased in DLB, together with Alzheimer's disease (AD) (p < 0.05, ANOVA). H{sub 3}-receptor binding was increased in the insular cortex and decreased in the temporal cortex of DLB, but not AD, cases (p < 0.05, ANOVA). H{sub 1}-receptor binding to tissue from patients with schizophrenia was

Exploring personality traits related to dopamine D2/3 receptor availability in striatal subregions of humans.

Science.gov (United States)

Caravaggio, Fernando; Fervaha, Gagan; Chung, Jun Ku; Gerretsen, Philip; Nakajima, Shinichiro; Plitman, Eric; Iwata, Yusuke; Wilson, Alan; Graff-Guerrero, Ariel

2016-04-01

While several studies have examined how particular personality traits are related to dopamine D2/3 receptor (D2/3R) availability in the striatum of humans, few studies have reported how multiple traits measured in the same persons are differentially related to D2/3R availability in different striatal sub-regions. We examined how personality traits measured with the Karolinska Scales of Personality are related to striatal D2/3R availability measured with [(11)C]-raclopride in 30 healthy humans. Based on previous the literature, five personality traits were hypothesized to be most likely related to D2/3R availability: impulsiveness, monotony avoidance, detachment, social desirability, and socialization. We found self-reported impulsiveness was negatively correlated with D2/3R availability in the ventral striatum and globus pallidus. After controlling for age and gender, monotony avoidance was also negatively correlated with D2/3R availability in the ventral striatum and globus pallidus. Socialization was positively correlated with D2/3R availability in the ventral striatum and putamen. After controlling for age and gender, the relationship between socialization and D2/3R availability in these regions survived correction for multiple comparisons (p-threshold=.003). Thus, within the same persons, different personality traits are differentially related to in vivo D2/3R availability in different striatal sub-regions. Copyright © 2016 Elsevier B.V. and ECNP. All rights reserved.

Magnetic resonance imaging of carbon monoxide poisoning in chronic stage

International Nuclear Information System (INIS)

Kojima, Shigeyuki; Kawamura, Mitsuru; Shibata, Noriyuki; Takahashi, Nobuyoshi; Hirayama, Keizo

1986-01-01

Magnetic resonance imaging (MRI) was evaluated in three patients with carbon monoxide (CO) poisoning in chronic stage by comparison with serial X-ray computed tomography (CT). In Case 1 and 3, no pallidal lesions believed to be the most common lesion of the gray matter in CO poisoning were found in the serial X-ray CT scans. In the other case (Case 2), the typical initial bilateral symmetrical low density areas in the globus pallidus were found to have decreased markedly in size and finally disappeared in the latter X-ray CT scan. But MRI using inversion recovery (IR) or spin echo (SE) pulse sequence clearly showed bilateral symmetrical decreased or increased signal intensity areas in the globus pallidus in all three cases. In Case 3, chronic CO poisoning was confirmed by the bilateral symmetrical pallidal lesions on MRI, although differential diagnosis was difficult. Furthermore, in Case 2, with pure alexia, MRI using IR or SE pulse sequence demonstrated a patchy decreased or increased signal intensity area in the subcortical white matter at the left angular gyrus, although X-ray CT scan showed no abnormal findings. MRI is useful in the diagnosis of CO poisoning, especially chronic CO poisoning, because necrosis, cavitation, demyelination, gliosis and so on due to hypoxia of CO poisoning were sensitively detected from changes in the proton density and the T1 or T2 relaxation time value on MRI. (J.P.N.)

CGP lil-gp 2.1;1.02 User's Manual

Science.gov (United States)

Janikow, Cezary Z.; DeWeese, Scott W.

1997-01-01

This document describes extensions provided to lil-gp facilitating dealing with constraints. This document deals specifically with lil-gp 1.02, and the resulting extension is referred to as CGP lil-gp 2.1; 1.02 (the first version is for the extension, the second for the utilized lil-gp version). Unless explicitly needed to avoid confusion, version numbers are omitted.

High kinetic energy plasma jet generation and its injection into the Globus-M spherical tokamak

International Nuclear Information System (INIS)

Voronin, A.V.; Gusev, V.K.; Petrov, Yu.V.; Sakharov, N.V.; Abramova, K.B.; Sklyarova, E.M.; Tolstyakov, S.Yu.

2005-01-01

Progress in the theoretical and experimental development of the plasma jet source and injection of hydrogen plasma and neutral gas jets into the Globus-M spherical tokamak is discussed. An experimental test bed is described for investigation of intense plasma jets that are generated by a double-stage plasma gun consisting of an intense source for neutral gas production and a conventional pulsed coaxial accelerator. A procedure for optimizing the accelerator parameters so as to achieve the maximum possible flow velocity with a limited discharge current and a reasonable length of the coaxial electrodes is presented. The calculations are compared with experiment. Plasma jet parameters, among them pressure distribution across the jet, flow velocity, plasma density, etc, were measured. Plasma jets with densities of up to 10 22 m -3 , total numbers of accelerated particles (1-5) x 10 19 , and flow velocities of 50-100 km s -1 were successfully injected into the plasma column of the Globus-M tokamak. Interferometric and Thomson scattering measurements confirmed deep jet penetration and a fast density rise ( 19 to 1 x 10 19 ) did not result in plasma degradation

Genome Sequence of Aeribacillus pallidus Strain GS3372, an Endospore-Forming Bacterium Isolated in a Deep Geothermal Reservoir.

Science.gov (United States)

Filippidou, Sevasti; Jaussi, Marion; Junier, Thomas; Wunderlin, Tina; Jeanneret, Nicole; Regenspurg, Simona; Li, Po-E; Lo, Chien-Chi; Johnson, Shannon; McMurry, Kim; Gleasner, Cheryl D; Vuyisich, Momchilo; Chain, Patrick S; Junier, Pilar

2015-08-27

The genome of strain GS3372 is the first publicly available strain of Aeribacillus pallidus. This endospore-forming thermophilic strain was isolated from a deep geothermal reservoir. The availability of this genome can contribute to the clarification of the taxonomy of the closely related Anoxybacillus, Geobacillus, and Aeribacillus genera. Copyright © 2015 Filippidou et al.

Mossbauer and SQUID Characterization of Iron in Human Tissue: Case of Globus Pallidus

Czech Academy of Sciences Publication Activity Database

Miglierini, M.; Boca, R.; Kopáni, M.; Lančok, Adriana

2014-01-01

Roč. 126, č. 1 (2014), s. 240-241 ISSN 0587-4246 R&D Projects: GA ČR GAP204/10/0035 Institutional support: RVO:61388980 Keywords : FERRITIN Subject RIV: CF - Physical ; The oretical Chemistry Impact factor: 0.530, year: 2014

Concurrent Presentation of Burning Mouth Syndrome and Globus Pharyngis in Enugu, Nigeria: A Ten-year Clinical Evaluation.

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Chukwuneke, Felix; Akpe, James; Okoye, Linda; Ekwueme, Christian; Obiakor, Anthonia; Amobi, Emmanuel; Egbunike, Doris

2014-01-01

To review 22 patients with globus pharyngis among a group of 39 patients who presented with burning mouth syndrome and to highlight the clinical presentation and treatment outcome of these oropharyngeal symptoms, often ignored by practicing oral surgeons. We carried out a retrospective review of 39 patients with burning mouth syndrome seen at oral surgery units of three specialist hospitals in Enugu, Nigeria between 2001 and 2010. The focus was on the 22 of these patients with burning mouth syndrome and globus pharyngis (the persistent sensation of having phlegm, a pill or some other sort of obstruction in the throat when there is none). Relevant information included patients' oral habits and dental status, past medical history, sociodemographic data, onset of symptoms and treatment outcome. Amongst the 22 patients, 8 (36.4%) were males while 14 (63.6%) were females, giving a male to female ratio of 1:1.8. Of the 8 male patients, 3 (37.5%) were retrenched workers, 2 (25%) were drug addicts, 2 (25%) had a history of psychiatric problems and 1 (12.5%) had post-radiation therapy due to diagnosis of adenocystic carcinoma. Amongst the 14 female patients, 6 (42.8%) were divorcees, 3 (21.4%) were unemployed and unmarried, 2 (14.3%) had menopausal problems, 2 (14.3%) had dental prostheses and 1 (7.2%) had a history of mental disorder. Globus pharyngis can present at the same time in some individuals with burning mouth syndrome. The emotional aetiological factor in this unusual ailment calls for proper examinations and a multidisciplinary approach in the management of patients who presented with burning mouth syndrome, especially with a history of depression.

Clinical and neuropathological findings of acute carbon monoxide toxicity in chihuahuas following smoke inhalation.

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Kent, Marc; Creevy, Kate E; Delahunta, Alexander

2010-01-01

Three adult Chihuahuas were presented for evaluation after smoke inhalation during a house fire. All three dogs received supportive care and supplemental oxygen. After initial improvement, the dogs developed seizures. Despite anticonvulsant therapy and supportive care, the dogs died. The brains of two dogs were examined. Lesions were identified that were compatible with acute carbon monoxide (CO) toxicity. Lesions were confined to the caudate nucleus, the globus pallidus, and the substantia nigra bilaterally, as well as the cerebellum, cerebral cortex, and dorsal thalamus. This case report describes the clinicopathological sequelae in acute CO toxicity.

Hyperintense basal ganglia lesions on T1-weighted MR images in asymptomatic patients with hepatic dysfunction

Energy Technology Data Exchange (ETDEWEB)

Saatci, I. [Dept. of Radiology, Hacettepe Univ. Hospital, Ankara (Turkey); Cila, A. [Dept. of Radiology, Hacettepe Univ. Hospital, Ankara (Turkey); Dincer, F.F. [Dept. of Radiology, Hacettepe Univ. Hospital, Ankara (Turkey)

1995-12-31

Cranial MRI findings in four patients who had hepatic dysfunction, including one with sole hepatic form of Wilson`s disease, were reported. The MR examinations revealed bilateral, symmetric hyperintensity in the globus pallidus, subthalamic nuclei and mesencephalon on T1-weighted images with no corresponding abnormality on T2-weighted sequences. The basal ganglia were normal on CT examinations in all patients. None of the patients had the clinical findings of hepatic encephalopathy. The MR findings in our patients did not correlate with the degree or duration of hepatic dysfunction. (orig.)

Basal ganglia calcification on CT in adult patients with Down's syndrome

International Nuclear Information System (INIS)

Ono, Yoshiro; Yoshida, Hironobu; Yoshimasu, Fumio; Higashi, Yuji.

1987-01-01

Fourteen adult cases with Down's syndrome were examined on cranial CT scan, and 5 of them (35.7 %) showed basal ganglia calcification (BGC). The incidence of BGC in the present cases was very high in comparison with the one in general population (0.3 ∼ 1.5 %). Abnormalities of calcium metabolism or dysfunctions of the basal ganglia were absent in each case with BGC. Calcifications were exclusively located in globus pallidus. It is considered that BGC found in the present cases may be due to the premature aging process in Down's syndrome. (author)

Global and regional brain atrophy is associated with low or retrograde facial vein flow in multiple sclerosis

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Dejan Jakimovski

2017-09-01

Full Text Available Increased collateral facial vein (FV flow may be associated with structural damage in patients with multiple sclerosis (MS. The objective was to assess differences in FV flow and magnetic resonance imaging (MRI-derived outcomes in MS. The study included 136 MS patients who underwent neck and head vascular system examination by echo-color Doppler. Inflammatory MRI markers were assessed on a 3T MRI using a semi-automated edge detection and contouring/ thresholding technique. MRI volumetric outcomes of whole brain (WB, gray matter (GM, white matter (WM, cortex, ventricular cerebrospinal fluid (vCSF, deep gray matter (DGM, thalamus, caudate nucleus (CN, putamen, globus pallidus (GP, and hippocampus were calculated. Independent t-test and ANCOVA, adjusted for age, were used to compare groups based on FV flow quartiles. Thirty-four MS patients with FV flow ≤327.8 mL/min (lowest quartile had significantly lower WB (P327.8 mL/min (higher quartiles. There were no differences in T1-, T2- and gadolinium- enhancing lesion volumes between the quartile groups. The lack of an association between FV blood flow and inflammatory MRI measures in MS patients, but an association with brain atrophy, suggests that the severity of neurodegenerative process may be related to hemodynamic alterations. MS patients with more advanced global and regional brain atrophy showed low or retrograde FV volume flow.

A real-time artifact reduction algorithm based on precise threshold during short-separation optical probe insertion in neurosurgery

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Weitao Li

2017-01-01

Full Text Available During neurosurgery, an optical probe has been used to guide the micro-electrode, which is punctured into the globus pallidus (GP to create a lesion that can relieve the cardinal symptoms. Accurate target localization is the key factor to affect the treatment. However, considering the scattering nature of the tissue, the “look ahead distance (LAD” of optical probe makes the boundary between the different tissues blurred and difficult to be distinguished, which is defined as artifact. Thus, it is highly desirable to reduce the artifact caused by LAD. In this paper, a real-time algorithm based on precise threshold was proposed to eliminate the artifact. The value of the threshold was determined by the maximum error of the measurement system during the calibration procession automatically. Then, the measured data was processed sequentially only based on the threshold and the former data. Moreover, 100μm double-fiber probe and two-layer and multi-layer phantom models were utilized to validate the precision of the algorithm. The error of the algorithm is one puncture step, which was proved in the theory and experiment. It was concluded that the present method could reduce the artifact caused by LAD and make the real boundary sharper and less blurred in real-time. It might be potentially used for the neurosurgery navigation.

Structure and Recognition of a Novel HIV-1 gp120-gp41 Interface Antibody that Caused MPER Exposure through Viral Escape

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Wibmer, Constantinos Kurt; Gorman, Jason; Ozorowski, Gabriel; Bhiman, Jinal N.; Sheward, Daniel J.; Elliott, Debra H.; Rouelle, Julie; Smira, Ashley; Joyce, M. Gordon; Ndabambi, Nonkululeko; Druz, Aliaksandr; Asokan, Mangai; Burton, Dennis R.; Connors, Mark; Abdool Karim, Salim S.; Mascola, John R.; Robinson, James E.; Ward, Andrew B.; Williamson, Carolyn; Kwong, Peter D.; Morris, Lynn; Moore, Penny L.; Desrosiers, Ronald C.

2017-01-11

A comprehensive understanding of the regions on HIV-1 envelope trimers targeted by broadly neutralizing antibodies may contribute to rational design of an HIV-1 vaccine. We previously identified a participant in the CAPRISA cohort, CAP248, who developed trimer-specific antibodies capable of neutralizing 60% of heterologous viruses at three years post-infection. Here, we report the isolation by B cell culture of monoclonal antibody CAP248-2B, which targets a novel membrane proximal epitope including elements of gp120 and gp41. Despite low maximum inhibition plateaus, often below 50% inhibitory concentrations, the breadth of CAP248-2B significantly correlated with donor plasma. Site-directed mutagenesis, X-ray crystallography, and negative-stain electron microscopy 3D reconstructions revealed how CAP248-2B recognizes a cleavage-dependent epitope that includes the gp120 C terminus. While this epitope is distinct, it overlapped in parts of gp41 with the epitopes of broadly neutralizing antibodies PGT151, VRC34, 35O22, 3BC315, and 10E8. CAP248-2B has a conformationally variable paratope with an unusually long 19 amino acid light chain third complementarity determining region. Two phenylalanines at the loop apex were predicted by docking and mutagenesis data to interact with the viral membrane. Neutralization by CAP248-2B is not dependent on any single glycan proximal to its epitope, and low neutralization plateaus could not be completely explained by N- or O-linked glycosylation pathway inhibitors, furin co-transfection, or pre-incubation with soluble CD4. Viral escape from CAP248-2B involved a cluster of rare mutations in the gp120-gp41 cleavage sites. Simultaneous introduction of these mutations into heterologous viruses abrogated neutralization by CAP248-2B, but enhanced neutralization sensitivity to 35O22, 4E10, and 10E8 by 10-100-fold. Altogether, this study expands the region of the HIV-1 gp120-gp41 quaternary interface that is a target for broadly neutralizing

Internalization and Axonal Transport of the HIV Glycoprotein gp120

Science.gov (United States)

Berth, Sarah; Caicedo, Hector Hugo; Sarma, Tulika; Morfini, Gerardo

2015-01-01

The HIV glycoprotein gp120, a neurotoxic HIV glycoprotein that is overproduced and shed by HIV-infected macrophages, is associated with neurological complications of HIV such as distal sensory polyneuropathy, but interactions of gp120 in the peripheral nervous system remain to be characterized. Here, we demonstrate internalization of extracellular gp120 in a manner partially independent of binding to its coreceptor CXCR4 by F11 neuroblastoma cells and cultured dorsal root ganglion neurons. Immunocytochemical and pharmacological experiments indicate that gp120 does not undergo trafficking through the endolysosomal pathway. Instead, gp120 is mainly internalized through lipid rafts in a cholesterol-dependent manner, with a minor fraction being internalized by fluid phase pinocytosis. Experiments using compartmentalized microfluidic chambers further indicate that, after internalization, endocytosed gp120 selectively undergoes retrograde but not anterograde axonal transport from axons to neuronal cell bodies. Collectively, these studies illuminate mechanisms of gp120 internalization and axonal transport in peripheral nervous system neurons, providing a novel framework for mechanisms for gp120 neurotoxicity. PMID:25636314

Structural Basis for Species Selectivity in the HIV-1 gp120-CD4 Interaction: Restoring Affinity to gp120 in Murine CD4 Mimetic Peptides

Directory of Open Access Journals (Sweden)

Kristin Kassler

2011-01-01

Full Text Available The first step of HIV-1 infection involves interaction between the viral glycoprotein gp120 and the human cellular receptor CD4. Inhibition of the gp120-CD4 interaction represents an attractive strategy to block HIV-1 infection. In an attempt to explore the known lack of affinity of murine CD4 to gp120, we have investigated peptides presenting the putative gp120-binding site of murine CD4 (mCD4. Molecular modeling indicates that mCD4 protein cannot bind gp120 due to steric clashes, while the larger conformational flexibility of mCD4 peptides allows an interaction. This finding is confirmed by experimental binding assays, which also evidenced specificity of the peptide-gp120 interaction. Molecular dynamics simulations indicate that the mCD4-peptide stably interacts with gp120 via an intermolecular β-sheet, while an important salt-bridge formed by a C-terminal lysine is lost. Fixation of the C-terminus by introducing a disulfide bridge between the N- and C-termini of the peptide significantly enhanced the affinity to gp120.

Production and properties of two novel exopolysaccharides synthesized by a thermophilic bacterium Aeribacillus pallidus 418.

Science.gov (United States)

Radchenkova, Nadja; Vassilev, Spasen; Panchev, Ivan; Anzelmo, Gianluca; Tomova, Iva; Nicolaus, Barbara; Kuncheva, Margarita; Petrov, Kaloyan; Kambourova, Margarita

2013-09-01

Synthesis of innovative exocellular polysaccharides (EPSs) was reported for few thermophilic microorganisms as one of the mechanisms for surviving at high temperature. Thermophilic aerobic spore-forming bacteria able to produce exopolysaccharides were isolated from hydrothermal springs in Bulgaria. They were referred to four species, such as Aeribacillus pallidus, Geobacillus toebii, Brevibacillus thermoruber, and Anoxybacillus kestanbolensis. The highest production was established for the strain 418, whose phylogenetic and phenotypic properties referred it to the species A. pallidus. Maltose and NH4Cl were observed to be correspondingly the best carbon and nitrogen sources and production yield was increased more than twofold in the process of culture condition optimization. After purification of the polymer fraction, a presence of two different EPSs, electroneutral EPS 1 and negatively charged EPS 2, in a relative weight ratio 3:2.2 was established. They were heteropolysaccharides consisting of unusual high variety of sugars (six for EPS 1 and seven for EPS 2). Six of the sugars were common for both EPSs. The main sugar in EPS 1 was mannose (69.3 %); smaller quantities of glucose (11.2 %), galactosamine (6.3 %), glucosamine (5.4 %), galactose (4.7 %), and ribose (2.9 %) were also identified. The main sugar in EPS 2 was also mannose (33.9 %), followed by galactose (17.9 %), glucose (15.5 %), galactosamine (11.7 %), glucosamine (8.1 %), ribose (5.3 %), and arabinose (4.9 %). Both polymers showed high molecular weight and high thermostability.

Cannabidiol changes P-gp and BCRP expression in trophoblast cell lines

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Valeria Feinshtein

2013-09-01

Full Text Available Objectives. Marijuana is the most commonly used illicit drug during pregnancy. Due to high lipophilicity, cannabinoids can easily penetrate physiological barriers like the human placenta and jeopardize the developing fetus. We evaluated the impact of cannabidiol (CBD, a major non-psychoactive cannabinoid, on P-glycoprotein (P-gp and Breast Cancer Resistance Protein (BCRP expression, and P-gp function in a placental model, BeWo and Jar choriocarcinoma cell lines (using P-gp induced MCF7 cells (MCF7/P-gp for comparison. Study design. Following the establishment of the basal expression of these transporters in the membrane fraction of all three cell lines, P-gp and BCRP protein and mRNA levels were determined following chronic (24–72 h exposure to CBD, by Western Blot and qPCR. CBD impact on P-gp efflux function was examined by uptake of specific P-gp fluorescent substrates (calcein-AM, DiOC2(3 and rhodamine123(rh123. Cyclosporine A (CsA served as a positive control. Results. Chronic exposure to CBD resulted in significant changes in the protein and mRNA levels of both transporters. While P-gp was down-regulated, BCRP levels were up-regulated in the choriocarcinoma cell lines. CBD had a remarkably different influence on P-gp and BCRP expression in MCF7/P-gp cells, demonstrating that these are cell type specific effects. P-gp dependent efflux (of calcein, DiOC2(3 and rh123 was inhibited upon short-term exposure to CBD. Conclusions. Our study shows that CBD might alter P-gp and BCRP expression in the human placenta, and inhibit P-gp efflux function. We conclude that marijuana use during pregnancy may reduce placental protective functions and change its morphological and physiological characteristics.

Local field potential recordings in a non-human primate model of Parkinsons disease using the Activa PC + S neurostimulator

Science.gov (United States)

Connolly, Allison T.; Muralidharan, Abirami; Hendrix, Claudia; Johnson, Luke; Gupta, Rahul; Stanslaski, Scott; Denison, Tim; Baker, Kenneth B.; Vitek, Jerrold L.; Johnson, Matthew D.

2015-12-01

Objective. Using the Medtronic Activa® PC + S system, this study investigated how passive joint manipulation, reaching behavior, and deep brain stimulation (DBS) modulate local field potential (LFP) activity in the subthalamic nucleus (STN) and globus pallidus (GP). Approach. Five non-human primates were implanted unilaterally with one or more DBS leads. LFPs were collected in montage recordings during resting state conditions and during motor tasks that facilitate the expression of parkinsonian motor signs. These recordings were made in the naïve state in one subject, in the parkinsonian state in two subjects, and in both naïve and parkinsonian states in two subjects. Main results. LFPs measured at rest were consistent over time for a given recording location and parkinsonian state in a given subject; however, LFPs were highly variable between subjects, between and within recording locations, and across parkinsonian states. LFPs in both naïve and parkinsonian states across all recorded nuclei contained a spectral peak in the beta band (10-30 Hz). Moreover, the spectral content of recorded LFPs was modulated by passive and active movement of the subjects’ limbs. LFPs recorded during a cued-reaching task displayed task-related beta desynchronization in STN and GP. The bidirectional capabilities of the Activa® PC + S also allowed for recording LFPs while delivering DBS. The therapeutic effect of STN DBS on parkinsonian rigidity outlasted stimulation for 30-60 s, but there was no correlation with beta band power. Significance. This study emphasizes (1) the variability in spontaneous LFPs amongst subjects and (2) the value of using the Activa® PC + S system to record neural data in the context of behavioral tasks that allow one to evaluate a subject’s symptomatology.

Local field potential recordings in a non-human primate model of Parkinsons disease using the Activa PC + S neurostimulator

Science.gov (United States)

Connolly, Allison T; Muralidharan, Abirami; Hendrix, Claudia; Johnson, Luke; Gupta, Rahul; Stanslaski, Scott; Denison, Tim; Baker, Kenneth B; Vitek, Jerrold L; Johnson, Matthew D

2016-01-01

Objective Using the Medtronic Activa® PC + S system, this study investigated how passive joint manipulation, reaching behavior, and deep brain stimulation (DBS) modulate local field potential (LFP) activity in the subthalamic nucleus (STN) and globus pallidus (GP). Approach Five non-human primates were implanted unilaterally with one or more DBS leads. LFPs were collected in montage recordings during resting state conditions and during motor tasks that facilitate the expression of parkinsonian motor signs. These recordings were made in the naïve state in one subject, in the parkinsonian state in two subjects, and in both naïve and parkinsonian states in two subjects. Main results LFPs measured at rest were consistent over time for a given recording location and parkinsonian state in a given subject; however, LFPs were highly variable between subjects, between and within recording locations, and across parkinsonian states. LFPs in both naïve and parkinsonian states across all recorded nuclei contained a spectral peak in the beta band (10–30 Hz). Moreover, the spectral content of recorded LFPs was modulated by passive and active movement of the subjects’ limbs. LFPs recorded during a cued-reaching task displayed task-related beta desynchronization in STN and GP. The bidirectional capabilities of the Activa® PC + S also allowed for recording LFPs while delivering DBS. The therapeutic effect of STN DBS on parkinsonian rigidity outlasted stimulation for 30–60 s, but there was no correlation with beta band power. Significance This study emphasizes (1) the variability in spontaneous LFPs amongst subjects and (2) the value of using the Activa® PC + S system to record neural data in the context of behavioral tasks that allow one to evaluate a subject’s symptomatology. PMID:26469737

The relationship between subcortical brain volume and striatal dopamine D2/3 receptor availability in healthy humans assessed with [11 C]-raclopride and [11 C]-(+)-PHNO PET.

Science.gov (United States)

Caravaggio, Fernando; Ku Chung, Jun; Plitman, Eric; Boileau, Isabelle; Gerretsen, Philip; Kim, Julia; Iwata, Yusuke; Patel, Raihaan; Chakravarty, M Mallar; Remington, Gary; Graff-Guerrero, Ariel

2017-11-01

Abnormalities in dopamine (DA) and brain morphology are observed in several neuropsychiatric disorders. However, it is not fully understood how these abnormalities may relate to one another. For such in vivo findings to be used as biomarkers for neuropsychiatric disease, it must be understood how variability in DA relates to brain structure under healthy conditions. We explored how the availability of striatal DA D 2/3 receptors (D 2/3 R) is related to the volume of subcortical brain structures in a sample of healthy humans. Differences in D 2/3 R availability measured with an antagonist radiotracer ([ 11 C]-raclopride) versus an agonist radiotracer ([ 11 C]-(+)-PHNO) were examined. Data from 62 subjects scanned with [ 11 C]-raclopride (mean age = 38.98 ± 14.45; 23 female) and 68 subjects scanned with [ 11 C]-(+)-PHNO (mean age = 38.54 ± 14.59; 25 female) were used. Subcortical volumes were extracted from T1-weighted images using the Multiple Automatically Generated Templates (MAGeT-Brain) algorithm. Partial correlations were used controlling for age, gender, and total brain volume. For [ 11 C]-(+)-PHNO, ventral caudate volumes were positively correlated with BP ND in the dorsal caudate and globus pallidus (GP). Ventral striatum (VS) volumes were positively correlated with BP ND in the VS. With [ 11 C]-raclopride, BP ND in the VS was negatively correlated with subiculum volume of the hippocampus. Moreover, BP ND in the GP was negatively correlated with the volume of the lateral posterior nucleus of the thalamus. Findings are purely exploratory and presented corrected and uncorrected for multiple comparisons. We hope they will help inform the interpretation of future PET studies where concurrent changes in D 2/3 R and brain morphology are observed. Hum Brain Mapp 38:5519-5534, 2017. © 2017 Wiley Periodicals, Inc. © 2017 Wiley Periodicals, Inc.

Structural delineation of a quaternary, cleavage-dependent epitope at the gp41-gp120 interface on intact HIV-1 Env trimers.

Science.gov (United States)

Blattner, Claudia; Lee, Jeong Hyun; Sliepen, Kwinten; Derking, Ronald; Falkowska, Emilia; de la Peña, Alba Torrents; Cupo, Albert; Julien, Jean-Philippe; van Gils, Marit; Lee, Peter S; Peng, Wenjie; Paulson, James C; Poignard, Pascal; Burton, Dennis R; Moore, John P; Sanders, Rogier W; Wilson, Ian A; Ward, Andrew B

2014-05-15

All previously characterized broadly neutralizing antibodies to the HIV-1 envelope glycoprotein (Env) target one of four major sites of vulnerability. Here, we define and structurally characterize a unique epitope on Env that is recognized by a recently discovered family of human monoclonal antibodies (PGT151-PGT158). The PGT151 epitope is comprised of residues and glycans at the interface of gp41 and gp120 within a single protomer and glycans from both subunits of a second protomer and represents a neutralizing epitope that is dependent on both gp120 and gp41. Because PGT151 binds only to properly formed, cleaved trimers, this distinctive property, and its ability to stabilize Env trimers, has enabled the successful purification of mature, cleaved Env trimers from the cell surface as a complex with PGT151. Here we compare the structural and functional properties of membrane-extracted Env trimers from several clades with those of the soluble, cleaved SOSIP gp140 trimer. Copyright © 2014 Elsevier Inc. All rights reserved.

Cortical stimulation evokes abnormal responses in the dopamine-depleted rat basal ganglia.

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Kita, Hitoshi; Kita, Takako

2011-07-13

The motor cortex (MC) sends massive projections to the basal ganglia. Motor disabilities in patients and animal models of Parkinson's disease (PD) may be caused by dopamine (DA)-depleted basal ganglia that abnormally process the information originating from MC. To study how DA depletion alters signal transfer in the basal ganglia, MC stimulation-induced (MC-induced) unitary responses were recorded from the basal ganglia of control and 6-hydroxydopamine-treated hemi-parkinsonian rats anesthetized with isoflurane. This report describes new findings about how DA depletion alters MC-induced responses. MC stimulation evokes an excitation in normally quiescent striatal (Str) neurons projecting to the globus pallidus external segment (GPe). After DA-depletion, the spontaneous firing of Str-GPe neurons increases, and MC stimulation evokes a shorter latency excitation followed by a long-lasting inhibition that was invisible under normal conditions. The increased firing activity and the newly exposed long inhibition generate tonic inhibition and a disfacilitation in GPe. The disfacilitation in GPe is then amplified in basal ganglia circuitry and generates a powerful long inhibition in the basal ganglia output nucleus, the globus pallidus internal segment. Intra-Str injections of a behaviorally effective dose of DA precursor l-3,4-dihydroxyphenylalanine effectively reversed these changes. These newly observed mechanisms also support the generation of pauses and burst activity commonly observed in the basal ganglia of parkinsonian subjects. These results suggest that the generation of abnormal response sequences in the basal ganglia contributes to the development of motor disabilities in PD and that intra-Str DA supplements effectively suppress abnormal signal transfer.

Significance of apparent diffusion coefficient measurement for the differential diagnosis of multiple system atrophy, progressive supranuclear palsy, and Parkinson's disease: evaluation by 3.0-T MR imaging

International Nuclear Information System (INIS)

Tsukamoto, Kazumichi; Kanasaki, Yoshiko; Kakite, Suguru; Fujii, Shinya; Kaminou, Toshio; Ogawa, Toshihide; Matsusue, Eiji

2012-01-01

The clinical differentiation of Parkinson's disease (PD) from multiple system atrophy (MSA) and progressive supranuclear palsy (PSP) may be challenging, especially in their early stages. The aim of this study was to evaluate the utility of apparent diffusion coefficient (ADC) measurement to distinguish among these degenerative disorders. Twenty-five MSA, 20 PSP, and 17 PD patients and 18 healthy controls were retrospectively studied. Axial diffusion-weighted and T2-weighted images were obtained using a 3-T MR system. Regions of interest (ROIs) were precisely placed in the midbrain, pons, putamen, globus pallidus, caudate nucleus, thalamus, superior cerebellar peduncle, middle cerebellar peduncle, cerebellar white matter, and cerebellar dentate nucleus, and the regional ADC (rADC) value was calculated in each ROI. In MSA, rADC values in the pons, middle cerebellar peduncle, cerebellar white matter, and cerebellar dentate nucleus were significantly higher than in PSP, PD, and controls. Furthermore, rADC values in the posterior putamen were significantly higher in MSA than in PSP and controls. In PSP, rADC values were significantly higher in the globus pallidus and midbrain than in MSA, PD, and controls. Furthermore, rADC values in the caudate nucleus and superior cerebellar peduncle were significantly higher in PSP than in MSA and controls. In PD, there were no significant differences in the rADC values compared to in MSA, PSP, and controls in all regions. Evaluation of rADC values in characteristic lesions in MSA, PSP, and PD by placing ROIs using 3-T systems can provide useful additional information for differentiating these disorders. (orig.)

[Case report: kleptomania and other psychiatric symptoms after carbon monoxide intoxication].

Science.gov (United States)

Gürlek Yüksel, Ebru; Taşkin, E Oryal; Yilmaz Ovali, Gülgün; Karaçam, Melek; Esen Danaci, Ayşen

2007-01-01

Carbon monoxide (CO) intoxication is usually a serious condition, which can result in neurological disturbances or death. In some patients with CO intoxication, but not usually, a biphasic pattern can be seen. In this condition, after antitoxic treatment, patients may completely recover and after a short recovery period, neurological and/or psychiatric symptoms appear again. This condition is known as delayed encephalopathy and its occurrence rate is between 0.06% and 11.8%. Herein, we report a case with delayed encephalopathy after CO intoxication, which began with neurological symptoms and continued with obsessive-compulsive disorder, depression, kleptomania, and psychotic disorder. The 41-year-old female patient had no psychiatric or neurological symptoms or disorders prior to CO intoxication. Increased signal intensity changes in the basal region of the left temporal lobe (including the cortex and subcortical white matter), globus pallidus (bilateral), and cerebellar cortical and subcortical white matter (bilaterally symmetrical) was detected on axial T2-weighted magnetic resonance imaging (MRI). In addition, there were atrophic changes in both cerebellar hemispheres. To the best of our knowledge, this is the first case of kleptomania described after CO intoxication in the literature. We discuss the organic etiology of kleptomania and the other psychiatric symptoms of this patient in the light of recent research. We concluded that the kleptomania seen in this patient was related to concurrent lesions in the temporal lobe and globus pallidus; in other words, her kleptomania may have been related to dysfunction simultaneously seen in both the temporolimbic and frontal-subcortical circuits.

[18F]fallypride characterization of striatal and extrastriatal D2/3 receptors in Parkinson's disease.

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Stark, Adam J; Smith, Christopher T; Petersen, Kalen J; Trujillo, Paula; van Wouwe, Nelleke C; Donahue, Manus J; Kessler, Robert M; Deutch, Ariel Y; Zald, David H; Claassen, Daniel O

2018-01-01

Parkinson's disease (PD) is characterized by widespread degeneration of monoaminergic (especially dopaminergic) networks, manifesting with a number of both motor and non-motor symptoms. Regional alterations to dopamine D 2/3 receptors in PD patients are documented in striatal and some extrastriatal areas, and medications that target D 2/3 receptors can improve motor and non-motor symptoms. However, data regarding the combined pattern of D 2/3 receptor binding in both striatal and extrastriatal regions in PD are limited. We studied 35 PD patients off-medication and 31 age- and sex-matched healthy controls (HCs) using PET imaging with [ 18 F]fallypride, a high affinity D 2/3 receptor ligand, to measure striatal and extrastriatal D 2/3 nondisplaceable binding potential (BP ND ). PD patients completed PET imaging in the off medication state, and motor severity was concurrently assessed. Voxel-wise evaluation between groups revealed significant BP ND reductions in PD patients in striatal and several extrastriatal regions, including the locus coeruleus and mesotemporal cortex. A region-of-interest (ROI) based approach quantified differences in dopamine D 2/3 receptors, where reduced BP ND was noted in the globus pallidus, caudate, amygdala, hippocampus, ventral midbrain, and thalamus of PD patients relative to HC subjects. Motor severity positively correlated with D 2/3 receptor density in the putamen and globus pallidus. These findings support the hypothesis that abnormal D 2/3 expression occurs in regions related to both the motor and non-motor symptoms of PD, including areas richly invested with noradrenergic neurons.

Videofluoroscopy of the pharynx and esophagus in patients with globus pharyngis. Comparison with static radiography; Die radiologische Abklaerung des Globus pharyngis. Vergleich der diagnostischen Wertigkeit von konventionellem Roentgen mit der Videokinematographie

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Schober, E. [Abt. Roentgen fuer Konservative Faecher, Universitaetsklinik fuer Radiodiagnostik, Wien (Austria); Schima, W. [Abt. Roentgen fuer Konservative Faecher, Universitaetsklinik fuer Radiodiagnostik, Wien (Austria); Pokieser, P. [Abt. Roentgen fuer Chirurgische Faecher, Universitaetsklinik fuer Radiodiagnostik, Wien (Austria)

1995-10-01

The symptom is associated with a multitude of pharyngoesophageal abnormalities. Our study compares the diagnostic yield of videofluoroscopy to that of static radiography in patients suffering from globus pharnygis. A total of 150 consecutive patients complaining of a lump in the throat, but without evidence of dysphagia, were studied in a standardized fashion with both methods. Videofluoroscopy combined with static radiography revealed morphological or functional abnormalities in 75% of our patients. The combination of the two methods yielded significantly more abnormalities in the pharynx and esophagus than videofluoroscopy or static radiography alone. Esophageal motor disorders, pharyngoesophageal sphincter dysfunction and pharyngeal residue of contrast material proved to be the most common abnormalities. In conclusion, videofluoroscopy combined with static radiography is mandatory in the radiological assessment of patients suffering from the globus sensation. (orig.) [Deutsch] Unsere Studie vergleicht die diagnostische Wertigkeit des konventionellen Roentgens mit jener der Videokineamtographie von Pharynx und Oesophagus bei der Abklaerung des Globusgefuehls. Wir haben 150 konsekutive Patienten mit Globusgefuehl, jedoch ohne Dysphagie mit beiden Methoden nach einem standardisierten Protokoll untersucht. Mittels der Kombination von konventionellem Roentgen mit der Videokinematographie fanden sich bei 75% der Patienten pathologische Veraenderungen. Durch die Kombination beider Methoden konnten signifikant mehr morphologische und funktionelle Stoerungen des Pharynx sowie Oesophagus aufgezeigt werden, als mit der alleinigen konventionellen Technik oder der alleinigen Videokinematographie. Die haeufigsten pathologischen Veraenderungen in unserem Kollektiv waren Oesophagusmotilitaetsstoerungen, eine Dyskinesie des pharyngooesophagealen Sphinkters sowie eine abnorme pharyngeale Kontrastmittelretention. Unsere Ergebnisse belegen eindeutig, dass die radiologische

MRI of the brain in chronic carbon monoxide poisoning

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Uchino, A. (Dept. of Radiology, Kyushu Univ. Hospital, Fukuoka (Japan)); Hasuo, K. (Dept. of Radiology, Kyushu Univ. Hospital, Fukuoka (Japan)); Shida, K. (Dept. of Neurology, Omuta Rosai Hospital (Japan)); Matsumoto, S. (Dept. of Radiology, Kyushu Univ. Hospital, Fukuoka (Japan)); Yasumori, K. (Dept. of Radiology, Kyushu Univ. Hospital, Fukuoka (Japan)); Masuda, K. (Dept. of Radiology, Kyushu Univ. Hospital, Fukuoka (Japan))

1994-07-01

We examined 13 patients with CO poisoning by MRI; all of them had been in an explosion in a coal mine 25 years previously. Symmetrical globus pallidus lesions were observed in 12, as was degeneration of the white matter, with focal cortical atrophy. The temporal parietal and occipital lobes were usually affected, the parietooccipital region being the most frequently and extensively damaged. Of the 12 patients with white matter degeneration 7 had definitely asymmetrical cortical and subcortical lesions. There were 6 patients with dilated temporal horns, probably due to atrophy of the hippocampal gyri. (orig./MG)

Cerebral glucose metabolism in Parkinson's disease

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Martin, W R.W.; Beckman, J H; Calne, D B; Adam, M J; Harrop, R; Rogers, J G; Ruth, T J; Sayre, C I; Pate, B D [British Columbia Univ., Vancouver (Canada). TRIUMF Facility

1984-02-01

Local cerebral glucose utilization was measured in patients with predominantly unilateral Parkinson's disease using sup(18)F-2-fluoro-deoxyglucose and positron emission tomography. Preliminary results indicate the presence of asymmetric metabolic rates in the inferior basal ganglia. The structure comprising the largest portion of basal ganglia at this level is globus pallidus. These findings are consistent with metabolic studies on animals with unilateral nigrostriatal lesions in which pallidal hypermetabolism on the lesioned side has been demonstrated. Increased pallidal activity is likely secondary to a loss of inhibitory dopaminergic input to the striatum from substantia nigra.

Cerebral glucose metabolism in Parkinson's disease

International Nuclear Information System (INIS)

Martin, W.R.W.; Beckman, J.H.; Calne, D.B.; Adam, M.J.; Harrop, R.; Rogers, J.G.; Ruth, T.J.; Sayre, C.I.; Pate, B.D.

1984-01-01

Local cerebral glucose utilization was measured in patients with predominantly unilateral Parkinson's disease using sup(18)F-2-fluoro-deoxyglucose and positron emission tomography. Preliminary results indicate the presence of asymmetric metabolic rates in the inferior basal ganglia. The structure comprising the largest portion of basal ganglia at this level is globus pallidus. These findings are consistent with metabolic studies on animals with unilateral nigrostriatal lesions in which pallidal hypermetabolism on the lesioned side has been demonstrated. Increased pallidal activity is likely secondary to a loss of inhibitory dopaminergic input to the striatum from substantia nigra

MRI of the brain in chronic carbon monoxide poisoning

International Nuclear Information System (INIS)

Uchino, A.; Hasuo, K.; Shida, K.; Matsumoto, S.; Yasumori, K.; Masuda, K.

1994-01-01

We examined 13 patients with CO poisoning by MRI; all of them had been in an explosion in a coal mine 25 years previously. Symmetrical globus pallidus lesions were observed in 12, as was degeneration of the white matter, with focal cortical atrophy. The temporal parietal and occipital lobes were usually affected, the parietooccipital region being the most frequently and extensively damaged. Of the 12 patients with white matter degeneration 7 had definitely asymmetrical cortical and subcortical lesions. There were 6 patients with dilated temporal horns, probably due to atrophy of the hippocampal gyri. (orig./MG)

Lacunar infarct during pallidotomy: case report

International Nuclear Information System (INIS)

Christoforidis, G.A.; Spickler, E.M.; Papaioannou, G.; Junn, F.

2001-01-01

A symptomatic lacunar infarct is an unusual complication which may develop during stereotactically guided pallidotomy using radiofrequency thermoablation. We describe a 54-year-old man with Parkinson's disease involving predominantly the right side, progressively deteriorating under medical management. He underwent stereotactically guided radiofrequency thermoablation of the posteroventral globus pallidus interna. Despite intraoperative microelectrode recording and stimulation, the patient developed right facial weakness and pronator drift during the procedure. MRI showed a small lacunar infarct in the left internal capsule, in addition to the appropriately placed ablative lesion. We discuss the potential mechanisms for this type of injury. (orig.)

The development of the region of basal nuclei in fetus using MRI of high field

International Nuclear Information System (INIS)

Geng Hequn; Zhang Zhonghe; Liu Shuwei

2010-01-01

Objective: To study the developmental process of the region of basal nuclei of postmortem fetuses by 3.0 T and 7.0 T MRI. Methods: One hundred and thirty-one postmortem fetuses of 14 to 40 weeks of gestational age (GA) were scanned by 3.0 T MR, of which 11 fetuses of 14-27 weeks of GA were chosen and scanned by 7.0 T MR. The time when the structures in the region of basal nuclei could be detected and the changes of MR signal intensity were analyzed for MRI of different Tesla. Results: On 3.0 T MRI, the dorsal thalamus could be delineated as early as 14 weeks of GA. The germinal matrix, caudate nucleus, and putamen could be visualized as early as 15 weeks of GA. The globus pallidus could be described as early as 18 weeks of GA, and the internal capsule and external capsule could be shown as early as 20 weeks of GA. The signal of the caudate nucleus during 15-30 weeks of GA was relatively hypointense on T 1 WI and hyperintense on T 2 WI, but during 31-40 weeks of GA, it was relatively hyperintense on T 1 WI and hypointense on T 2 WI. The putamen had a relatively high signal intensity on T 1 WI and low signal intensity on T 2 WI during 15-17 weeks of GA, and it appeared patchy during 18-25 weeks of GA, then it had a relatively low signal intensity on T 1 WI and high signal intensity on T 2 WI during 26-30 weeks of GA, and during 31-40 weeks of GA, its signal intensity was relatively high on T 1 WI and low on T 2 WI. The globus pallidus had a relatively high signal intensity on T 1 WI and low signal intensity on T 2 WI during 20- 40 weeks of GA. Compared to the 3.0 T MRI, the T 2 images of 7.0 T MRI were more clear, and most structures in the region of basal nuclei could be clearly displayed as early as 16 weeks of GA, such as the germinal matrix, caudate nucleus, dorsal thalamus, putamen, globus pallidus, internal capsule, and extemal capsule. The claustrum could be delineated as early as 18 weeks of GA on 7.0 T MRI. Conclusions: 3.0 T MRI could show the development

Anti-HIV double variable domain immunoglobulins binding both gp41 and gp120 for targeted delivery of immunoconjugates.

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Ryan B Craig

Full Text Available BACKGROUND: Anti-HIV immunoconjugates targeted to the HIV envelope protein may be used to eradicate the latent reservoir of HIV infection using activate-and-purge protocols. Previous studies have identified the two target epitopes most effective for the delivery of cytotoxic immunoconjugates the CD4-binding site of gp120, and the hairpin loop of gp41. Here we construct and test tetravalent double variable domain immunoglobulin molecules (DVD-Igs that bind to both epitopes. METHODS: Synthetic genes that encode DVD-Igs utilizing V-domains derived from human anti-gp120 and anti-gp41 Abs were designed and expressed in 293F cells. A series of constructs tested different inter-V-linker domains and orientations of the two V domains. Antibodies were tested for binding to recombinant Ag and native Env expressed on infected cells, for neutralization of infectious HIV, and for their ability to deliver cytotoxic immunoconjugates to infected cells. FINDINGS: The outer V-domain was the major determinant of binding and functional activity of the DVD-Ig. Function of the inner V-domain and bifunctional binding required at least 15 AA in the inter-V-domain linker. A molecular model showing the spatial orientation of the two epitopes is consistent with this observation. Linkers that incorporated helical domains (A[EAAAK](nA resulted in more effective DVD-Igs than those based solely on flexible domains ([GGGGS](n. In general, the DVD-Igs outperformed the less effective parental antibody and equaled the activity of the more effective. The ability of the DVD-Igs to deliver cytotoxic immunoconjugates in the absence of soluble CD4 was improved over that of either parent. CONCLUSIONS: DVD-Igs can be designed that bind to both gp120 and gp41 on the HIV envelope. DVD-Igs are effective in delivering cytotoxic immunoconjugates. The optimal design of these DVD-Igs, in which both domains are fully functional, has not yet been achieved.

Diet, digestion, and food preferences of Galapagos land iguanas. [Conolophus pallidus

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Christian, K.A.; Tracy, C.R.; Porter, W.P.

1984-01-01

The choice of food types and the length of time food passed through the gastrointestinal tract were determined in free-ranging Conolophus pallidus on Isla Santa Fe, Galapogos throughout the year. Natural foods were analyzed for energy, percent cellulose, percent nitrogen, and calcium as indices of the quality of food. Foods of highest quality were found to be among the preferred foods, but not all preferred foods were of high quality with respect to the nutrients measured. Passage time of food through the gastrointestinal tract, digestive efficiency, and digestion of cellulose were determined on captive Conolophus subcristatus. Ability to digest cellulose and digestive efficiency varied among five caged iguanas. Intra- and interspecific variabilities in digestive capacities result from variability in ecological factors, and interspecific variability among iguanines probably reflects differences in colic anatomy and the ability to absorb nutrients from the hindgut. 23 references, 4 tables.

Educational CPD: how UK GP trainers develop themselves as teachers.

Science.gov (United States)

Waters, Mark; Wall, David

2007-09-01

There is little in the literature giving the perspective of UK General Practice (GP) trainers on their development as teachers. What motivates GP trainers develop themselves as teachers? What obstacles to their professional development do GP trainers perceive? A questionnaire to all GP trainers in the West Midlands Deanery in 2004. 360/444 (81%) questionnaires were returned. 56.6% of GP trainers had another educational role in addition to training GP Registrars in the practice. 15.8% of trainers possessed an educational qualification. 13 had completed a Certificate in Medical Education and 28 were engaged in study towards that qualification. Trainers wanted more time to spend on their development as teachers than they presently have, and would then be interested in a wider variety of learning methods. However, 56.6% of trainers would still not choose to undertake a university-accredited course. Female GP trainers perceived more difficulty in obtaining protected time for their development as teachers (Educational CPD) (p = 0.021), were significantly less sure of their partners' support for this development (p = 0.033), and were more likely to agree with trainers undertaking a Certificate in Medical Education (p = 0.003). Having an additional educational role did not affect trainers' ability to take protected time, but significantly increased the amount of time aspired to (p = 0.005). Nothing made more difference to trainers' perception of their ability to undertake Educational CPD than did the perceived attitude of their partners. Educational CPD was very important to GP trainers, but getting protected time was difficult. Consideration of the needs and opinions of partners was a very strong barrier to trainers taking sufficient protected time. Given more available time, GP trainers would be more likely to consider gaining academic qualifications in education. However, this was not be something that all trainers wanted.

Draft Genome Sequence of Aeribacillus pallidus Strain 8m3, a Thermophilic Hydrocarbon-Oxidizing Bacterium Isolated from the Dagang Oil Field (China)

OpenAIRE

Poltaraus, Andrey B.; Sokolova, Diyana S.; Grouzdev, Denis S.; Ivanov, Timophey M.; Malakho, Sophia G.; Korshunova, Alena V.; Rozanov, Aleksey S.; Tourova, Tatiyana P.; Nazina, Tamara N.

2016-01-01

The draft genome sequence of Aeribacillus pallidus strain 8m3, a thermophilic aerobic oil-oxidizing bacterium isolated from production water from the Dagang high-temperature oil field, China, is presented here. The genome is annotated to provide insights into the genomic and phenotypic diversity of the genus Aeribacillus.

Prediction of the Secondary Structure of HIV-1 gp120

DEFF Research Database (Denmark)

Hansen, Jan; Lund, Ole; Nielsen, Jens O.

1996-01-01

Fourier transform infrared spectroscopy. The predicted secondary structure of gp120 compared well with data from NMR analysis of synthetic peptides from the V3 loop and the C4 region. As a first step towards modeling the tertiary structure of gp120, the predicted secondary structure may guide the design......The secondary structure of HIV-1 gp120 was predicted using multiple alignment and a combination of two independent methods based on neural network and nearest-neighbor algorithms. The methods agreed on the secondary structure for 80% of the residues in BH10 gp120. Six helices were predicted in HIV...

Exploring resilience in rural GP registrars--implications for training.

Science.gov (United States)

Walters, Lucie; Laurence, Caroline O; Dollard, Joanne; Elliott, Taryn; Eley, Diann S

2015-07-02

Resilience can be defined as the ability to rebound from adversity and overcome difficult circumstances. General Practice (GP) registrars face many challenges in transitioning into general practice, and additional stressors and pressures apply for those choosing a career in rural practice. At this time of international rural generalist medical workforce shortages, it is important to focus on the needs of rural GP registrars and how to support them to become resilient health care providers. This study sought to explore GP registrars' perceptions of their resilience and strategies they used to maintain resilience in rural general practice. In this qualitative interpretive research, semi-structured interviews were recorded, transcribed and analysed using an inductive approach. Initial coding resulted in a coding framework which was refined using constant comparison and negative case analysis. Authors developed consensus around the final conceptual model. Eighteen GP registrars from: Australian College of Rural and Remote Medicine Independent Pathway, and three GP regional training programs with rural training posts. Six main themes emerged from the data. Firstly, rural GP registrars described four dichotomous tensions they faced: clinical caution versus clinical courage; flexibility versus persistence; reflective practice versus task-focused practice; and personal connections versus professional commitment. Further themes included: personal skills for balance which facilitated resilience including optimistic attitude, self-reflection and metacognition; and finally GP registrars recognised the role of their supervisors in supporting and stretching them to enhance their clinical resilience. Resilience is maintained as on a wobble board by balancing professional tensions within acceptable limits. These limits are unique to each individual, and may be expanded through personal growth and professional development as part of rural general practice training.

A multi-system approach assessing the interaction of anticonvulsants with P-gp.

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David Dickens

Full Text Available 30% of epilepsy patients receiving antiepileptic drugs (AEDs are not fully controlled by therapy. The drug transporter hypothesis for refractory epilepsy proposes that P-gp is over expressed at the epileptic focus with a role of P-gp in extruding AEDs from the brain. However, there is controversy regarding whether all AEDs are substrates for this transporter. Our aim was to investigate transport of phenytoin, lamotrigine and carbamazepine by using seven in-vitro transport models. Uptake assays in CEM/VBL cell lines, oocytes expressing human P-gp and an immortalised human brain endothelial cell line (hCMEC/D3 were carried out. Concentration equilibrium transport assays were performed in Caco-2, MDCKII ±P-gp and LLC-PK1±P-gp in the absence or presence of tariquidar, an inhibitor of P-gp. Finally, primary porcine brain endothelial cells were used to determine the apparent permeability (Papp of the three AEDs in the absence or presence of P-gp inhibitors. We detected weak transport of phenytoin in two of the transport systems (MDCK and LLC-PK1 cells transfected with human P-gp but not in the remaining five. No P-gp interaction was observed for lamotrigine or carbamazepine in any of the seven validated in-vitro transport models. Neither lamotrigine nor carbamazepine was a substrate for P-gp in any of the model systems tested. Our data suggest that P-gp is unlikely to contribute to the pathogenesis of refractory epilepsy through transport of carbamazepine or lamotrigine.

Screening and Identification of ssDNA Aptamer for Human GP73

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Jingchun Du

2015-01-01

Full Text Available As one tumor marker of HCC, Golgi Protein 73 (GP73 is given more promise in the early diagnosis of HCC, and aptamers have been developed to compete with antibodies as biorecognition probes in different detection system. In this study, we utilized GP73 to screen specific ssDNA aptamers by SELEX technique. First, GP73 proteins were expressed and purified by prokaryotic expression system and Nickle ion affinity chromatography, respectively. At the same time, the immunogenicity of purified GP73 was confirmed by Western blotting. The enriched ssDNA library with high binding capacity for GP73 was obtained after ten rounds of SELEX. Then, thirty ssDNA aptamers were sequenced, in which two ssDNA aptamers with identical DNA sequence were confirmed, based on the alignment results, and designated as A10-2. Furthermore, the specific antibody could block the binding of A10-2 to GP73, and the specific binding of A10-2 to GP73 was also supported by the observation that several tumor cell lines exhibited variable expression level of GP73. Significantly, the identified aptamer A10-2 could distinguish normal and cancerous liver tissues. So, our results indicate that the aptamer A10-2 might be developed into one molecular probe to detect HCC from normal liver specimens.

A multilevel approach to examining cephalopod growth using Octopus pallidus as a model.

Science.gov (United States)

Semmens, Jayson; Doubleday, Zoë; Hoyle, Kate; Pecl, Gretta

2011-08-15

Many aspects of octopus growth dynamics are poorly understood, particularly in relation to sub-adult or adult growth, muscle fibre dynamics and repro-somatic investment. The growth of 5 month old Octopus pallidus cultured in the laboratory was investigated under three temperature regimes over a 12 week period: seasonally increasing temperatures (14-18°C); seasonally decreasing temperatures (18-14°C); and a constant temperature mid-way between seasonal peaks (16°C). Differences in somatic growth at the whole-animal level, muscle tissue structure and rate of gonad development were investigated. Continuous exponential growth was observed, both at a group and at an individual level, and there was no detectable effect of temperature on whole-animal growth rate. Juvenile growth rate (from 1 to 156 days) was also monitored prior to the controlled experiment; exponential growth was observed, but at a significantly faster rate than in the older experimental animals, suggesting that O. pallidus exhibit a double-exponential two-phase growth pattern. There was considerable variability in size-at-age even between individuals growing under identical thermal regimes. Animals exposed to seasonally decreasing temperatures exhibited a higher rate of gonad development compared with animals exposed to increasing temperatures; however, this did not coincide with a detectable decline in somatic growth rate or mantle condition. The ongoing production of new mitochondria-poor and mitochondria-rich muscle fibres (hyperplasia) was observed, indicated by a decreased or stable mean muscle fibre diameter concurrent with an increase in whole-body size. Animals from both seasonal temperature regimes demonstrated higher rates of new mitochondria-rich fibre generation relative to those from the constant temperature regime, but this difference was not reflected in a difference in growth rate at the whole-body level. This is the first study to record ongoing hyperplasia in the muscle tissue of an

External pallidal stimulation improves parkinsonian motor signs and modulates neuronal activity throughout the basal ganglia thalamic network.

Science.gov (United States)

Vitek, Jerrold L; Zhang, Jianyu; Hashimoto, Takao; Russo, Gary S; Baker, Kenneth B

2012-01-01

Deep brain stimulation (DBS) of the internal segment of the globus pallidus (GPi) and the subthalamic nucleus (STN) are effective for the treatment of advanced Parkinson's disease (PD). We have shown previously that DBS of the external segment of the globus pallidus (GPe) is associated with improvements in parkinsonian motor signs; however, the mechanism of this effect is not known. In this study, we extend our findings on the effect of STN and GPi DBS on neuronal activity in the basal ganglia thalamic network to include GPe DBS using the 1-methyl-4-phenyl-1.2.3.6-tetrahydropyridine (MPTP) monkey model. Stimulation parameters that improved bradykinesia were associated with changes in the pattern and mean discharge rate of neuronal activity in the GPi, STN, and the pallidal [ventralis lateralis pars oralis (VLo) and ventralis anterior (VA)] and cerebellar [ventralis lateralis posterior pars oralis (VPLo)] receiving areas of the motor thalamus. Population post-stimulation time histograms revealed a complex pattern of stimulation-related inhibition and excitation for the GPi and VA/VLo, with a more consistent pattern of inhibition in STN and excitation in VPLo. Mean discharge rate was reduced in the GPi and STN and increased in the VPLo. Effective GPe DBS also reduced bursting in the STN and GPi. These data support the hypothesis that therapeutic DBS activates output from the stimulated structure and changes the temporal pattern of neuronal activity throughout the basal ganglia thalamic network and provide further support for GPe as a potential therapeutic target for DBS in the treatment of PD. Copyright © 2011 Elsevier Inc. All rights reserved.

Harsh corporal punishment is associated with increased T2 relaxation time in dopamine-rich regions.

Science.gov (United States)

Sheu, Yi-Shin; Polcari, Ann; Anderson, Carl M; Teicher, Martin H

2010-11-01

Harsh corporal punishment (HCP) was defined as frequent parental administration of corporal punishment (CP) for discipline, with occasional use of objects such as straps, or paddles. CP is linked to increased risk for depression and substance abuse. We examine whether long-term exposure to HCP acts as sub-traumatic stressor that contributes to brain alterations, particularly in dopaminergic pathways, which may mediate their increased vulnerability to drug and alcohol abuse. Nineteen young adults who experienced early HCP but no other forms of maltreatment and twenty-three comparable controls were studied. T2 relaxation time (T2-RT) measurements were performed with an echo planar imaging TE stepping technique and T2 maps were calculated and analyzed voxel-by-voxel to locate regional T2-RT differences between groups. Previous studies indicated that T2-RT provides an indirect index of resting cerebral blood volume. Region of interest (ROI) analyses were also conducted in caudate, putamen, nucleus accumbens, anterior cingulate cortex, dorsolateral prefrontal cortex, thalamus, globus pallidus and cerebellar hemispheres. Voxel-based relaxometry showed that HCP was associated with increased T2-RT in right caudate and putamen. ROI analyses also revealed increased T2-RT in dorsolateral prefrontal cortex, substantia nigra, thalamus and accumbens but not globus pallidus or cerebellum. There were significant associations between T2-RT measures in dopamine target regions and use of drugs and alcohol, and memory performance. Alteration in the paramagnetic or hemodynamic properties of dopaminergic cell body and projection regions were observed in subjects with HCP, and these findings may relate to their increased risk for drug and alcohol abuse. Copyright 2010 Elsevier Inc. All rights reserved.

Inter regional correlations of glucose metabolism between the basal ganglia and different cortical areas: an ultra-high resolution PET/MRI fusion study using {sup 18}F-FDG

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Kim, J.H. [Research Institute for Advanced Industrial Technology, Korea University, Sejong (Korea, Republic of); Son, Y.D.; Kim, H.K.; Oh, C.H., E-mail: ohch@korea.ac.kr [College of Health Science, Gachon University, Incheon, (Korea, Republic of); Kim, J.M. [College of Science and Technology, Korea University, Sejong (Korea, Republic of); Kim, Y.B. [Gachon University School of Medicine, Incheon (Korea, Republic of); Lee, C. [Bioimaging Research Team, Korea Basic Science Institute, Cheongju (Korea, Republic of)

2018-02-01

Basal ganglia have complex functional connections with the cerebral cortex and are involved in motor control, executive functions of the forebrain, such as the planning of movement, and cognitive behaviors based on their connections. The aim of this study was to provide detailed functional correlation patterns between the basal ganglia and cerebral cortex by conducting an inter regional correlation analysis of the {sup 18}F-fluorodeoxyglucose ({sup 18}F-FDG) positron emission tomography (PET) data based on precise structural information. Fifteen participants were scanned with 7-Tesla magnetic resonance imaging (MRI) and high resolution research tomography (HRRT)-PET fusion system using {sup 18}F-FDG. For detailed inter regional correlation analysis, 24 subregions of the basal ganglia including pre-commissural dorsal caudate, post-commissural caudate, pre-commissural dorsal putamen, post-commissural putamen, internal globus pallidus, and external globus pallidus and 80 cerebral regions were selected as regions of interest on the MRI image and their glucose metabolism were calculated from the PET images. Pearson's product-moment correlation analysis was conducted for the inter regional correlation analysis of the basal ganglia. Functional correlation patterns between the basal ganglia and cerebral cortex were not only consistent with the findings of previous studies, but also showed new functional correlation between the dorsal striatum (i.e., caudate nucleus and putamen) and insula. In this study, we established the detailed basal ganglia subregional functional correlation patterns using {sup 18}F-FDG PET/MRI fusion imaging. Our methods and results could potentially be an important resource for investigating basal ganglia dysfunction as well as for conducting functional studies in the context of movement and psychiatric disorders. (author)

Abnormal brain activation and connectivity to standardized disorder-related visual scenes in social anxiety disorder.

Science.gov (United States)

Heitmann, Carina Yvonne; Feldker, Katharina; Neumeister, Paula; Zepp, Britta Maria; Peterburs, Jutta; Zwitserlood, Pienie; Straube, Thomas

2016-04-01

Our understanding of altered emotional processing in social anxiety disorder (SAD) is hampered by a heterogeneity of findings, which is probably due to the vastly different methods and materials used so far. This is why the present functional magnetic resonance imaging (fMRI) study investigated immediate disorder-related threat processing in 30 SAD patients and 30 healthy controls (HC) with a novel, standardized set of highly ecologically valid, disorder-related complex visual scenes. SAD patients rated disorder-related as compared with neutral scenes as more unpleasant, arousing and anxiety-inducing than HC. On the neural level, disorder-related as compared with neutral scenes evoked differential responses in SAD patients in a widespread emotion processing network including (para-)limbic structures (e.g. amygdala, insula, thalamus, globus pallidus) and cortical regions (e.g. dorsomedial prefrontal cortex (dmPFC), posterior cingulate cortex (PCC), and precuneus). Functional connectivity analysis yielded an altered interplay between PCC/precuneus and paralimbic (insula) as well as cortical regions (dmPFC, precuneus) in SAD patients, which emphasizes a central role for PCC/precuneus in disorder-related scene processing. Hyperconnectivity of globus pallidus with amygdala, anterior cingulate cortex (ACC) and medial prefrontal cortex (mPFC) additionally underlines the relevance of this region in socially anxious threat processing. Our findings stress the importance of specific disorder-related stimuli for the investigation of altered emotion processing in SAD. Disorder-related threat processing in SAD reveals anomalies at multiple stages of emotion processing which may be linked to increased anxiety and to dysfunctionally elevated levels of self-referential processing reported in previous studies. © 2016 Wiley Periodicals, Inc.

MR contrast of ferritin and hemosiderin in the brain: comparison among gradient-echo, conventional spin-echo and fast spin-echo sequences

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Haque, Tabassum Laz; Miki, Yukio; Kanagaki, Mitsunori; Takahashi, Takahiro; Yamamoto, Akira; Konishi, Junya; Nozaki, Kazuhiko; Hashimoto, Nobuo; Konishi, Junji

2003-12-01

Objective: To compare the magnetic resonance image contrasts due to ferritin and hemosiderin in the brain tissue among different pulse sequences. Materials and methods: Fourteen patients with cavernous hemangioma in the brain prospectively underwent MR imaging with T2*-weighted gradient-echo (GRE), T2-weighted conventional spin-echo (SE) and fast spin-echo (FSE) sequences. The relative contrast ratios (CRs) of the hypointense part of cavernous hemangioma, globus pallidus and putamen to the deep frontal white matter were measured on each pulse sequence and statistically analyzed using analysis of variance followed by paired t-test. Results: In the hypointense part of cavernous hemangioma, relative CRs were significantly lower on T2*-weighted GRE than on T2-weighted SE images (P=0.0001), and on T2-weighted SE than on T2-weighted FSE images (P=0.0001). In the globus pallidus, relative CRs were significantly lower on T2-weighted SE than on T2*-weighted GRE images (P=0.002), and on T2*-weighted GRE than on T2-weighted FSE images (P=0.0002). In the putamen, relative CRs were significantly lower on T2-weighted SE than on T2*-weighted GRE images (P=0.001), and there was no significant difference between CRs on T2-weighted FSE and T2*-weighted GRE images (P=0.90). Conclusion: Hemosiderin showed best image contrast on T2*-weighted GRE images but ferritin showed more prominent image contrast on T2-weighted SE than on T2*-weighted GRE images, which may help to determine an appropriate pulse sequence in neurological diseases associated with excessive ferritin accumulation.

MR contrast of ferritin and hemosiderin in the brain: comparison among gradient-echo, conventional spin-echo and fast spin-echo sequences

International Nuclear Information System (INIS)

Haque, Tabassum Laz; Miki, Yukio; Kanagaki, Mitsunori; Takahashi, Takahiro; Yamamoto, Akira; Konishi, Junya; Nozaki, Kazuhiko; Hashimoto, Nobuo; Konishi, Junji

2003-01-01

Objective: To compare the magnetic resonance image contrasts due to ferritin and hemosiderin in the brain tissue among different pulse sequences. Materials and methods: Fourteen patients with cavernous hemangioma in the brain prospectively underwent MR imaging with T2*-weighted gradient-echo (GRE), T2-weighted conventional spin-echo (SE) and fast spin-echo (FSE) sequences. The relative contrast ratios (CRs) of the hypointense part of cavernous hemangioma, globus pallidus and putamen to the deep frontal white matter were measured on each pulse sequence and statistically analyzed using analysis of variance followed by paired t-test. Results: In the hypointense part of cavernous hemangioma, relative CRs were significantly lower on T2*-weighted GRE than on T2-weighted SE images (P=0.0001), and on T2-weighted SE than on T2-weighted FSE images (P=0.0001). In the globus pallidus, relative CRs were significantly lower on T2-weighted SE than on T2*-weighted GRE images (P=0.002), and on T2*-weighted GRE than on T2-weighted FSE images (P=0.0002). In the putamen, relative CRs were significantly lower on T2-weighted SE than on T2*-weighted GRE images (P=0.001), and there was no significant difference between CRs on T2-weighted FSE and T2*-weighted GRE images (P=0.90). Conclusion: Hemosiderin showed best image contrast on T2*-weighted GRE images but ferritin showed more prominent image contrast on T2-weighted SE than on T2*-weighted GRE images, which may help to determine an appropriate pulse sequence in neurological diseases associated with excessive ferritin accumulation

Inter regional correlations of glucose metabolism between the basal ganglia and different cortical areas: an ultra-high resolution PET/MRI fusion study using 18F-FDG

International Nuclear Information System (INIS)

Kim, J.H.; Son, Y.D.; Kim, H.K.; Oh, C.H.; Kim, J.M.; Kim, Y.B.; Lee, C.

2018-01-01

Basal ganglia have complex functional connections with the cerebral cortex and are involved in motor control, executive functions of the forebrain, such as the planning of movement, and cognitive behaviors based on their connections. The aim of this study was to provide detailed functional correlation patterns between the basal ganglia and cerebral cortex by conducting an inter regional correlation analysis of the 18 F-fluorodeoxyglucose ( 18 F-FDG) positron emission tomography (PET) data based on precise structural information. Fifteen participants were scanned with 7-Tesla magnetic resonance imaging (MRI) and high resolution research tomography (HRRT)-PET fusion system using 18 F-FDG. For detailed inter regional correlation analysis, 24 subregions of the basal ganglia including pre-commissural dorsal caudate, post-commissural caudate, pre-commissural dorsal putamen, post-commissural putamen, internal globus pallidus, and external globus pallidus and 80 cerebral regions were selected as regions of interest on the MRI image and their glucose metabolism were calculated from the PET images. Pearson's product-moment correlation analysis was conducted for the inter regional correlation analysis of the basal ganglia. Functional correlation patterns between the basal ganglia and cerebral cortex were not only consistent with the findings of previous studies, but also showed new functional correlation between the dorsal striatum (i.e., caudate nucleus and putamen) and insula. In this study, we established the detailed basal ganglia subregional functional correlation patterns using 18 F-FDG PET/MRI fusion imaging. Our methods and results could potentially be an important resource for investigating basal ganglia dysfunction as well as for conducting functional studies in the context of movement and psychiatric disorders. (author)

Multi-modal and targeted imaging improves automated mid-brain segmentation

Science.gov (United States)

Plassard, Andrew J.; D'Haese, Pierre F.; Pallavaram, Srivatsan; Newton, Allen T.; Claassen, Daniel O.; Dawant, Benoit M.; Landman, Bennett A.

2017-02-01

The basal ganglia and limbic system, particularly the thalamus, putamen, internal and external globus pallidus, substantia nigra, and sub-thalamic nucleus, comprise a clinically relevant signal network for Parkinson's disease. In order to manually trace these structures, a combination of high-resolution and specialized sequences at 7T are used, but it is not feasible to scan clinical patients in those scanners. Targeted imaging sequences at 3T such as F-GATIR, and other optimized inversion recovery sequences, have been presented which enhance contrast in a select group of these structures. In this work, we show that a series of atlases generated at 7T can be used to accurately segment these structures at 3T using a combination of standard and optimized imaging sequences, though no one approach provided the best result across all structures. In the thalamus and putamen, a median Dice coefficient over 0.88 and a mean surface distance less than 1.0mm was achieved using a combination of T1 and an optimized inversion recovery imaging sequences. In the internal and external globus pallidus a Dice over 0.75 and a mean surface distance less than 1.2mm was achieved using a combination of T1 and FGATIR imaging sequences. In the substantia nigra and sub-thalamic nucleus a Dice coefficient of over 0.6 and a mean surface distance of less than 1.0mm was achieved using the optimized inversion recovery imaging sequence. On average, using T1 and optimized inversion recovery together produced significantly improved segmentation results than any individual modality (p<0.05 wilcox sign-rank test).

Draft Genome Sequence of Aeribacillus pallidus Strain 8m3, a Thermophilic Hydrocarbon-Oxidizing Bacterium Isolated from the Dagang Oil Field (China).

Science.gov (United States)

Poltaraus, Andrey B; Sokolova, Diyana S; Grouzdev, Denis S; Ivanov, Timophey M; Malakho, Sophia G; Korshunova, Alena V; Rozanov, Aleksey S; Tourova, Tatiyana P; Nazina, Tamara N

2016-06-09

The draft genome sequence of Aeribacillus pallidus strain 8m3, a thermophilic aerobic oil-oxidizing bacterium isolated from production water from the Dagang high-temperature oil field, China, is presented here. The genome is annotated to provide insights into the genomic and phenotypic diversity of the genus Aeribacillus. Copyright © 2016 Poltaraus et al.

Innate immunity glycoprotein gp-340 variants may modulate human susceptibility to dental caries

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Johansson Ingegerd

2007-06-01

Full Text Available Abstract Background Bacterial adhesion is an important determinant of colonization and infection, including dental caries. The salivary scavenger receptor cysteine-rich glycoprotein gp-340, which mediates adhesion of Streptococcus mutans (implicated in caries, harbours three major size variants, designated gp-340 I to III, each specific to an individual saliva. Here we have examined the association of the gp-340 I to III polymorphisms with caries experience and adhesion of S. mutans. Methods A case-referent study was performed in 12-year-old Swedish children with high (n = 19 or low (n = 19 caries experiences. We measured the gp-340 I to III saliva phenotypes and correlated those with multiple outcome measures for caries experience and saliva adhesion of S. mutans using the partial least squares (PLS multivariate projection technique. In addition, we used traditional statistics and 2-year caries increment to verify the established PLS associations, and bacterial adhesion to purified gp-340 I to III proteins to support possible mechanisms. Results All except one subject were typed as gp-340 I to III (10, 23 and 4, respectively. The gp-340 I phenotype correlated positively with caries experience (VIP = 1.37 and saliva adhesion of S. mutans Ingbritt (VIP = 1.47. The gp-340 II and III phenotypes tended to behave in the opposite way. Moreover, the gp-340 I phenotype tended to show an increased 2-year caries increment compared to phenotypes II/III. Purified gp-340 I protein mediated markedly higher adhesion of S. mutans strains Ingbritt and NG8 and Lactococcus lactis expressing AgI/II adhesins (SpaP or PAc compared to gp-340 II and III proteins. In addition, the gp-340 I protein appeared over represented in subjects positive for Db, an allelic acidic PRP variant associated with caries, and subjects positive for both gp-340 I and Db tended to experience more caries than those negative for both proteins. Conclusion Gp-340 I behaves as a caries

Massive calcification in basal ganglia, thalamus and cerebellum caused by postoperative hypoparathyroidism

International Nuclear Information System (INIS)

Toneva, T.; Mlachkova, D.; Kaitazki, L.; Boneva, J.; Yordanova, S.

2015-01-01

The depicted case is of a 65 year old woman, who was admitted to hospital with complaints of excess sweating, dizziness and loss of consciousness. Symptomatic epilepsy was established after examination from a neurologist. A CT scan showed hyperdense symmetrical striation of the hemisphere of the small brain (parasagittal); symmetrical double-sided calcifications in the caudate nucleus, globus pallidus, thalamus and medial to the capsula interna; snake-like calcifications of the sulcus (occipital, parasagittai). Paraclinical tests have found hypocalcemia and hypoparathyroidism. Past illnesses: resection of the thyroid due to a nodose struma 20 years before. Key words: Calcifications in Basal Ganglia. Calcifications in the Cerebrum. Hypoparathyroidism

[Cerebral MRT in neurofibromatosis: gliosis versus neoplasia?].

Science.gov (United States)

Mautner, V F; Pressler, M; Fünsterer, C; Schneider, E

1989-08-01

15 patients aged 1-39 years with documented neurofibromatosis had MR examinations of the cerebrum within the scope of a basic diagnosis and therapy programme. Clinical examination did not lead to pathologic findings for 7 of the patients; 3 patients suffered from general developmental disabilities. A neurologico-psychiatric examination showed pathological findings in 5 patients. Signal-intense foci in proton density and T2-weighted MR images were found in the globus pallidus, thalamus, hippocampus, cerebellum and midbrain. In 2 patients, these foci could be found as well in T1-weighted images. Differentiation between gliosis areas and low grade astrocytomas was not possible in MR.

Hallervorden Spatz syndrome: magnetic resonance findings. Case report; Sindrome de Hallervorden Spatz: achados na ressonancia magnetica. Relato de caso

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Farage, Luciano; Castro, Mario Augusto Padula; Macedo, Tulio Augusto Alves [Universidade Federal de Uberlandia, MG (Brazil). Hospital de Clinicas. Setor de Radiologia; Assis, Marcelo Cardoso de [Universidade Federal de Uberlandia, MG (Brazil). Faculdade de Medicina. Dept. de Cirurgia; Souza, Lincoln Pereira de; Freitas, Luiz Oliveira de [Universidade Federal de Uberlandia, MG (Brazil). Dept. de Clinica Medica

2004-09-01

Hallervorden-Spatz syndrome is a neuro degenerative disease, autosomic recessive with two clinical features: early and late onset. Psychiatric, pyramidal and extrapyramidal signs are present in the late subtype. We report the case of a 41-old woman with extrapyramidal signs. Magnetic resonance imaging (MRI) showed the eye-of-the-tiger sign in the medial globus pallidus. This is due to a gliosis (increased signal) and accumulation of surrounding iron (decreased signal intensity) in long T R sequences. There is a strong relationship between MRI findings and the gene mutation responsible for this disease. It makes the MRI sensible for diagnosing this syndrome. (author)

[Right extremities pain caused by a malacia lesion in the left putamen:a resting functional magnetic resonance imaging of the marginal division of the human brain].

Science.gov (United States)

Chen, Zhi-Ye; Ma, Lin

2014-04-01

To explore the role of marginal division of the human brain in the pain modulation. Resting functional magnetic resonance imaging was applied in a patient with right extremities pain caused by a malacia lesion in the left putamen and in 8 healthy volunteers. Marginal division was defined using manual drawing on structure images, and was applied to the computation of fuctional connectivity maps. The functional connectivities in the left marginal division showed an evident decrease in the patient when compared with healthy controls. These connectivities were mainly located in the bilateral head of caudate nucleus, putamen, and left globus pallidus. The marginal division may be involved in the pain modulation.

Fast micrographia: An unusual but distinctive sign

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Umaiorubahan Meenakshisundaram

2013-01-01

Full Text Available Fast micrographia is a rare clinical sign, which is reported in patients with pallidal pathology. A 68-year-old male presented with hypophonia and short shuffling gait with decreased arm swing. About 3 weeks before, he had an acute myocardial infarction and a period of hemodynamic and respiratory distress during which he required mechanical ventilatory support. He was found to have a fast handwriting with micrographia from the outset. His rapid alternating hand and finger movements were normal. Magnetic resonance imaging (MRI of the brain showed features of hypoxic ischemic encephalopathy including hyperintensities on T1 and T2 weighted images in the globus pallidus, and putamen bilaterally.

Hallervorden Spatz syndrome: magnetic resonance findings. Case report

International Nuclear Information System (INIS)

Farage, Luciano; Castro, Mario Augusto Padula; Macedo, Tulio Augusto Alves; Assis, Marcelo Cardoso de; Souza, Lincoln Pereira de; Freitas, Luiz Oliveira de

2004-01-01

Hallervorden-Spatz syndrome is a neuro degenerative disease, autosomic recessive with two clinical features: early and late onset. Psychiatric, pyramidal and extrapyramidal signs are present in the late subtype. We report the case of a 41-old woman with extrapyramidal signs. Magnetic resonance imaging (MRI) showed the eye-of-the-tiger sign in the medial globus pallidus. This is due to a gliosis (increased signal) and accumulation of surrounding iron (decreased signal intensity) in long T R sequences. There is a strong relationship between MRI findings and the gene mutation responsible for this disease. It makes the MRI sensible for diagnosing this syndrome. (author)

Comprehensive functional analysis of N-linked glycans on Ebola virus GP1.

Science.gov (United States)

Lennemann, Nicholas J; Rhein, Bethany A; Ndungo, Esther; Chandran, Kartik; Qiu, Xiangguo; Maury, Wendy

2014-01-28

Ebola virus (EBOV) entry requires the virion surface-associated glycoprotein (GP) that is composed of a trimer of heterodimers (GP1/GP2). The GP1 subunit contains two heavily glycosylated domains, the glycan cap and the mucin-like domain (MLD). The glycan cap contains only N-linked glycans, whereas the MLD contains both N- and O-linked glycans. Site-directed mutagenesis was performed on EBOV GP1 to systematically disrupt N-linked glycan sites to gain an understanding of their role in GP structure and function. All 15 N-glycosylation sites of EBOV GP1 could be removed without compromising the expression of GP. The loss of these 15 glycosylation sites significantly enhanced pseudovirion transduction in Vero cells, which correlated with an increase in protease sensitivity. Interestingly, exposing the receptor-binding domain (RBD) by removing the glycan shield did not allow interaction with the endosomal receptor, NPC1, indicating that the glycan cap/MLD domains mask RBD residues required for binding. The effects of the loss of GP1 N-linked glycans on Ca(2+)-dependent (C-type) lectin (CLEC)-dependent transduction were complex, and the effect was unique for each of the CLECs tested. Surprisingly, EBOV entry into murine peritoneal macrophages was independent of GP1 N-glycans, suggesting that CLEC-GP1 N-glycan interactions are not required for entry into this important primary cell. Finally, the removal of all GP1 N-glycans outside the MLD enhanced antiserum and antibody sensitivity. In total, our results provide evidence that the conserved N-linked glycans on the EBOV GP1 core protect GP from antibody neutralization despite the negative impact the glycans have on viral entry efficiency. Filovirus outbreaks occur sporadically throughout central Africa, causing high fatality rates among the general public and health care workers. These unpredictable hemorrhagic fever outbreaks are caused by multiple species of Ebola viruses, as well as Marburg virus. While filovirus

Selection for Dutch postgraduate GP training; time for improvement

NARCIS (Netherlands)

Vermeulen, M.I.; Kuyvenhoven, M.M.; Zuithoff, N.P.; Tromp, F.; Graaf, Y. van der; Pieters, R.H.

2012-01-01

Background: In the Netherlands we select candidates for the postgraduate GP training by assessing personal qualities in interviews. Because of differences in the ratio of number of candidates and number of vacancies between the eight departments of GP training we questioned whether the risk of being

Characterization of Human Colorectal Cancer MDR1/P-gp Fab Antibody

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Xuemei Zhang

2013-01-01

Full Text Available In this study, the peptide sized 21 kDa covering P-gp transmembrane region was first prepared for generating a novel mouse monoclonal antibody Fab fragment with biological activity against multiple drug resistance protein P-gp21 by phage display technology. Phage-displayed antibody library prepared from mice spleen tissues was selected against the recombinant protein P-gp21 with five rounds of panning. A number of clones expressing Fab bound to P-gp21, showing neutralized activity in vitro, were isolated and screened by enzyme-linked immunosorbent assay based on its recognition properties to P-gp21 and human colorectal cancer tissue homogenate, resulting in identification of an optimal recombinant Fab clone (Number 29. Further characterization by recloning number 29 into an expression vector showed significant induction of the Fab antibody in the clone number 29 by Isopropyl β-D-1-thiogalactopyranoside (IPTG. After purified by HiTrap Protein L, the specificity of the Fab antibody to P-gp21 was also confirmed. Not only was the targeted region of this monoclonal Fab antibody identified as a 16-peptide epitope (ALKDKKELEGSGKIAT comprising residues 883–898 within the transmembrane (TM domain of human P-gp, but also the binding ability with it was verified. The clinical implication of our results for development of personalized therapy of colorectal cancer will be further studied.

Transport inhibition of digoxin using several common P-gp expressing cell lines is not necessarily reporting only on inhibitor binding to P-gp.

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Annie Albin Lumen

Full Text Available We have reported that the P-gp substrate digoxin required basolateral and apical uptake transport in excess of that allowed by digoxin passive permeability (as measured in the presence of GF120918 to achieve the observed efflux kinetics across MDCK-MDR1-NKI (The Netherlands Cancer Institute confluent cell monolayers. That is, GF120918 inhibitable uptake transport was kinetically required. Therefore, IC50 measurements using digoxin as a probe substrate in this cell line could be due to inhibition of P-gp, of digoxin uptake transport, or both. This kinetic analysis is now extended to include three additional cell lines: MDCK-MDR1-NIH (National Institute of Health, Caco-2 and CPT-B2 (Caco-2 cells with BCRP knockdown. These cells similarly exhibit GF120918 inhibitable uptake transport of digoxin. We demonstrate that inhibition of digoxin transport across these cell lines by GF120918, cyclosporine, ketoconazole and verapamil is greater than can be explained by inhibition of P-gp alone. We examined three hypotheses for this non-P-gp inhibition. The inhibitors can: (1 bind to a basolateral digoxin uptake transporter, thereby inhibiting digoxin's cellular uptake; (2 partition into the basolateral membrane and directly reduce membrane permeability; (3 aggregate with digoxin in the donor chamber, thereby reducing the free concentration of digoxin, with concomitant reduction in digoxin uptake. Data and simulations show that hypothesis 1 was found to be uniformly acceptable. Hypothesis 2 was found to be uniformly unlikely. Hypothesis 3 was unlikely for GF120918 and cyclosporine, but further studies are needed to completely adjudicate whether hetero-dimerization contributes to the non-P-gp inhibition for ketoconazole and verapamil. We also find that P-gp substrates with relatively low passive permeability such as digoxin, loperamide and vinblastine kinetically require basolateral uptake transport over that allowed by +GF120918 passive permeability, while

Study and preparation of 99Tcm-GP kit for lung ventilation imaging

International Nuclear Information System (INIS)

Zhu Lin; Meng Fanmin; Zhang Jihong; Hong Tao; Liu Yunzhong; Liu Xiujie

1997-01-01

The preparation of the lyophilizing reagent, D-glucose-l-phosphate (GP) kit and the method of using this kit to label 99 Tc m to form 99 Tc m -GP for lung ventilation imaging at room temperature in a simple, rapid procedure are described. The stability of the lyophilizing reagent kit under various stock conditions is examined. The results show that all of the 99 Tc m -GP yields by the lyophilizing reagent kit are above 95% at 4 degree C (cold), 20-25 degree C (room temperature) and 40 degree C (oven) for 180, 90 and 3 days, respectively. The clinical practice indicates that in comparison with 99 Tc m -DTPA, 99 Tc m -GP has remarkable difference (P 99 Tc m -GP is an ideal radioaerosol for SPECT studies of lung ventilation. It has high alveolar deposition rate but low adhesion in the major airways compared to those of 99 Tc m -DTPA. 99 Tc m -GP also features prolonged pulmonary clearance time

GP registrar well-being: a cross-sectional survey

OpenAIRE

Schattner, Peter; Mazalin, Dennis; Pier, Ciaran; Wainer, Jo; Ling, Mee Yoke

2010-01-01

Abstract Objectives To investigate the major stressors affecting GP registrars, how those at risk can be best identified and the most useful methods of managing or reducing their stress. Design, setting and participants Cross-sectional postal questionnaire of all GP registrars in one large regional training provider's catchment area. Main outcome measures The Depression, Anxiety and Stress Scale (DASS), a specifically developed Registrar Stressor Scale consisting of five subscales of potentia...

Attitudes towards obesity treatment in GP training practices: a focus group study

NARCIS (Netherlands)

Jochemsen-van der Leeuw, H. G. A.; van Dijk, N.; Wieringa-de Waard, M.

2011-01-01

Both patients and government expect the GP to treat obesity. Previous studies reported a negative attitude of GPs towards this task. Little is known about the attitude of GP trainees. To assess the attitude and other factors that influence the willingness and ability of GP trainees to provide

Reduction of cerebral glucose utilization by the HIV envelope glycoprotein Gp-120

Energy Technology Data Exchange (ETDEWEB)

Kimes, A.S.; London, E.D.; Szabo, G.; Raymon, L.; Tabakoff, B. (Neuropharmacology Laboratory, National Institute on Drug Abuse, Baltimore, MD (USA))

1991-05-01

Gp-120 is a glycoprotein constituent of the human immunodeficiency virus (HIV) envelope. The effects of gp-120 on cerebral glucose utilization in rats were studied by the quantitative 2-deoxy-D-(1-14C) glucose method. Intracerebroventricular injection of gp-120 significantly reduced glucose utilization in the lateral habenula and the suprachiasmatic nucleus and decreased the global cerebral metabolic rate for glucose. The findings suggest that gp-120 and closely related peptides can alter neuronal function, thereby contributing to the sequelae of HIV infection.

Reduction of cerebral glucose utilization by the HIV envelope glycoprotein Gp-120

International Nuclear Information System (INIS)

Kimes, A.S.; London, E.D.; Szabo, G.; Raymon, L.; Tabakoff, B.

1991-01-01

Gp-120 is a glycoprotein constituent of the human immunodeficiency virus (HIV) envelope. The effects of gp-120 on cerebral glucose utilization in rats were studied by the quantitative 2-deoxy-D-[1-14C] glucose method. Intracerebroventricular injection of gp-120 significantly reduced glucose utilization in the lateral habenula and the suprachiasmatic nucleus and decreased the global cerebral metabolic rate for glucose. The findings suggest that gp-120 and closely related peptides can alter neuronal function, thereby contributing to the sequelae of HIV infection

Determinants of a GP visit and cervical cancer screening examination in Great Britain.

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Alexander Michael Labeit

Full Text Available In the UK, women are requested to attend a cervical cancer test every 3 years as part of the NHS Cervical Screening Programme. This analysis compares the determinants of a cervical cancer screening examination with the determinants of a GP visit in the same year and investigates if cervical cancer screening participation is more likely for women who visit their GP.A recursive probit model was used to analyse the determinants of GP visits and cervical cancer screening examinations. GP visits were considered to be endogenous in the cervical cancer screening examination. The analysed sample consisted of 52,551 observations from 8,386 women of the British Household Panel Survey.The analysis showed that a higher education level and a worsening self-perceived health status increased the probability of a GP visit, whereas smoking decreased the probability of a GP visit. GP visits enhanced the uptake of a cervical cancer screening examination in the same period. The only variables which had the same positive effect on both dependent variables were higher education and living with a partner. The probability of a cervical cancer screening examination increased also with previous cervical cancer screening examinations and being in the recommended age groups. All other variables had different results for the uptake of a GP visit or a cervical cancer screening examination.Most of the determinants of visiting a GP and cervical cancer screening examination differ from each other and a GP visit enhances the uptake of a smear test.

Continuous cultivation of a thermophilic bacterium Aeribacillus pallidus 418 for production of an exopolysaccharide applicable in cosmetic creams.

Science.gov (United States)

Radchenkova, N; Panchev, I; Vassilev, S; Kuncheva, M; Dobreva, S; Kambourova, M

2015-11-01

The aim of this study was to evaluate the effectiveness of continuous cultivation approach for exopolysaccharide (EPS) production by a thermophilic micro-organism and the potential of the synthesized EPS for application in cosmetic industry. Study on the ability of Aeribacillus pallidus 418, isolated as a good EPS producer, to synthesize the polymer in continuous cultures showed higher production in comparison with batch cultures. The degree of the EPS in the precipitate after continuous cultivation significantly increased. Non-Newtonian pseudoplastic and thixotropic behaviour of EPS determines the ability of the received cream to become more fluid after increasing time of application on the skin. This study demonstrates a highly efficient way for production of EPS from a continuous growth culture of A. pallidus 418 that have many advantages and can outperform batch culture by eliminating time for cleaning and sterilization of the vessel and the comparatively long lag phases before the organisms enter a brief period of high productivity. The valuable physico-chemical properties of the synthesized EPS influenced positively the properties of a commercial cream. EPSs from thermophilic micro-organisms are of special interest due to the advantages of the thermophilic processes and nonpathogenic nature of the polymer molecules. However, their industrial application is hindered by the comparatively low biomass and correspondingly EPS yield. Suggested continuous approach for EPS could have an enormous economic potential for an industrial scale production of thermophilic EPSs. © 2015 The Society for Applied Microbiology.

GP registrar well-being: a cross-sectional survey.

Science.gov (United States)

Schattner, Peter; Mazalin, Dennis; Pier, Ciaran; Wainer, Jo; Ling, Mee Yoke

2010-02-09

To investigate the major stressors affecting GP registrars, how those at risk can be best identified and the most useful methods of managing or reducing their stress. Cross-sectional postal questionnaire of all GP registrars in one large regional training provider's catchment area. The Depression, Anxiety and Stress Scale (DASS), a specifically developed Registrar Stressor Scale consisting of five subscales of potential stressors, plus closed questions on how to identify and manage stress in GP registrars. Survey response rate of 51% (102/199). Rural difficulties followed by achieving a work/life balance were the principal stressors. Ten percent of registrars were mildly or moderately depressed or anxious (DASS) and 7% mild to moderately anxious (DASS). Registrars preferred informal means of identifying those under stress (a buddy system and talks with their supervisors); similarly, they preferred to manage stress by discussions with family and friends, debriefing with peers and colleagues, or undertaking sport and leisure activities. This study supports research which confirms that poor psychological well-being is an important issue for a significant minority of GP trainees. Regional training providers should ensure that they facilitate formal and informal strategies to identify those at risk and assist them to cope with their stress.

HIV-1 gp41 Fusion Intermediate: A Target for HIV Therapeutics

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Chungen Pan

2010-02-01

Full Text Available Human immunodeficiency virus (HIV-1 infection is initiated by the binding of gp120 envelope glyco-protein to its cell receptor (CD4 and a coreceptor (CXCR4 or CCR5, followed by a series of conformational changes in the gp41 transmembrane subunit. These changes include insertion of fusion peptide into the target cell membrane and association of C-heptad repeat (CHR peptide with the N-heptad repeat (NHR trimer, a pre-hairpin fusion intermediate. A stable six-helix bundle core is then formed, bringing the viral envelope and target cell membrane into close proximity for fusion. Peptides derived from the CHR region, such as T20 and C34, inhibit HIV-1 fusion by interacting with the gp41 fusion intermediate. A number of anti-HIV-1 peptides and small molecule compounds targeting the gp41 NHR-trimer have been identified. By combining HIV fusion/entry inhibitors targeting different sites in the gp41 fusion intermediate, a potent synergistic effect takes place, resulting in a potential new therapeutic strategy for the HIV infection/AIDS. Here, we present an overview of the current development of anti-HIV drugs, particularly those targeting the gp41 fusion intermediate.

Correlation between Relaxometry and Diffusion Tensor Imaging in the Globus Pallidus of Huntington's Disease Patients

Czech Academy of Sciences Publication Activity Database

Syka, Michael; Keller, J.; Klempíř, J.; Rulseh, A. M.; Roth, J.; Jech, R.; Voříšek, Ivan; Vymazal, J.

2015-01-01

Roč. 10, č. 3 (2015), e0118907 E-ISSN 1932-6203 R&D Projects: GA ČR(CZ) GAP303/11/2378 Institutional support: RVO:68378041 Keywords : basal ganglia * gray-matter * human brain Subject RIV: FH - Neurology Impact factor: 3.057, year: 2015

GP and pharmacist inter-professional learning - a grounded theory study.

Science.gov (United States)

Cunningham, David E; Ferguson, Julie; Wakeling, Judy; Zlotos, Leon; Power, Ailsa

2016-05-01

Practice Based Small Group Learning (PBSGL) is an established learning resource for primary care clinicians in Scotland and is used by one-third of general practitioners (GPs). Scottish Government and UK professional bodies have called for GPs and pharmacists to work more closely together to improve care. To gain GPs' and pharmacists' perceptions and experiences of learning together in an inter-professional PBSGL pilot. Qualitative research methods involving established GP PBSGL groups in NHS Scotland recruiting one or two pharmacists to join them. A grounded theory method was used. GPs were interviewed in focus groups by a fellow GP, and pharmacists were interviewed individually by two researchers, neither being a GP or a pharmacist. Interviews were audio-recorded, transcribed and analysed using grounded theory methods. Data saturation was achieved and confirmed. Three themes were identified: GPs' and pharmacists' perceptions and experiences of inter-professional learning; Inter-professional relationships and team-working; Group identity and purpose of existing GP groups. Pharmacists were welcomed into GP groups and both professions valued inter-professional PBSGL learning. Participants learned from each other and both professions gained a wider perspective of the NHS and of each others' roles in the organisation. Inter-professional relationships, communication and team-working were strengthened and professionals regarded each other as peers and friends.

Enhancing field GP engagement in hospital-based studies. Rationale, design, main results and participation in the diagest 3-GP motivation study

Directory of Open Access Journals (Sweden)

Berkhout Christophe

2012-06-01

Full Text Available Abstract Background Diagest 3 was a study aimed at lowering the risk of developing type 2 diabetes within 3 years after childbirth. Women with gestational diabetes were enrolled in the study. After childbirth, the subjects showed little interest in the structured education programme and did not attend workshops. Their general practitioners (GPs were approached to help motivate the subjects to participate in Diagest 3, but the GPs were reluctant. The present study aimed to understand field GPs’ attitudes towards hospital-based studies, and to develop strategies to enhance their involvement and reduce subject drop-out rates. Methods We used a three-step process: step one used a phenomenological approach exploring the beliefs, attitudes, motivations and environmental factors contributing to the GPs’ level of interest in the study. Data were collected in face-to-face interviews and coded by hand and with hermeneutic software to develop distinct GP profiles. Step two was a cross-sectional survey by questionnaire to determine the distribution of the profiles in the GP study population and whether completion of an attached case report form (CRF was associated with a particular GP profile. In step three, we assessed the impact of the motivation study on participation rates in the main study. Results Fifteen interviews were conducted to achieve data saturation. Theorisation led to the definition of 4 distinct GP profiles. The response rate to the questionnaire was 73%, but dropped to 52% when a CRF was attached. The link between GP profiles and the rate of CRF completion remains to be verified. The GPs provided data on the CRF that was of comparable quality to those collected in the main trial. Our analysis showed that the motivation study increased overall participation in the main study by 23%, accounting for 16% (24/152 of all final visits for 536 patients who were initially enrolled in the Diagest 3 study. Conclusions When a hospital-led study

Enhancing field GP engagement in hospital-based studies. Rationale, design, main results and participation in the Diagest 3-GP motivation study.

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Berkhout, Christophe; Vandaele-Bétancourt, Marie; Robert, Stéphane; Lespinasse, Solène; Mitha, Gamil; Bradier, Quentin; Vambergue, Anne; Fontaine, Pierre

2012-06-21

Diagest 3 was a study aimed at lowering the risk of developing type 2 diabetes within 3 years after childbirth. Women with gestational diabetes were enrolled in the study. After childbirth, the subjects showed little interest in the structured education programme and did not attend workshops. Their general practitioners (GPs) were approached to help motivate the subjects to participate in Diagest 3, but the GPs were reluctant. The present study aimed to understand field GPs' attitudes towards hospital-based studies, and to develop strategies to enhance their involvement and reduce subject drop-out rates. We used a three-step process: step one used a phenomenological approach exploring the beliefs, attitudes, motivations and environmental factors contributing to the GPs' level of interest in the study. Data were collected in face-to-face interviews and coded by hand and with hermeneutic software to develop distinct GP profiles. Step two was a cross-sectional survey by questionnaire to determine the distribution of the profiles in the GP study population and whether completion of an attached case report form (CRF) was associated with a particular GP profile. In step three, we assessed the impact of the motivation study on participation rates in the main study. Fifteen interviews were conducted to achieve data saturation. Theorisation led to the definition of 4 distinct GP profiles. The response rate to the questionnaire was 73%, but dropped to 52% when a CRF was attached. The link between GP profiles and the rate of CRF completion remains to be verified. The GPs provided data on the CRF that was of comparable quality to those collected in the main trial. Our analysis showed that the motivation study increased overall participation in the main study by 23%, accounting for 16% (24/152) of all final visits for 536 patients who were initially enrolled in the Diagest 3 study. When a hospital-led study explores issues in primary care, its design must anticipate GP

Are there practical opportunities for developing leadership skills during GP training and beyond? A survey of GP trainees and trainers in South East Scotland.

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Curry, Nicola; Denney, MeiLing

2016-01-01

There is currently a lack of formal training in leadership skills, particularly during GP training. This study aimed to explore the current training and practical opportunities which exist, specifically exploring the views of GP trainees and trainers. An electronic questionnaire was sent to 266 GP trainees and trainers in south-east Scotland. Questions focused on respondents' experience of leadership-specific training and opportunities to engage with leadership roles. There were a total of 76 respondents (28.6% response rate). Response rate was 19.0% in trainees and 34.6% in trainers. A majority of respondents (80.0%) were established GPs. Of those who had received training in leadership, most (72.1%) underwent this after qualifying as a GP. Respondents identified a range of leadership roles within and outside the practice covering clinical and non-clinical areas. Most were interested in future leadership roles (46.7% moderately interested; 28% very interested). More time, training opportunities and the presence of GP role models were motivating factors in terms of participants' readiness to take on future leadership roles. Signposting trainees, trainers and general practitioners to leadership opportunities and training would be relatively easy but addressing a lack of motivating factors at a local level is essential. The effectiveness of such training and opportunities for experiential learning in leadership roles requires further research.

The effect of gender medicine education in GP training: a prospective cohort study.

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Dielissen, Patrick; Verdonk, Petra; Waard, Magreet Wieringa-de; Bottema, Ben; Lagro-Janssen, Toine

2014-11-01

The purpose of this study is to compare the change in general practitioner (GP) trainees' gender awareness following a modular gender medicine programme or a mainstream gender medicine programme. In 2007, a prospective study was conducted in three cohorts of in total 207 GP trainees who entered GP training in the Netherlands. The outcome measure was the Nijmegen Gender Awareness in Medicine Scale and a 16-item gender knowledge questionnaire. Two gender medicine teaching methods were compared: a modular approach (n = 75) versus a mainstream approach (n = 72). Both strategies were compared with a control cohort (n = 60). Statistical analysis included analysis of variance and t-tests. The overall response rates for the modular, mainstream and control cohort were 78, 72 and 82 %, respectively. There was a significant difference in change in gender knowledge scores between the modular cohort compared with the mainstream and control cohort (p = 0.049). There were no statistical differences between the cohorts on gender sensitivity and gender role ideology. At entry and end, female GP trainees demonstrated significantly higher gender awareness than male GP trainees. A modular teaching method is not a more favourable educational method to teach gender medicine in GP training. Female GP trainees are more gender aware, but male GP trainees are not unaware of gender-related issues.

GP registrar well-being: a cross-sectional survey

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Schattner Peter

2010-02-01

Full Text Available Abstract Objectives To investigate the major stressors affecting GP registrars, how those at risk can be best identified and the most useful methods of managing or reducing their stress. Design, setting and participants Cross-sectional postal questionnaire of all GP registrars in one large regional training provider's catchment area. Main outcome measures The Depression, Anxiety and Stress Scale (DASS, a specifically developed Registrar Stressor Scale consisting of five subscales of potential stressors, plus closed questions on how to identify and manage stress in GP registrars. Results Survey response rate of 51% (102/199. Rural difficulties followed by achieving a work/life balance were the principal stressors. Ten percent of registrars were mildly or moderately depressed or anxious (DASS and 7% mild to moderately anxious (DASS. Registrars preferred informal means of identifying those under stress (a buddy system and talks with their supervisors; similarly, they preferred to manage stress by discussions with family and friends, debriefing with peers and colleagues, or undertaking sport and leisure activities. Conclusions This study supports research which confirms that poor psychological well-being is an important issue for a significant minority of GP trainees. Regional training providers should ensure that they facilitate formal and informal strategies to identify those at risk and assist them to cope with their stress.

The cranial MRI in severe cerebral palsy

International Nuclear Information System (INIS)

Yamada, Kazutaka; Itoh, Masahiro; Fueki, Noboru; Hirasawa, Kyoko; Suzuki, Noriko; Kurata, Kiyoko; Sato, Junichi; Morimatsu, Yoshio; Yagishita, Akira.

1993-01-01

The magnetic resonance examination was performed in 38 patients with severe cerebral palsy (CP; 15 males and 23 females) who had both motor delay (unable to move anywhere) and mental retardation (I.Q. or D.Q. below 30). Neuroimaging findings were compared with the CP type, etiology, and grade of understanding of language. Cranial magnetic resonance imagings (MRI) in CP were divided into five types. In type 1, nine predominantly showed cyst-liked ventricles and periventricular hyperintensity on T 2 -weighted imaging (PVH) and only scarred basal ganglia and thalamus were visible. All suffered from neonatal asphyxia and the clinical type was rigospastic tetraplegia (RST). In type 2, eleven predominantly showed PVH and hyperintensity on T 2 -weighted (HT2) in basal ganglia and thalamus. All suffered from neonatal asphyxia and the clinical type was RST or rigospastic diplegia. In type 3, five showed PVH and three had cortical atrophy. All suffered from neonatal asphyxia and the clinical type was spastic diplegia. In type 4, four predominantly showed HT2 in putamen and thalamus. Three had cortical atrophy. All suffered from neonatal asphyxia. The clinical type was athetotic CP (ATH). In type 5, nine predominantly showed HT2 in globus pallidus. Four had cortical atrophy and two had hippocampal atrophy. All suffered from neonatal jaundice and the clinical type was ATH. All patients who suffered from neonatal asphyxia and spastic CP had MRI in PVH. All patients who suffered from neonatal asphyxia and ATH showed HT2 in putamen and thalamus. Almost patients who suffered from neonatal jaundice and ATH showed HT2 in globus pallidus. With athetotic CP, cases with atrophy of the cerebral cortex and/or hippocampus were lower grade of understanding of language than no atrophy of both. The results of studies of MRI are in agreement with neuropathological findings. (author)

The cranial MRI in severe cerebral palsy; A comparative study with clinical data

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Yamada, Kazutaka; Itoh, Masahiro; Fueki, Noboru; Hirasawa, Kyoko; Suzuki, Noriko; Kurata, Kiyoko (Metropolitan Medical Center of the Severely Handicapped, Tokyo (Japan)); Sato, Junichi; Morimatsu, Yoshio; Yagishita, Akira

1993-09-01

The magnetic resonance examination was performed in 38 patients with severe cerebral palsy (CP; 15 males and 23 females) who had both motor delay (unable to move anywhere) and mental retardation (I.Q. or D.Q. below 30). Neuroimaging findings were compared with the CP type, etiology, and grade of understanding of language. Cranial magnetic resonance imagings (MRI) in CP were divided into five types. In type 1, nine predominantly showed cyst-liked ventricles and periventricular hyperintensity on T[sub 2]-weighted imaging (PVH) and only scarred basal ganglia and thalamus were visible. All suffered from neonatal asphyxia and the clinical type was rigospastic tetraplegia (RST). In type 2, eleven predominantly showed PVH and hyperintensity on T[sub 2]-weighted (HT2) in basal ganglia and thalamus. All suffered from neonatal asphyxia and the clinical type was RST or rigospastic diplegia. In type 3, five showed PVH and three had cortical atrophy. All suffered from neonatal asphyxia and the clinical type was spastic diplegia. In type 4, four predominantly showed HT2 in putamen and thalamus. Three had cortical atrophy. All suffered from neonatal asphyxia. The clinical type was athetotic CP (ATH). In type 5, nine predominantly showed HT2 in globus pallidus. Four had cortical atrophy and two had hippocampal atrophy. All suffered from neonatal jaundice and the clinical type was ATH. All patients who suffered from neonatal asphyxia and spastic CP had MRI in PVH. All patients who suffered from neonatal asphyxia and ATH showed HT2 in putamen and thalamus. Almost patients who suffered from neonatal jaundice and ATH showed HT2 in globus pallidus. With athetotic CP, cases with atrophy of the cerebral cortex and/or hippocampus were lower grade of understanding of language than no atrophy of both. The results of studies of MRI are in agreement with neuropathological findings. (author).

Temporal changes of CB1 cannabinoid receptor in the basal ganglia as a possible structure-specific plasticity process in 6-OHDA lesioned rats.

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Gabriela P Chaves-Kirsten

Full Text Available The endocannabinoid system has been implicated in several neurobiological processes, including neurodegeneration, neuroprotection and neuronal plasticity. The CB1 cannabinoid receptors are abundantly expressed in the basal ganglia, the circuitry that is mostly affected in Parkinson's Disease (PD. Some studies show variation of CB1 expression in basal ganglia in different animal models of PD, however the results are quite controversial, due to the differences in the procedures employed to induce the parkinsonism and the periods analyzed after the lesion. The present study evaluated the CB1 expression in four basal ganglia structures, namely striatum, external globus pallidus (EGP, internal globus pallidus (IGP and substantia nigra pars reticulata (SNpr of rats 1, 5, 10, 20, and 60 days after unilateral intrastriatal 6-hydroxydopamine injections, that causes retrograde dopaminergic degeneration. We also investigated tyrosine hydroxylase (TH, parvalbumin, calbindin and glutamic acid decarboxylase (GAD expression to verify the status of dopaminergic and GABAergic systems. We observed a structure-specific modulation of CB1 expression at different periods after lesions. In general, there were no changes in the striatum, decreased CB1 in IGP and SNpr and increased CB1 in EGP, but this increase was not sustained over time. No changes in GAD and parvalbumin expression were observed in basal ganglia, whereas TH levels were decreased and the calbindin increased in striatum in short periods after lesion. We believe that the structure-specific variation of CB1 in basal ganglia in the 6-hydroxydopamine PD model could be related to a compensatory process involving the GABAergic transmission, which is impaired due to the lack of dopamine. Our data, therefore, suggest that the changes of CB1 and calbindin expression may represent a plasticity process in this PD model.

Quantitative comparison between a multiecho sequence and a single-echo sequence for susceptibility-weighted phase imaging.

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Gilbert, Guillaume; Savard, Geneviève; Bard, Céline; Beaudoin, Gilles

2012-06-01

The aim of this study was to investigate the benefits arising from the use of a multiecho sequence for susceptibility-weighted phase imaging using a quantitative comparison with a standard single-echo acquisition. Four healthy adult volunteers were imaged on a clinical 3-T system using a protocol comprising two different three-dimensional susceptibility-weighted gradient-echo sequences: a standard single-echo sequence and a multiecho sequence. Both sequences were repeated twice in order to evaluate the local noise contribution by a subtraction of the two acquisitions. For the multiecho sequence, the phase information from each echo was independently unwrapped, and the background field contribution was removed using either homodyne filtering or the projection onto dipole fields method. The phase information from all echoes was then combined using a weighted linear regression. R2 maps were also calculated from the multiecho acquisitions. The noise standard deviation in the reconstructed phase images was evaluated for six manually segmented regions of interest (frontal white matter, posterior white matter, globus pallidus, putamen, caudate nucleus and lateral ventricle). The use of the multiecho sequence for susceptibility-weighted phase imaging led to a reduction of the noise standard deviation for all subjects and all regions of interest investigated in comparison to the reference single-echo acquisition. On average, the noise reduction ranged from 18.4% for the globus pallidus to 47.9% for the lateral ventricle. In addition, the amount of noise reduction was found to be strongly inversely correlated to the estimated R2 value (R=-0.92). In conclusion, the use of a multiecho sequence is an effective way to decrease the noise contribution in susceptibility-weighted phase images, while preserving both contrast and acquisition time. The proposed approach additionally permits the calculation of R2 maps. Copyright © 2012 Elsevier Inc. All rights reserved.

The relative phases of basal ganglia activities dynamically shape effective connectivity in Parkinson's disease.

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Cagnan, Hayriye; Duff, Eugene Paul; Brown, Peter

2015-06-01

Optimal phase alignment between oscillatory neural circuits is hypothesized to optimize information flow and enhance system performance. This theory is known as communication-through-coherence. The basal ganglia motor circuit exhibits exaggerated oscillatory and coherent activity patterns in Parkinson's disease. Such activity patterns are linked to compromised motor system performance as evinced by bradykinesia, rigidity and tremor, suggesting that network function might actually deteriorate once a certain level of net synchrony is exceeded in the motor circuit. Here, we characterize the processes underscoring excessive synchronization and its termination. To this end, we analysed local field potential recordings from the subthalamic nucleus and globus pallidus of five patients with Parkinson's disease (four male and one female, aged 37-64 years). We observed that certain phase alignments between subthalamic nucleus and globus pallidus amplified local neural synchrony in the beta frequency band while others either suppressed it or did not induce any significant change with respect to surrogates. The increase in local beta synchrony directly correlated with how long the two nuclei locked to beta-amplifying phase alignments. Crucially, administration of the dopamine prodrug, levodopa, reduced the frequency and duration of periods during which subthalamic and pallidal populations were phase-locked to beta-amplifying alignments. Conversely ON dopamine, the total duration over which subthalamic and pallidal populations were aligned to phases that left beta-amplitude unchanged with respect to surrogates increased. Thus dopaminergic input shifted circuit dynamics from persistent periods of locking to amplifying phase alignments, associated with compromised motoric function, to more dynamic phase alignment and improved motoric function. This effect of dopamine on local circuit resonance suggests means by which novel electrical interventions might prevent resonance

Gadolinium Deposition in Human Brain Tissues after Contrast-enhanced MR Imaging in Adult Patients without Intracranial Abnormalities.

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McDonald, Robert J; McDonald, Jennifer S; Kallmes, David F; Jentoft, Mark E; Paolini, Michael A; Murray, David L; Williamson, Eric E; Eckel, Laurence J

2017-11-01

Purpose To determine whether gadolinium deposits in neural tissues of patients with intracranial abnormalities following intravenous gadolinium-based contrast agent (GBCA) exposure might be related to blood-brain barrier integrity by studying adult patients with normal brain pathologic characteristics. Materials and Methods After obtaining antemortem consent and institutional review board approval, the authors compared postmortem neuronal tissue samples from five patients who had undergone four to 18 gadolinium-enhanced magnetic resonance (MR) examinations between 2005 and 2014 (contrast group) with samples from 10 gadolinium-naive patients who had undergone at least one MR examination during their lifetime (control group). All patients in the contrast group had received gadodiamide. Neuronal tissues from the dentate nuclei, pons, globus pallidus, and thalamus were harvested and analyzed with inductively coupled plasma mass spectrometry (ICP-MS), transmission electron microscopy with energy-dispersive x-ray spectroscopy, and light microscopy to quantify, localize, and assess the effects of gadolinium deposition. Results Tissues from the four neuroanatomic regions of gadodiamide-exposed patients contained 0.1-19.4 μg of gadolinium per gram of tissue in a statistically significant dose-dependent relationship (globus pallidus: ρ = 0.90, P = .04). In contradistinction, patients in the control group had undetectable levels of gadolinium with ICP-MS. All patients had normal brain pathologic characteristics at autopsy. Three patients in the contrast group had borderline renal function (estimated glomerular filtration rate the contrast group was localized to the capillary endothelium and neuronal interstitium and, in two cases, within the nucleus of the cell. Conclusion Gadolinium deposition in neural tissues after GBCA administration occurs in the absence of intracranial abnormalities that might affect the permeability of the blood-brain barrier. These findings

Efficacy and Safety of Deep Brain Stimulation in Tourette Syndrome: The International Tourette Syndrome Deep Brain Stimulation Public Database and Registry.

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Martinez-Ramirez, Daniel; Jimenez-Shahed, Joohi; Leckman, James Frederick; Porta, Mauro; Servello, Domenico; Meng, Fan-Gang; Kuhn, Jens; Huys, Daniel; Baldermann, Juan Carlos; Foltynie, Thomas; Hariz, Marwan I; Joyce, Eileen M; Zrinzo, Ludvic; Kefalopoulou, Zinovia; Silburn, Peter; Coyne, Terry; Mogilner, Alon Y; Pourfar, Michael H; Khandhar, Suketu M; Auyeung, Man; Ostrem, Jill Louise; Visser-Vandewalle, Veerle; Welter, Marie-Laure; Mallet, Luc; Karachi, Carine; Houeto, Jean Luc; Klassen, Bryan Timothy; Ackermans, Linda; Kaido, Takanobu; Temel, Yasin; Gross, Robert E; Walker, Harrison C; Lozano, Andres M; Walter, Benjamin L; Mari, Zoltan; Anderson, William S; Changizi, Barbara Kelly; Moro, Elena; Zauber, Sarah Elizabeth; Schrock, Lauren E; Zhang, Jian-Guo; Hu, Wei; Rizer, Kyle; Monari, Erin H; Foote, Kelly D; Malaty, Irene A; Deeb, Wissam; Gunduz, Aysegul; Okun, Michael S

2018-03-01

Collective evidence has strongly suggested that deep brain stimulation (DBS) is a promising therapy for Tourette syndrome. To assess the efficacy and safety of DBS in a multinational cohort of patients with Tourette syndrome. The prospective International Deep Brain Stimulation Database and Registry included 185 patients with medically refractory Tourette syndrome who underwent DBS implantation from January 1, 2012, to December 31, 2016, at 31 institutions in 10 countries worldwide. Patients with medically refractory symptoms received DBS implantation in the centromedian thalamic region (93 of 163 [57.1%]), the anterior globus pallidus internus (41 of 163 [25.2%]), the posterior globus pallidus internus (25 of 163 [15.3%]), and the anterior limb of the internal capsule (4 of 163 [2.5%]). Scores on the Yale Global Tic Severity Scale and adverse events. The International Deep Brain Stimulation Database and Registry enrolled 185 patients (of 171 with available data, 37 females and 134 males; mean [SD] age at surgery, 29.1 [10.8] years [range, 13-58 years]). Symptoms of obsessive-compulsive disorder were present in 97 of 151 patients (64.2%) and 32 of 148 (21.6%) had a history of self-injurious behavior. The mean (SD) total Yale Global Tic Severity Scale score improved from 75.01 (18.36) at baseline to 41.19 (20.00) at 1 year after DBS implantation (P tic subscore improved from 21.00 (3.72) at baseline to 12.91 (5.78) after 1 year (P tic subscore improved from 16.82 (6.56) at baseline to 9.63 (6.99) at 1 year (P Tourette syndrome but also with important adverse events. A publicly available website on outcomes of DBS in patients with Tourette syndrome has been provided.

The histamine system in human brain. Changes in neurological and psychiatric disorders

International Nuclear Information System (INIS)

Goodchild, R.E.

1999-09-01

Autoradiographical examination of the distribution of H 1 - and H 3 - histamine receptor subtypes, using [ 3 H]-mepyramine and [ 3 H]-R-(α) methylhistamine respectively, found high H 1 -receptor binding densities in neocortex, dentate gyrus and basolateral amygdala, with low binding in all subdivisions of the thalamus and other subcortical areas. H 3 -receptor binding was enriched within the nucleus accumbens, globus pallidus and substantia nigra, whilst was low in the hippocampus, subthalamic nucleus, temporal cortex, motor and somatosensory thalamic areas and basolateral amygdala. In situ hybridisation found H 2 -receptor mRNA located in the striatum, thalamus, hippocampal pyramidal cell layer and dentate gyrus, and specific laminae of neocortex. Comparison of autoradiographically determined H 1 -, H 2 - and H 3 -receptor binding densities between normal and pathological cases found significantly decreased (p 3 -receptor binding in Huntington's disease (HD), with unaltered binding in the insular cortex. A significant correlation (p 1 -receptor was increased (p 2 - (measured using [ 125 I]-iodoaminopotentidine) and H 3 -receptor binding densities were normal in all areas examined. H 1 -receptor binding was also increased in the hippocampus of Lewy-body dementia (DLB) cases (p 2 -receptor binding densities were decreased in DLB, together with Alzheimer's disease (AD) (p 3 -receptor binding was increased in the insular cortex and decreased in the temporal cortex of DLB, but not AD, cases (p 1 -receptor binding to tissue from patients with schizophrenia was significantly reduced in all cortical (p 2 -receptor binding was unaltered in all areas, however H 3 -receptor binding was increased in the posterior putamen (p < 0.05), and highly significantly decreased (p < 0.005, Students two-tailed T-Test) in the external globus pallidus in schizophrenia. (author)

Mutation of Elfn1 in mice causes seizures and hyperactivity.

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Jackie Dolan

Full Text Available A growing number of proteins with extracellular leucine-rich repeats (eLRRs have been implicated in directing neuronal connectivity. We previously identified a novel family of eLRR proteins in mammals: the Elfns are transmembrane proteins with 6 LRRs, a fibronectin type-3 domain and a long cytoplasmic tail. The recent discovery that Elfn1 protein, expressed postsynaptically, can direct the elaboration of specific electrochemical properties of synapses between particular cell types in the hippocampus strongly reinforces this hypothesis. Here, we present analyses of an Elfn1 mutant mouse line and demonstrate a functional requirement for this gene in vivo. We first carried out detailed expression analysis of Elfn1 using a β-galactosidase reporter gene in the knockout line. Elfn1 is expressed in distinct subsets of interneurons of the hippocampus and cortex, and also in discrete subsets of cells in the habenula, septum, globus pallidus, dorsal subiculum, amygdala and several other regions. Elfn1 is expressed in diverse cell types, including local GABAergic interneurons as well as long-range projecting GABAergic and glutamatergic neurons. Elfn1 protein localises to axons of excitatory neurons in the habenula, and long-range GABAergic neurons of the globus pallidus, suggesting the possibility of additional roles for Elfn1 in axons or presynaptically. While gross anatomical analyses did not reveal any obvious neuroanatomical abnormalities, behavioural analyses clearly illustrate functional effects of Elfn1 mutation. Elfn1 mutant mice exhibit seizures, subtle motor abnormalities, reduced thigmotaxis and hyperactivity. The hyperactivity is paradoxically reversible by treatment with the stimulant amphetamine, consistent with phenotypes observed in animals with habenular lesions. These analyses reveal a requirement for Elfn1 in brain function and are suggestive of possible relevance to the etiology and pathophysiology of epilepsy and attention

Dynamical analysis of Parkinsonian state emulated by hybrid Izhikevich neuron models

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Liu, Chen; Wang, Jiang; Yu, Haitao; Deng, Bin; Wei, Xile; Li, Huiyan; Loparo, Kenneth A.; Fietkiewicz, Chris

2015-11-01

Computational models play a significant role in exploring novel theories to complement the findings of physiological experiments. Various computational models have been developed to reveal the mechanisms underlying brain functions. Particularly, in the development of therapies to modulate behavioral and pathological abnormalities, computational models provide the basic foundations to exhibit transitions between physiological and pathological conditions. Considering the significant roles of the intrinsic properties of the globus pallidus and the coupling connections between neurons in determining the firing patterns and the dynamical activities of the basal ganglia neuronal network, we propose a hypothesis that pathological behaviors under the Parkinsonian state may originate from combined effects of intrinsic properties of globus pallidus neurons and synaptic conductances in the whole neuronal network. In order to establish a computational efficient network model, hybrid Izhikevich neuron model is used due to its capacity of capturing the dynamical characteristics of the biological neuronal activities. Detailed analysis of the individual Izhikevich neuron model can assist in understanding the roles of model parameters, which then facilitates the establishment of the basal ganglia-thalamic network model, and contributes to a further exploration of the underlying mechanisms of the Parkinsonian state. Simulation results show that the hybrid Izhikevich neuron model is capable of capturing many of the dynamical properties of the basal ganglia-thalamic neuronal network, such as variations of the firing rates and emergence of synchronous oscillations under the Parkinsonian condition, despite the simplicity of the two-dimensional neuronal model. It may suggest that the computational efficient hybrid Izhikevich neuron model can be used to explore basal ganglia normal and abnormal functions. Especially it provides an efficient way of emulating the large-scale neuron network

Maternal pravastatin prevents altered fetal brain development in a preeclamptic CD-1 mouse model.

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Alissa R Carver

Full Text Available Using an animal model, we have previously shown that preeclampsia results in long-term adverse neuromotor outcomes in the offspring, and this phenotype was prevented by antenatal treatment with pravastatin. This study aims to localize the altered neuromotor programming in this animal model and to evaluate the role of pravastatin in its prevention.For the preeclampsia model, pregnant CD-1 mice were randomly allocated to injection of adenovirus carrying sFlt-1 or its control virus carrying mFc into the tail vein. Thereafter they received pravastatin (sFlt-1-pra "experimental group" or water (sFlt-1 "positive control" until weaning. The mFc group ("negative control" received water. Offspring at 6 months of age were sacrificed, and whole brains underwent magnetic resonance imaging (MRI. MRIs were performed using an 11.7 Tesla vertical bore MRI scanner. T2 weighted images were acquired to evaluate the volumes of 28 regions of interest, including areas involved in adaptation and motor, spatial and sensory function. Cytochemistry and cell quantification was performed using neuron-specific Nissl stain. One-way ANOVA with multiple comparison testing was used for statistical analysis.Compared with control offspring, male sFlt-1 offspring have decreased volumes in the fimbria, periaquaductal gray, stria medullaris, and ventricles and increased volumes in the lateral globus pallidus and neocortex; however, female sFlt-1 offspring showed increased volumes in the ventricles, stria medullaris, and fasciculus retroflexus and decreased volumes in the inferior colliculus, thalamus, and lateral globus pallidus. Neuronal quantification via Nissl staining exhibited decreased cell counts in sFlt-1 offspring neocortex, more pronounced in males. Prenatal pravastatin treatment prevented these changes.Preeclampsia alters brain development in sex-specific patterns, and prenatal pravastatin therapy prevents altered neuroanatomic programming in this animal model.

Sample size requirements for one-year treatment effects using deep gray matter volume from 3T MRI in progressive forms of multiple sclerosis.

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Kim, Gloria; Chu, Renxin; Yousuf, Fawad; Tauhid, Shahamat; Stazzone, Lynn; Houtchens, Maria K; Stankiewicz, James M; Severson, Christopher; Kimbrough, Dorlan; Quintana, Francisco J; Chitnis, Tanuja; Weiner, Howard L; Healy, Brian C; Bakshi, Rohit

2017-11-01

The subcortical deep gray matter (DGM) develops selective, progressive, and clinically relevant atrophy in progressive forms of multiple sclerosis (PMS). This patient population is the target of active neurotherapeutic development, requiring the availability of outcome measures. We tested a fully automated MRI analysis pipeline to assess DGM atrophy in PMS. Consistent 3D T1-weighted high-resolution 3T brain MRI was obtained over one year in 19 consecutive patients with PMS [15 secondary progressive, 4 primary progressive, 53% women, age (mean±SD) 50.8±8.0 years, Expanded Disability Status Scale (median, range) 5.0, 2.0-6.5)]. DGM segmentation applied the fully automated FSL-FIRST pipeline ( http://fsl.fmrib.ox.ac.uk ). Total DGM volume was the sum of the caudate, putamen, globus pallidus, and thalamus. On-study change was calculated using a random-effects linear regression model. We detected one-year decreases in raw [mean (95% confidence interval): -0.749 ml (-1.455, -0.043), p = 0.039] and annualized [-0.754 ml/year (-1.492, -0.016), p = 0.046] total DGM volumes. A treatment trial for an intervention that would show a 50% reduction in DGM brain atrophy would require a sample size of 123 patients for a single-arm study (one-year run-in followed by one-year on-treatment). For a two-arm placebo-controlled one-year study, 242 patients would be required per arm. The use of DGM fraction required more patients. The thalamus, putamen, and globus pallidus, showed smaller effect sizes in their on-study changes than the total DGM; however, for the caudate, the effect sizes were somewhat larger. DGM atrophy may prove efficient as a short-term outcome for proof-of-concept neurotherapeutic trials in PMS.

Clinical studies of the calcification of the basal ganglia as disclosed by computed tomography

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Node, Yoji; Nakazawa, Shozo (Nippon Medical School, Tokyo)

1983-04-01

One hundred and twenty-nine of the 12,645 patients (1.0%) were found to have attenuating changes suggesting calcification of the basal ganglia. Thirty-seven of those patients were male and 92 were female. The calcification was bilateral and grossly symmetric in 108 of these patients (83.7%), while it was unilateral in 21 (16.3%). In the unilaterally located cases, 15 were on the left side and 6 were on the right side. In 128 of these patients (99.2%), calcification was located in the globus pallidus. Only one patient, whose diagnosis was hypoparathyroidism, had calcification in both the globus pallidus and the head of the caudate nucleus. The patients' ages ranged from 10 to 85 years (mean, 58), but 88.4% of the patients were more than 40 years old at the time of the CT scanning. The attenuation values of the lesions varied from 35 to 375 EMI units (mean, 55.7). Skull radiographs were performed in 120 of the 129 patients. Calcification was detected in only one patient, a 76-year-old woman, whose diagnosis was myasthenia gravis. The clinical diagnoses of the 129 patients were as follows: 37, headache; 22, cerebrovascular diseases (19, occlusive cerebrovascular diseases); 20, vertigo and/or tinnitus; 12, psychiatric disorders; 5, Parkinson's Syndrome; 2, hypopara thyroidism; 2, Fahr's disease; 2, familial basal ganglia calcification; 2, epilepsy, and 25, miscellaneous (including carcinoma, brain tumor, and trauma). Nervous system abnormalities were observed in 41 of the 129 patients (31.2%). Mental signs, such as disturbance of recent memory, mental retardation, and dementia, were noted in 14 patients. Movement disorders were noted in 13 patients. Other nervous-system abnormalities were sensory disturbances (5 patients) and seizures (4 patients). Abnormal EEG activities were noted in 9 patients; three patients showed epileptic activity, and six had a pathologically slow rhythm.

Clinical studies of the calcification of the basal ganglia as disclosed by computed tomography

Energy Technology Data Exchange (ETDEWEB)

Node, Yoji; Nakazawa, Shozo [Nippon Medical School, Tokyo

1983-04-01

One hundred and twenty-nine of the 12,645 patients (1.0%) were found to have attenuating changes suggesting calcification of the basal ganglia. Thirty-seven of those patients were male and 92 were female. The calcification was bilateral and grossly symmetric in 108 of these patients (83.7%), while it was unilateral in 21 (16.3%). In the unilaterally located cases, 15 were on the left side and 6 were on the right side. In 128 of these patients (99.2%), calcification was located in the globus pallidus. Only one patient, whose diagnosis was hypoparathyroidism, had calcification in both the globus pallidus and the head of the caudate nucleus. The patients' ages ranged from 10 to 85 years (mean, 58), but 88.4% of the patients were more than 40 years old at the time of the CT scanning. The attenuation values of the lesions varied from 35 to 375 EMI units (mean, 55.7). Skull radiographs were performed in 120 of the 129 patients. Calcification was detected in only one patient, a 76-year-old woman, whose diagnosis was myasthenia gravis. The clinical diagnoses of the 129 patients were as follows: 37, headache; 22, cerebrovascular diseases (19, occlusive cerebrovascular diseases); 20, vertigo and/or tinnitus; 12, psychiatric disorders; 5, Parkinson's Syndrome; 2, hypopara thyroidism; 2, Fahr's disease; 2, familial basal ganglia calcification; 2, epilepsy, and 25, miscellaneous (including carcinoma, brain tumor, and trauma). Nervous system abnormalities were observed in 41 of the 129 patients (31.2%). Mental signs, such as disturbance of recent memory, mental retardation, and dementia, were noted in 14 patients. Movement disorders were noted in 13 patients. Other nervous-system abnormalities were sensory disturbances (5 patients) and seizures (4 patients). Abnormal EEG activities were noted in 9 patients; three patients showed epileptic activity, and six had a pathologically slow rhythm.

Clinical studies of the calcification of the basal ganglia as disclosed by computed tomography

International Nuclear Information System (INIS)

Node, Yoji; Nakazawa, Shozo

1983-01-01

One hundred and twenty-nine of the 12,645 patients (1.0%) were found to have attenuating changes suggesting calcification of the basal ganglia. Thirty-seven of those patients were male and 92 were female. The calcification was bilateral and grossly symmetric in 108 of these patients (83.7%), while it was unilateral in 21 (16.3%). In the unilaterally located cases, 15 were on the left side and 6 were on the right side. In 128 of these patients (99.2%), calcification was located in the globus pallidus. Only one patient, whose diagnosis was hypoparathyroidism, had calcification in both the globus pallidus and the head of the caudate nucleus. The patients' ages ranged from 10 to 85 years (mean, 58), but 88.4% of the patients were more than 40 years old at the time of the CT scanning. The attenuation values of the lesions varied from 35 to 375 EMI units (mean, 55.7). Skull radiographs were performed in 120 of the 129 patients. Calcification was detected in only one patient, a 76-year-old woman, whose diagnosis was myasthenia gravis. The clinical diagnoses of the 129 patients were as follows: 37, headache; 22, cerebrovascular diseases (19, occlusive cerebrovascular diseases); 20, vertigo and/or tinnitus; 12, psychiatric disorders; 5, Parkinson's Syndrome; 2, hypopara thyroidism; 2, Fahr's disease; 2, familial basal ganglia calcification; 2, epilepsy, and 25, miscellaneous (including carcinoma, brain tumor, and trauma). Nervous system abnormalities were observed in 41 of the 129 patients (31.2%). Mental signs, such as disturbance of recent memory, mental retardation, and dementia, were noted in 14 patients. Movement disorders were noted in 13 patients. Other nervous-system abnormalities were sensory disturbances (5 patients) and seizures (4 patients). Abnormal EEG activities were noted in 9 patients; three patients showed epileptic activity, and six had a pathologically slow rhythm. (J.P.N.)

Crystallogenesis of bacteriophage P22 tail accessory factor gp26 at acidic and neutral pH

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Cingolani, Gino, E-mail: cingolag@upstate.edu; Andrews, Dewan [Department of Biochemistry and Molecular Biology, SUNY Upstate Medical University, 750 East Adams Street, Syracuse, NY 13210 (United States); Casjens, Sherwood [Department of Pathology, Division of Cell Biology and Immunology, University of Utah Medical School, Salt Lake City, UT 84112 (United States); Department of Biochemistry and Molecular Biology, SUNY Upstate Medical University, 750 East Adams Street, Syracuse, NY 13210 (United States)

2006-05-01

The crystallogenesis of bacteriophage P22 tail-fiber gp26 is described. To study possible pH-induced conformational changes in gp26 structure, native trimeric gp26 has been crystallized at acidic pH (4.6) and a chimera of gp26 fused to maltose-binding protein (MBP-gp26) has been crystallized at neutral and alkaline pH (7-10). Gp26 is one of three phage P22-encoded tail accessory factors essential for stabilization of viral DNA within the mature capsid. In solution, gp26 exists as an extended triple-stranded coiled-coil protein which shares profound structural similarities with class I viral membrane-fusion protein. In the cryo-EM reconstruction of P22 tail extracted from mature virions, gp26 forms an ∼220 Å extended needle structure emanating from the neck of the tail, which is likely to be brought into contact with the cell’s outer membrane when the viral DNA-injection process is initiated. To shed light on the potential role of gp26 in cell-wall penetration and DNA injection, gp26 has been crystallized at acidic, neutral and alkaline pH. Crystals of native gp26 grown at pH 4.6 diffract X-rays to 2.0 Å resolution and belong to space group P2{sub 1}, with a dimer of trimeric gp26 molecules in the asymmetric unit. To study potential pH-induced conformational changes in the gp26 structure, a chimera of gp26 fused to maltose-binding protein (MBP-gp26) was generated. Hexagonal crystals of MBP-gp26 were obtained at neutral and alkaline pH using the high-throughput crystallization robot at the Hauptman–Woodward Medical Research Institute, Buffalo, NY, USA. These crystals diffract X-rays to beyond 2.0 Å resolution. Structural analysis of gp26 crystallized at acidic, neutral and alkaline pH is in progress.

The quaternary structure of the amidase from Geobacillus pallidus RAPc8 is revealed by its crystal packing

International Nuclear Information System (INIS)

Agarkar, Vinod B.; Kimani, Serah W.; Cowan, Donald A.; Sayed, Muhammed F.-R.; Sewell, B. Trevor

2006-01-01

The amidase from G. pallidus RAPc8, a moderate thermophile, converts amides to the corresponding acids and ammonia and has application as an industrial catalyst. RAPc8 amidase has been cloned, expressed and purified, and then crystallized using the hanging-drop vapour-diffusion method. The amidase from Geobacillus pallidus RAPc8, a moderate thermophile, is a member of the nitrilase enzyme superfamily. It converts amides to the corresponding acids and ammonia and has application as an industrial catalyst. RAPc8 amidase has been cloned and functionally expressed in Escherichia coli and has been purified by heat treatment and a number of chromatographic steps. The enzyme was crystallized using the hanging-drop vapour-diffusion method. Crystals produced in the presence of 1.2 M sodium citrate, 400 mM NaCl, 100 mM sodium acetate pH 5.6 were selected for X-ray diffraction studies. A data set having acceptable statistics to 1.96 Å resolution was collected under cryoconditions using an in-house X-ray source. The space group was determined to be primitive cubic P4 2 32, with unit-cell parameter a = 130.49 (±0.05) Å. The structure was solved by molecular replacement using the backbone of the hypothetical protein PH0642 from Pyrococcus horikoshii (PDB code 1j31) with all non-identical side chains substituted with alanine as a probe. There is one subunit per asymmetric unit. The subunits are packed as trimers of dimers with D3 point-group symmetry around the threefold axis in such a way that the dimer interface seen in the homologues is preserved

The pancreatic zymogen granule membrane protein, GP2, binds Escherichia coli type 1 Fimbriae

Directory of Open Access Journals (Sweden)

Lowe Anson W

2009-07-01

Full Text Available Abstract Background GP2 is the major membrane protein present in the pancreatic zymogen granule, and is cleaved and released into the pancreatic duct along with exocrine secretions. The function of GP2 is unknown. GP2's amino acid sequence is most similar to that of uromodulin, which is secreted by the kidney. Recent studies have demonstrated uromodulin binding to bacterial Type 1 fimbria. The fimbriae serve as adhesins to host receptors. The present study examines whether GP2 also shares similar binding properties to bacteria with Type 1 fimbria. Commensal and pathogenic bacteria, including E. coli and Salmonella, express type 1 fimbria. Methods An in vitro binding assay was used to assay the binding of recombinant GP2 to defined strains of E. coli that differ in their expression of Type 1 fimbria or its subunit protein, FimH. Studies were also performed to determine whether GP2 binding is dependent on the presence of mannose residues, which is a known determinant for FimH binding. Results GP2 binds E. coli that express Type 1 fimbria. Binding is dependent on GP2 glycosylation, and specifically the presence of mannose residues. Conclusion GP2 binds to Type 1 fimbria, a bacterial adhesin that is commonly expressed by members of the Enterobacteriacae family.

Proteomics computational analyses suggest that baculovirus GP64 superfamily proteins are class III penetrenes

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Garry Robert F

2008-02-01

Full Text Available Abstract Background Members of the Baculoviridae encode two types of proteins that mediate virus:cell membrane fusion and penetration into the host cell. Alignments of primary amino acid sequences indicate that baculovirus fusion proteins of group I nucleopolyhedroviruses (NPV form the GP64 superfamily. The structure of these viral penetrenes has not been determined. The GP64 superfamily includes the glycoprotein (GP encoded by members of the Thogotovirus genus of the Orthomyxoviridae. The entry proteins of other baculoviruses, group II NPV and granuloviruses, are class I penetrenes. Results Class III penetrenes encoded by members of the Rhabdoviridae and Herpesviridae have an internal fusion domain comprised of beta sheets, other beta sheet domains, an extended alpha helical domain, a membrane proximal stem domain and a carboxyl terminal anchor. Similar sequences and structural/functional motifs that characterize class III penetrenes are located collinearly in GP64 of group I baculoviruses and related glycoproteins encoded by thogotoviruses. Structural models based on a prototypic class III penetrene, vesicular stomatitis virus glycoprotein (VSV G, were established for Thogoto virus (THOV GP and Autographa california multiple NPV (AcMNPV GP64 demonstrating feasible cysteine linkages. Glycosylation sites in THOV GP and AcMNPV GP64 appear in similar model locations to the two glycosylation sites of VSV G. Conclusion These results suggest that proteins in the GP64 superfamily are class III penetrenes.

77 FR 73635 - Northwest Storage GP, LLC; Notice of Application

Science.gov (United States)

2012-12-11

...) 1254 to a proposed 346-megawatt (MW) power plant located within the north industrial area of the Port...] Northwest Storage GP, LLC; Notice of Application Take notice that on November 21, 2012, Northwest Storage GP, LLC. (Northwest) filed with the Federal Energy Regulatory Commission an application under section 7 of...

Zolpidem in Progressive Supranuclear Palsy

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Sandip K. Dash

2013-01-01

Full Text Available Progressive supranuclear palsy (PSP is a progressive neurodegenerative disorder, characterized by motor symptoms, postural instability, personality changes, and cognitive impairment. There is no effective treatment for this disorder. Reduced neurotransmission of GABA in the striatum and globus pallidus may contribute to the symptoms of motor and cognitive symptoms seen in PSP. Zolpidem is a GABA agonist of the benzodiazepine subreceptor BZ1. Here a nondiabetic, normotensive case of PSP is (Progressive Supranuclear Palsy described, which showed improvement in swallowing, speech, and gaze paresis after zolpidem therapy and possible mechanism of actions are discussed. However, more trials are needed with large number of patients to confirm the effectiveness of zolpidem in progressive supranuclear palsy.

Extrahepatic portal vein obstruction with parkinsonism and symmetric hyperintense basal ganglia on T1 weighted MRI

Directory of Open Access Journals (Sweden)

Jayalakshmi Sita

2006-01-01

Full Text Available Abnormal high signal in the globus pallidus on T1 weighted magnetic resonance imaging (MRI of the brain has been well described in patients with chronic liver disease. It may be related to liver dysfunction or portal-systemic shunting. We report a case of extra hepatic portal vein obstruction with portal hypertension and esophageal varices that presented with extra pyramidal features. T1 weighted MRI brain scans showed increased symmetrical signal intensities in the basal ganglia. Normal hepatic function in this patient emphasizes the role of portal- systemic communications in the development of these hyperintensities, which may be due to deposition of paramagnetic substances like manganese in the basal ganglia.

Multifocal dystonia, Clinical feature of Hallervorden-Spatz

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Ghelichkhani H

1998-09-01

Full Text Available Hallervorden-spatz disease is an inherited metabolic disorder with autosomal recessive trait. Onset is in late childhood or early adolescence. Clinical manifestation is variable but pyramidal and extrapyramidal signs are often prominent. Many of patients show progressive dementia and extrapyramidal symptoms. Ataxia or myoclonus is reported in the course of the disease in individual cases. Focal dystonias including tongue, eyelids (blepharospasm and optic atrophy, retinitis pigmentosa, rarely familial parkinsonism are also reported. Pathologically pigmentary degeneration of globus pallidus, substantia nigra (pars reticular and red nucleus is characteristic. In our case the main clinical feature was multifocal dystonia without obvious pyramidal or other extrapyramidal symptoms, and diagnosis was based on clinical and MRI findings.

Introducing a GP copayment in Australia: Who would carry the cost burden?

Science.gov (United States)

Elkins, Rosemary Kate; Schurer, Stefanie

2017-05-01

Recent policy changes designed to contain unsustainable health expenditure growth imply that many more Australians may soon be charged a copayment to consult a GP. We explore the distributional consequences associated with a range of hypothetical GP copayment scenarios using nationally-representative Australian survey data. For each scenario, we estimate the cost burden that individuals and households across the income distribution would need to absorb to maintain their current GP service utilisation. Even when concessional patients are charged a third or a quarter of the non-concessional copayment rate, the average estimated cost burden in the lowest income quartile is typically between three and six times that of the highest, and the average cost burden for women is significantly higher than for men within every income quartile. These disparities are intensified for those with a chronic illness. We conclude that the widespread implementation of GP copayments would disproportionately burden lower-income families, who experience higher rates of chronic illness, higher demand for GP services, and lower capacity to absorb price increases. The regressive nature of GP copayments is reduced when concessional and child patients are exempted entirely, highlighting the importance of supporting GPs-particularly in disadvantaged areas-to maintain bulk-billing arrangements for vulnerable patient groups. Copyright © 2017 Elsevier B.V. All rights reserved.

The Effects of IGF-1 on Trk Expressing DRG Neurons with HIV-gp120- Induced Neurotoxicity.

Science.gov (United States)

Li, Hao; Liu, Zhen; Chi, Heng; Bi, Yanwen; Song, Lijun; Liu, Huaxiang

2016-01-01

HIV envelope glycoprotein gp120 is the main protein that causes HIVassociated sensory neuropathy. However, the underlying mechanisms of gp120-induced neurotoxicity are still unclear. There are lack effective treatments for relieving HIV-related neuropathic symptoms caused by gp120-induced neurotoxicity. In the present study, tyrosine kinase receptor (Trk)A, TrkB, and TrkC expression in primary cultured dorsal root ganglion (DRG) neurons with gp120-induced neurotoxicity was investigated. The effects of IGF-1 on distinct Trk-positive DRG neurons with gp120-induced neurotoxicity were also determined. The results showed that gp120 not only dose-dependently induced DRG neuronal apoptosis and inhibited neuronal survival and neurite outgrowth, but also decreased distinct Trk expression levels. IGF-1 rescued DRG neurons from apoptosis and improved neuronal survival of gp120 neurotoxic DRG neurons in vitro. IGF-1 also improved TrkA and TrkB, but not TrkC, expression in gp120 neurotoxic conditions. The effects of IGF-1 could be blocked by preincubation with the phosphatidylinositol 3-kinase (PI3K) inhibitor LY294002. These results suggested that gp120 may have a wide range of neurotoxicity on different subpopulations of DRG neurons, while IGF-1 might only relieve some subpopulations of DRG neurons with gp120-induced neurotoxicity. These data provide novel information of mechanisms of gp120 neurotoxicity on primary sensory neurons and the potential therapeutic effects of IGF-1 on gp120-induced neurotoxicity.

Exploring resilience in rural GP registrars ? implications for training

OpenAIRE

Walters, Lucie; Laurence, Caroline O.; Dollard, Joanne; Elliott, Taryn; Eley, Diann S.

2015-01-01

Background Resilience can be defined as the ability to rebound from adversity and overcome difficult circumstances. General Practice (GP) registrars face many challenges in transitioning into general practice, and additional stressors and pressures apply for those choosing a career in rural practice. At this time of international rural generalist medical workforce shortages, it is important to focus on the needs of rural GP registrars and how to support them to become resilient health care pr...

Validating glycoprotein non-metastatic melanoma B (gpNMB, osteoactivin), a new biomarker of Gaucher disease.

Science.gov (United States)

Murugesan, Vagishwari; Liu, Jun; Yang, Ruhua; Lin, Haiquin; Lischuk, Andrew; Pastores, Gregory; Zhang, Xiaokui; Chuang, Wei-Lien; Mistry, Pramod K

2018-02-01

In the spleens of Gaucher disease mice and patients, there is a striking elevation of expression of glycoprotein non-Metastatic Melanoma B (gpNMB). We conducted a study in a large cohort of patients with Gaucher disease to assess the utility of serum levels of soluble fragment of gpNMB as a biomarker of disease activity. There was >15-fold elevation of gpNMB in sera of untreated patients with Gaucher disease. gpNMB levels correlated with overall disease severity as well as the severity of individual organ compartments: liver, spleen, bone and hematological disease. Imiglucerase enzyme replacement therapy resulted in significant reduction of gpNMB. Serum levels of gpNMB were highly correlated with accumulation of bioactive lipid substrate of Gaucher disease, glucosylsphingosine as well as established biomarkers, chitotriosidase and chemokine, CCL18. Our results suggest utility of gpNMB as a biomarker of Gaucher disease to monitor individual patients and cohorts of patients for disease progression or response to therapy. Investigation of gpNMB in Gaucher disease pathophysiology is likely to illuminate our understanding disease mechanisms. Copyright © 2016 Elsevier Inc. All rights reserved.

Membrane insertion and assembly of epitope-tagged gp9 at the tip of the M13 phage

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Kuhn Andreas

2011-09-01

Full Text Available Abstract Background Filamentous M13 phage extrude from infected Escherichia coli with a tip structure composed of gp7 and gp9. This tip structure is extended by the assembly of the filament composed of the major coat protein gp8. Finally, gp3 and gp6 terminate the phage structure at the proximal end. Up to now, gp3 has been the primary tool for phage display technology. However, gp7, gp8 and gp9 could also be used for phage display and these phage particles should bind to two different or more surfaces when the modified coat proteins are combined. Therefore, we tested here if the amino-terminal end of gp9 can be modified and whether the modified portion is exposed and detectable on the M13 phage particles. Results The amino-terminal region of gp9 was modified by inserting short sequences that encode antigenic epitopes. We show here that the modified gp9 proteins correctly integrate into the membrane using the membrane insertase YidC exposing the modified epitope into the periplasm. The proteins are then efficiently assembled onto the phage particles. Also extensions up to 36 amino acid residues at the amino-terminal end of gp9 did not interfere with membrane integration and phage assembly. The exposure of the antigenic tags on the phage was visualised with immunogold labelling by electron microscopy and verified by dot blotting with antibodies to the tags. Conclusions Our results suggest that gp9 at the phage tip is suitable for the phage display technology. The modified gp9 can be supplied in trans from a plasmid and fully complements M13 phage with an amber mutation in gene 9. The modified phage tip is very well accessible to antibodies.

Enhanced energy efficiency by means of low temperature differences. Subcritical CO{sub 2} cascade in Globus Handelshof Saarbruecken-Guedingen; Hohe Energieeffizienz durch kleine Temperaturdifferenzen. Unterkritische CO{sub 2}-Kaskade im Globus Handelshof Saarbruecken-Guedingen

Energy Technology Data Exchange (ETDEWEB)

Schmid, Wolfgang [Wolfgang Schmid Pressebuero fuer Technische Gebaeudeausruestung, Muenchen (Germany)

2011-06-15

Green coldness is on the advance for the most German grocery chains. Especially, in the course of the R22 exit, more and more shopping centers opt for natural refrigerants or for a cascade solution with CO{sub 2} for the deep freezing and R404a for a normal refrigeration and air conditioning. Elektro-Kaeltebau Moersch GmbH (Saarburg, Federal Republic of Germany) is one of the green refrigeration system builders from the first hour in the implementation of energy-efficient and climate friendly refrigeration plants in the food sector. One of the current projects is the incorporation of a CO{sub 2}/R404A cascade during the operation in the Globus Handelshof in Saarbruecken-Guedingen (Federal Republic of Germany).

Engineering and exploitation of a fluorescent HIV-1 gp120 for live cell CD4 binding assays

Energy Technology Data Exchange (ETDEWEB)

Costantini, Lindsey M. [Department of Anatomy and Structural Biology, Albert Einstein College of Medicine, 1300 Morris Park Avenue, Bronx, NY 10461 (United States); Irvin, Susan C. [Department of Pediatrics, Albert Einstein College of Medicine, 1300 Morris Park Avenue, Bronx, NY 10461 (United States); Department of Microbiology and Immunology, Albert Einstein College of Medicine, 1300 Morris Park Avenue, Bronx, NY 10461 (United States); Kennedy, Steven C. [Department of Pediatrics, Albert Einstein College of Medicine, 1300 Morris Park Avenue, Bronx, NY 10461 (United States); Guo, Feng [Department of Anatomy and Structural Biology, Albert Einstein College of Medicine, 1300 Morris Park Avenue, Bronx, NY 10461 (United States); Goldstein, Harris; Herold, Betsy C. [Department of Pediatrics, Albert Einstein College of Medicine, 1300 Morris Park Avenue, Bronx, NY 10461 (United States); Department of Microbiology and Immunology, Albert Einstein College of Medicine, 1300 Morris Park Avenue, Bronx, NY 10461 (United States); Snapp, Erik L., E-mail: erik-lee.snapp@einstein.yu.edu [Department of Anatomy and Structural Biology, Albert Einstein College of Medicine, 1300 Morris Park Avenue, Bronx, NY 10461 (United States)

2015-02-15

The HIV-1 envelope glycoprotein, gp120, binds the host cell receptor, CD4, in the initial step of HIV viral entry and infection. This process is an appealing target for the development of inhibitory drugs and neutralizing antibodies. To study gp120 binding and intracellular trafficking, we engineered a fluorescent fusion of the humanized gp120 JRFL HIV-1 variant and GFP. Gp120-sfGFP is glycosylated with human sugars, robustly expressed, and secreted from cultured human cells. Protein dynamics, quality control, and trafficking can be visualized in live cells. The fusion protein can be readily modified with different gp120 variants or fluorescent proteins. Finally, secreted gp120-sfGFP enables a sensitive and easy binding assay that can quantitatively screen potential inhibitors of gp120-CD4 binding on live cells via fluorescence imaging or laser scanning cytometry. This adaptable research tool should aid in studies of gp120 cell biology and the development of novel anti-HIV drugs. - Highlights: • Development of fluorescent protein labeled HIV-1 envelope gp120. • Imaging of gp120 dynamics and trafficking in live cells. • Quantitative visual assay of antibody-mediated inhibition of gp120 binding to CD4 on live cells.

Engineering and exploitation of a fluorescent HIV-1 gp120 for live cell CD4 binding assays

International Nuclear Information System (INIS)

Costantini, Lindsey M.; Irvin, Susan C.; Kennedy, Steven C.; Guo, Feng; Goldstein, Harris; Herold, Betsy C.; Snapp, Erik L.

2015-01-01

The HIV-1 envelope glycoprotein, gp120, binds the host cell receptor, CD4, in the initial step of HIV viral entry and infection. This process is an appealing target for the development of inhibitory drugs and neutralizing antibodies. To study gp120 binding and intracellular trafficking, we engineered a fluorescent fusion of the humanized gp120 JRFL HIV-1 variant and GFP. Gp120-sfGFP is glycosylated with human sugars, robustly expressed, and secreted from cultured human cells. Protein dynamics, quality control, and trafficking can be visualized in live cells. The fusion protein can be readily modified with different gp120 variants or fluorescent proteins. Finally, secreted gp120-sfGFP enables a sensitive and easy binding assay that can quantitatively screen potential inhibitors of gp120-CD4 binding on live cells via fluorescence imaging or laser scanning cytometry. This adaptable research tool should aid in studies of gp120 cell biology and the development of novel anti-HIV drugs. - Highlights: • Development of fluorescent protein labeled HIV-1 envelope gp120. • Imaging of gp120 dynamics and trafficking in live cells. • Quantitative visual assay of antibody-mediated inhibition of gp120 binding to CD4 on live cells

Resistance of a human immunodeficiency virus type 1 isolate to a small molecule CCR5 inhibitor can involve sequence changes in both gp120 and gp41

International Nuclear Information System (INIS)

Anastassopoulou, Cleo G.; Ketas, Thomas J.; Depetris, Rafael S.; Thomas, Antonia M.; Klasse, Per Johan; Moore, John P.

2011-01-01

Here, we describe the genetic pathways taken by a human immunodeficiency virus type 1 (HIV-1) isolate, D101.12, to become resistant to the small molecule CCR5 inhibitor, vicriviroc (VCV), in vitro. Resistant D101.12 variants contained at least one substitution in the gp120 V3 region (H308P), plus one of two patterns of gp41 sequence changes involving the fusion peptide (FP) and a downstream residue: G514V+V535M or M518V+F519L+V535M. Studies of Env-chimeric and point-substituted viruses in peripheral blood mononuclear cells (PBMC) and TZM-bl cells showed that resistance can arise from the cooperative action of gp120 and gp41 changes, while retaining CCR5 usage. Modeling the VCV inhibition data from the two cell types suggests that D101.12 discriminates between high- and low-VCV affinity forms of CCR5 less than D1/85.16, a resistant virus with three FP substitutions.

Induction of regulatory T cells by high-dose gp96 suppresses murine liver immune hyperactivation.

Directory of Open Access Journals (Sweden)

Xinghui Li

Full Text Available Immunization with high-dose heat shock protein gp96, an endoplasmic reticulum counterpart of the Hsp90 family, significantly enhances regulatory T cell (Treg frequency and suppressive function. Here, we examined the potential role and mechanism of gp96 in regulating immune-mediated hepatic injury in mice. High-dose gp96 immunization elicited rapid and long-lasting protection of mice against concanavalin A (Con A-and anti-CD137-induced liver injury, as evidenced by decreased alanine aminotransaminase (ALT levels, hepatic necrosis, serum pro-inflammatory cytokines (IFN-γ, TNF-α, and IL-6, and number of IFN-γ (+ CD4(+ and IFN-γ (+ CD8(+ T cells in the spleen and liver. In contrast, CD4(+CD25(+Foxp3(+ Treg frequency and suppressive function were both increased, and the protective effect of gp96 could be generated by adoptive transfer of Treg cells from gp96-immunized mice. In vitro co-culture experiments demonstrated that gp96 stimulation enhanced Treg proliferation and suppressive function, and up-regulation of Foxp3, IL-10, and TGF-β1 induced by gp96 was dependent on TLR2- and TLR4-mediated NF-κB activation. Our work shows that activation of Tregs by high-dose gp96 immunization protects against Con A- and anti-CD137-induced T cell-hepatitis and provides therapeutic potential for the development of a gp96-based anti-immune hyperactivation vaccine against immune-mediated liver destruction.

Insight derived from molecular dynamics simulations into molecular motions, thermodynamics and kinetics of HIV-1 gp120.

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Peng Sang

Full Text Available Although the crystal structures of the HIV-1 gp120 core bound and pre-bound by CD4 are known, the details of dynamics involved in conformational equilibrium and transition in relation to gp120 function have remained elusive. The homology models of gp120 comprising the N- and C-termini and loops V3 and V4 in the CD4-bound and CD4-unbound states were built and subjected to molecular dynamics (MD simulations to investigate the differences in dynamic properties and molecular motions between them. The results indicate that the CD4-bound gp120 adopted a more compact and stable conformation than the unbound form during simulations. For both the unbound and bound gp120, the large concerted motions derived from essential dynamics (ED analyses can influence the size/shape of the ligand-binding channel/cavity of gp120 and, therefore, were related to its functional properties. The differences in motion direction between certain structural components of these two forms of gp120 were related to the conformational interconversion between them. The free energy calculations based on the metadynamics simulations reveal a more rugged and complex free energy landscape (FEL for the unbound than for the bound gp120, implying that gp120 has a richer conformational diversity in the unbound form. The estimated free energy difference of ∼-6.0 kJ/mol between the global minimum free energy states of the unbound and bound gp120 indicates that gp120 can transform spontaneously from the unbound to bound states, revealing that the bound state represents a high-probability "ground state" for gp120 and explaining why the unbound state resists crystallization. Our results provide insight into the dynamics-and-function relationship of gp120, and facilitate understandings of the thermodynamics, kinetics and conformational control mechanism of HIV-1 gp120.

Why are some patients in treatment for advanced cancer reluctant to consult their GP?

DEFF Research Database (Denmark)

Åbom, Birgit; Pfeiffer, Per

2009-01-01

and therefore consulted the doctor or the staff at the cancer treatment centre before seeking advice from their GP. Some patients found that the GP was not familiar enough with the treatments given; others that they did not want to inconvenience the busy GP with what they perceived to be minor non...

Recrystallized graphite utilization as the first wall material in Globus-M spherical tokamak

International Nuclear Information System (INIS)

Gusev, V.; Novokhatsky, A.N.; Petrov, Y.V.; Sakharov, N.V.; Terukov, E.I.; Trapeznikova, I.N.; Denisov, E.A.; Kurdumov, A.A.; Kompaniec, T.N.; Lebedev, V.M.; Litunovstkii, N.V.; Mazul, I.

2007-01-01

Full text of publication follows: Globus-M spherical tokamak, built at A.F. Ioffe Physico-Technical Institute in 1999 is the first Russian spherical tokamak and has the broad area of research in controlled fusion [1]. Besides small aspect ratio (A=1.5) the distinguishing feature of the tokamak is the powerful energy supply system and auxiliary heating, which give opportunity to reach high specific power deposition up to few W/cm 3 . The utmost plasma current density and B/R ratio among spherical tokamaks allow operation in the range of high plasma densities ∼ 10 20 m -3 . This feature results in big power density loads to the first wall due to small plasma-wall spacing. The area of the first wall amour was gradually increased during few years since 2003, and nowadays reaches almost 90% of the inner vessel surface faced to plasma. Plasma facing protecting tiles are manufactured from recrystallized graphite doped by different elements (Ti, Si, B). Additionally the plasma facing surface was protected by films deposited during boronization. The tendency of short time and long time scale plasma parameters variation are discussed including the plasma performance improvement with increase of protected area. Technology of tiles preparation before installation into the tokamak vessel is briefly described, as well as technology of plasma facing armor preparation before the plasma experiments. Few protecting tiles doped by different elements which were exposed to plasma fluxes of dissimilar power densities for a long time were extracted from the vacuum vessel. The analysis of tiles material (RGT-91) to hold (accumulate) deuterium was made. The distribution of absorbed deuterium concentration along poloidal coordinate was measured. The elementary composition of the films deposited on the tiles was studied by Rutherford back scattering technique and by nuclear resonance reaction method. Other modern methods of surface and structural analysis of material exposed to prolonged

Recrystallized graphite utilization as the first wall material in Globus-M spherical tokamak

Energy Technology Data Exchange (ETDEWEB)

Gusev, V.; Novokhatsky, A.N.; Petrov, Y.V.; Sakharov, N.V.; Terukov, E.I.; Trapeznikova, I.N. [A.F. IOFFE Physico-technical Institute, Russian Academy of Sciences, St Petersburg (Russian Federation); Denisov, E.A.; Kurdumov, A.A.; Kompaniec, T.N. [St. Petersburg State Univ., Research Institute of Physics (Russian Federation); Lebedev, V.M. [B.P. Konstantinov Nuclear Physics Institute, Russian Academy of Science, Gatchina (Russian Federation); Litunovstkii, N.V. [D.V. Efremov Institute of Electrophysical Apparatus, St.Petersburg (Russian Federation); Mazul, I. [Development of Plasma Facing Materials and Components Laboratory, EFREMOV INSTITUTE, St Petersbourg (Russian Federation)

2007-07-01

Full text of publication follows: Globus-M spherical tokamak, built at A.F. Ioffe Physico-Technical Institute in 1999 is the first Russian spherical tokamak and has the broad area of research in controlled fusion [1]. Besides small aspect ratio (A=1.5) the distinguishing feature of the tokamak is the powerful energy supply system and auxiliary heating, which give opportunity to reach high specific power deposition up to few W/cm{sup 3}. The utmost plasma current density and B/R ratio among spherical tokamaks allow operation in the range of high plasma densities {approx} 10{sup 20} m{sup -3}. This feature results in big power density loads to the first wall due to small plasma-wall spacing. The area of the first wall amour was gradually increased during few years since 2003, and nowadays reaches almost 90% of the inner vessel surface faced to plasma. Plasma facing protecting tiles are manufactured from recrystallized graphite doped by different elements (Ti, Si, B). Additionally the plasma facing surface was protected by films deposited during boronization. The tendency of short time and long time scale plasma parameters variation are discussed including the plasma performance improvement with increase of protected area. Technology of tiles preparation before installation into the tokamak vessel is briefly described, as well as technology of plasma facing armor preparation before the plasma experiments. Few protecting tiles doped by different elements which were exposed to plasma fluxes of dissimilar power densities for a long time were extracted from the vacuum vessel. The analysis of tiles material (RGT-91) to hold (accumulate) deuterium was made. The distribution of absorbed deuterium concentration along poloidal coordinate was measured. The elementary composition of the films deposited on the tiles was studied by Rutherford back scattering technique and by nuclear resonance reaction method. Other modern methods of surface and structural analysis of material

Impact of Leishmania metalloprotease GP63 on macrophage signaling

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Isnard, Amandine; Shio, Marina T.; Olivier, Martin

2012-01-01

The intramacrophage protozoan parasites of Leishmania genus have developed sophisticated ways to subvert the innate immune response permitting their infection and propagation within the macrophages of the mammalian host. Several Leishmania virulence factors have been identified and found to be of importance for the development of leishmaniasis. However, recent findings are now further reinforcing the critical role played by the zinc-metalloprotease GP63 as a virulence factor that greatly influence host cell signaling mechanisms and related functions. GP63 has been found to be involved not only in the cleavage and degradation of various kinases and transcription factors, but also to be the major molecule modulating host negative regulatory mechanisms involving for instance protein tyrosine phosphatases (PTPs). Those latter being well recognized for their pivotal role in the regulation of a great number of signaling pathways. In this review article, we are providing a complete overview about the role of Leishmania GP63 in the mechanisms underlying the subversion of macrophage signaling and functions. PMID:22919663

Incorporating and evaluating an integrated gender-specific medicine curriculum: a survey study in Dutch GP training

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Dielissen, Patrick W; Bottema, Ben JAM; Verdonk, Petra; Lagro-Janssen, Toine LM

2009-01-01

Background We recently set standards for gender-specific medicine training as an integrated part of the GP training curriculum. This paper describes the programme and evaluation of this training. Methods The programme is designed for GP registrars throughout the 3-year GP training. The modules emphasize interaction, application, and clinically integrated learning and teaching methods in peer groups. In 2005 - 2008, after completion of each tutorial, GP registrars were asked to fill in a questionnaire on a 5-point Likert scale to assess the programme's methods and content. GP registrars were also asked to identify two learning points related to the programme. Results The teaching programme consists of five 3-hour modules that include gender themes related to and frequently seen by GPs such as in doctor-patient communication and cardiovascular disease. GP registrars evaluated the training course positively. The written learning points suggest that GP registrars have increased their awareness of why attention to gender-specific information is relevant. Conclusion In summary, gender-specific medicine training has been successfully integrated into an existing GP training curriculum. The modules and teaching methods are transferable to other training institutes for postgraduate training. The evaluation of the teaching programme shows a positive impact on GP registrars' gender awareness. PMID:19737396

Incorporating and evaluating an integrated gender-specific medicine curriculum: a survey study in Dutch GP training

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Lagro-Janssen Toine LM

2009-09-01

Full Text Available Abstract Background We recently set standards for gender-specific medicine training as an integrated part of the GP training curriculum. This paper describes the programme and evaluation of this training. Methods The programme is designed for GP registrars throughout the 3-year GP training. The modules emphasize interaction, application, and clinically integrated learning and teaching methods in peer groups. In 2005 - 2008, after completion of each tutorial, GP registrars were asked to fill in a questionnaire on a 5-point Likert scale to assess the programme's methods and content. GP registrars were also asked to identify two learning points related to the programme. Results The teaching programme consists of five 3-hour modules that include gender themes related to and frequently seen by GPs such as in doctor-patient communication and cardiovascular disease. GP registrars evaluated the training course positively. The written learning points suggest that GP registrars have increased their awareness of why attention to gender-specific information is relevant. Conclusion In summary, gender-specific medicine training has been successfully integrated into an existing GP training curriculum. The modules and teaching methods are transferable to other training institutes for postgraduate training. The evaluation of the teaching programme shows a positive impact on GP registrars' gender awareness.

Malignant Neuroleptic Syndrome following Deep Brain Stimulation Surgery of Globus Pallidus Pars Internus in Cerebral Palsy

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Jae Meen Lee

2016-02-01

Full Text Available Neuroleptic malignant syndrome (NMS is a rare but potentially lethal outcome caused by sudden discontinuation or dose reduction of dopaminergic agents. We report an extremely rare case of NMS after deep brain stimulation (DBS surgery in a cerebral palsy (CP patient without the withdrawal of dopaminergic agents. A 19-year-old girl with CP was admitted for DBS due to medically refractory dystonia and rigidity. Dopaminergic agents were not stopped preoperatively. DBS was performed uneventfully under monitored anesthesia. Dopaminergic medication was continued during the postoperative period. She manifested spasticity and muscle rigidity, and was high fever resistant to anti-pyretic drugs at 2 h postoperative. At postoperative 20 h, she suffered cardiac arrest and expired, despite vigorous cardiopulmonary resuscitation. NMS should be considered for hyperthermia and severe spasticity in CP patients after DBS surgery, irrespective of continued dopaminergic medication.

65 nm LP/GP mix low cost platform for multi-media wireless and consumer applications

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Tavel, B.; Duriez, B.; Gwoziecki, R.; Basso, M. T.; Julien, C.; Ortolland, C.; Laplanche, Y.; Fox, R.; Sabouret, E.; Detcheverry, C.; Boeuf, F.; Morin, P.; Barge, D.; Bidaud, M.; Biénacel, J.; Garnier, P.; Cooper, K.; Chapon, J. D.; Trouiller, Y.; Belledent, J.; Broekaart, M.; Gouraud, P.; Denais, M.; Huard, V.; Rochereau, K.; Difrenza, R.; Planes, N.; Marin, M.; Boret, S.; Gloria, D.; Vanbergue, S.; Abramowitz, P.; Vishnubhotla, L.; Reber, D.; Stolk, P.; Woo, M.; Arnaud, F.

2006-04-01

A complete 65 nm CMOS platform, called LP/GP Mix, has been developed employing thick oxide transistor (IO), Low Power (LP) and General Purpose (GP) devices on the same chip. Dedicated to wireless multi-media and consumer applications, this new triple gate oxide platform is low cost (+1mask only) and saves over 35% of dynamic power with the use of the low operating voltage GP. The LP/GP mix shows competitive digital performance with a ring oscillator (FO = 1) speed equal to 7 ps per stage (GP) and 6T-SRAM static power lower than 10 pA/cell (LP). Compatible with mixed-signal design requirements, transistors show high voltage gain, low mismatch factor and low flicker noise. Moreover, to address mobile phone demands, excellent RF performance has been achieved with FT = 160 GHz for LP and 280 GHz for GP nMOS transistors.

Production and characterization of a new antibacterial peptide obtained from Aeribacillus pallidus SAT4.

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Muhammad, Syed Aun; Ahmed, Safia

2015-12-01

A novel thermophilic bacterial strain of the genus Aeribacillus was isolated from Thar Dessert Pakistan. This strain showed significant antibacterial activity against Micrococcus luteus , Staphylococcus aureus , and Pseudomonas aerugin osa. The strain coded as 'SAT4' resembled with Aeribacillus pallidus in the morphological, biochemical and molecular tests. The production of antibacterial metabolites by SAT4 was optimized. These active metabolites were precipitated by 50% ammonium sulphate and purified through sephadex G-75 gel permeation chromatography and reverse phase HPLC. The molecular weight of 37 kDa was examined by SDS-PAGE. The structural elucidation of the purified product was studied by FTIR, 1 H and 13 C NMR. The X-ray diffractions study showed that the crystals belonged to the primitive orthorhombic lattice ( a  = 12.137, b  = 13.421, c  = 14.097 Å) and 3D structure (proposed name: Aeritracin) was determined. This new peptide antibacterial molecule can get a position in pharmaceutical and biotechnological industrial research.

Esters of the Marine-Derived Triterpene Sipholenol A Reverse P-GP-Mediated Drug Resistance

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Yongchao Zhang

2015-04-01

Full Text Available Our previous studies showed that several sipholane triterpenes, sipholenol A, sipholenone E, sipholenol L and siphonellinol D, have potent reversal effect for multidrug resistance (MDR in cancer cells that overexpressed P-glycoprotein (P-gp/ABCB1. Through comparison of cytotoxicity towards sensitive and multi-drug resistant cell lines, we identified that the semisynthetic esters sipholenol A-4-O-acetate and sipholenol A-4-O-isonicotinate potently reversed P-gp-mediated MDR but had no effect on MRP1/ABCC1 and BCRP/ABCG2-mediated MDR. The results from [3H]-paclitaxel accumulation and efflux studies suggested that these two triterpenoids were able to increase the intracellular accumulation of paclitaxel by inhibiting its active efflux. In addition, western blot analysis revealed that these two compounds did not alter the expression levels of P-gp when treated up to 72 h. These sipholenol derivatives also stimulated the ATPase activity of P-gp membranes, which suggested that they might be substrates of P-gp. Moreover, in silico molecular docking studies revealed the virtual binding modes of these two compounds into human homology model of P-gp. In conclusion, sipholenol A-4-O-acetate and sipholenol A-4-O-isonicotinate efficiently inhibit the P-gp and may represent potential reversal agents for the treatment of multidrug resistant cancers.

The Astringency of the GP Algorithm for Forecasting Software Failure Data Series

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Yong-qiang Zhang

2007-05-01

Full Text Available The forecasting of software failure data series by Genetic Programming (GP can be realized without any assumptions before modeling. This discovery has transformed traditional statistical modeling methods as well as improved consistency for model applicability. The individuals' different characteristics during the evolution of generations, which are randomly changeable, are treated as Markov random processes. This paper also proposes that a GP algorithm with "optimal individuals reserved strategy" is the best solution to this problem, and therefore the adaptive individuals finally will be evolved. This will allow practical applications in software reliability modeling analysis and forecasting for failure behaviors. Moreover it can verify the feasibility and availability of the GP algorithm, which is applied to software failure data series forecasting on a theoretical basis. The results show that the GP algorithm is the best solution for software failure behaviors in a variety of disciplines.

Disrupting neuronal transmission: Mechanism of DBS?

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Satomi eChiken

2014-03-01

Full Text Available Applying high-frequency stimulation to deep brain rain structure, known as deep brain stimulation (DBS, has now been recognized an effective therapeutic option for a wide range of neurological and psychiatric disorders. DBS targeting the basal ganglia thalamo-cortical loop, especially the internal segment of the globus pallidus, subthalamic nucleus and thalamus, has been widely employed as a successful surgical therapy for movement disorders, such as Parkinson’s disease, dystonia and tremor. However, the neurophysiological mechanism underling the action of DBS remains unclear and is still under debate: does DBS inhibit or excite local neuronal elements? In this review, we will examine this question and propose the alternative interpretation: DBS dissociates inputs and outputs, resulting in disruption of abnormal signal transmission.

Renal Failure in Dementia with Lewy Bodies Presenting as Catatonia

Science.gov (United States)

Fekete, Robert

2013-01-01

Catatonia, originally described by Karl Kahlbaum in 1874, may be regarded as a set of clinical features found in a subtype of schizophrenia, but the syndrome may also stem from organic causes including vascular parkinsonism, brain masses, globus pallidus lesions, metabolic derangements, and pharmacologic agents, especially first generation antipsychotics. Catatonia may include paratonia, waxy flexibility (cerea flexibilitas), stupor, mutism, echolalia, and catalepsy (abnormal posturing). A case of catatonia as a result of acute renal failure in a patient with dementia with Lewy bodies is described. This patient recovered after intravenous fluid administration and reinstitution of the atypical dopamine receptor blocking agent quetiapine, but benzodiazepines and amantadine are additional possible treatments. Recognition of organic causes of catatonia leads to timely treatment and resolution of the syndrome. PMID:23466522

Synthesis and preliminary biological evaluation of [{sup 123}I]Me{sub 2}Pyr, a new potential ligand for imaging of central cannabinoid CB{sub 1} receptors

Energy Technology Data Exchange (ETDEWEB)

Gielow, P. [Department of Nuclear Medicine, University School of Medicine, Carl-Neuberg-Str. 1, D-30625 Hannover (Germany)]. E-mail: gielow.peter@mh-hannover.de; Klinge, P. [International Neuroscience Institute, Alexis Carrel Str. 4, D-30625 Hannover (Germany); Knapp, W.H. [Department of Nuclear Medicine, University School of Medicine, Carl-Neuberg-Str. 1, D-30625 Hannover (Germany); Berding, G. [Department of Nuclear Medicine, University School of Medicine, Carl-Neuberg-Str. 1, D-30625 Hannover (Germany)

2006-07-15

A synthesis of 1-(2,4-dichlorophenyl)-5-(4-[{sup 123}I]iodophenyl)-4-methyl-1H-pyrazole -3-carboxylic acid N',N'-dimethyl-hydrazide ([{sup 123}I]Me{sub 2}Pyr), a new radioiodinated analogue of the high-affinity cannabinoid CB{sub 1} receptor antagonist SR141716A, is described. Labelling was achieved by radioiododestannylation of the tributylstannyl precursor with [{sup 123}I]iodide in the presence of chloramine T. HPLC purification afforded the labelled product in 48% radiochemical yield. Preliminary rat brain biodistribution studies with the {sup 125}I labelled compound revealed high uptake in the substantia nigra, the globus pallidus externus and the cerebellum, which is consistent with the known distribution of CB{sub 1} receptors.

High signal of the striatum in sporadic Creutzfeldt-Jakob disease: sequential change on T2-weighted MRI

International Nuclear Information System (INIS)

Uemura, A.; O'uchi, T.; Sakamoto, T.; Yashiro, N.

2002-01-01

The object of this study is to describe the sequential change of high signal of the striatum on T2-weighted MRI in sporadic Creutzfeldt-Jakob disease (CJD). Three cases of autopsy-proven sporadic CJD and a total of 18 serial MR images are included in this study. The degree of high signal of the striatum on T2-weighted MRI was evaluated by two neuroradiologists and divided into four grades by mutual agreement. Initial MRI of all three cases showed a slightly high signal of the bilateral striatum, and the conspicuity of the high signal became more prominent as the disease progressed. In each case the pathological change of striatum and globus pallidus was compared with the high signal on the last MR image. (orig.)

High signal of the striatum in sporadic Creutzfeldt-Jakob disease: sequential change on T2-weighted MRI

Energy Technology Data Exchange (ETDEWEB)

Uemura, A.; O' uchi, T.; Sakamoto, T.; Yashiro, N. [Department of Radiology, Kameda Medical Center, Kamogawa, Chiba (Japan)

2002-04-01

The object of this study is to describe the sequential change of high signal of the striatum on T2-weighted MRI in sporadic Creutzfeldt-Jakob disease (CJD). Three cases of autopsy-proven sporadic CJD and a total of 18 serial MR images are included in this study. The degree of high signal of the striatum on T2-weighted MRI was evaluated by two neuroradiologists and divided into four grades by mutual agreement. Initial MRI of all three cases showed a slightly high signal of the bilateral striatum, and the conspicuity of the high signal became more prominent as the disease progressed. In each case the pathological change of striatum and globus pallidus was compared with the high signal on the last MR image. (orig.)

Magnetic resonance imaging of dystonic states

International Nuclear Information System (INIS)

Rutledge, J.N.; Hilal, S.K.; Silver, A.J.; Defendini, R.; Fahn, S.

1988-01-01

Interest in movement disorders is heightened by the recent capability of mapping the distribution of macromolecular complexes of Fe(III) in the brain using heavily T2-weighted images. This is accomplished through contrast caused by their T2 effect, a local inhomogeneity in the magnetic field which dephases spin and results in loss of signal. It is a unique characteristic of the extra-pyramidal system that its nuclei contain high concentrations of iron. The areas especially rich are the substantia nigra and globus pallidus. Lesser amounts of iron are found in the red nucleus, dentate nucleus, nigrostriatal tract, putamen, and caudate nucleus. The reasons for increased concentration of iron in nuclei related to movement are incompletely understood and are reviewed in this chapter

A Case Of Transient Ischemic Attack Presenting As Hemichroea

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Hasan Hüseyin Özdemir

2013-12-01

Full Text Available Chorea is defined as; involuntary movements of the distal parts of limbs which have arrhythmic, rapid, bouncing or smooth, simple or complex properties. Choreiform movements occur when putamen, globus pallidus and subthalamic nucleus are affected. Chorea can be observed during the course of metabolic and vascular diseases, neurodegenerative or hereditary diseases. Chorea may be a rare symptom of cerebral hypoperfusion. Transient ischemic attack is an event that occurs in short term characterized by a temporary ischemia of brain. A wide variety of symptoms can be seen depending on the localization of cerebral hypoperfusion. Hemichorea is a very rare finding observed during transient ischemic attacks. In this article hemichorea in a case of symptomatic transient ischemic attack is discussed with relevant literature.

An interesting case of metabolic dystonia: L-2 hydroxyglutaric aciduria

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Padma Balaji

2014-01-01

Full Text Available L-2-hydroxyglutaric aciduria (L-2-HGA, a neurometabolic disorder caused by mutations in the L-2 hydroxyglutarate dehydrogenase (L-2-HGDH gene, presents with psychomotor retardation, cerebellar ataxia, extrapyramidal symptoms, macrocephaly and seizures. Characteristic magnetic resonance imaging findings include subcortical cerebral white matter abnormalities with T2 hyperintensities of the dentate nucleus, globus pallidus, putamen and caudate nucleus. The diagnosis can be confirmed by elevated urinary L-2 hydroxyglutaric acid and mutational analysis of the L-2-HGDH gene. We report two siblings with dystonia diagnosed by classical neuroimaging findings with elevated urinary 2 hydroxyglutaric acid. Riboflavin therapy has shown promising results in a subset of cases, thus highlighting the importance of making the diagnosis in these patients.

Cerebellar and basal ganglion involvement in Langerhans cell histiocytosis

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Saatci, I.; Baskan, O.; Haliloglu, M.; Aydingoz, U. [Department of Radiology, Hacettepe University Hospital, Sihhiye 06100, Ankara (Turkey)

1999-06-01

Langerhans cell histiocytosis (LCH) is a disease of unknown cause characterised by proliferation of histiocytic granulomas in tissues; the primary cerebral manifestation is diabetes insipidus caused by hypothalamic infiltration. We present a patient in whom, except for the absence of high signal on T 1 weighting in the posterior pituitary, consistent with central diabetes insipidus, MRI showed no evidence of hypothalamic involvement by histiocytosis, despite the long duration of the disease. However, there was bilateral, symmetrical involvement of the cerebellum and globus pallidus in addition to a calvarial lesion. High signal in the cerebellar white matter on T 2-weighted images may represent demyelination, gliosis and cell loss, as previously reported on pathologic examination. (orig.) With 5 figs., 22 refs.

Relationship between child epilepsy and MRI findings in von Recklinghausen Neurofibromatosis (NF 1)

International Nuclear Information System (INIS)

Yasujima, Hidehiro; Komatsu, Mikio; Sakurai, Takashi; Kodama, Soichi

1994-01-01

Fourteen children meeting the NIH consensus diagnostic criteria for NF 1 were evaluated at the Department of Pediatrics, Himeji Red Cross Hospital. MRI and EEG were examined in all patients, respectively. Four of 14 patients had a history of epilepsy, two had suffered West syndrome, one had complex partial seizures and one had secondary generalized partial epilepsy. Seven (50%) of 14 patients showed abnormal MRI; three (75%) of 4 patients with epilepsy and four (40%) of 10 patients with epilepsy showed low intensity on T 1 -weighted images and hyperintensity on T 2 -weighted images in the globus pallidus and brain stem. These results suggest that children with NF 1 have a spectrum of MRI abnormalities, irrespective of existence of epilepsy. (author)

Occlusion of Heubner's artery

International Nuclear Information System (INIS)

Sato, Manabu; Kidooka, Minoru

1982-01-01

A case of occlusion of the left Heubner's artery in a right-handed, 51-year-old man is reported. Cardinal clinical features were transient right hemiparesis and mental disturbance, especially intellectual defect. Low density areas were found at CT in the globus pallidus, putamen, anterior limb of the internal capsule and a part of the caudate nucleus. It is well known that the occlusion of the Heubner's artery causes transient motor paresis of upper extremity on the contralaterl side. However, in the case where the Heubner's artery is remarkably well developed when compared with the medial striate arteries as was the case in this patient, it should be noted that the occlusion of the Heubner's artery may well causes grave mental disturbance, in addition. (author)

Family effects on the rurality of GP's work location: a longitudinal panel study.

Science.gov (United States)

McGrail, Matthew R; Russell, Deborah J; O'Sullivan, Belinda G

2017-10-19

Reduced opportunities for children's schooling and spouse's/partner's employment are identified internationally as key barriers to general practitioners (GPs) working rurally. This paper aims to measure longitudinal associations between the rurality of GP work location and having (i) school-aged children and (ii) a spouse/partner in the workforce. Participants included 4377 GPs responding to at least two consecutive annual surveys of the Medicine in Australia: Balancing Employment and Life (MABEL) national longitudinal study between 2008 and 2014. The main outcome, GP work location, was categorised by remoteness and population size. Five sequential binary school-age groupings were defined according to whether a GP had no children, only preschool children (aged 0-4 years), at least one primary-school child (aged 5-11 years), at least one child in secondary school (aged 12-18 years), and all children older than secondary school (aged ≥ 19). Partner in the workforce was defined by whether a GP had a partner who was either currently working or looking for work, or not. Separate generalised estimating equation models, which aggregated consecutive annual observations per GP, tested associations between work location and (i) educational stages and (ii) partner employment, after adjusting for key covariates. Male GPs with children in secondary school were significantly less likely to work rurally (inclusive of > 50 000 regional centres through to the smallest rural towns of locations were not significantly associated with the educational stage of their children. Having a partner in the workforce was not associated with work location for male GPs, whereas female GPs with a partner in the workforce were significantly less likely to work in smaller rural/remote communities (location is related to key family needs which differ according to GP gender and educational stages of children. Such non-professional factors are likely to be dynamic across the GP's lifespan and

Immunodiagnosis of paracoccidioidomycosis due to Paracoccidioides brasiliensis using a latex test: detection of specific antibody anti-gp43 and specific antigen gp43.

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Priscila Oliveira Dos Santos

2015-02-01

Full Text Available Paracoccidioidomycosis (PCM is a life-threatening systemic disease and is a neglected public health problem in many endemic regions of Latin America. Though several diagnostic methods are available, almost all of them present with some limitations.A latex immunoassay using sensitized latex particles (SLPs with gp43 antigen, the immunodominant antigen of Paracoccidioides brasiliensis, or the monoclonal antibody mAb17c (anti-gp43 was evaluated for antibody or antigen detection in sera, cerebrospinal fluid (CSF, and bronchoalveolar lavage (BAL from patients with PCM due to P. brasiliensis. The gp43-SLPs performed optimally to detect specific antibodies with high levels of sensitivity (98.46%, 95% CI 91.7-100.0, specificity (93.94%, 95% CI 87.3-97.7, and positive (91.4% and negative (98.9% predictive values. In addition, we propose the use of mAb17c-SLPs to detect circulating gp43, which would be particularly important in patients with immune deficiencies who fail to produce normal levels of immunoglobulins, achieving good levels of sensitivity (96.92%, 95% CI 89.3-99.6, specificity (88.89%, 95% CI 81.0-94.3, and positive (85.1% and negative (97.8% predictive values. Very good agreement between latex tests and double immune diffusion was observed for gp43-SLPs (k = 0.924 and mAb17c-SLPs (k = 0.850, which reinforces the usefulness of our tests for the rapid diagnosis of PCM in less than 10 minutes. Minor cross-reactivity occurred with sera from patients with other fungal infections. We successfully detected antigens and antibodies from CSF and BAL samples. In addition, the latex test was useful for monitoring PCM patients receiving therapy.The high diagnostic accuracy, low cost, reduced assay time, and simplicity of this new latex test offer the potential to be commercialized and makes it an attractive diagnostic assay for use not only in clinics and medical mycology laboratories, but mainly in remote locations with limited laboratory infrastructure

HIV-1 specific IgA detected in vaginal secretions of HIV uninfected women participating in a microbicide trial in Southern Africa are primarily directed toward gp120 and gp140 specificities.

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Kelly E Seaton

Full Text Available Many participants in microbicide trials remain uninfected despite ongoing exposure to HIV-1. Determining the emergence and nature of mucosal HIV-specific immune responses in such women is important, since these responses may contribute to protection and could provide insight for the rational design of HIV-1 vaccines.We first conducted a pilot study to compare three sampling devices (Dacron swabs, flocked nylon swabs and Merocel sponges for detection of HIV-1-specific IgG and IgA antibodies in vaginal secretions. IgG antibodies from HIV-1-positive women reacted broadly across the full panel of eight HIV-1 envelope (Env antigens tested, whereas IgA antibodies only reacted to the gp41 subunit. No Env-reactive antibodies were detected in the HIV-negative women. The three sampling devices yielded equal HIV-1-specific antibody titers, as well as total IgG and IgA concentrations. We then tested vaginal Dacron swabs archived from 57 HIV seronegative women who participated in a microbicide efficacy trial in Southern Africa (HPTN 035. We detected vaginal IgA antibodies directed at HIV-1 Env gp120/gp140 in six of these women, and at gp41 in another three women, but did not detect Env-specific IgG antibodies in any women.Vaginal secretions of HIV-1 infected women contained IgG reactivity to a broad range of Env antigens and IgA reactivity to gp41. In contrast, Env-binding antibodies in the vaginal secretions of HIV-1 uninfected women participating in the microbicide trial were restricted to the IgA subtype and were mostly directed at HIV-1 gp120/gp140.

Which positive factors determine the GP satisfaction in clinical practice? A systematic literature review.

Science.gov (United States)

Le Floch, B; Bastiaens, H; Le Reste, J Y; Lingner, H; Hoffman, R D; Czachowski, S; Assenova, R; Koskela, T H; Klemenc-Ketis, Z; Nabbe, P; Sowinska, A; Montier, T; Peremans, L

2016-09-13

Looking at what makes General Practitioners (GPs) happy in their profession, may be important in increasing the GP workforce in the future. The European General Practice Research Network (EGPRN) created a research team (eight national groups) in order to clarify the factors involved in GP job satisfaction throughout Europe. The first step of this study was a literature review to explore how the satisfaction of GPs had been studied before. The research question was "Which factors are related to GP satisfaction in Clinical Practice?" Systematic literature review according to the PRISMA statement. The databases searched were Pubmed, Embase and Cochrane. All articles were identified, screened and included by two separate research teams, according to inclusion or exclusion criteria. Then, a qualitative appraisal was undertaken. Next, a thematic analysis process was undertaken to capture any issue relevant to the research question. The number of records screened was 458. One hundred four were eligible. Finally, 17 articles were included. The data revealed 13 subthemes, which were grouped into three major themes for GP satisfaction. First there were general profession-related themes, applicable to many professions. A second group of issues related specifically to a GP setting. Finally, a third group was related to professional life and personal issues. A number of factors leading to GP job satisfaction, exist in literature They should be used by policy makers within Europe to increase the GP workforce. The research team needs to undertake qualitative studies to confirm or enhance those results.

'Just a GP': a mixed method study of undermining of general practice as a career choice in the UK.

Science.gov (United States)

Alberti, Hugh; Banner, Kimberley; Collingwood, Helen; Merritt, Kymberlee

2017-11-03

Failure to recruit sufficient applicants to general practice (GP) training has been a problem both nationally and internationally for many years and undermining of GP is one possible contributing factor. The aim of our study was to ascertain what comments, both negative and positive, are being made in UK clinical settings to GP trainees about GP and to further explore these comments and their influence on career choice. We conducted a mixed methods study. We surveyed all foundation doctors and GP trainees within one region of Health Education England regarding any comments they experienced relating to a career in GP. We also conducted six focus groups with early GP trainees to discuss any comments that they experienced and whether these comments had any influence on their or others career choice. Positive comments reported by trainees centred around the concept that choosing GP is a positive, family-focused choice which facilities a good work-life balance. Workload was the most common negative comment, alongside the notion of being 'just a GP'; the belief that GP is boring, a waste of training and a second-class career choice. The reasons for and origin of the comments are multifactorial in nature. Thematic analysis of the focus groups identified key factors such as previous exposure to and experience of GP, family members who were GPs, GP role models, demographics of the clinician and referral behaviour. Trainees perceived that negative comments may be discouraging others from choosing GP as a career. Our study demonstrates that negative comments towards GP as a career do exist within clinical settings and are having a potential impact on poor recruitment rates to GP training. We have identified areas in which further negative comments could be prevented by changing perceptions of GP as a career. Additional time spent in GP as undergraduates and postgraduates, and positive GP role models, could particularly benefit recruitment. We recommend that undermining of GP

Conformational alterations in the CD4 binding cavity of HIV-1 gp120 influencing gp120-CD4 interactions and fusogenicity of HIV-1 envelopes derived from brain and other tissues

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Ramsland Paul A

2011-06-01

Full Text Available Abstract Background CD4-binding site (CD4bs alterations in gp120 contribute to HIV-1 envelope (Env mediated fusogenicity and the ability of gp120 to utilize low levels of cell-surface CD4. In a recent study, we constructed three-dimensional models of gp120 to illustrate CD4bs conformations associated with enhanced fusogenicity and enhanced CD4-usage of a modestly-sized panel of blood-derived HIV-1 Envs (n = 16. These conformations were characterized by a wider aperture of the CD4bs cavity, as constrained by the inner-most atoms at the gp120 V1V2 stem and the V5 loop. Here, we sought to provide further validation of the utility of these models for understanding mechanisms that influence Env function, by characterizing the structure-function relationships of a larger panel of Envs derived from brain and other tissues (n = 81. Findings Three-dimensional models of gp120 were generated by our recently validated homology modelling protocol. Analysis of predicted CD4bs structures showed correlations between the aperture width of the CD4bs cavity and ability of the Envs to mediate cell-cell fusion, scavenge low-levels of cell-surface CD4, bind directly to soluble CD4, and bind to the Env mAb IgG1b12 whose epitope overlaps the gp120 CD4bs. These structural alterations in the CD4bs cavity were associated with repositioning of the V5 loop. Conclusions Using a large, independent panel of Envs, we can confirm the utility of three-dimensional gp120 structural models for illustrating CD4bs alterations that can affect Env function. Furthermore, we now provide new evidence that these CD4bs alterations augment the ability of gp120 to interact with CD4 by increasing the exposure of the CD4bs.

Larger Subcortical Gray Matter Structures and Smaller Corpora Callosa at Age 5 Years in HIV Infected Children on Early ART

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Steven R. Randall

2017-11-01

Full Text Available Sub-Saharan Africa is home to 90% of HIV infected (HIV+ children. Since the advent of antiretroviral therapy (ART, HIV/AIDS has transitioned to a chronic condition where central nervous system (CNS damage may be ongoing. Although, most guidelines recommend early ART to reduce CNS viral reservoirs, the brain may be more vulnerable to potential neurotoxic effects of ART during the rapid development phase in the first years of life. Here we investigate differences in subcortical volumes between 5-year-old HIV+ children who received early ART (before age 18 months and uninfected children using manual tracing of Magnetic Resonance Images. Participants included 61 Xhosa children (43 HIV+/18 uninfected, mean age = 5.4 ± 0.3 years, 25 male from the children with HIV early antiretroviral (CHER trial; 27 children initiated ART before 12 weeks of age (ART-Before12Wks and 16 after 12 weeks (ART-After12Wks. Structural images were acquired on a 3T Allegra MRI in Cape Town and manually traced using MultiTracer. Volumetric group differences (HIV+ vs. uninfected; ART-Before12Wks vs. ART-After12Wks were examined for the caudate, nucleus accumbens (NA, putamen (Pu, globus pallidus (GP, and corpus callosum (CC, as well as associations within infected children of structure volumes with age at ART initiation and CD4/CD8 as a proxy for immune health. HIV+ children had significantly larger NA and Pu volumes bilaterally and left GP volumes than controls, whilst CC was smaller. Bilateral Pu was larger in both treatment groups compared to controls, while left GP and bilateral NA were enlarged only in ART-After12Wks children. CC was smaller in both treatment groups compared to controls, and smaller in ART-After12Wks compared to ART-Before12Wks. Within infected children, delayed ART initiation was associated with larger Pu volumes, effects that remained significant when controlling for sex and duration of treatment interruption (left β = 0.447, p = 0.005; right β = 0

Triage of febrile children at a GP cooperative : determinants of a consultation

NARCIS (Netherlands)

Monteny, Miriam; Berger, Marjolein Y.; van der Wouden, Johannes C.; Broekman, Berth J.; Koes, Bart W.

Background Most febrile children contacting a GP cooperative are seen by a GP, although the incidence of serious illness is low. The guidelines for triage might not be suitable in primary care. Aim To investigate the determinants related to the outcome of triage in febrile children. Design of study

Influences on GP coping and resilience: a qualitative study in primary care.

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Cheshire, Anna; Ridge, Damien; Hughes, John; Peters, David; Panagioti, Maria; Simon, Chantal; Lewith, George

2017-06-01

'Neoliberal' work policies, austerity, NHS restructuring, and increased GP consultation rates provide the backdrop against increasing reports of GP burnout and an impending shortage of GPs. To explore GPs' experiences of workplace challenges and stresses, and their coping strategies, particularly focusing on understanding the impact of recent NHS workplace change. Study design was qualitative, with data collected from two focus groups and seven one-to-one telephone interviews. Focus groups and one-to-one telephone interviews explored the experiences of GPs currently practising in England, recruited through convenience sampling. Data were collected using a semi-structured interview approach and analysed using thematic analysis. There were 22 GP participants recruited: focus groups ( n = 15) and interviews ( n = 7). Interviewees understood GPs to be under intense and historically unprecedented pressures, which were tied to the contexts in which they work, with important moral implications for 'good' doctoring. Many reported that being a full-time GP was too stressful: work-related stress led to mood changes, sleep disruption, increases in anxiety, and tensions with loved ones. Some had subsequently sought ways to downsize their clinical workload. Workplace change resulted in little time for the things that helped GP resilience: a good work-life balance and better contact with colleagues. Although some GPs were coping better than others, GPs acknowledged that there was only so much an individual GP could do to manage their stress, given the external work issues they faced. GPs experience their emotional lives and stresses as being meaningfully shaped by NHS factors. To support GPs to provide effective care, resilience building should move beyond the individual to include systemic work issues. © British Journal of General Practice 2017.

Blended learning in CME: the perception of GP trainers.

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Te Pas, E; Meinema, J G; Visser, M R M; van Dijk, N

2016-05-01

Blended learning (the combination of electronic methods with traditional teaching methods) has the potential to combine the best of traditional education with the best of computer-mediated training. We chose to develop such an intervention for GP trainers who were undertaking a Continuing Medical Education (CME) course in evidence-based medicine (EBM). This study reports on our experience and investigated the factors influencing the perception on usefulness and logistics of blended learning for learners in CME. In total, 170 GP trainers participated in the intervention. We used questionnaires, observations during the four face-to-face meetings and evaluations in the e-course over one year. Additionally we organised focus groups to gain insight in some of the outcomes of the questionnaires and interpretations of the observations. The GP trainers found the design and the educational method (e-course in combination with meetings) attractive, instructive and complementary. Factors influencing their learning were (1) educational design, (2) educational method, (3) topic of the intervention, (4) time (planning), (5) time (intervention), (6) learning style, (7) technical issues, (8) preconditions and (9) level of difficulty. A close link between daily practice and the educational intervention was considered an important precondition for the success of the intervention in this group of learners. GP trainers were positive about blended learning: they found e-learning a useful way to gain knowledge and the meetings a pleasant way of transferring the knowledge into practice. Although some preconditions should be taken into consideration during its development and implementation, they would participate in similarly designed learning in the future.

How can educators support general practice (GP) trainees to develop resilience to prevent burnout?

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Sales, Bryony; Macdonald, Alexandra; Scallan, Samantha; Crane, Sue

2016-11-01

Burnout impacts adversely on professional and personal life, and holds implications for patient care. Current research on burnout mainly focuses on established general practitioners but it is unclear how early the signs of burnout really start. This work seeks to identify whether specific GP trainee groups are particularly at risk of burnout and the aspects of training they find stressful. A longitudinal cohort study, collecting qualitative and quantitative data through a single mode of data collection (questionnaire) took place with trainees from all GP training years (ST1-3), across a vocational training scheme (n = 48). Data gathered included the Oldenburg Burnout Inventory (OLBI). Higher than anticipated levels of burnout were displayed by all trainees. A sub-group self reporting higher levels of burnout comprised all-female, UK-trained-at-undergraduate GP trainees, with a partner but no children. Top reported stressors included knowledge/uncertainty, workload/time pressures and ePortfolio. Less than 50% of trainees perceived their burnout levels to be as high as their OLBI showing potential lack of insight. This research demonstrates that high levels of burnout are experienced in GP trainees as early as the first year of training. Early identification of burnout amongst trainees is essential by GP educators to help protect the future GP workforce.

Expression of HIV gp120 protein increases sensitivity to the rewarding properties of methamphetamine in mice

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Kesby, James P.; Hubbard, David T.; Markou, Athina; Semenova, Svetlana

2012-01-01

Methamphetamine abuse and human immunodeficiency virus (HIV) infection induce neuropathological changes in corticolimbic brain areas involved in reward and cognitive function. Little is known about the combined effects of methamphetamine and HIV infection on cognitive and reward processes. The HIV/gp120 protein induces neurodegeneration in mice, similar to HIV-induced pathology in humans. We investigated the effects of gp120 expression on associative learning, preference for methamphetamine and non-drug reinforcers, and sensitivity to the conditioned rewarding properties of methamphetamine in transgenic (tg) mice expressing HIV/gp120 protein (gp120-tg). gp120-tg mice learned the operant response for food at the same rate as non-tg mice. In the two-bottle choice procedure with restricted access to drugs, gp120-tg mice exhibited greater preference for methamphetamine and saccharin than non-tg mice, whereas preference for quinine was similar between genotypes. Under conditions of unrestricted access to methamphetamine, the mice exhibited a decreased preference for increasing methamphetamine concentrations. However, male gp120-tg mice showed a decreased preference for methamphetamine at lower concentrations than non-tg male mice. gp120-tg mice developed methamphetamine-induced conditioned place preference at lower methamphetamine doses compared with non-tg mice. No differences in methamphetamine pharmacokinetics were found between genotypes. These results indicate that gp120-tg mice exhibit no deficits in associative learning or reward/motivational function for a natural reinforcer. Interestingly, gp120 expression resulted in increased preference for methamphetamine and a highly palatable non-drug reinforcer (saccharin) and increased sensitivity to methamphetamine-induced conditioned reward. These data suggest that HIV-positive individuals may have increased sensitivity to methamphetamine, leading to high methamphetamine abuse potential in this population. PMID

Clinicopathological correlations of podoplanin (gp38 expression in rheumatoid synovium and its potential contribution to fibroblast platelet crosstalk.

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Manuel J Del Rey

Full Text Available Synovial fibroblasts (SF undergo phenotypic changes in rheumatoid arthritis (RA that contribute to inflammatory joint destruction. This study was undertaken to evaluate the clinical and functional significance of ectopic podoplanin (gp38 expression by RA SF.Expression of gp38 and its CLEC2 receptor was analyzed by immunohistochemistry in synovial arthroscopic biopsies from RA patients and normal and osteoarthritic controls. Correlation between gp38 expression and RA clinicopathological variables was analyzed. In patients rebiopsied after anti-TNF-α therapy, changes in gp38 expression were determined. Platelet-SF coculture and gp38 silencing in SF were used to analyze the functional contribution of gp38 to SF migratory and invasive properties, and to SF platelet crosstalk.gp38 was abundantly but variably expressed in RA, and it was undetectable in normal synovial tissues. Among clinicopathologigal RA variables, significantly increased gp38 expression was only found in patients with lymphoid neogenesis (LN, and RF or ACPA autoantibodies. Cultured synovial but not dermal fibroblasts showed strong constitutive gp38 expression that was further induced by TNF-α. In RA patients, anti-TNF-α therapy significantly reduced synovial gp38 expression. In RA synovium, CLEC2 receptor expression was only observed in platelets. gp38 silencing in cultured SF did not modify their migratory and invasive properties but reduced the expression of IL-6 and IL-8 genes induced by SF-platelet interaction.In RA, synovial expression of gp38 is strongly associated to LN and it is reduced after anti-TNF-α therapy. Interaction between gp38 and CLEC2 platelet receptor is feasible in RA synovium in vivo and can specifically contribute to gene expression by SF.

Structural and functional characterization of EIAV gp45 fusion peptide proximal region and asparagine-rich layer

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Duan, Liangwei; Du, Jiansen [State Key Laboratory of Medicinal Chemical Biology, College of Life Sciences, Nankai University, Tianjin 300071 (China); Wang, Xuefeng; Zhou, Jianhua; Wang, Xiaojun [State Key Laboratory of Veterinary Biotechnology, Harbin Veterinary Research Institute, Chinese Academy of Agricultural Sciences, Harbin 150001 (China); Liu, Xinqi, E-mail: liu2008@nankai.edu.cn [State Key Laboratory of Medicinal Chemical Biology, College of Life Sciences, Nankai University, Tianjin 300071 (China)

2016-04-15

Equine infectious anaemia virus (EIAV) and human immunodeficiency virus (HIV) are members of the lentiviral genus. Similar to HIV gp41, EIAV gp45 is a fusogenic protein that mediates fusion between the viral particle and the host cell membrane. The crystal structure of gp45 reported reveals a different conformation in the here that includes the fusion peptide proximal region (FPPR) and neighboring asparagine-rich layer compared with previous HIV-1 gp41 structures. A complicated hydrogen-bond network containing a cluster of solvent molecules appears to be critical for the stability of the gp45 helical bundle. Interestingly, viral replication was relatively unaffected by site-directed mutagenesis of EIAV, in striking contrast to that of HIV-1. Based on these observations, we speculate that EIAV is more adaptable to emergent mutations, which might be important for the evolution of EIAV as a quasi-species, and could potentially contribute to the success of the EIAV vaccine. - Highlights: • The crystal structure of EIAV gp45 was determined. • The fusion peptide proximal region adopts a novel conformation different to HIV-1. • The asparagine-rich layer includes an extensive hydrogen-bond network. • These regions of EIAV are highly tolerant to mutations. • The results provide insight into the mechanism of gp41/gp45-mediated membrane fusion.

Patients' perceptions of GP non-verbal communication: a qualitative study.

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Marcinowicz, Ludmila; Konstantynowicz, Jerzy; Godlewski, Cezary

2010-02-01

During doctor-patient interactions, many messages are transmitted without words, through non-verbal communication. To elucidate the types of non-verbal behaviours perceived by patients interacting with family GPs and to determine which cues are perceived most frequently. In-depth interviews with patients of family GPs. Nine family practices in different regions of Poland. At each practice site, interviews were performed with four patients who were scheduled consecutively to see their family doctor. Twenty-four of 36 studied patients spontaneously perceived non-verbal behaviours of the family GP during patient-doctor encounters. They reported a total of 48 non-verbal cues. The most frequent features were tone of voice, eye contact, and facial expressions. Less frequent were examination room characteristics, touch, interpersonal distance, GP clothing, gestures, and posture. Non-verbal communication is an important factor by which patients spontaneously describe and evaluate their interactions with a GP. Family GPs should be trained to better understand and monitor their own non-verbal behaviours towards patients.

Plasma formation and first OH experiments in GLOBUS-M tokamak

International Nuclear Information System (INIS)

Gusev, V.K.; Aleksandrov, S.V.; Burtseva, T.A.

2001-01-01

The paper reports results of experimental campaigns on plasma ohmic heating, performed during 1999-2000 on the spherical tokamak Globus-M. Later experimental results with tokamak fed by thyristor rectifiers are presented in detail. The toroidal magnetic field and plasma pulse duration in these experiments were significantly increased. The method of stray magnetic field compensation is described. The technology of vacuum vessel conditioning, including boronization of the vessel performed at the end of the experiments, is briefly discussed. Also discussed is the influence of ECR preioniziation on the breakdown conditions. Experimental data on plasma column formation and current ramp-up in different regimes of operation with the magnetic flux of the central solenoid (CS) limited to ∼100 mVs are presented. Ramp-up of the plasma current of 0.25 MA for the time interval ∼0.03 s with about 0.02 s flat-top at the toroidal field (TF) strength of 0.35 T allows the conclusion that power supplies, control system and wall conditioning work well. The same conclusion can be drawn from observation of plasma density behavior the density is completely controlled with external gas puff and the influence of the wall is negligible after boronization. The magnetic flux consumption efficiency is discussed. The results of magnetic equilibrium simulations are presented and compared with experiment. (author)

Cognitive deficits associated with combined HIV gp120 expression and chronic methamphetamine exposure in mice

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Kesby, James P.; Markou, Athina; Semenova, Svetlana

2014-01-01

Methamphetamine abuse is common among individuals infected by human immunodeficiency virus (HIV). Neurocognitive outcomes tend to be worse in methamphetamine users with HIV. However, it is unclear whether discrete cognitive domains are susceptible to impairment after combined HIV infection and methamphetamine abuse. The expression of HIV/gp120 protein induces neuropathology in mice similar to HIV-induced pathology in humans. We investigated the separate and combined effects of methamphetamine exposure and gp120 expression on cognitive function in transgenic (gp120-tg) and control mice. The mice underwent an escalating methamphetamine binge regimen and were tested in novel object/location recognition, object-in-place recognition, and Barnes maze tests. gp120 expression disrupted performance in the object-in-place test (i.e., similar time spent with all objects, regardless of location), indicating deficits in associative recognition memory. gp120 expression also altered reversal learning in the Barnes maze, suggesting impairments in executive function. Methamphetamine exposure impaired spatial strategy in the Barnes maze, indicating deficits in spatial learning. Methamphetamine-exposed gp120-tg mice had the lowest spatial strategy scores in the final acquisition trials in the Barnes maze, suggesting greater deficits in spatial learning than all of the other groups. Although HIV infection involves interactions between multiple proteins and processes, in addition to gp120, our findings in gp120-tg mice suggest that humans with the dual insult of HIV infection and methamphetamine abuse may exhibit a broader spectrum of cognitive deficits than those with either factor alone. Depending on the cognitive domain, the combination of both insults may exacerbate deficits in cognitive performance compared with each individual insult. PMID:25476577

A review of a GP registrar-run mobile health clinic for homeless people.

Science.gov (United States)

O'Carroll, A; Irving, N; O'Neill, J; Flanagan, E

2017-08-01

Homeless people have excessively high morbidity and mortality rates, yet they face barriers accessing primary care. A mobile health clinic, staffed by GP registrars, was developed to provide services to homeless people, particularly rough sleepers and sex workers. The aims were to improve access to primary care and to challenge the stereotypes and prejudices of GP registrars through direct contact with homeless people. This was a qualitative study; questionnaires were completed on the mobile health clinic and two focus groups were conducted. All service users were asked to complete a questionnaire over a 3 month period. Two focus groups were conducted with 6 and 14 GP registrars who had worked on the bus. There was an 80% response rate (116 of 145). Fifty-two percent had no Medical Card meaning that they had no way to access the free primary care to which they are entitled. Had the clinic not been available, over half would not have sought further treatment and 16% would have gone to an Emergency Department. Ninety-one percent of users rated the service 10/10. The focus groups found that GP registrars who worked on the mobile health clinic had decreased negative stereotypes, increased empathy, and more knowledge of homeless issues. Furthermore, they intended to ensure that homeless people will not face discrimination in their future practice. A GP Registrar-run Mobile Health Clinic achieved its aims of improving access to primary care for rough sleepers and sex workers, and challenging stereotypes of GP Registrars.

Pharmacologic MRI (phMRI) as a tool to differentiate Parkinson's disease-related from age-related changes in basal ganglia function.

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Andersen, Anders H; Hardy, Peter A; Forman, Eric; Gerhardt, Greg A; Gash, Don M; Grondin, Richard C; Zhang, Zhiming

2015-02-01

The prevalence of both parkinsonian signs and Parkinson's disease (PD) per se increases with age. Although the pathophysiology of PD has been studied extensively, less is known about the functional changes taking place in the basal ganglia circuitry with age. To specifically address this issue, 3 groups of rhesus macaques were studied: normal middle-aged animals (used as controls), middle-aged animals with 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced parkinsonism, and aged animals (>20 years old) with declines in motor function. All animals underwent the same behavioral and pharmacologic magnetic resonance imaging (phMRI) procedures to measure changes in basal ganglia function in response to dopaminergic drug challenges consisting of apomorphine administration followed by either a D1 (SCH23390) or a D2 (raclopride) receptor antagonist. Significant functional changes were predominantly seen in the external segment of the globus pallidus (GPe) in aged animals and in the striatum (caudate nucleus and putamen) in MPTP-lesioned animals. Despite significant differences seen in the putamen and GPe between MPTP-lesioned versus aged animals, a similar response profile to dopaminergic stimulations was found between these 2 groups in the internal segment of the GP. In contrast, the pharmacologic responses seen in the control animals were much milder compared with the other 2 groups in all the examined areas. Our phMRI findings in MPTP-lesioned parkinsonian and aged animals suggest that changes in basal ganglia function in the elderly may differ from those seen in parkinsonian patients and that phMRI could be used to distinguish PD from other age-associated functional alterations in the brain. Copyright © 2015 Elsevier Inc. All rights reserved.

Social relationships and GP use of middle-aged and older adults in Europe: a moderator analysis.

Science.gov (United States)

Bremer, Daniel; Lüdecke, Daniel; Vonneilich, Nico; von dem Knesebeck, Olaf

2018-04-07

This paper investigates (1) how social relationships (SRs) relate to the frequency of general practitioner (GP) visits among middle-aged and older adults in Europe, (2) if SRs moderate the association between self-rated health and GP visits, and (3) how the associations vary regarding employment status. Data stem from the Survey of Health, Ageing and Retirement in Europe project (wave 4, 56 989 respondents, 50 years or older). GP use was assessed by frequency of contacts with GPs in the last 12 months. Predictors were self-rated health and structural (Social Integration Index (SII), social contact frequency) and functional (emotional closeness) aspects of SR. Regressions were used to measure the associations between GP use and those predictors. Sociodemographic and socioeconomic factors were used as covariates. Additional models were computed with interactions. Analyses did not reveal significant associations of functional and structural aspects of SR with frequency of GP visits (SII: incidence rate ratio (IRR)=0.99, 95% CI 0.97 to 1.01, social contact frequency: IRR=1.04, 95% CI 1.00 to 1.07, emotional closeness: IRR=1.02, 95% CI 1.00 to 1.04). Moderator analyses showed that 'high social contact frequency people' with better health had more statistically significant GP visits than 'low social contact frequency people' with better health. Furthermore, people with poor health and an emotionally close network showed a significantly higher number of GP visits compared with people with same health, but less close networks. Three-way interaction analyses indicated employment status specific behavioural patterns with regard to SR and GP use, but coefficients were mostly not significant. All in all, the not employed groups showed a higher number of GP visits. Different indicators of SR showed statistically insignificantly associations with GP visits. Consequently, the relevance of SR may be rated rather low in quantitative terms for investigating GP use behaviour

Patient satisfaction with out-of-hours GP cooperatives: a longitudinal study.

Science.gov (United States)

Smits, Marleen; Huibers, Linda; Oude Bos, Anita; Giesen, Paul

2012-12-01

For over a decade, out-of-hours primary care in the Netherlands has been provided by general practitioner (GP) cooperatives. In the past years, quality improvements have been made and patients have become acquainted with the service. This may have increased patient satisfaction. The objective of this study was to examine changes in patient satisfaction with GP cooperatives over time. Longitudinal observational study. A validated patient satisfaction questionnaire was distributed in 2003-2004 (T1) and 2007-2008 (T2). Items were rated on a scale from 0 to 10 (1 = very bad; 10 = excellent). Eight GP cooperatives in the Netherlands. Stratified sample of 9600 patients. Response was 55% at T1 (n = 2634) and 51% at T2 (n = 2462). Expectations met; satisfaction with triage nurses, GPs, and organization. For most patients the care received at the GP cooperative met their expectations (T1: 86.1% and T2: 88.4%). Patients were satisfied with the triage nurses (overall grade T1: 7.73 and T2: 7.99), GPs (T1: 8.04 and T2: 8.25), and organization (overall grade T1: 7.60 and T2: 7.78). Satisfaction with triage nurses showed the largest increase over time. The quality and effectiveness of advice or treatment were given relatively low grades. Of all organizational aspects, the lowest grades were given for waiting times and information about the cooperative. In general, patients were initially satisfied with GP cooperatives and satisfaction had even increased four years later. However, there is room for improvement in the content of the advice, waiting times, and information supply. More research is needed into satisfaction of specific patient groups.

Using photography to enhance GP trainees' reflective practice and professional development.

Science.gov (United States)

Rutherford; Forde, Emer; Priego-Hernandez, Jacqueline; Butcher, Aurelia; Wedderburn, Clare

2018-02-08

The capacity and the commitment to reflect are integral to the practice of medicine and are core components of most general practitioners (GP) training programmes. Teaching through the humanities is a growing area within medical education, but one which is often considered a voluntary 'add-on' for the interested doctor. This article describes an evaluation of a highly innovative pedagogical project which used photography as a means to enhance GP trainees' reflective capacity, self-awareness and professional development. Photography was used as a tool to develop GP trainees' skills in recognising and articulating the attitudes, feelings and values that might impact on their clinical work and to enhance their confidence in their ability to deal with these concerns/issues. We submit that photography is uniquely well suited for facilitating insight and self-reflection because it provides the ability to record 'at the touch of a button' those scenes and images to which our attention is intuitively drawn without the need for-or the interference of-conscious decisions. This allows us the opportunity to reflect later on the reasons for our intuitive attraction to these scenes. These photography workshops were a compulsory part of the GP training programme and, despite the participants' traditional scientific backgrounds, the results clearly demonstrate the willingness of participants to accept-even embrace-the use of art as a tool for learning. The GP trainees who took part in this project acknowledged it to be beneficial for both their personal and professional development. © 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.

Alphavirus Replicon DNA Vectors Expressing Ebola GP and VP40 Antigens Induce Humoral and Cellular Immune Responses in Mice

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Shoufeng Ren

2018-01-01

Full Text Available Ebola virus (EBOV causes severe hemorrhagic fevers in humans, and no approved therapeutics or vaccine is currently available. Glycoprotein (GP is the major protective antigen of EBOV, and can generate virus-like particles (VLPs by co-expression with matrix protein (VP40. In this study, we constructed a recombinant Alphavirus Semliki Forest virus (SFV replicon vector DREP to express EBOV GP and matrix viral protein (VP40. EBOV VLPs were successfully generated and achieved budding from 293 cells after co-transfection with DREP-based GP and VP40 vectors (DREP-GP+DREP-VP40. Vaccination of BALB/c mice with DREP-GP, DREP-VP40, or DREP-GP+DREP-VP40 vectors, followed by immediate electroporation resulted in a mixed IgG subclass production, which recognized EBOV GP and/or VP40 proteins. This vaccination regimen also led to the generation of both Th1 and Th2 cellular immune responses in mice. Notably, vaccination with DREP-GP and DREP-VP40, which produces both GP and VP40 antigens, induced a significantly higher level of anti-GP IgG2a antibody and increased IFN-γ secreting CD8+ T-cell responses relative to vaccination with DREP-GP or DREP-VP40 vector alone. Our study indicates that co-expression of GP and VP40 antigens based on the SFV replicon vector generates EBOV VLPs in vitro, and vaccination with recombinant DREP vectors containing GP and VP40 antigens induces Ebola antigen-specific humoral and cellular immune responses in mice. This novel approach provides a simple and efficient vaccine platform for Ebola disease prevention.

Patient influences on satisfaction and loyalty for GP services.

Science.gov (United States)

Rundle-Thiele, Sharyn; Russell-Bennett, Rebekah

2010-04-01

Little is known about the influence that patients themselves have on their loyalty to a general practitioner (GP). Consequently, a theoretical framework that draws on diverse literature is proposed to suggest that along with satisfaction, patient loyalty is an important outcome for GPs. Comprising 174 Australian patients, this study identified that knowledgeable patients reported lower levels of loyalty while older patients and patients visiting a GP more frequently reported higher levels of loyalty. The results suggest that extending patient-centered care practices to encompass all patients may be warranted in order to improve patient satisfaction and loyalty. Further, future research opportunities abound, with intervention and dyadic research methodologies recommended.

Cloning of gp-340, a putative opsonin receptor for lung surfactant protein D

DEFF Research Database (Denmark)

Holmskov, U; Mollenhauer, J; Madsen, J

1999-01-01

in a soluble form and in association with the membranes of alveolar macrophages. The primary structure of gp-340 has been established by molecular cloning, which yielded a 7,686-bp cDNA sequence encoding a polypeptide chain of 2, 413 amino acids. The domain organization features 13 scavenger receptor cysteine...... in a way that suggested capping, whereas other macrophages showed strong intracellular staining within the phagosome/phagolysosome compartments. In some macrophages, SP-D and gp-340 were located in the same cellular compartment. Immunoreactive gp-340 was also found in epithelial cells of the small...

Production and characterization of a new antibacterial peptide obtained from Aeribacillus pallidus SAT4

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Syed Aun Muhammad

2015-12-01

Full Text Available A novel thermophilic bacterial strain of the genus Aeribacillus was isolated from Thar Dessert Pakistan. This strain showed significant antibacterial activity against Micrococcus luteus, Staphylococcus aureus, and Pseudomonas aeruginosa. The strain coded as ‘SAT4’ resembled with Aeribacillus pallidus in the morphological, biochemical and molecular tests. The production of antibacterial metabolites by SAT4 was optimized. These active metabolites were precipitated by 50% ammonium sulphate and purified through sephadex G-75 gel permeation chromatography and reverse phase HPLC. The molecular weight of 37 kDa was examined by SDS-PAGE. The structural elucidation of the purified product was studied by FTIR, 1H and 13C NMR. The X-ray diffractions study showed that the crystals belonged to the primitive orthorhombic lattice (a = 12.137, b = 13.421, c = 14.097 Å and 3D structure (proposed name: Aeritracin was determined. This new peptide antibacterial molecule can get a position in pharmaceutical and biotechnological industrial research.

Investigation of the function of the putative self-association site of Epstein-Barr virus (EBV) glycoprotein 42 (gp42)

International Nuclear Information System (INIS)

Rowe, Cynthia L.; Matsuura, Hisae; Jardetzky, Theodore S.; Longnecker, Richard

2011-01-01

The Epstein-Barr virus (EBV) glycoprotein 42 (gp42) is a type II membrane protein essential for entry into B cells but inhibits entry into epithelial cells. X-ray crystallography suggests that gp42 may form dimers when bound to human leukocyte antigen (HLA) class II receptor (Mullen et al., 2002) or multimerize when not bound to HLA class II (Kirschner et al., 2009). We investigated this self-association of gp42 using several different approaches. We generated soluble mutants of gp42 containing mutations within the self-association site and found that these mutants have a defect in fusion. The gp42 mutants bound to gH/gL and HLA class II, but were unable to bind wild-type gp42 or a cleavage mutant of gp42. Using purified gp42, gH/gL, and HLA, we found these proteins associate 1:1:1 by gel filtration suggesting that gp42 dimerization or multimerization does not occur or is a transient event undetectable by our methods.

Crystal Structure of the Carboxy-Terminal Region of the Bacteriophage T4 Proximal Long Tail Fiber Protein Gp34

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Meritxell Granell

2017-06-01

Full Text Available Long tail fibers of bacteriophage T4 are formed by proteins gp34, gp35, gp36, and gp37, with gp34 located at the phage-proximal end and gp37 at the phage-distal, receptor-binding end. We have solved the structure of the carboxy-terminal region of gp34, consisting of amino acids 894–1289, by single-wavelength anomalous diffraction and extended the structure to amino acids 744–1289 using data collected from crystals containing longer gp34-fragments. The structure reveals three repeats of a mixed α-β fibrous domain in residues 744 to 877. A triple-helical neck connects to an extended triple β-helix domain (amino acids 900–1127 punctuated by two β-prism domains. Next, a β-prism domain decorated with short helices and extended β-helices is present (residues 1146–1238, while the C-terminal end is capped with another short β-helical region and three β-hairpins. The structure provides insight into the stability of the fibrous gp34 protein.

A Critical View on In Vitro Analysis of P-glycoprotein (P-gp) Transport Kinetics.

Science.gov (United States)

Saaby, Lasse; Brodin, Birger

2017-09-01

Transport proteins expressed in the different barriers of the human body can have great implications on absorption, distribution, and excretion of drug compounds. Inhibition or saturation of a transporter can potentially alter these absorbtion, distribution, metabolism and elimination properties and thereby also the pharmacokinetic profile and bioavailability of drug compounds. P-glycoprotein (P-gp, ABCB1) is an efflux transporter which is present in most of the barriers of the body, including the small intestine, the blood-brain barrier, the liver, and the kidney. In all these tissues, P-gp may mediate efflux of drug compounds and may also be a potential site for drug-drug interactions. Consequently, there is a need to be able to predict the saturation and inhibition of P-gp and other transporters in vivo. For this purpose, Michaelis-Menten steady-state analysis has been applied to estimate kinetic parameters, such as K m and V max , for carrier-mediated transport, whereas half-maximal inhibitor concentration (IC 50 ) and the disassociation constant for an inhibitor/P-gp complex (K i ) have been determined to estimate P-gp inhibition. This review addresses in vitro methods commonly used to study P-gp transport kinetics and aims at providing a critical evaluation of the application of steady-state Michaelis-Menten analysis of kinetic parameters for substrate/P-gp interactions. Copyright © 2017 American Pharmacists Association®. Published by Elsevier Inc. All rights reserved.

Curcumin improves synaptic plasticity impairment induced by HIV-1gp120 V3 loop

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Ling-ling Shen

2015-01-01

Full Text Available Curcumin has been shown to significantly improve spatial memory impairment induced by HIV-1 gp120 V3 in rats, but the electrophysiological mechanism remains unknown. Using extracellular microelectrode recording techniques, this study confirmed that the gp120 V3 loop could suppress long-term potentiation in the rat hippocampal CA1 region and synaptic plasticity, and that curcumin could antagonize these inhibitory effects. Using a Fura-2/AM calcium ion probe, we found that curcumin resisted the effects of the gp120 V3 loop on hippocampal synaptosomes and decreased Ca 2+ concentration in synaptosomes. This effect of curcumin was identical to nimodipine, suggesting that curcumin improved the inhibitory effects of gp120 on synaptic plasticity, ameliorated damage caused to the central nervous system, and might be a potential neuroprotective drug.

Conserved region at the COOH terminus of human immunodeficiency virus gp120 envelope protein contains an immunodominant epitope

International Nuclear Information System (INIS)

Palker, T.J.; Matthews, T.J.; Clark, M.E.

1987-01-01

A highly immunogenic epitope from a conserved COOH-terminal region of the human immunodeficiency virus (HIV) gp120 envelope protein has been identified with antisera from HIV-seropositive subjects and a synthetic peptide (SP-22) containing 15 amino acids from this region (Ala-Pro-Thr-Lys-Ala-Lys-Arg-Arg-Val-Val-Gln-Arg-Glu-Lys-Arg). Peptide SP-22 absorbed up to 100% of anti-gp120 antibody reactivity from select HIV + patient sera in immunoblot assays and up to 79% of serum anti-gp120 antibody reactivity in competition RIA. In RIA, 45% of HIV-seropositive subjects had antibodies that bound to peptide SP-22. Human anti-SP-22 antibodies that bound to and were eluted from an SP-22 affinity column reacted with gp120 in RIA and immunoblot assays but did not neutralize HIV or inhibit HIV-induced syncytium formation in vitro, even though these antibodies comprised 70% of all anti-gp120 antibodies in the test serum. In contrast, the remaining 30% of SP-22 nonreactive anti-gp120 antibodies did not react with gp120 in immunoblot assays but did react in RIA and neutralized HIV in vitro. Thus, ≅ 50% of HIV-seropositive patients make high titers of nonneutralizing antibodies to an immunodominant antigen on gp120 defined by SP-22. Moreover, the COOH terminus of gp120 contains the major antigen or antigens identified by human anti-gp120 antibodies in immunoblot assays

Gp120 stability on HIV-1 virions and Gag-Env pseudovirions is enhanced by an uncleaved Gag core

International Nuclear Information System (INIS)

Hammonds, Jason; Chen Xuemin; Ding Lingmei; Fouts, Timothy; De Vico, Anthony; Megede, Jan zur; Barnett, Susan; Spearman, Paul

2003-01-01

Human immunodeficiency virus type-1 (HIV-1) particles incorporate a trimeric envelope complex (Env) made of gp120 (SU) and gp41 (TM) heterodimers. It has been previously established that soluble CD4 (sCD4) interaction leads to shedding of gp120 from viral particles, and that gp120 may also be easily lost from virions during incubation or particle purification procedures. In the design of HIV particle or pseudovirion-based HIV vaccines, it may be important to develop strategies to maximize the gp120 content of particles. We analyzed the gp120 retention of HIV-1 laboratory-adapted isolates and primary isolates following incubation with sCD4 and variations in temperature. NL4-3 shed gp120 readily in a temperature- and sCD4-dependent manner. Surprisingly, inactivation of the viral protease led to markedly reduced shedding of gp120. Gp120 shedding was shown to vary markedly between HIV-1 strains, and was not strictly determined by whether the isolate was adapted to growth on immortalized T cell lines or was a primary isolate. Pseudovirions produced by expression of codon-optimized gag and env genes also demonstrated enhanced gp120 retention when an immature core structure was maintained. Pseudovirions of optimal stability were produced through a combination of an immature Gag protein core and a primary isolate Env. These results support the feasibility of utilizing pseudovirion particles as immunogens for the induction of humoral responses directed against native envelope structures

Binding kinetics of aptamers to gp120 derived from HIV-1 subtype C

CSIR Research Space (South Africa)

Millroy, L

2011-02-01

Full Text Available aptamers with specific and strong affinity to the HIV-1 envelope glycoprotein gp120 and act as novel HIV-1 entry inhibitor drugs or as targeted drug delivery systems to HIV-1 infected cells. Prior to any downstream applications, novel gp120 aptamers need...

Circuits regulating pleasure and happiness:the evolution of reward-seeking and misery-fleeing behavioral mechanisms in vertebrates

Directory of Open Access Journals (Sweden)

Anton J.M. Loonen

2015-10-01

Full Text Available The very first free-moving animals in the oceans over 540 million years ago must have been able to obtain food, territory and shelter, as well as reproduce. Therefore, they would have needed regulatory mechanisms to induce movements enabling achievement of these prerequisites for survival. It can be useful to consider these mechanisms in primitive chordates, which represent our earliest ancestors, to develop hypotheses addressing how these essential parts of human behavior are regulated and relate to more sophisticated behavioral manifestations such as mood. An animal comparable to lampreys was the earliest known vertebrate with a modern forebrain consisting of old and new cortical parts. Lampreys have a separate dorsal pallium, the forerunner of the most recently developed part of the cerebral cortex. In addition, the lamprey extrapyramidal system, which regulates movement, is modern. However, in lampreys and their putative forerunners, the hagfishes, the striatum, which is the input part of this extrapyramidal system, probably corresponds to the human centromedial amygdala, which in higher vertebrates is part of a system mediating fear and anxiety. Both animals have well-developed nuclear habenulae, which are involved in several critical behaviors; in lampreys this system regulates the reward system that reinforces appetitive-seeking behavior or the avoidance system that reinforces flight behavior resulting from negative inputs. Lampreys also have a distinct glutamatergic nucleus, the so-called habenula-projection globus pallidus, which receives input from glutamatergic and GABAergic signals and gives output to the lateral habenula. Via this route, this nucleus influences midbrain monoaminergic nuclei and regulates the food acquisition system. These various structures involved in motor regulation in the lampreys may be conserved in humans and include two complementary mechanisms for reward reinforcement and avoidance behaviors. The first

Sustained effects of ecstasy on the human brain: a prospective neuroimaging study in novel users.

Science.gov (United States)

de Win, Maartje M L; Jager, Gerry; Booij, Jan; Reneman, Liesbeth; Schilt, Thelma; Lavini, Cristina; Olabarriaga, Sílvia D; den Heeten, Gerard J; van den Brink, Wim

2008-11-01

Previous studies have suggested toxic effects of recreational ecstasy use on the serotonin system of the brain. However, it cannot be excluded that observed differences between users and non-users are the cause rather than the consequence of ecstasy use. As part of the Netherlands XTC Toxicity (NeXT) study, we prospectively assessed sustained effects of ecstasy use on the brain in novel ecstasy users using repeated measurements with a combination of different neuroimaging parameters of neurotoxicity. At baseline, 188 ecstasy-naive volunteers with high probability of first ecstasy use were examined. After a mean period of 17 months follow-up, neuroimaging was repeated in 59 incident ecstasy users and 56 matched persistent ecstasy-naives and their outcomes were compared. Neuroimaging included [(123)I]beta-carbomethoxy-3beta-(4-iodophenyl)tropane (CIT) SPECT to measure serotonin transporter densities as indicators of serotonergic function; (1)H-MR spectroscopy ((1)H-MRS) to measure brain metabolites as indicators of neuronal damage; diffusion tensor imaging (DTI) to measure the apparent diffusion coefficient and fractional anisotropy (FA) of the diffusional motion of water molecules in the brain as indicators of axonal integrity; and perfusion weighted imaging (PWI) to measure regional relative cerebral blood volume (rrCBV) which indicates brain perfusion. With this approach, both structural ((1)H-MRS and DTI) and functional ([(123)I]beta-CIT SPECT and PWI) aspects of neurotoxicity were combined. Compared to persistent ecstasy-naives, novel low-dose ecstasy users (mean 6.0, median 2.0 tablets) showed decreased rrCBV in the globus pallidus and putamen; decreased FA in thalamus and frontoparietal white matter; increased FA in globus pallidus; and increased apparent diffusion coefficient in the thalamus. No changes in serotonin transporter densities and brain metabolites were observed. These findings suggest sustained effects of ecstasy on brain microvasculature, white

Circuits regulating pleasure and happiness: the evolution of reward-seeking and misery-fleeing behavioral mechanisms in vertebrates.

Science.gov (United States)

Loonen, Anton J M; Ivanova, Svetlana A

2015-01-01

The very first free-moving animals in the oceans over 540 million years ago must have been able to obtain food, territory, and shelter, as well as reproduce. Therefore, they would have needed regulatory mechanisms to induce movements enabling achievement of these prerequisites for survival. It can be useful to consider these mechanisms in primitive chordates, which represent our earliest ancestors, to develop hypotheses addressing how these essential parts of human behavior are regulated and relate to more sophisticated behavioral manifestations such as mood. An animal comparable to lampreys was the earliest known vertebrate with a modern forebrain consisting of old and new cortical parts. Lampreys have a separate dorsal pallium, the forerunner of the most recently developed part of the cerebral cortex. In addition, the lamprey extrapyramidal system (EPS), which regulates movement, is modern. However, in lampreys and their putative forerunners, the hagfishes, the striatum, which is the input part of this EPS, probably corresponds to the human centromedial amygdala, which in higher vertebrates is part of a system mediating fear and anxiety. Both animals have well-developed nuclear habenulae, which are involved in several critical behaviors; in lampreys this system regulates the reward system that reinforces appetitive-seeking behavior or the avoidance system that reinforces flight behavior resulting from negative inputs. Lampreys also have a distinct glutamatergic nucleus, the so-called habenula-projection globus pallidus, which receives input from glutamatergic and GABAergic signals and gives output to the lateral habenula. Via this route, this nucleus influences midbrain monoaminergic nuclei and regulates the food acquisition system. These various structures involved in motor regulation in the lampreys may be conserved in humans and include two complementary mechanisms for reward reinforcement and avoidance behaviors. The first system is associated with

Biodistribution study of [I-123] ADAM in mice brain using quantitative autoradiography

International Nuclear Information System (INIS)

Lin, K.J.; Yen, T.C.; Tzen, K.Y.; Ye, X.X.; Hwang, J.J.; Wey, S.P.; Ting, G.

2002-01-01

Aim: Autoradiography with radioluminography is a delicate method to characterize newly developed radiotracers and to apply them to pharmacological studies. Herein, we reported a biodistribution result of [I-123] ADAM (2-((2-((dimethylamino)methyl)phenyl)thio)-5- iodophenylamine) in mice brain quantitatively using imaging plates. Materials and Methods: 1mCi [I-123] ADAM was injected into male ICR mice through tail veins. Brains were removed at sequential time points ranging from 0.5hr to 4hr after injection. The whole brain was cut into 14mm thick coronal sections using a cyrotome. The sections were thaw-mounted on glass plate and apposed placed on an imaging plate with filter paper standards for 24 hours. Imaging reading was done by a Fuji FLA5000 device. Regions of interest were placed on the globus pallidus, hypothalamus, substantia nigra, raphe nuclei and cerebellum corresponding to the sterotaxic atlas, and the PSL/mm 2 values were measured. The specific binding was expressed as the ratios of (targets - cerebellum) to cerebellum. Results: Autoradiography study of brain showed that the [I-123] ADAM was accumulated at serotonin transporter rich sites, including the olfactory tubercle, globus pallidus, thalamus nuclei, hypothalamus, substantia nigra, interpeduncular nucleus, amygdala and raphe nuclei. Biodistribution of [I-123] ADAM in mice brain using quantitative autoradiography method showed a high specific binding in the substantia nigra and hypothalamus and the time-activity curve peaked at 120 min post-injection. Compatible specific binding result was achieved in the region of hypothalamus as compared with previous study by other group using conventional tissue micro-dissection method (Synapse 38:403-412, 2000). However, higher specific binding was observed in certain small brain regions including substantia nigra, raphe nuclei due to improved spatial resolution of the quantitative autoradiography technique. Conclusion: Our result showed that the

[Deep brain recording and length of surgery in stereotactic and functional neurosurgery for movement disorders].

Science.gov (United States)

Teijeiro, Juan; Macías, Raúl J; Maragoto, Carlos; García, Iván; Alvarez, Mario; Quintanal, Nelson E

2014-01-01

Our objectives were to study the length of multi-unit recordings (MURs) of brain activity in 20 years of movement disorder neurosurgeries and to determine the number of times in which it was necessary for the teams using single-unit recording (SUR) to explore all the electrode tracks in the simultaneously recorded sites (SRS). This was a retrospective descriptive statistical analysis of MUR length on 4,296 tracks in 952 surgeries. The exclusion criteria were: tracks with fewer than 5 recorded signals, tracks that had a signal length different from the habitual 2s, or there being unusual situations not related to the MUR, as well as the first 20 surgeries of each surgical target. This yielded a total of 3,448 tracks in 805 surgeries. We also determined the number of the total 952 surgeries in which all the tracks in the SURs of the SRS were explored. The mean and its confidence interval (P=.05) of time per MUR track were 5.49±0.16min in subthalamic nucleus surgery, 8.82±0.24min in the medial or internal globus pallidus) and 18.51±1.31min in the ventral intermediate nucleus of the thalamus. For the total sum of tracks per surgery, in 75% of cases the total time was less than 39min in subthalamic nucleus, almost 42min in the medial or internal globus pallidus and less than 1h and 17min in ventral intermediate nucleus of the thalamus. All the tracks in the SUR SRS were explored in only 4.2% of the surgeries. The impact of MUR on surgical time is acceptable for this guide in objective localization for surgical targets, without having to use several simultaneous electrodes (not all indispensable in most of the cases). Consequently, there is less risk for the patient. Copyright © 2013 Sociedad Española de Neurocirugía. Published by Elsevier España. All rights reserved.

Imaging dopamine D3 receptors in the human brain with positron emission tomography, [11C]PHNO, and a selective D3 receptor antagonist.

Science.gov (United States)

Searle, Graham; Beaver, John D; Comley, Robert A; Bani, Massimo; Tziortzi, Andri; Slifstein, Mark; Mugnaini, Manolo; Griffante, Cristiana; Wilson, Alan A; Merlo-Pich, Emilio; Houle, Sylvain; Gunn, Roger; Rabiner, Eugenii A; Laruelle, Marc

2010-08-15

Dopamine D(3) receptors are involved in the pathophysiology of several neuropsychiatric conditions. [(11)C]-(+)-PHNO is a radiolabeled D(2) and D(3) agonist, suitable for imaging the agonist binding sites (denoted D(2HIGH) and D(3)) of these receptors with positron emission tomography (PET). PET studies in nonhuman primates documented that, in vivo, [(11)C]-(+)-PHNO displays a relative selectivity for D(3) compared with D(2HIGH) receptor sites and that the [(11)C]-(+)-PHNO signal is enriched in D(3) contribution compared with conventional ligands such as [(11)C] raclopride. To define the D(3) contribution (f(PHNO)(D3)) to [(11)C]-(+)-PHNO binding potential (BP(ND)) in healthy humans, 52 PET scans were obtained in 19 healthy volunteers at baseline and following oral administration of various doses of the selective D(3) receptor antagonist, GSK598809. The impact of GSK598809 on [(11)C]-(+)-PHNO was regionally selective. In dorsal regions of the striatum, GSK598809 did not significantly affect [(11)C]-(+)-PHNO BP(ND) (f(PHNO)(D3) approximately 0%). Conversely, in the substantia nigra, GSK598809 dose-dependently reduced [(11)C]-(+)-PHNO binding to nonspecific level (f(PHNO)(D3) approximately 100%). In ventral striatum (VST), globus pallidus and thalamus (THA), [(11)C]-(+)-PHNO BP(ND) was attributable to a combination of D(2HIGH) and D(3) receptor sites, with f(PHNO)(D3) of 26%, 67% and 46%, respectively. D(3) receptor binding potential (BP(ND)(D3)) was highest in globus pallidus (1.90) and substantial nigra (1.39), with lower levels in VST (.77) and THA (.18) and negligible levels in dorsal striatum. This study elucidated the pharmacologic nature of the [(11)C]-(+)-PHNO signal in healthy subjects and provided the first quantification of D(3) receptor availability with PET in the living human brain. Copyright 2010 Society of Biological Psychiatry. Published by Elsevier Inc. All rights reserved.

CXCL10 Decreases GP73 Expression in Hepatoma Cells at the Early Stage of Hepatitis C Virus (HCV Infection

Directory of Open Access Journals (Sweden)

Yuan Liu

2013-12-01

Full Text Available Golgi protein 73 (GP73, which is up-regulated in hepatocellular carcinoma (HCC, has recently been identified as a novel serum marker for HCC diagnosis. Several reports also noted the increased levels of GP73 expression in chronic liver disease in patients with acute hepatitis of various etiologies, chronic Hepatitis C virus (HCV infection and alcoholic liver disease. The molecular mechanisms of GP73 expression in HCV related liver disease still need to be determined. In this study, we aimed to evaluate the effect of HCV infection on GP73 expression. GP73 was highly expressed in Huh7, Hep3B, 293T and HUVEC cells, and was low-expressed in HepG2 cells. HCV infection led to down-regulation of GP73 in Huh7 and HepG2/CD81 cells at the early stage of infection. CXCL10 decreased GP73 expression in Huh7 and HepG2 cells. Up-regulation of GP73 was noted in hepatocytes with cytopathic effect at advanced stage of HCV infection, and further research is needed to determine the unknown factors affecting GP73 expression. In conclusion, our study provided additional evidence for the roles of GP73 in liver disease.

P-gp expression in brown trout erythrocytes: evidence of a detoxification mechanism in fish erythrocytes.

Science.gov (United States)

Valton, Emeline; Amblard, Christian; Wawrzyniak, Ivan; Penault-Llorca, Frederique; Bamdad, Mahchid

2013-12-05

Blood is a site of physiological transport for a great variety of molecules, including xenobiotics. Blood cells in aquatic vertebrates, such as fish, are directly exposed to aquatic pollution. P-gp are ubiquitous "membrane detoxification proteins" implicated in the cellular efflux of various xenobiotics, such as polycyclic aromatic hydrocarbons (PAHs), which may be pollutants. The existence of this P-gp detoxification system inducible by benzo [a] pyrene (BaP), a highly cytotoxic PAH, was investigated in the nucleated erythrocytes of brown trout. Western blot analysis showed the expression of a 140-kDa P-gp in trout erythrocytes. Primary cultures of erythrocytes exposed to increasing concentrations of BaP showed no evidence of cell toxicity. Yet, in the same BaP-treated erythrocytes, P-gp expression increased significantly in a dose-dependent manner. Brown trout P-gp erythrocytes act as membrane defence mechanism against the pollutant, a property that can be exploited for future biomarker development to monitor water quality.

N-terminal substitutions in HIV-1 gp41 reduce the expression of non-trimeric envelope glycoproteins on the virus

International Nuclear Information System (INIS)

Dey, Antu K.; David, Kathryn B.; Ray, Neelanjana; Ketas, Thomas J.; Klasse, Per J.; Doms, Robert W.; Moore, John P.

2008-01-01

The native, functional HIV-1 envelope glycoprotein (Env) complex is a trimer of two non-covalently associated subunits: the gp120 surface glycoprotein and the gp41 transmembrane glycoprotein. However, various non-functional forms of Env are present on virus particles and HIV-1-infected cells, some of which probably arise as the native complex decays. The aberrant forms include gp120-gp41 monomers and oligomers, as well as gp41 subunits from which gp120 has dissociated. The presence of non-functional Env creates binding sites for antibodies that do not recognize native Env complexes and that are, therefore, non-neutralizing. Non-native Env forms (monomers, dimers, tetramers and aggregates) can also arise when soluble gp140 proteins, lacking the cytoplasmic and transmembrane domains of gp41, are expressed for vaccine studies. We recently identified five amino acids in the gp41 N-terminal region (I535, Q543, S553, K567 and R588) that promote gp140 trimerization. We have now studied their influence on the function and antigenic properties of JR-FL Env expressed on the surfaces of pseudoviruses and Env-transfected cells. The 5 substitutions in gp41 reduce the expression of non-trimeric gp160s, without affecting trimer levels. Pseudovirions bearing the mutant Env are fully infectious with similar kinetics of Env-mediated fusion. Various non-neutralizing antibodies bind less strongly to the Env mutant, but neutralizing antibody binding is unaffected. Hence the gp41 substitutions do not adversely affect Env structure, supporting their use for making new Env-based vaccines. The mutant Env might also help in studies intended to correlate antibody binding to virus neutralization. Of note is that the 5 residues are much more frequent, individually or collectively, in viruses from subtypes other than B

Role for the disulfide-bonded region of human immunodeficiency virus type 1 gp41 in receptor-triggered activation of membrane fusion function

International Nuclear Information System (INIS)

Bellamy-McIntyre, Anna K.; Baer, Severine; Ludlow, Louise; Drummer, Heidi E.; Poumbourios, Pantelis

2010-01-01

The conserved disulfide-bonded region (DSR) of the human immunodeficiency virus type 1 (HIV-1) fusion glycoprotein, gp41, mediates association with the receptor-binding glycoprotein, gp120. Interactions between gp120, CD4 and chemokine receptors activate the fusion activity of gp41. The introduction of W596L and W610F mutations to the DSR of HIV-1 QH1549.13 blocked viral entry and hemifusion without affecting gp120-gp41 association. The fusion defect correlated with inhibition of CD4-triggered gp41 pre-hairpin formation, consistent with the DSR mutations having decoupled receptor-induced conformational changes in gp120 from gp41 activation. Our data implicate the DSR in sensing conformational changes in the gp120-gp41 complex that lead to fusion activation.

GeoDataspaces: Simplifying Data Management Tasks with Globus

Science.gov (United States)

Malik, T.; Chard, K.; Tchoua, R. B.; Foster, I.

2014-12-01

Data and its management are central to modern scientific enterprise. Typically, geoscientists rely on observations and model output data from several disparate sources (file systems, RDBMS, spreadsheets, remote data sources). Integrated data management solutions that provide intuitive semantics and uniform interfaces, irrespective of the kind of data source are, however, lacking. Consequently, geoscientists are left to conduct low-level and time-consuming data management tasks, individually, and repeatedly for discovering each data source, often resulting in errors in handling. In this talk we will describe how the EarthCube GeoDataspace project is improving this situation for seismologists, hydrologists, and space scientists by simplifying some of the existing data management tasks that arise when developing computational models. We will demonstrate a GeoDataspace, bootstrapped with "geounits", which are self-contained metadata packages that provide complete description of all data elements associated with a model run, including input/output and parameter files, model executable and any associated libraries. Geounits link raw and derived data as well as associating provenance information describing how data was derived. We will discuss challenges in establishing geounits and describe machine learning and human annotation approaches that can be used for extracting and associating ad hoc and unstructured scientific metadata hidden in binary formats with data resources and models. We will show how geounits can improve search and discoverability of data associated with model runs. To support this model, we will describe efforts related towards creating a scalable metadata catalog that helps to maintain, search and discover geounits within the Globus network of accessible endpoints. This talk will focus on the issue of creating comprehensive personal inventories of data assets for computational geoscientists, and describe a publishing mechanism, which can be used to

GP50 as a promising early diagnostic antigen for Taenia multiceps infection in goats by indirect ELISA.

Science.gov (United States)

Huang, Xing; Xu, Jing; Wang, Yu; Guo, Cheng; Chen, Lin; Gu, Xiaobin; Lai, Weimin; Peng, Xuerong; Yang, Guangyou

2016-12-01

Coenurosis is caused by coenurus, the metacestode of Taenia multiceps, which mainly parasitizes the brain and spinal cord of cattle, sheep and goats. To date, no widely-approved methods are available to identify early coenurus infection. In this study, we identified a full-length cDNA that encodes GP50 (TmGP50) from the transcriptome of T. multiceps, and then cloned and expressed in E. coli. The native proteins in adult stage and coenurus were located via immunofluorescence assays, while the potential of recombinant TmGP50 protein (rTmGP50) for indirect ELISA-based serodiagnostics was assessed using native goat sera. In addition, we orally infected 20 goats with mature T. multiceps eggs. Praziquantel (10%) was given to 10 of the goats 45 days post-infection (p.i.). Blood samples were collected for 17 weeks p.i. from the 20 goats and anti-rTmGP50 antibodies were evaluated using the indirect ELISA established here. The TmGP50 contains an 897 bp open reading frame, in which signal sequence resides in 1 ~ 48 sites and mature polypeptide consists of 282 amino acid residues. Immunofluorescence staining showed that native TmGP50 was localized to the microthrix and parenchymatous zone of the adult parasite and coenurus, and the coenurus cystic wall. The indirect ELISA based on rTmGP50 exhibited a sensitivity of 95.0% and a specificity of 92.6% when detecting GP50 antibodies in sera of naturally infected goats and sheep. In goats experimentally infected with T. multiceps, anti-TmGP50 antibody was detectable from 2 to 17 weeks p.i. in the control group, while the antibody fell below the cut-off value about 3 weeks after praziquantel treatment. Our results indicate that recombinant TmGP50 is a suitable early diagnostic antigen for coenurus infection in goats.

Leishmania major surface protease Gp63 interferes with the function of human monocytes and neutrophils in vitro

DEFF Research Database (Denmark)

Sørensen, A L; Hey, A S; Kharazmi, A

1994-01-01

In the present study the effect of Leishmania major surface protease Gp63 on the chemotaxis and oxidative burst response of human peripheral blood monocytes and neutrophils was investigated. It was shown that prior incubation of cells with Gp63 inhibited chemotaxis of neutrophils but not monocytes...... towards the chemotactic peptide f-met-leu-phe. On the other hand, chemotaxis of both neutrophils and monocytes towards zymosan-activated serum containing C5a was inhibited by Gp63. Monocyte and neutrophil chemiluminescence response to opsonized zymosan was reduced by preincubation of the cells with Gp63...... in a concentration-dependent manner. Notably, monocytes were inhibited to a much greater degree than neutrophils by a given concentration of Gp63, and they were also inhibited at much lower concentrations of the protease. The inhibitory effect of Gp63 on chemotaxis and chemiluminescence was completely abolished...

Characterisation of different forms of the accessory gp3 canine coronavirus type I protein identified in cats.

Science.gov (United States)

d'Orengiani, Anne-Laure Pham-Hung d'Alexandry; Duarte, Lidia; Pavio, Nicole; Le Poder, Sophie

2015-04-16

ORF3 is a supplemental open reading frame coding for an accessory glycoprotein gp3 of unknown function, only present in genotype I canine strain (CCoV-I) and some atypical feline FCoV strains. In these latter hosts, the ORF3 gene systematically displays one or two identical deletions leading to the synthesis of truncated proteins gp3-Δ1 and gp3-Δ2. As deletions in CoV accessory proteins have already been involved in tissue or host switch, studies of these different gp3 proteins were conducted in canine and feline cell. All proteins oligomerise through covalent bonds, are N-glycosylated and are maintained in the ER in non-infected but also in CCoV-II infected cells, without any specific retention signal. However, deletions influence their level of expression. In canine cells, all proteins are expressed with similar level whereas in feline cells, the expression of gp3-Δ1 is higher than the two other forms of gp3. None of the gp3 proteins modulate the viral replication cycle of heterologous genotype II CCoV in canine cell line, leading to the conclusion that the gp3 proteins are probably advantageous only for CCoV-I and atypical FCoV strains. Copyright © 2015 Elsevier B.V. All rights reserved.

Using photography to enhance GP trainees’ reflective practice and professional development.

OpenAIRE

Rutherford,; Forde, Emer; Priego-Hernández, J.; Butcher, Aurelia; Wedderburn, Clare

2018-01-01

The capacity and the commitment to reflect are integral to the practice of medicine and are core components of most GP training programmes. Teaching through the Humanities is a growing area within medical education, but one which is often considered a voluntary ‘add on’ for the interested doctor. This article describes an evaluation of a highly innovative pedagogical project which used photography as a means to enhance GP trainees’ reflective capacity, self awareness and professional developm...

HIV-1 gp120 and drugs of abuse: interactions in the central nervous system.

Science.gov (United States)

Silverstein, Peter S; Shah, Ankit; Weemhoff, James; Kumar, Santosh; Singh, D P; Kumar, Anil

2012-07-01

HIV-1 infection is a global public health problem with more than 34 million people living with HIV infection. Although great strides have been made in treating this epidemic with therapeutic agents, the increase in patient life span has been coincident with an increase in the prevalence of HIV-associated neurocognitive disorders (HAND). HAND is thought to result from the neurotoxic effects of viral proteins that are shed from HIV-infected microglial cells. One of the primary neurotoxins responsible for this effect is the HIV-1 glycoprotein gp120. Exposure of neurons to gp120 has been demonstrated to cause apoptosis in neurons, as well as numerous indirect effects such as an increase in inflammatory cytokines, an increase in oxidative stress, and an increase in permeability of the blood-brain barrier. In many patients, the use of drugs of abuse (DOA) exacerbates the neurotoxic effects of gp120. Cocaine, methamphetamine and morphine are three DOAs that are commonly used by those infected with HIV-1. All three of these DOAs have been demonstrated to increase oxidative stress in the CNS as well as to increase permeability of the blood-brain barrier. Numerous model systems have demonstrated that these DOAs have the capability of exacerbating the neurotoxic effects of gp120. This review will summarize the neurotoxic effects of gp120, the deleterious effects of cocaine, methamphetamine and morphine on the CNS, and the combined effects of gp120 in the context of these drugs.

Comparative Glycoprofiling of HIV gp120 Immunogens by Capillary Electrophoresis and MALDI Mass Spectrometry

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Guttman, Miklós; Váradi, Csaba; Lee, Kelly K.; Guttman, András

2015-01-01

The Human Immunodeficiency Virus (HIV) envelope glycoprotein (Env) is the primary antigenic feature on the surface of the virus and is of key importance in HIV vaccinology. Vaccine trials with the gp120 subunit of Env are ongoing with the recent RV144 trial showing moderate efficacy. gp120 is densely covered with N-linked glycans that are thought to help evade the host's humoral immune response. To assess how the global glycosylation patterns vary between gp120 constructs, the glycan profiles of several gp120s were examined by capillary electrophoresis with laser induced fluorescence detection and MALDI-MS. The glycosylation profiles were found to be similar for chronic vs. transmitter/founder isolates and only varied moderately between gp120s from different clades. This study revealed that the addition of specific tags, such as the gD tag used in the RV144 trial, had significant effects on the overall glycosylation patterns. Such effects are likely to influence the immunogenicity of various Env immunogens and should be considered for future vaccine strategies, emphasizing the importance of the glycosylation analysis approach described in this paper. PMID:25809283

Serological responses in chimpanzees inoculated with human immunodeficiency virus glycoprotein (gp120) subunit vaccine

International Nuclear Information System (INIS)

Arthur, L.O.; Pyle, S.W.; Nara, P.L.

1987-01-01

The major envelope glycoprotein of a human immunodeficiency virus (HIV) has been purified and was utilized as a prototype vaccine in chimpanzees. The 120,000-dalton glycoprotein (gp120) was purified from membranes of human T-lymphotropic virus (HTLV)-IIIB-infected cells and the final preparation contained low levels to no detectable HTLV-IIIB core antigen (p24) and low levels of endotoxin. Chimpanzees inoculated with gp120 responded by developing antibodies that precipitated radiolabeled gp120 and neutralized in vitro infection of HTLV-IIIB. Antibodies to HTLV-IIIB p24 were not detected in the gp120-immunized chimpanzees. Peripheral blood leukocytes from the vaccinated animals were examined for T4 + and T8 + cells, and no decrease in the T4/T8 ratio was found, indicating that immunization with a ligand (gp120) that binds to T4 has not detectable adverse effect on the population of T4 + cells. The only current animal model that can be reproducibly infected with HIV is the chimpanzee. Immunization of chimpanzees with HIV proteins will provide an experimental system for testing the effectiveness of prototype vaccines for preventing HIV infection in vivo

Membrane binding properties of EBV gp110 C-terminal domain; evidences for structural transition in the membrane environment

International Nuclear Information System (INIS)

Park, Sung Jean; Seo, Min-Duk; Lee, Suk Kyeong; Lee, Bong Jin

2008-01-01

Gp110 of Epstein-Barr virus (EBV) mainly localizes on nuclear/ER membranes and plays a role in the assembly of EBV nucleocapsid. The C-terminal tail domain (gp110 CTD) is essential for the function of gp110 and the nuclear/ER membranes localization of gp110 is ruled by its C-terminal unique nuclear localization signal (NLS), consecutive four arginines. In the present study, the structural properties of gp110 CTD in membrane mimics were investigated using CD, size-exclusion chromatography, and NMR, to elucidate the effect of membrane environment on the structural transition and to compare the structural feature of the protein in the solution state with that of the membrane-bound form. CD and NMR analysis showed that gp110 CTD in a buffer solution appears to adopt a stable folding intermediate which lacks compactness, and a highly helical structure is formed only in membrane environments. The helical content of gp110 CTD was significantly affected by the negative charge as well as the size of membrane mimics. Based on the elution profiles of the size-exclusion chromatography, we found that gp110 CTD intrinsically forms a trimer, revealing that a trimerization region may exist in the C-terminal domain of gp110 like the ectodomain of gp110. The mutation of NLS (RRRR) to RTTR does not affect the overall structure of gp110 CTD in membrane mimics, while the helical propensity in a buffer solution was slightly different between the wild-type and the mutant proteins. This result suggests that not only the helicity induced in membrane environment but also the local structure around NLS may be related to trafficking to the nuclear membrane. More detailed structural difference between the wild-type and the mutant in membrane environment was examined using synthetic two peptides including the wild-type NLS and the mutant NLS

Twiddler's syndrome in a patient with a deep brain stimulation device for generalized dystonia

DEFF Research Database (Denmark)

Astradsson, Arnar; Schweder, Patrick M; Joint, Carole

2011-01-01

Deep brain stimulation (DBS) is the technique of neurostimulation of deep brain structures for the treatment of conditions such as essential tremor, dystonia, Parkinson's disease and chronic pain syndromes. The procedure uses implanted deep brain stimulation electrodes connected to extension leads...... and an implantable pulse generator (IPG). Hardware failure related to the DBS procedure is not infrequent, and includes electrode migration and disconnection. We describe a patient who received bilateral globus pallidus internus DBS for dystonia with initially good clinical response, but the device eventually failed....... Radiographs showed multiple twisting of the extension leads with disconnection from the brain electrodes and a diagnosis of Twiddler's syndrome was made. Twiddler's syndrome was first described in patients with cardiac pacemakers. Patients with mental disability, elderly and obese patients are at increased...

Renal Failure in Dementia with Lewy Bodies Presenting as Catatonia

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Robert Fekete

2013-01-01

Full Text Available Catatonia, originally described by Karl Kahlbaum in 1874, may be regarded as a set of clinical features found in a subtype of schizophrenia, but the syndrome may also stem from organic causes including vascular parkinsonism, brain masses, globus pallidus lesions, metabolic derangements, and pharmacologic agents, especially first generation antipsychotics. Catatonia may include paratonia, waxy flexibility (cerea flexibilitas, stupor, mutism, echolalia, and catalepsy (abnormal posturing. A case of catatonia as a result of acute renal failure in a patient with dementia with Lewy bodies is described. This patient recovered after intravenous fluid administration and reinstitution of the atypical dopamine receptor blocking agent quetiapine, but benzodiazepines and amantadine are additional possible treatments. Recognition of organic causes of catatonia leads to timely treatment and resolution of the syndrome.

The Pathogenicity of Anti-β2GP1-IgG Autoantibodies Depends on Fc Glycosylation

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Christoph Fickentscher

2015-01-01

Full Text Available To analyze the glycosylation of anti-β2GP1, we investigated purified IgG from healthy children, patients with APS, and asymptomatic adult carriers of antiphospholipid antibodies. We observed that in the sera of healthy children and of patients with APS, IgG3 and IgG2 were predominant, respectively. The potentially protective anti-β2GP1-IgM was lower in the sera of healthy children. Although anti-β2GP1-associated C1q did not differ between children and patients with antiphospholipid syndrome, the associated C3c was significantly higher in the sera of healthy children. This indicates a more efficient clearance of anti-β2GP1 immune complexes in the healthy children. This clearance is not accompanied by inflammation or coagulatory events. It is likely that the most important pathogenic factor of the anti-β2GP1-IgG is related to the different glycosylation observed in healthy and diseased individuals. We detected a significantly higher sialylation of anti-β2GP1-IgG isolated from the sera of healthy children and asymptomatic adults when compared with that of patients with clinically apparent antiphospholipid syndrome. Low sialylated IgG reportedly ameliorates inflammation and inflammation promotes hyposialylation. Thus, both reactions create a vicious circle that precipitates the pathology of the antiphospholipid syndrome including thrombus-formation. We conclude that the increased sialylation of anti-β2GP1-IgG of sera of healthy individuals limits their pathogenicity.

Genome profiling (GP method based classification of insects: congruence with that of classical phenotype-based one.

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Shamim Ahmed

Full Text Available Ribosomal RNAs have been widely used for identification and classification of species, and have produced data giving new insights into phylogenetic relationships. Recently, multilocus genotyping and even whole genome sequencing-based technologies have been adopted in ambitious comparative biology studies. However, such technologies are still far from routine-use in species classification studies due to their high costs in terms of labor, equipment and consumables.Here, we describe a simple and powerful approach for species classification called genome profiling (GP. The GP method composed of random PCR, temperature gradient gel electrophoresis (TGGE and computer-aided gel image processing is highly informative and less laborious. For demonstration, we classified 26 species of insects using GP and 18S rDNA-sequencing approaches. The GP method was found to give a better correspondence to the classical phenotype-based approach than did 18S rDNA sequencing employing a congruence value. To our surprise, use of a single probe in GP was sufficient to identify the relationships between the insect species, making this approach more straightforward.The data gathered here, together with those of previous studies show that GP is a simple and powerful method that can be applied for actually universally identifying and classifying species. The current success supported our previous proposal that GP-based web database can be constructible and effective for the global identification/classification of species.

Correlation between the GP78 Gene Polymorphism and Coronary Atherosclerotic Heart Disease

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Long Wang

2018-01-01

Full Text Available Objective: To study the correlation between the GP78 gene polymorphism and blood fat, blood glucose, blood pressure and coronary atherosclerotic heart disease. Methods: A total of 72 patients with coronary atherosclerotic heart disease were selected as the observation group, and 68 healthy participants were selected as the control group. The gp78 gene polymorphism of both groups was studied via polymerase chain reaction-restriction fragment length polymorphism (RFLP. At the same time, the multiple expression quantities of the GP78 gene in the tissues of both groups were tested via fluorogenic quantitative PCR, enzyme-linked immunosorbent assay (ELISA and Western-blotting assay. Furthermore, the blood fat, blood glucose and blood pressure of subjects in both groups were tested. Results: The percentages of the gp78 gene polymorphisms of Arg/Arg, Arg/Gly and Gly/Gly at the 145 locus of the study subjects in the observation group were 12.3%, 43.2% and 44.5%, respectively, while those in the control group were 74.3%, 11.2% and 14.5%, respectively, and there were significant differences between both groups. Based on the test results of the blood fat, blood glucose and blood pressure of the objects in the observation group and control group, significant differences were found between the two groups (P<0.05. Conclusion: There was a significant correlation between the 145 locus of the gp89 gene and coronary atherosclerotic heart disease, indexes of blood fat, blood glucose and blood pressure. Keywords: blood fat, blood glucose, blood pressure, coronary sclerosis, heart disease

The learner’s perspective in GP teaching practices with multi-level learners: a qualitative study

Science.gov (United States)

2014-01-01

Background Medical students, junior hospital doctors on rotation and general practice (GP) registrars are undertaking their training in clinical general practices in increasing numbers in Australia. Some practices have four levels of learner. This study aimed to explore how multi-level teaching (also called vertical integration of GP education and training) is occurring in clinical general practice and the impact of such teaching on the learner. Methods A qualitative research methodology was used with face-to-face, semi-structured interviews of medical students, junior hospital doctors, GP registrars and GP teachers in eight training practices in the region that taught all levels of learners. Interviews were audio-recorded and transcribed. Qualitative analysis was conducted using thematic analysis techniques aided by the use of the software package N-Vivo 9. Primary themes were identified and categorised by the co-investigators. Results 52 interviews were completed and analysed. Themes were identified relating to both the practice learning environment and teaching methods used. A practice environment where there is a strong teaching culture, enjoyment of learning, and flexible learning methods, as well as learning spaces and organised teaching arrangements, all contribute to positive learning from a learners’ perspective. Learners identified a number of innovative teaching methods and viewed them as positive. These included multi-level learner group tutorials in the practice, being taught by a team of teachers, including GP registrars and other health professionals, and access to a supernumerary GP supervisor (also termed “GP consultant teacher”). Other teaching methods that were viewed positively were parallel consulting, informal learning and rural hospital context integrated learning. Conclusions Vertical integration of GP education and training generally impacted positively on all levels of learner. This research has provided further evidence about the

Lessons learned from an Internet GP information system.

Science.gov (United States)

Briggs, J S; Bradley, M P

1998-01-01

We describe the prototype of an application that in actual use would allow GPs to find out more information about consultants at hospitals. This would aid the GP in making the decision about which consultant a patient should be referred to. The requirements of the application from the GP's perspective are described, together with some of the issues that have to be resolved before hospitals can provide the necessary information in a standard format. The application is implemented as a client--server system using standard Internet technologies such as Java and HTML. This architecture has a number of advantages but also revealed some issues concerning security and the format of data, among other things. The project showed that there is a desire for such a system and that that desire can be fulfilled at a relatively low cost.

Oncostatin M induces heat hypersensitivity by gp130-dependent sensitization of TRPV1 in sensory neurons

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Langeslag Michiel

2011-12-01

Full Text Available Abstract Oncostatin M (OSM is a member of the interleukin-6 cytokine family and regulates eg. gene activation, cell survival, proliferation and differentiation. OSM binds to a receptor complex consisting of the ubiquitously expressed signal transducer gp130 and the ligand binding OSM receptor subunit, which is expressed on a specific subset of primary afferent neurons. In the present study, the effect of OSM on heat nociception was investigated in nociceptor-specific gp130 knock-out (SNS-gp130-/- and gp130 floxed (gp130fl/fl mice. Subcutaneous injection of pathophysiologically relevant concentrations of OSM into the hind-paw of C57BL6J wild type mice significantly reduced paw withdrawal latencies to heat stimulation. In contrast to gp130fl/fl mice, OSM did not induce heat hypersensitivity in vivo in SNS-gp130-/- mice. OSM applied at the receptive fields of sensory neurons in in vitro skin-nerve preparations showed that OSM significantly increased the discharge rate during a standard ramp-shaped heat stimulus. The capsaicin- and heat-sensitive ion channel TRPV1, expressed on a subpopulation of nociceptive neurons, has been shown to play an important role in inflammation-induced heat hypersensitivity. Stimulation of cultured dorsal root ganglion neurons with OSM resulted in potentiation of capsaicin induced ionic currents. In line with these recordings, mice with a null mutation of the TRPV1 gene did not show any signs of OSM-induced heat hypersensitivity in vivo. The present data suggest that OSM induces thermal hypersensitivity by directly sensitizing nociceptors via OSMR-gp130 receptor mediated potentiation of TRPV1.

Admission and poor performance of trainees in the postgraduate GP training in the Netherlands

NARCIS (Netherlands)

Vermeulen, M.I.

2014-01-01

Until 2014 the selection for the Dutch postgraduate GP training was conducted locally, on the eight GP departments. The procedure consisted of a letter of application and a semi-structured interview. We investigated to what extend department of choice, candidates’ characteristics and qualities

'I need her to be a doctor': patients' experiences of presenting health information from the internet in GP consultations.

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Bowes, Parvathy; Stevenson, Fiona; Ahluwalia, Sanjiv; Murray, Elizabeth

2012-11-01

Patients are increasingly using the internet for health-related information and may bring this to a GP consultation. There is scant information about why patients do this and what they expect from their GP. The aim was to explore patients' motivation in presenting information, their perception of the GP's response and what they wanted from their doctor. Qualitative study based in North London involving patients with experience of bringing health information from the internet to their GP. Semi-structured face-to-face and telephone interviews using a critical incident technique, recorded, transcribed verbatim, and subjected to thematic analysis by a multidisciplinary team of researchers. Twenty-six interviews were completed. Participants reported using the internet to become better informed about their health and hence make best use of the limited time available with the GP and to enable the GP to take their problem more seriously. Patients expected their GP to acknowledge the information; discuss, explain, or contextualise it; and offer a professional opinion. Patients tended to prioritise the GP opinion over the internet information. However, if the GP appeared disinterested, dismissive or patronising patients reported damage to the doctor-patient relationship, occasionally to the extent of seeking a second opinion or changing their doctor. This is the first in-depth qualitative study to explore why patients present internet information to their GP within the consultation and what they want when they do this. This information should help GPs respond appropriately in such circumstances.

GPs' experiences with out-of-hours GP cooperatives: a survey study from the Netherlands.

Science.gov (United States)

Smits, Marleen; Keizer, Ellen; Huibers, Linda; Giesen, Paul

2014-09-01

Out-of-hours primary care has been provided by general practitioner (GP) cooperatives since the year 2000 in the Netherlands. Early studies in countries with similar organizational structures showed positive GP experiences. However, nowadays it is said that GPs experience a high workload at the cooperative and that they outsource a considerable part of their shifts. To examine positive and negative experiences of GPs providing out-of-hours primary care, and the frequency and reasons for outsourcing shifts. A cross-sectional observational survey among 688 GPs connected to six GP cooperatives in the Netherlands, using a web-based questionnaire. The response was 55% (n = 378). The main reasons for working in GP cooperatives were to retain registration as GP (79%) and remain experienced in acute care (74%). GPs considered the peak hours (81%) and the high number of patients (73%) as the most negative aspects. Most GPs chose to provide the out-of-hours shifts themselves: 85% outsourced maximally 25% of their shifts. The percentage of outsourced shifts increased with age. Main reasons for outsourcing were the desire to have more private time (76%); the high workload in daytime practice (71%); and less the workload during out-of-hours (46%). GPs are motivated to work in out-of-hours GP cooperatives, and they outsource few shifts. GPs consider the peak load and the large number of (non-urgent) help requests as the most negative aspects. To motivate and involve GPs for 7 × 24-h primary care, it is important to set limits on their workload.

Mutations in gp41 are correlated with coreceptor tropism but do not improve prediction methods substantially.

Science.gov (United States)

Thielen, Alexander; Lengauer, Thomas; Swenson, Luke C; Dong, Winnie W Y; McGovern, Rachel A; Lewis, Marilyn; James, Ian; Heera, Jayvant; Valdez, Hernan; Harrigan, P Richard

2011-01-01

The main determinants of HIV-1 coreceptor usage are located in the V3-loop of gp120, although mutations in V2 and gp41 are also known. Incorporation of V2 is known to improve prediction algorithms; however, this has not been confirmed for gp41 mutations. Samples with V3 and gp41 genotypes and Trofile assay (Monogram Biosciences, South San Francisco, CA, USA) results were taken from the HOMER cohort (n=444) and from patients screened for the MOTIVATE studies (n=1,916; 859 with maraviroc outcome data). Correlations of mutations with tropism were assessed using Fisher's exact test and prediction models trained using support vector machines. Models were validated by cross-validation, by testing models from one dataset on the other, and by analysing virological outcome. Several mutations within gp41 were highly significant for CXCR4 usage; most strikingly an insertion occurring in 7.7% of HOMER-R5 and 46.3% of HOMER-X4 samples (MOTIVATE 5.7% and 25.2%, respectively). Models trained on gp41 sequence alone achieved relatively high areas under the receiver-operating characteristic curve (AUCs; HOMER 0.713 and MOTIVATE 0.736) that were almost as good as V3 models (0.773 and 0.884, respectively). However, combining the two regions improved predictions only marginally (0.813 and 0.902, respectively). Similar results were found when models were trained on HOMER and validated on MOTIVATE or vice versa. The difference in median log viral load decrease at week 24 between patients with R5 and X4 virus was 1.65 (HOMER 2.45 and MOTIVATE 0.79) for V3 models, 1.59 for gp41-models (2.42 and 0.83, respectively) and 1.58 for the combined predictor (2.44 and 0.86, respectively). Several mutations within gp41 showed strong correlation with tropism in two independent datasets. However, incorporating gp41 mutations into prediction models is not mandatory because they do not improve substantially on models trained on V3 sequences alone.

Host-Primed Ebola Virus GP Exposes a Hydrophobic NPC1 Receptor-Binding Pocket, Revealing a Target for Broadly Neutralizing Antibodies.

Science.gov (United States)

Bornholdt, Zachary A; Ndungo, Esther; Fusco, Marnie L; Bale, Shridhar; Flyak, Andrew I; Crowe, James E; Chandran, Kartik; Saphire, Erica Ollmann

2016-02-23

The filovirus surface glycoprotein (GP) mediates viral entry into host cells. Following viral internalization into endosomes, GP is cleaved by host cysteine proteases to expose a receptor-binding site (RBS) that is otherwise hidden from immune surveillance. Here, we present the crystal structure of proteolytically cleaved Ebola virus GP to a resolution of 3.3 Å. We use this structure in conjunction with functional analysis of a large panel of pseudotyped viruses bearing mutant GP proteins to map the Ebola virus GP endosomal RBS at molecular resolution. Our studies indicate that binding of GP to its endosomal receptor Niemann-Pick C1 occurs in two distinct stages: the initial electrostatic interactions are followed by specific interactions with a hydrophobic trough that is exposed on the endosomally cleaved GP1 subunit. Finally, we demonstrate that monoclonal antibodies targeting the filovirus RBS neutralize all known filovirus GPs, making this conserved pocket a promising target for the development of panfilovirus therapeutics. Ebola virus uses its glycoprotein (GP) to enter new host cells. During entry, GP must be cleaved by human enzymes in order for receptor binding to occur. Here, we provide the crystal structure of the cleaved form of Ebola virus GP. We demonstrate that cleavage exposes a site at the top of GP and that this site binds the critical domain C of the receptor, termed Niemann-Pick C1 (NPC1). We perform mutagenesis to find parts of the site essential for binding NPC1 and map distinct roles for an upper, charged crest and lower, hydrophobic trough in cleaved GP. We find that this 3-dimensional site is conserved across the filovirus family and that antibody directed against this site is able to bind cleaved GP from every filovirus tested and neutralize viruses bearing those GPs. Copyright © 2016 Bornholdt et al.

[Expression and significance of P-gp/mdr1 mRNA, MRP and LRP in non-Hodgkin's lymphoma].

Science.gov (United States)

Li, Le; Su, Li-ping; Ma, Li; Zhao, Jin; Zhu, Lei; Zhou, Yong-an

2009-03-01

To explore the expression and clinical significance of P-glycoprotein (P-gp)/mdr1mRNA, multidrug resistance-associated protein (MRP) and lung resistance protein (LRP) in newly diagnosed non-Hodgkin's lymphoma. mdr1 mRNA of in 41 patients with non-Hodgkin's lymphoma was assayed by semi-quantitative RT-PCR. The expressions of P-gp, MRP and LRP proteins in lymph node viable blasts were identified by flow cytometry. The results were compared with those obtained from control cases, and the correlation of the changes with clinical outcomes was analyzed. (1) Among the 41 cases, the positive expression of P-gp protein was detected in 8 cases, MRP in 7 cases, LRP in 15 cases, and mdr 1 mRNA in 11 cases. (2) The P-gp and LRP levels in NHL were significantly higher than those in control group, but MRP wasn't. The P-gp over-expression was significantly associated with mdr1mRNA (r = 0.396, P = 0.01). No correlation was showed among the expressions of P-gp, MRP and LRP. (3) Patients with P-gp expression had a poorer outcome of chemotherapy than those with P-gp-negative (P = 0.005). P-gp expression was significantly associated with higher clinical stage (P = 0.046) and elevated serum lactate dehydrogenase level (P = 0.032), but not associated with malignant degree (P = 0.298). MRP had no impact on the outcome of chemotherapy (P = 0.212), and wasn't significantly associated with higher clinical stage (P = 0.369), elevated LDH (P = 0.762) and higher malignant degree (P = 0.451). Patients with LRP expression had a poorer outcome of chemotherapy than those LRP-negative (P = 0.012). LRP expression was significantly associated with higher clinical stage (P = 0.0019), elevated LDH (P = 0.02) and higher malignant degree (P = 0.01). The data of this study indicate that P-gp and LRP expressions but not MRP expression are important in the mechanism of drug resistance associated with a poor clinical outcome in previously untreated NHL.

N-acetylcysteine prevents HIV gp 120-related damage of human cultured astrocytes: correlation with glutamine synthase dysfunction

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Costa Nicola

2007-12-01

Full Text Available Abstract Background HIV envelope gp 120 glycoprotein is released during active HIV infection of brain macrophages thereby generating inflammation and oxidative stress which contribute to the development of the AIDS-Dementia Complex (ADC. Gp120 has also been found capable to generate excitotoxic effect on brain tissue via enhancement of glutamatergic neurotransmission, leading to neuronal and astroglial damage, though the mechanism is still to be better understood. Here we investigated on the effect of N-acetylcysteine (NAC, on gp120-induced damage in human cultured astroglial cells and the possible contribution of gp120-related reacting oxygen species (ROS in the imbalanced activity of glutamine synthase (GS, the enzyme that metabolizes glutamate into glutamine within astroglial cells playing a neuroprotective role in brain disorders. Results Incubation of Lipari human cultured astroglial cells with gp 120 (0.1–10 nM produced a significant reduction of astroglial cell viability and apoptosis as evaluated by TUNEL reaction and flow cytometric analysis (FACS. This effect was accompanied by lipid peroxidation as detected by means of malondialdehyde assay (MDA. In addition, gp 120 reduced both glutamine concentration in astroglial cell supernatants and GS expression as detected by immunocytochemistry and western blotting analysis. Pre-treatment of cells with NAC (0.5–5 mM, dose-dependently antagonised astroglial apoptotic cell death induced by gp 120, an effect accompanied by significant attenuation of MDA accumulation. Furthermore, both effects were closely associated with a significant recovery of glutamine levels in cell supernatants and by GS expression, thus suggesting that overproduction of free radicals might contribute in gp 120-related dysfunction of GS in astroglial cells. Conclusion In conclusion, the present experiments demonstrate that gp 120 is toxic to astroglial cells, an effect accompanied by lipid peroxidation and by altered

Marburg Virus Glycoprotein GP2: pH-Dependent Stability of the Ectodomain α-Helical Bundle†

Science.gov (United States)

Harrison, Joseph S.; Koellhoffer, Jayne F.; Chandran, Kartik; Lai, Jonathan R.

2012-01-01

Marburg virus (MARV) and Ebola virus (EBOV) constitute the family Filoviridae of enveloped viruses (filoviruses) that cause severe hemorrhagic fever. Infection by MARV is required for fusion between the host cell and viral membranes, a process that is mediated by the two subunits of the envelope glycoprotein GP1 (surface subunit) and GP2 (transmembrane subunit). Upon viral attachment and uptake, it is believed that the MARV viral fusion machinery is triggered by host factors and environmental conditions found in the endosome. Next, conformational rearrangements in the GP2 ectodomain result in the formation of a highly stable six-helix bundle; this refolding event provides the energetic driving force for membrane fusion. Both GP1 and GP2 from EBOV have been extensively studied, but there is little information available for the MARV glycoproteins. Here we have expressed two variants of the MARV GP2 ectodomain in Escherichia coli and analyzed their biophysical properties. Circular dichroism indicates that the MARV GP2 ectodomain adopts an α-helical conformation, and one variant sediments as a trimer by equilibrium analytical ultracentrifugation. Denaturation studies indicate the α-helical structure is highly stable at pH 5.3 (unfolding energy, ΔGunf H2O, of 33.4 ± 2.5 kcal/mol and melting temperature, Tm, of 75.3 ± 2.1 °C for one variant). Furthermore, we found the α-helical stability to be strongly dependent on pH with higher stability under lower pH conditions (Tm values ranging from ~92 °C at pH 4.0 to ~38 °C at pH 8.0). Mutational analysis suggests two glutamic acid residues (E579 and E580) are partially responsible for this pH-dependent behavior. Based on these results, we hypothesize that pH-dependent folding stability of the MARV GP2 ectodomain provides a mechanism to control conformational preferences such that the six-helix bundle ‘post-fusion’ state is preferred under conditions of appropriately matured endosomes. PMID:22369502

Nuclear pore complex assembly and maintenance in POM121- and gp210-deficient cells

DEFF Research Database (Denmark)

Stavru, Fabrizia; Nautrup-Pedersen, Gitte; Cordes, Volker C

2006-01-01

So far, POM121 and gp210 are the only known anchoring sites of vertebrate nuclear pore complexes (NPCs) within the lipid bilayer of the nuclear envelope (NE) and, thus, are excellent candidates for initiating the NPC assembly process. Indeed, we demonstrate that POM121 can recruit several...... as depletion of POM121 from human fibroblasts, which do not express gp210, further suggest that NPCs can assemble or at least persist in a POM121- and gp210-free form. This points to extensive redundancies in protein-protein interactions within NPCs and suggests that vertebrate NPCs contain additional membrane...

Binding of radiolabeled asbestos fibers to guinea pig (gp) alveolar macrophages (AM)

International Nuclear Information System (INIS)

Giannotti, M.A.; Tewson, T.J.; Francsechini, M.P.; Scheule, R.K.; Holian, A.

1990-01-01

The mechanism by which fibrogenic particulates cause pulmonary fibrosis in humans is not understood, but is likely to involve the AM. Using two fibrogenic particulates, namely, chrysotile (CHR) and crocidolite (CRO) asbestos and gpAM as components of an in vitro model system, the authors have shown that CHR stimulates the gpAM to release superoxide anion, but CRO does not. To examine whether this difference in stimulatory abilities is a result of differences in cell-asbestos binding they have developed an efficient procedure that radiolabels asbestos fibers while retaining their bioactivity. The fibers are labeled with 68 Ge. The 68 Ge decays into 68 Ga, which then can be detected by its characteristic position emission. Both CHR and CRO asbestos were radiolabled successfully. Mild reaction conditions and short reaction times were found under which >90% of the added 68 Ge and 68 Ga bound to the fibers. The radiolabel was retained even after washing the fibers extensively with physiologic buffers. A density gradient procedure was developed to quantitate the binding of asbestos to gpAM in suspension. The binding of both fibers increased with time over one hr. Thus, these results indicate that although both CHR and CRO interact with the gpAM, only CHR interacts productively to stimulate superoxide anion release

77 FR 20807 - Northwest Pipeline GP; Notice of Application

Science.gov (United States)

2012-04-06

... diameter pipelines away from an adjacent surface coal mine west of Kemmerer, Wyoming. Northwest also... directed to Pam Barnes, Manager Certificates and Tariffs, Northwest Pipeline GP, 295 Chipeta Way, Salt Lake...

Determining the Structure of an Unliganded and Fully Glycosylated SIV gp120 Envelope Glycoprotein

Energy Technology Data Exchange (ETDEWEB)

Chen, Bing; Vogan, Erik M.; Gong, Haiyun; Skehel, John J.; Wiley, Don C.; Harrison, Stephen C. (Harvard-Med); (NIMR)

2010-07-13

HIV/SIV envelope glycoproteins mediate the first steps in viral infection. They are trimers of a membrane-anchored polypeptide chain, cleaved into two fragments known as gp120 and gp41. The structure of HIV gp120 bound with receptor (CD4) has been known for some time. We have now determined the structure of a fully glycosylated SIV gp120 envelope glycoprotein in an unliganded conformation by X-ray crystallography at 4.0 {angstrom} resolution. We describe here our experimental and computational approaches, which may be relevant to other resolution-limited crystallographic problems. Key issues were attention to details of beam geometry mandated by small, weakly diffracting crystals, and choice of strategies for phase improvement, starting with two isomorphous derivatives and including multicrystal averaging. We validated the structure by analyzing composite omit maps, averaged among three distinct crystal lattices, and by calculating model-based, SeMet anomalous difference maps. There are at least four ordered sugars on many of the thirteen oligosaccharides.

Commissioning of the iGp Feedback System at DAΦNE

International Nuclear Information System (INIS)

Drago, A.; Fox, J.D.; Teytelman, D.; Tobiyama, M.

2011-01-01

The iGp (Integrated Gigasample Processor) is an innovative digital bunch-by-bunch feedback system developed by a KEK / SLAC / INFN-LNF joint collaboration. The processing unit can sample at 500 MHz and compute the bunch-by-bunch output signal for up to ∼5000 bunches. The feedback gateware code is implemented inside just one FPGA (Field Programmable Gate Array) chip, a Xilinx Virtex-II. The FPGA implements two banks of 16-tap FIR (Finite Impulse Response) filters. Each filter is realtime programmable through the operator interface. At DAΦNE, the Frascati Φ-Factory, two iGp units have been commissioned in the April 2007. The iGp systems have substituted the previous betatron feedback systems. This insertion has been very fast and has shown no problems involving just a substitution of the old, less flexible, digital systems, letting unchanged the baseband analog frontend and backend. The commissioning has been very simple, due to the complete and powerful EPICS operator interface, working well in local and remote operations. The software includes also tools for analyzing post processor data. A description of the commissioning with the operations done is reported.

Dynamic causal modeling revealed dysfunctional effective connectivity in both, the cortico-basal-ganglia and the cerebello-cortical motor network in writers' cramp

Directory of Open Access Journals (Sweden)

Inken Rothkirch

Full Text Available Writer's cramp (WC is a focal task-specific dystonia characterized by sustained or intermittent muscle contractions while writing, particularly with the dominant hand. Since structural lesions rarely cause WC, it has been assumed that the disease might be caused by a functional maladaptation within the sensory-motor system. Therefore, our objective was to examine the differences between patients suffering from WC and a healthy control (HC group with regard to the effective connectivity that describes causal influences one brain region exerts over another within the motor network. The effective connectivity within a network including contralateral motor cortex (M1, supplementary motor area (SMA, globus pallidus (GP, putamen (PU and ipsilateral cerebellum (CB was investigated using dynamic causal modeling (DCM for fMRI. Eight connectivity models of functional motor systems were compared. Fifteen WC patients and 18 age-matched HC performed a sequential, five-element finger-tapping task with the non-dominant and non-affected left hand within a 3 T MRI-scanner as quickly and accurately as possible. The task was conducted in a fixed block design repeated 15 times and included 30 s of tapping followed by 30 s of rest. DCM identified the same model in WC and HC as superior for reflecting basal ganglia and cerebellar motor circuits of healthy subjects. The M1-PU, as well as M1-CB connectivity, was more strongly influenced by tapping in WC, but the intracortical M1-SMA connection was more facilitating in controls. Inhibiting influences originating from GP to M1 were stronger in controls compared to WC patients whereby facilitating influences the PU exerts over CB and CB exerts over M1 were not as strong. Although the same model structure explains the given data best, DCM confirms previous research demonstrating a malfunction in effective connectivity intracortically (M1-SMA and in the cortico-basal ganglia circuitry in WC. In addition, DCM analysis

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

Values of serum AFP, GGTⅡ and GP73 in diagnosis of primary hepatocellular carcinoma

Directory of Open Access Journals (Sweden)

ZHU Chen

2014-10-01

Full Text Available ObjectiveTo explore the early diagnostic values of serum alpha-fetoprotein (AFP, gamma-glutamyltransferase Ⅱ (GGTⅡ, and Golgi protein 73 (GP73 in patients with primary hepatocellular carcinoma (PHC. MethodsThe serum specimens of 100 patients with liver diseases (50 cases of hepatitis and liver cirrhosis and 50 cases of PHC and 50 healthy people were collected in our hospital from February 2013 to February 2014. Electrochemical luminescence technique, specific immuno-membrane adsorption assay, and enzyme-linked immunosorbent assay were used to measure the serum levels of AFP, GGTⅡ, and GP73. Comparison of continuous data between multiple groups was made by analysis of variance, and comparison between two groups was made by q test. The receiver operating characteristic (ROC curves of single or combined test results were made, and the areas under the ROC curves (AUCs were calculated. The sensitivity, specificity, and AUCs of AFP, GGTⅡ, GP73, and the combined test were analyzed and compared. ResultsThe level of serum GGTⅡ in the PHC group was significantly different compared with those in the other two groups (F=16.224, P＜0.05, but there was no significant difference between the normal group and the hepatitis and liver cirrhosis group (P＞0.05. Significant differences in serum levels of AFP and GP73 were observed by paired comparison between the PHC group, hepatitis and liver cirrhosis group, and normal group (F=193.128, F=20.231, P＜0.05 for both. When assayed alone, the specificities of GP73, GGTⅡ, and AFP were 69%, 64% and 51%, respectively, and the sensitivities were 92%, 84%, and 76%, respectively. In combined test, the specificity was 94.6% and the sensitivity was 98.8%. ConclusionThe GP73 test is the best performer in the single assays. Combined test of serum AFP, GGTⅡ, and GP73 shows a good diagnostic value for PHC with greatly improved specificity and sensitivity.

Antioxidant enzyme gene delivery to protect from HIV-1 gp120-induced neuronal apoptosis.

Science.gov (United States)

Agrawal, L; Louboutin, J-P; Reyes, B A S; Van Bockstaele, E J; Strayer, D S

2006-12-01

Human immunodeficiency virus-1 (HIV-1) infection in the central nervous system (CNS) may lead to neuronal loss and progressively deteriorating CNS function: HIV-1 gene products, especially gp120, induce free radical-mediated apoptosis. Reactive oxygen species (ROS), are among the potential mediators of these effects. Neurons readily form ROS after gp120 exposure, and so might be protected from ROS-mediated injury by antioxidant enzymes such as Cu/Zn-superoxide dismutase (SOD1) and/or glutathione peroxidase (GPx1). Both enzymes detoxify oxygen free radicals. As they are highly efficient gene delivery vehicles for neurons, recombinant SV40-derived vectors were used for these studies. Cultured mature neurons derived from NT2 cells and primary fetal neurons were transduced with rSV40 vectors carrying human SOD1 and/or GPx1 cDNAs, then exposed to gp120. Apoptosis was measured by terminal deoxynucleotidyl transferase-mediated nick end labeling (TUNEL) assay. Transduction efficiency of both neuron populations was >95%, as assayed by immunostaining. Transgene expression was also ascertained by Western blotting and direct assays of enzyme activity. Gp120 induced apoptosis in a high percentage of unprotected NT2-N. Transduction with SV(SOD1) and SV(GPx1) before gp120 challenge reduced neuronal apoptosis by >90%. Even greater protection was seen in cells treated with both vectors in sequence. Given singly or in combination, they protect neuronal cells from HIV-1-gp120 induced apoptosis. We tested whether rSV40 s can deliver antioxidant enzymes to the CNS in vivo: intracerebral injection of SV(SOD1) or SV(GPx1) into the caudate putamen of rat brain yielded excellent transgene expression in neurons. In vivo transduction using SV(SOD1) also protected neurons from subsequent gp120-induced apoptosis after injection of both into the caudate putamen of rat brain. Thus, SOD1 and GPx1 can be delivered by SV40 vectors in vitro or in vivo. This approach may merit consideration for

A single amino acid substitution modulates low-pH-triggered membrane fusion of GP64 protein in Autographa californica and Bombyx mori nucleopolyhedroviruses

International Nuclear Information System (INIS)

Katou, Yasuhiro; Yamada, Hayato; Ikeda, Motoko; Kobayashi, Michihiro

2010-01-01

We have previously shown that budded viruses of Bombyx mori nucleopolyhedrovirus (BmNPV) enter the cell cytoplasm but do not migrate into the nuclei of non-permissive Sf9 cells that support a high titer of Autographa californica multicapsid nucleopolyhedrovirus (AcMNPV) multiplication. Here we show, using the syncytium formation assay, that low-pH-triggered membrane fusion of BmNPV GP64 protein (Bm-GP64) is significantly lower than that of AcMNPV GP64 protein (Ac-GP64). Mutational analyses of GP64 proteins revealed that a single amino acid substitution between Ac-GP64 H155 and Bm-GP64 Y153 can have significant positive or negative effects on membrane fusion activity. Studies using bacmid-based GP64 recombinant AcMNPV harboring point-mutated ac-gp64 and bm-gp64 genes showed that Ac-GP64 H155Y and Bm-GP64 Y153H substitutions decreased and increased, respectively, the multiplication and cell-to-cell spread of progeny viruses. These results indicate that Ac-GP64 H155 facilitates the low-pH-triggered membrane fusion reaction between virus envelopes and endosomal membranes.

Surfactant protein D binds to human immunodeficiency virus (HIV) envelope protein gp120 and inhibits HIV replication

DEFF Research Database (Denmark)

Meschi, Joseph; Crouch, Erika C; Skolnik, Paul

2005-01-01

The envelope protein (gp120) of human immunodeficiency virus (HIV) contains highly conserved mannosylated oligosaccharides. These glycoconjugates contribute to resistance to antibody neutralization, and binding to cell surface lectins on macrophages and dendritic cells. Mannose-binding lectin (MBL......) binds to gp120 and plays a role in defence against the virus. In this study it is demonstrated that surfactant protein D (SP-D) binds to gp120 and inhibits HIV infectivity at significantly lower concentrations than MBL. The binding of SP-D was mediated by its calcium-dependent carbohydrate......-binding activity and was dependent on glycosylation of gp120. Native dodecameric SP-D bound to HIV gp120 more strongly than native trimeric SP-D. Since one common polymorphic form of SP-D is predominantly expressed as trimers and associated with lower blood levels, these individuals may have less effective innate...

Antigenicity and Immunogenicity of RV144 Vaccine AIDSVAX Clade E Envelope Immunogen Is Enhanced by a gp120 N-Terminal Deletion

Science.gov (United States)

Liao, Hua-Xin; Tomaras, Georgia D.; Bonsignori, Mattia; Tsao, Chun-Yen; Hwang, Kwan-Ki; Chen, Haiyan; Lloyd, Krissey E.; Bowman, Cindy; Sutherland, Laura; Jeffries, Thomas L.; Kozink, Daniel M.; Stewart, Shelley; Anasti, Kara; Jaeger, Frederick H.; Parks, Robert; Yates, Nicole L.; Overman, R. Glenn; Sinangil, Faruk; Berman, Phillip W.; Pitisuttithum, Punnee; Kaewkungwal, Jaranit; Nitayaphan, Sorachai; Karasavva, Nicos; Rerks-Ngarm, Supachai; Kim, Jerome H.; Michael, Nelson L.; Zolla-Pazner, Susan; Santra, Sampa; Letvin, Norman L.; Harrison, Stephen C.

2013-01-01

An immune correlates analysis of the RV144 HIV-1 vaccine trial revealed that antibody responses to the gp120 V1/V2 region correlated inversely with infection risk. The RV144 protein immunogens (A244-rp120 and MN-rgp120) were modified by an N-terminal 11-amino-acid deletion (Δ11) and addition of a herpes simplex virus (HSV) gD protein-derived tag (gD). We investigated the effects of these modifications on gp120 expression, antigenicity, and immunogenicity by comparing unmodified A244 gp120 with both Δ11 deletion and gD tag and with Δ11 only. Analysis of A244 gp120, with or without Δ11 or gD, demonstrated that the Δ11 deletion, without the addition of gD, was sufficient for enhanced antigenicity to gp120 C1 region, conformational V2, and V1/V2 gp120 conformational epitopes. RV144 vaccinee serum IgGs bound more avidly to A244 gp120 Δ11 than to the unmodified gp120, and their binding was blocked by C1, V2, and V1/V2 antibodies. Rhesus macaques immunized with the three different forms of A244 gp120 proteins gave similar levels of gp120 antibody titers, although higher antibody titers developed earlier in A244 Δ11 gp120-immunized animals. Conformational V1/V2 monoclonal antibodies (MAbs) gave significantly higher levels of blocking of plasma IgG from A244 Δ11 gp120-immunized animals than IgG from animals immunized with unmodified A244 gp120, thus indicating a qualitative difference in the V1/V2 antibodies induced by A244 Δ11 gp120. These results demonstrate that deletion of N-terminal residues in the RV144 A244 gp120 immunogen improves both envelope antigenicity and immunogenicity. PMID:23175357

Do practice nurse solve future GP capacity problems?

NARCIS (Netherlands)

Lamkaddem, M.; Haan, J. de; Bakker, D. de

2003-01-01

Background: Task delegation is viewed as an important policy instrument to counter foreseen future shortages in GP capacity in the Netherlands. Therefore, a national programme to introduce practice nurses in general practice was launched in 1998 by the National Association of General Practice. In

Potable Water Treatment Facility General Permit (PWTF GP) ...

Science.gov (United States)

2017-08-28

The Final PWTF GP establishes permit eligibility conditions, Notice of Intent (NOI) requirements, effluent limitations, standards, prohibitions, and best management practices for facilities that discharge to waters in the Commonwealth of Massachusetts (including both Commonwealth and Indian country lands) and the State of New Hampshire.

Specific assay measuring binding of /sup 125/I-Gp 120 from HIV to T4/sup +//CD4/sup +/ cells

Energy Technology Data Exchange (ETDEWEB)

Lundin, K.; Nygren, A.; Ramstedt, U.; Gidlund, M.; Wigzell, H.; Arthur, L.O.; Robey, W.G.; Morein, B.

1987-02-26

The HIV (HTLV-III) envelope glycoprotein, Gp120, was isolated from virus-infected tissue culture cells using affinity chromatography. A radioimmunoassay was developed to determine the degree of iodinated Gp120 to target CD4/sup +/ (T4/sup +/) cells. /sup 125/I-Gp120 could be shown to selectively bind to CD4/sup +/ cells only. The Gp120 remained bound to these cells after repeated washes. Monoclonal anti-CD4 antibodies block the binding of Gp120 to CD4/sup +/ cells. Monoclonal antibodies to other cell surface components do not interfere with /sup 125/I-Gp120 binding. All IgG antibodies from HIV seropositive donors tested block /sup 125/I-GP120 binding, though with variable titers. The authors believe that this assay provides further proof for the use of CD4 (T4) as a component of the receptor for HIV. It represents a safe, objective and sensitive method for the analysis of Gp120-CD4 interactions, as well as the potential of antibodies to interfere with this binding. (Auth.). 24 refs.; 2 figs.; 8 tabs.

Analysis of purified gp96 preparations from rat and mouse livers using 2-D gel electrophoresis and tandem mass spectrometry.

Science.gov (United States)

Fairburn, B; Muthana, M; Hopkinson, K; Slack, L K; Mirza, S; Georgiou, A S; Espigares, E; Wong, C; Pockley, A G

2006-09-01

The stress protein gp96 exhibits a number of immunological activities, the majority of studies into which have used gp96 purified from a variety of tissues. On the basis of 1-D gel electrophoresis, the purity of these preparations has been reported to range between 70% and 99%. This study analyzed gp96 preparations from rat and mouse livers using 2-D gel electrophoresis and liquid chromatography electrospray ionization tandem mass spectrometry (MS-MS). The procedure for purifying gp96 was reproducible, as similar protein profiles were observed in replicate gels of gp96 preparations. The purity of the preparations was typically around 70%, with minor co-purified proteins of varying molecular weights and mobilities being present. Dominant bands at 95-100 kDa in preparations from Wistar rats and C57BL/6 mice were identified as gp96 by ECL Western blotting. Multiple bands having similar, yet distinct molecular weights and differing pI mobility on ECL Western blots were confirmed as being gp96 in preparations from Wistar rats using MS-MS. The most striking feature of the 2-D gel analysis was the presence of additional dominant bands at 55 kDa in preparations from Wistar rats, and at 75-90 kDa in preparations from C57BL/6 mice. These were identified as gp96 by ECL Western blotting and, in the case of preparations from Wistar rats, by MS-MS. Although the lower molecular weight, gp96-related molecules might be partially degraded gp96, their reproducible presence, definition and characteristics suggest that they are alternative, species-specific isoforms of the molecule. A 55 kDa protein which exhibited a lower pI value than gp96 was present in all preparations and this was identified as calreticulin, another putative immunoregulatory molecule. This study confirms the reproducibility of the gp96 purification protocol and reveals the presence of multiple gp96 isoforms, some of which likely result from post-translational modifications such as differential glycosylation and

Study of coherence strain of GP II zones in an aged aluminum composite

International Nuclear Information System (INIS)

Hernández-Rivera, J.L.; Rivera, J.J. Cruz; Koch, C.T.; Özdöl, V.B.; Martínez-Sánchez, R.

2012-01-01

Highlights: ► Precipitation sequence was changed in 2024 Al alloy. ► Image artifacts ought to the mask size and shape increased the real strain value. ► The strain distribution around experimental GP area was non uniform and more complex than reference. ► The origin of this strain distribution are related to mechanisms by which GP precipitates lose coherence. - Abstract: Strain mapping using the geometric phase analysis (GPA) technique was applied to Al–GP II (Guinier–Preston) nanoscale precipitates, using both high resolution transmission electron microscopy (HRTEM) micrographs as well as the exit wave function (EWF) obtained by focal series reconstruction. The experimental strain results were compared with strain maps obtained from an atomic model which consisted of an Al supercell containing a GP II precipitate. It was built as a reference from literature data. The experimental results demonstrate a complex strain distribution and larger fluctuations than the reference strain maps. These differences were found to be partly a consequence of image artifacts produced by the technique as well as complex microstructural events which were present at the development stage studied.

Curcumin protects microglia and primary rat cortical neurons against HIV-1 gp120-mediated inflammation and apoptosis.

Directory of Open Access Journals (Sweden)

Luyan Guo

Full Text Available Curcumin is a molecule found in turmeric root that has anti-inflammatory, antioxidant, and anti-tumor properties and has been widely used as both an herbal drug and a food additive to treat or prevent neurodegenerative diseases. To explore whether curcumin is able to ameliorate HIV-1-associated neurotoxicity, we treated a murine microglial cell line (N9 and primary rat cortical neurons with curcumin in the presence or absence of neurotoxic HIV-1 gp120 (V3 loop protein. We found that HIV-1 gp120 profoundly induced N9 cells to produce reactive oxygen species (ROS, tumor necrosis factor-α (TNF-α and monocyte chemoattractant protein-1 (MCP-1. HIV-1 gp120 also induced apoptosis of primary rat cortical neurons. Curcumin exerted a powerful inhibitory effect against HIV-1 gp120-induced neuronal damage, reducing the production of ROS, TNF-α and MCP-1 by N9 cells and inhibiting apoptosis of primary rat cortical neurons. Curcumin may exert its biological activities through inhibition of the delayed rectification and transient outward potassium (K(+ current, as curcumin effectively reduced HIV-1 gp120-mediated elevation of the delayed rectification and transient outward K(+ channel current in neurons. We conclude that HIV-1 gp120 increases ROS, TNF-α and MCP-1 production in microglia, and induces cortical neuron apoptosis by affecting the delayed rectification and transient outward K(+ channel current. Curcumin reduces production of ROS and inflammatory mediators in HIV-1-gp120-stimulated microglia, and protects cortical neurons against HIV-1-mediated apoptosis, most likely through inhibition of HIV-1 gp120-induced elevation of the delayed rectification and transient outward K(+ current.

In vitro and in vivo evaluation of the effects of piperine on P-gp function and expression

International Nuclear Information System (INIS)

Han Yi; Chin Tan, Theresa May; Lim, Lee-Yong

2008-01-01

Piperine, a major component of black pepper, is used as spice and nutrient enhancer. The purpose of the present study was to evaluate the effects of acute and prolonged piperine exposure on cellular P-gp expression and function in vitro and in vivo. Piperine at concentrations ranging from 10 to 100 μM, determined by MTT assay to be non-cytotoxic, was observed to inhibit P-gp mediated efflux transport of [ 3 H]-digoxin across L-MDR1 and Caco-2 cell monolayers. The acute inhibitory effect was dependent on piperine concentration, with abolishment of [ 3 H]-digoxin polarized transport attained at 50 μM of piperine. In contrast, prolonged (48 and 72 h) co-incubation of Caco-2 cell monolayers with piperine (50 and 100 μM) increased P-gp activity through an up-regulation of cellular P-gp protein and MDR1 mRNA levels. The up-regulated protein was functionally active, as demonstrated by a higher degree of [ 3 H]-digoxin efflux across the cell monolayers, but the induction was readily reversed by the removal of the spice from the culture medium. Peroral administration of piperine at the dose of 112 μg/kg body weight/day to male Wistar rats for 14 consecutive days also led to increased intestinal P-gp levels. However, there was a concomitant reduction in the rodent liver P-gp although the kidney P-gp level was unaffected. Our data suggest that caution should be exercised when piperine is to be co-administered with drugs that are P-gp substrates, particularly for patients whose diet relies heavily on pepper

Energetics of dendrimer binding to HIV-1 gp120-CD4 complex and mechanismic aspects of its role as an entry-inhibitor

International Nuclear Information System (INIS)

Saurabh, Suman; Sahoo, Anil Kumar; Maiti, Prabal K.

2016-01-01

Experiments and computational studies have established that de-protonated dendrimers (SPL7013 and PAMAM) act as entry-inhibitors of HIV. SPL7013 based Vivagel is currently under clinical development. The dendrimer binds to gp120 in the gp120-CD4 complex, destabilizes it by breaking key contacts between gp120 and CD4 and prevents viral entry into target cells. In this work, we provide molecular details and energetics of the formation of the SPL7013-gp120-CD4 ternary complex and decipher modes of action of the dendrimer in preventing viral entry. It is also known from experiments that the dendrimer binds weakly to gp120 that is not bound to CD4. It binds even more weakly to the CD4-binding region of gp120 and thus cannot directly block gp120-CD4 complexation. In this work, we examine the feasibility of dendrimer binding to the gp120-binding region of CD4 and directly blocking gp120-CD4 complex formation. We find that the process of the dendrimer binding to CD4 can compete with gp120-CD4 binding due to comparable free energy change for the two processes, thus creating a possibility for the dendrimer to directly block gp120-CD4 complexation by binding to the gp120-binding region of CD4. (paper)

Energetics of dendrimer binding to HIV-1 gp120-CD4 complex and mechanismic aspects of its role as an entry-inhibitor

Science.gov (United States)

Saurabh, Suman; Sahoo, Anil Kumar; Maiti, Prabal K.

2016-10-01

Experiments and computational studies have established that de-protonated dendrimers (SPL7013 and PAMAM) act as entry-inhibitors of HIV. SPL7013 based Vivagel is currently under clinical development. The dendrimer binds to gp120 in the gp120-CD4 complex, destabilizes it by breaking key contacts between gp120 and CD4 and prevents viral entry into target cells. In this work, we provide molecular details and energetics of the formation of the SPL7013-gp120-CD4 ternary complex and decipher modes of action of the dendrimer in preventing viral entry. It is also known from experiments that the dendrimer binds weakly to gp120 that is not bound to CD4. It binds even more weakly to the CD4-binding region of gp120 and thus cannot directly block gp120-CD4 complexation. In this work, we examine the feasibility of dendrimer binding to the gp120-binding region of CD4 and directly blocking gp120-CD4 complex formation. We find that the process of the dendrimer binding to CD4 can compete with gp120-CD4 binding due to comparable free energy change for the two processes, thus creating a possibility for the dendrimer to directly block gp120-CD4 complexation by binding to the gp120-binding region of CD4.

Structural and biochemical characterization of phage λ FI protein (gpFI) reveals a novel mechanism of DNA packaging chaperone activity.

Science.gov (United States)

Popovic, Ana; Wu, Bin; Arrowsmith, Cheryl H; Edwards, Aled M; Davidson, Alan R; Maxwell, Karen L

2012-09-14

One of the final steps in the morphogenetic pathway of phage λ is the packaging of a single genome into a preformed empty head structure. In addition to the terminase enzyme, the packaging chaperone, FI protein (gpFI), is required for efficient DNA packaging. In this study, we demonstrate an interaction between gpFI and the major head protein, gpE. Amino acid substitutions in gpFI that reduced the strength of this interaction also decreased the biological activity of gpFI, implying that this head binding activity is essential for the function of gpFI. We also show that gpFI is a two-domain protein, and the C-terminal domain is responsible for the head binding activity. Using nuclear magnetic resonance spectroscopy, we determined the three-dimensional structure of the C-terminal domain and characterized the helical nature of the N-terminal domain. Through structural comparisons, we were able to identify two previously unannotated prophage-encoded proteins with tertiary structures similar to gpFI, although they lack significant pairwise sequence identity. Sequence analysis of these diverse homologues led us to identify related proteins in a variety of myo- and siphophages, revealing that gpFI function has a more highly conserved role in phage morphogenesis than was previously appreciated. Finally, we present a novel model for the mechanism of gpFI chaperone activity in the DNA packaging reaction of phage λ.

Characterization of humoral responses to soluble trimeric HIV gp140 from a clade A Ugandan field isolate.

Science.gov (United States)

Visciano, Maria Luisa; Tagliamonte, Maria; Stewart-Jones, Guillaume; Heyndrickx, Leo; Vanham, Guido; Jansson, Marianne; Fomsgaard, Anders; Grevstad, Berit; Ramaswamy, Meghna; Buonaguro, Franco M; Tornesello, Maria Lina; Biswas, Priscilla; Scarlatti, Gabriella; Buonaguro, Luigi

2013-07-08

Trimeric soluble forms of HIV gp140 envelope glycoproteins represent one of the closest molecular structures compared to native spikes present on intact virus particles. Trimeric soluble gp140 have been generated by several groups and such molecules have been shown to induce antibodies with neutralizing activity against homologous and heterologous viruses. In the present study, we generated a recombinant trimeric soluble gp140, derived from a previously identified Ugandan A-clade HIV field isolate (gp14094UG018). Antibodies elicited in immunized rabbits show a broad binding pattern to HIV envelopes of different clades. An epitope mapping analysis reveals that, on average, the binding is mostly focused on the C1, C2, V3, V5 and C5 regions. Immune sera show neutralization activity to Tier 1 isolates of different clades, demonstrating cross clade neutralizing activity which needs to be further broadened by possible structural modifications of the clade A gp14094UG018. Our results provide a rationale for the design and evaluation of immunogens and the clade A gp14094UG018 shows promising characteristics for potential involvement in an effective HIV vaccine with broad activity.

Leukemia: Derived heat shock protein gp96-peptide complex ...

African Journals Online (AJOL)

Jane

2011-06-27

Jun 27, 2011 ... Leukemia is a malignant clonal disease in hematopoietic stem cells that is typically treated with chemotherapy and radiotherapy. However ..... with autologous tumor-derived heatshock protein gp96 after liver resection for ...

HIV-gp120 and physical dependence to buprenorphine.

Science.gov (United States)

Palma, J; Abood, M E; Benamar, K

2015-05-01

Opioids are among the most effective and commonly used analgesics in clinical practice for severe pain. However, the use of opioid medications is clinically limited by several adverse properties including dependence. While opioid dependence is a complex health condition, the treatment of HIV-infected individuals with opioid dependence presents additional challenges. The goal of this study was to examine the physical dependence to buprenorphine in the context of HIV. Young adult male rats (Sprague-Dawley) were pretreated with HIV-1 envelope glycoprotein 120 (gp120) injected into the periaqueductal gray area (PAG) and we examined the impact on physical dependence to opioid. It was found that the physical dependence to methadone occurred earlier than that to buprenorphine, and that gp120 did not enhance or precipitate the buprenorphine withdrawal. The results suggest that buprenorphine could be the better therapeutic option to manage opioid dependence in HIV. Copyright © 2015. Published by Elsevier Ireland Ltd.

Studies on adsorptions of metallic ions in water by zirconium glyphosate (ZrGP): Behaviors and mechanisms

International Nuclear Information System (INIS)

Jia Yunjie; Zhang Yuejuan; Wang Runwei; Fan Faying; Xu Qinghong

2012-01-01

A new adsorbent named zirconium glyphosate [Zr(O 3 PCH 2 NHCH 2 COOH) 2 ·0.5H 2 O, denoted as ZrGP] and its selective adsorptions to Pb 2+ , Cd 2+ , Mg 2+ and Ca 2+ ions in water were reported in this paper. Compared to other zirconium adsorbents, such as zirconium phosphate [Zr(HPO 4 ) 2 ], ZrGP exhibited highly selective adsorption to Pb 2+ in solution which contained Pb 2+ , Cd 2+ , Mg 2+ and Ca 2+ ions. The loaded ZrGP with metallic ions can be efficaciously regenerated by aqueous solution of HCl (1.0 M) without any noticeable capacity loss, and almost all of it can be reused and recycled. The memory effect on structural regeneration of ZrGP was also found when Mg 2+ and Ca 2+ were adsorbed. To be specific, the structure of ZrGP was destroyed due to adsorbing these two ions, but it could be regenerated after the loaded materials were dipped in HCl solution (1.0 M) for several minutes to remove metallic ions.

Strategies for induction of catalytic antibodies toward HIV-1 glycoprotein gp120 in autoimmune prone mice.

Science.gov (United States)

Durova, Oxana M; Vorobiev, Ivan I; Smirnov, Ivan V; Reshetnyak, Andrew V; Telegin, Georgy B; Shamborant, Olga G; Orlova, Nadezda A; Genkin, Dmitry D; Bacon, Andrew; Ponomarenko, Natalia A; Friboulet, Alain; Gabibov, Alexander G

2009-11-01

Tremendous efforts to produce an efficient vaccine for HIV infection have been unsuccessful. The ability of HIV to utilize sophisticated mechanisms to escape killing by host immune system rises dramatic problems in the development of antiviral therapeutics. The HIV infection proceeds by interaction of coat viral glycoprotein gp120 trimer with CD4(+) receptor of the lymphocyte. Thus this surface antigen may be regarded as a favorable target for immunotherapy. In the present study, we have developed three different strategies to produce gp120-specific response in autoimmune prone mice (SJL strain) as potential tools for production "catalytic vaccine". Therefore (i) reactive immunization by peptidylphosphonate, structural part of the coat glycoprotein, (ii) immunization by engineered fused epitopes of gp120 and encephalogenic peptide, a part of myelin basic protein, and (iii) combined vaccination by DNA and corresponding gp120 fragments incorporated into liposomes were investigated. In the first two cases monoclonal antibodies and their recombinant fragments with amidolytic and gp120-specific proteolytic activities were characterized. In the last case, catalytic antibodies with virus neutralizing activity proved in cell line models were harvested.

Membrane topology analysis of HIV-1 envelope glycoprotein gp41

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Xiao Dan

2010-11-01

Full Text Available Abstract Background The gp41 subunit of the HIV-1 envelope glycoprotein (Env has been widely regarded as a type I transmembrane protein with a single membrane-spanning domain (MSD. An alternative topology model suggested multiple MSDs. The major discrepancy between the two models is that the cytoplasmic Kennedy sequence in the single MSD model is assigned as the extracellular loop accessible to neutralizing antibodies in the other model. We examined the membrane topology of the gp41 subunit in both prokaryotic and mammalian systems. We attached topological markers to the C-termini of serially truncated gp41. In the prokaryotic system, we utilized a green fluorescent protein (GFP that is only active in the cytoplasm. The tag protein (HaloTag and a membrane-impermeable ligand specific to HaloTag was used in the mammalian system. Results In the absence of membrane fusion, both the prokaryotic and mammalian systems (293FT cells supported the single MSD model. In the presence of membrane fusion in mammalian cells (293CD4 cells, the data obtained seem to support the multiple MSD model. However, the region predicted to be a potential MSD is the highly hydrophilic Kennedy sequence and is least likely to become a MSD based on several algorithms. Further analysis revealed the induction of membrane permeability during membrane fusion, allowing the membrane-impermeable ligand and antibodies to cross the membrane. Therefore, we cannot completely rule out the possible artifacts. Addition of membrane fusion inhibitors or alterations of the MSD sequence decreased the induction of membrane permeability. Conclusions It is likely that a single MSD model for HIV-1 gp41 holds true even in the presence of membrane fusion. The degree of the augmentation of membrane permeability we observed was dependent on the membrane fusion and sequence of the MSD.

Cloning, expression and preliminary crystallographic analysis of the equine infectious anaemia virus (EIAV) gp45 ectodomain

International Nuclear Information System (INIS)

Sun, Pei-Long; Lv, Shu-Xia; Zhou, Jian-Hua; Liu, Xin-Qi

2011-01-01

The equine infectious anaemia virus gp45 ectodomain was cloned, expressed and crystallized. Preliminary crystallographic analysis showed that the protein belonged to space group P6 3 and contained one molecule per asymmetric unit. Like human immunodeficiency virus (HIV), equine infectious anaemia virus (EIAV) belongs to the lentivirus genus. The first successful lentiviral vaccine was developed for EIAV. Thus, EIAV may serve as a valuable model for HIV vaccine research. EIAV glycoprotein 45 (gp45) plays a similar role to gp41 in HIV by mediating virus–host membrane fusion. The gp45 ectodomain was constructed according to the structure of HIV gp41, with removal of the disulfide-bond loop region. The protein was expressed in Escherichia coli and crystallized following purification. However, most of the crystals grew as aggregates and could not be used for data collection. By extensively screening hundreds of crystals, a 2.7 Å resolution data set was collected from a single crystal. The crystal belonged to space group P6 3 , with unit-cell parameters a = b = 46.84, c = 101.61 Å, α = β = 90, γ = 120°. Molecular replacement was performed using the coordinates of various lengths of HIV gp41 as search models. A long bent helix was identified and a well defined electron-density map around the long helix was obtained. This primary model provided the starting point for further refinement

The characteristics of general practice and the attractiveness of working as a GP: medical students' views.

Science.gov (United States)

Landstrom, Bjorn; Mattsson, Bengt; Nordin, Per; Rudebeck, Carl E

2014-03-15

The aim of the study was to investigate medical students' views on general practice based on their experiences in training, and to find out whether there were certain views associated with the intention to become a GP. A questionnaire, based on our earlier studies about GP working behaviour, was handed out to medical students in terms 1, 3, 5, 7, 10 and 11 of undergraduate studies in Gothenburg, Sweden. The analysis comprised statistical descriptions and comparisons. The students regarded general practice positively. They found the work environment good, the GP's awareness of patients' living conditions necessary, and that GP work requires medical breadth. The status of the GP in the medical profession was not considered high. One-fourth of the students strongly agreed with the possibility of a future as a GP. This attitude was statistically associated with support to the statements that general practice offers a good work environment and should be a major component in undergraduate training. Students with a negative attitude to working as GPs were also negative to having a major component of general practice in undergraduate training. Medical students with a positive stated attitude towards becoming GPs support changes in undergraduate training to include more general practice. The risk of increasing a negative attitude should be considered when changes are discussed.

Functional, non-clonal IgMa-restricted B cell receptor interactions with the HIV-1 envelope gp41 membrane proximal external region.

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Laurent Verkoczy

Full Text Available The membrane proximal external region (MPER of HIV-1 gp41 has several features that make it an attractive antibody-based vaccine target, but eliciting an effective gp41 MPER-specific protective antibody response remains elusive. One fundamental issue is whether the failure to make gp41 MPER-specific broadly neutralizing antibodies like 2F5 and 4E10 is due to structural constraints with the gp41 MPER, or alternatively, if gp41 MPER epitope-specific B cells are lost to immunological tolerance. An equally important question is how B cells interact with, and respond to, the gp41 MPER epitope, including whether they engage this epitope in a non-canonical manner i.e., by non-paratopic recognition via B cell receptors (BCR. To begin understanding how B cells engage the gp41 MPER, we characterized B cell-gp41 MPER interactions in BALB/c and C57BL/6 mice. Surprisingly, we found that a significant (approximately 7% fraction of splenic B cells from BALB/c, but not C57BL/6 mice, bound the gp41 MPER via their BCRs. This strain-specific binding was concentrated in IgM(hi subsets, including marginal zone and peritoneal B1 B cells, and correlated with enriched fractions (approximately 15% of gp41 MPER-specific IgM secreted by in vitro-activated splenic B cells. Analysis of Igh(a (BALB/c and Igh(b (C57BL/6 congenic mice demonstrated that gp41 MPER binding was controlled by determinants of the Igh(a locus. Mapping of MPER gp41 interactions with IgM(a identified MPER residues distinct from those to which mAb 2F5 binds and demonstrated the requirement of Fc C(H regions. Importantly, gp41 MPER ligation produced detectable BCR-proximal signaling events, suggesting that interactions between gp41 MPER and IgM(a determinants may elicit partial B cell activation. These data suggest that low avidity, non-paratopic interactions between the gp41 MPER and membrane Ig on naïve B cells may interfere with or divert bnAb responses.

Phosphorylation of varicella-zoster virus glycoprotein gpI by mammalian casein kinase II and casein kinase I

International Nuclear Information System (INIS)

Grose, C.; Jackson, W.; Traugh, J.A.

1989-01-01

Varicella-zoster virus (VZV) glycoprotein gpI is the predominant viral glycoprotein within the plasma membranes of infected cells. This viral glycoprotein is phosphorylated on its polypeptide backbone during biosynthesis. In this report, the authors investigated the protein kinases which participate in the phosphorylation events. Under in vivo conditions, VZV gpI was phosphorylated on its serine and threonine residues by protein kinases present within lysates of either VZV-infected or uninfected cells. Because this activity was diminished by heparin, a known inhibitor of casein kinase II, isolated gpI was incubated with purified casein kinase II and shown to be phosphorylated in an in vitro assay containing [γ- 32 P]ATP. The same glycoprotein was phosphorylated when [ 32 P]GTP was substituted for [ 32 P]ATP in the protein kinase assay. They also tested whether VZV gpI was phosphorylated by two other ubiquitous mammalian protein kinases--casein kinase I and cyclic AMP-dependent kinase--and found that only casein kinase I modified gpI. When the predicted 623-amino-acid sequence of gpI was examined, two phosphorylation sites known to be optimal for casein kinase II were observed. In summary, this study showed that VZV gpI was phosphorylated by each of two mammalian protein kinases (casein kinase I and casein kinase II) and that potential serine-threonine phosphorylation sites for each of these two kinases were present in the viral glycoprotein

Host-Primed Ebola Virus GP Exposes a Hydrophobic NPC1 Receptor-Binding Pocket, Revealing a Target for Broadly Neutralizing Antibodies

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Zachary A. Bornholdt

2016-02-01

Full Text Available The filovirus surface glycoprotein (GP mediates viral entry into host cells. Following viral internalization into endosomes, GP is cleaved by host cysteine proteases to expose a receptor-binding site (RBS that is otherwise hidden from immune surveillance. Here, we present the crystal structure of proteolytically cleaved Ebola virus GP to a resolution of 3.3 Å. We use this structure in conjunction with functional analysis of a large panel of pseudotyped viruses bearing mutant GP proteins to map the Ebola virus GP endosomal RBS at molecular resolution. Our studies indicate that binding of GP to its endosomal receptor Niemann-Pick C1 occurs in two distinct stages: the initial electrostatic interactions are followed by specific interactions with a hydrophobic trough that is exposed on the endosomally cleaved GP1 subunit. Finally, we demonstrate that monoclonal antibodies targeting the filovirus RBS neutralize all known filovirus GPs, making this conserved pocket a promising target for the development of panfilovirus therapeutics.

CD4-binding site alterations in CCR5-using HIV-1 envelopes influencing gp120-CD4 interactions and fusogenicity

International Nuclear Information System (INIS)

Sterjovski, Jasminka; Churchill, Melissa J.; Roche, Michael; Ellett, Anne; Farrugia, William; Wesselingh, Steven L.; Cunningham, Anthony L.; Ramsland, Paul A.; Gorry, Paul R.

2011-01-01

CD4-binding site (CD4bs) alterations in gp120 contribute to different pathophysiological phenotypes of CCR5-using (R5) HIV-1 strains, but the potential structural basis is unknown. Here, we characterized functionally diverse R5 envelope (Env) clones (n = 16) to elucidate potential structural alterations within the gp120 CD4bs that influence Env function. Initially, we showed that the magnitude of gp120-CD4-binding correlates with increased fusogenicity and reduced CD4 dependence. Analysis of three-dimensional gp120 structural models revealed two CD4bs variants, D279 and N362, that were associated with reduced CD4 dependence. Further structural analysis showed that a wider aperture of the predicted CD4bs cavity, as constrained by the inner-most atoms at the gp120 V1V2 stem and the V5 loop, was associated with amino acid alterations within V5 and correlated with increased gp120-CD4 binding and increased fusogenicity. Our results provide evidence that the gp120 V5 loop may alter CD4bs conformation and contribute to increased gp120-CD4 interactions and Env fusogenicity.

A functional F analogue of AcMNPV GP64 is from the Agrotis segetum granulovirus

NARCIS (Netherlands)

Yin, F.; Wang, M.; Tan, Y.; Deng, F.; Vlak, J.M.; Hu, Z.H.; Wang, H.

2008-01-01

The envelope fusion protein F of Plutella xylostella granulovirus is a computational analogue of the GP64 envelope fusion protein of Autographa californica nucleopolyhedrovirus (AcMNPV). Granulovirus (GV) F proteins were thought to be unable to functionally replace GP64 in the AcMNPV pseudotyping

iP-gp , a novel cell line with tight barrier function and expression of human P-glycoprotein (ABCB1) for drug screening

DEFF Research Database (Denmark)

Brodin, Birger; Ozgür, Burak; Saaby, Lasse

that new API's are evaluated with respect to P-gp interactions.  Aim : The aim of the present work was to validate the suitability of the newly developed iP-gp cell line for investigating P-gp interactions with human P-gp. Methods: IPEC-J2 MDR1 (iP-gp) cells were cultured on permeable supports for 17......Background : The efflux transporter P-glycoprotein (P-gp, product of the MDR1/ABCB1 gene) hinders uptake of drug compounds to the brain, limits intestinal uptake, is a cause of resistance to chemoterapeutics and a potential "site" for drug-drug interaction. Regulatory agencies therefore recommend.......04 +/- 0.01 µM in transport experiments including digoxin and rhodamine 123, respectively. Summary/Conclusion : The iP-gp cell line may become a useful screening tool for interactions between drug compounds and human P-gp....

Selected Thermophysical Properties of 2,2 Dimethylcyclopentyl Methylphosphonofluoridate (GP) and 2,2 Dimethylcyclopentanol (DMCP)

Science.gov (United States)

2016-09-01

chromatography using a thermal conductivity detector (GC-TCD). Table 1. Sample Information for GP and DMCP Chemical Name Mole Fraction Purity...Proving Ground, MD, 1983; UNCLASSIFIED Report (ADC033491). 23. Weast, R.C. CRC Handbook of Chemistry and Physics, 53rd ed.; CRC Press: Boca Raton, FL...gas chromatography GD pinacolyl methylphosphonofluoridate GF cyclohexyl methylphosphonofluoridate GP 2,2-dimethylcyclopentyl

Th1-like human T-cell clones recognizing Leishmania gp63 inhibit Leishmania major in human macrophages

DEFF Research Database (Denmark)

Kemp, M; Hey, A S; Bendtzen, K

1994-01-01

The major surface protease of Leishmania major, gp63, has been suggested as a vaccine candidate for cutaneous leishmaniasis. In this study gp63 was purified from L. major promastigotes. A panel of human T-cell clones recognizing this protein were generated from individuals who had previously had...... resembling Th1 cells. Autologous mononuclear cells and Epstein-Barr virus-transformed B cell lines were equally efficient in presenting the antigen to the T cells. The gp63 reactive T cells induced resistance to infection in cultured human macrophages by L. major. The data confirm that human CD4+ T cells...... recognizing gp63 can take part in the host defence against L. major infections....

Electro-acupuncture stimulation acts on the basal ganglia output pathway to ameliorate motor impairment in Parkinsonian model rats.

Science.gov (United States)

Jia, Jun; Li, Bo; Sun, Zuo-Li; Yu, Fen; Wang, Xuan; Wang, Xiao-Min

2010-04-01

The role of electro-acupuncture (EA) stimulation on motor symptoms in Parkinson's disease (PD) has not been well studied. In a rat hemiparkinsonian model induced by unilateral transection of the medial forebrain bundle (MFB), EA stimulation improved motor impairment in a frequency-dependent manner. Whereas EA stimulation at a low frequency (2 Hz) had no effect, EA stimulation at a high frequency (100 Hz) significantly improved motor coordination. However, neither low nor high EA stimulation could significantly enhance dopamine levels in the striatum. EA stimulation at 100 Hz normalized the MFB lesion-induced increase in midbrain GABA content, but it had no effect on GABA content in the globus pallidus. These results suggest that high-frequency EA stimulation improves motor impairment in MFB-lesioned rats by increasing GABAergic inhibition in the output structure of the basal ganglia.

Changes in 5-HT4 receptor and 5-HT transporter binding in olfactory bulbectomized and glucocorticoid receptor heterozygous mice

DEFF Research Database (Denmark)

Licht, Cecilie L; Kirkegaard, Lisbeth; Zueger, Maha

2010-01-01

. The olfactory bulbectomized mice displayed increased activity in the open field test, a characteristic depression-like feature of this model. After bulbectomy, 5-HT(4) receptor binding was increased in the ventral hippocampus (12%) but unchanged in the dorsal hippocampus, frontal and caudal caudate putamen......]citalopram in two murine models of depression-related states, olfactory bulbectomy and glucocorticoid receptor heterozygous (GR(+/-)) mice. The olfactory bulbectomy model is characterized by 5-HT system changes, while the GR(+/-) mice have a deficit in hypothalamic-pituitary-adrenal (HPA) system control....... Among post hoc analyzed regions, there was a 14% decrease in 5-HT(4) receptor binding in the olfactory tubercles. The 5-HTT binding was unchanged in the hippocampus and caudate putamen of bulbectomized mice but post hoc analysis showed small decreases in lateral septum and lateral globus pallidus...

Benzodiazepine effect of 125I-iomazenil-benzodiazepine receptor binding and serum corticosterone level in a rat model

International Nuclear Information System (INIS)

Fukumitsu, Nobuyoshi; Ogi, Shigeyuki; Uchiyama, Mayuki; Mori, Yutaka

2005-01-01

To test the change in free or unoccupied benzodiazepine receptor (BZR) density in response to diazepam, we investigated 125 I-iomazenil ( 125 I-IMZ) binding and serum corticosterone levels in a rat model. Wistar male rats, which received psychological stress using a communication box for 5 days, were divided into two groups according to the amount of administered diazepam: no diazepam [D (0)] group and 10 mg/kg per day [D (10)] group of 12 rats each. The standardized uptake value (SUV) of 125 I-IMZ of the D (10) group were significantly lower (P 125 I-IMZ, it is clear that diazepam competed with endogenous ligand for the free BZR sites, and the frontal, parietal and temporal cortices, globus pallidus, hippocampus, amygdala and hypothalamus are important areas in which 125 I-IMZ binding is strongly affected by administration of diazepam

Delayed Encephalopathy of Carbon Monoxide Intoxication and Treatment with Hyperbaric Oxygen: A Case Report

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Fatma Polat

2012-09-01

Full Text Available Delayed encephalopathy (DE is a neuropsychiatric syndrome that can arise generally within 20 days of acute carbon monoxide (CO intoxication after apparent recovery and involves variable degrees of cognitive deficits, personality changes, movement disorders and focal neurologic deficits. We report a 35-year-old female patient with delayed encephalopathy due to CO intoxication, presenting with cognitive impairment and mild parkinsonism despite receiving hyberbaric oxigen therapy (HBO. Magnetic resonance imaging showed abnormal signal intensity and decreased diffusivity at both caudate nuclei and globus pallidus. She continued to receive additional HBO therapy and complete recovery was reached within six months. The positive effect of early HBO therapy of selected patients in reversing the acute effects of CO intoxication is appearant. We here also review the beneficial effect of HBO in preventing or limitating the late neurocognitive deficits associated with severe CO intoxication

The role of membrane microdomains in transmembrane signaling through the epithelial glycoprotein Gp140/CDCP1

Science.gov (United States)

Alvares, Stacy M.; Dunn, Clarence A.; Brown, Tod A.; Wayner, Elizabeth E.; Carter, William G.

2008-01-01

Cell adhesion to the extracellular matrix (ECM) via integrin adhesion receptors initiates signaling cascades leading to changes in cell behavior. While integrin clustering is necessary to initiate cell attachment to the matrix, additional membrane components are necessary to mediate the transmembrane signals and the cell adhesion response that alter downstream cell behavior. Many of these signaling components reside in glycosphingolipid-rich and cholesterol-rich membrane domains such as Tetraspanin Enriched Microdomains (TEMs)/Glycosynapse 3 and Detergent-Resistant Microdomains (DRMs), also known as lipid rafts. In the following article, we will review examples of how components in these membrane microdomains modulate integrin adhesion after initial attachment to the ECM. Additionally, we will present data on a novel adhesion-responsive transmembrane glycoprotein Gp140/CUB Domain Containing Protein 1, which clusters in epithelial cell-cell contacts. Gp140 can then be phosphorylated by Src Family Kinases at tyrosine 734 in response to outside-in signals- possibly through interactions involving the extracellular CUB domains. Data presented here suggests that outside-in signals through Gp140 in cell-cell contacts assemble membrane clusters that associate with membrane microdomains to recruit and activate SFKs. Active SFKs then mediate phosphorylation of Gp140, SFK and PKCδ with Gp140 acting as a transmembrane scaffold for these kinases. We propose that the clustering of Gp140 and signaling components in membrane microdomains in cell-cell contacts contributes to changes in cell behavior. PMID:18269919

Broad and potent HIV-1 neutralization by a human antibody that binds the gp41-gp120 interface

Energy Technology Data Exchange (ETDEWEB)

Huang, Jinghe; Kang, Byong H.; Pancera, Marie; Lee, Jeong Hyun; Tong, Tommy; Feng, Yu; Imamichi, Hiromi; Georgiev, Ivelin S.; Chuang, Gwo-Yu; Druz, Aliaksandr; Doria-Rose, Nicole A.; Laub, Leo; Sliepen, Kwinten; van Gils, Marit J.; de la Peña, Alba Torrents; Derking, Ronald; Klasse, Per-Johan; Migueles, Stephen A.; Bailer, Robert T.; Alam, Munir; Pugach, Pavel; Haynes, Barton F.; Wyatt, Richard T.; Sanders, Rogier W.; Binley, James M.; Ward, Andrew B.; Mascola, John R.; Kwong, Peter D.; Connors, Mark [NIH

2015-10-15

The isolation of human monoclonal antibodies is providing important insights into the specificities that underlie broad neutralization of HIV-1 (reviewed in ref. 1). Here we report a broad and extremely potent HIV-specific monoclonal antibody, termed 35O22, which binds a novel HIV-1 envelope glycoprotein (Env) epitope. 35O22 neutralized 62% of 181 pseudoviruses with a half-maximum inhibitory concentration (IC₅₀) <50 μg ml^-1. The median IC₅₀ of neutralized viruses was 0.033 μg ml^-1, among the most potent thus far described. 35O22 did not bind monomeric forms of Env tested, but did bind the trimeric BG505 SOSIP.664. Mutagenesis and a reconstruction by negative-stain electron microscopy of the Fab in complex with trimer revealed that it bound to a conserved epitope, which stretched across gp120 and gp41. The specificity of 35O22 represents a novel site of vulnerability on HIV Env, which serum analysis indicates to be commonly elicited by natural infection. Binding to this new site of vulnerability may thus be an important complement to current monoclonal-antibody-based approaches to immunotherapies, prophylaxis and vaccine design.

Studies on adsorptions of metallic ions in water by zirconium glyphosate (ZrGP): Behaviors and mechanisms

Energy Technology Data Exchange (ETDEWEB)

Jia Yunjie; Zhang Yuejuan [State Key Laboratory of Chemical Resource Engineering, Beijing University of Chemical Technology, Box. 98, No.15, Beisanhuan donglu, Beijing 100029 (China); Wang Runwei [State Key Laboratory of Inorganic Synthesis and Preparative Chemistry, Jilin University, Changchun 130012 (China); Fan Faying [State Key Laboratory of Chemical Resource Engineering, Beijing University of Chemical Technology, Box. 98, No.15, Beisanhuan donglu, Beijing 100029 (China); Xu Qinghong, E-mail: xuqh@mail.buct.edu.cn [State Key Laboratory of Chemical Resource Engineering, Beijing University of Chemical Technology, Box. 98, No.15, Beisanhuan donglu, Beijing 100029 (China)

2012-01-15

A new adsorbent named zirconium glyphosate [Zr(O{sub 3}PCH{sub 2}NHCH{sub 2}COOH){sub 2}{center_dot}0.5H{sub 2}O, denoted as ZrGP] and its selective adsorptions to Pb{sup 2+}, Cd{sup 2+}, Mg{sup 2+} and Ca{sup 2+} ions in water were reported in this paper. Compared to other zirconium adsorbents, such as zirconium phosphate [Zr(HPO{sub 4}){sub 2}], ZrGP exhibited highly selective adsorption to Pb{sup 2+} in solution which contained Pb{sup 2+}, Cd{sup 2+}, Mg{sup 2+} and Ca{sup 2+} ions. The loaded ZrGP with metallic ions can be efficaciously regenerated by aqueous solution of HCl (1.0 M) without any noticeable capacity loss, and almost all of it can be reused and recycled. The memory effect on structural regeneration of ZrGP was also found when Mg{sup 2+} and Ca{sup 2+} were adsorbed. To be specific, the structure of ZrGP was destroyed due to adsorbing these two ions, but it could be regenerated after the loaded materials were dipped in HCl solution (1.0 M) for several minutes to remove metallic ions.

Attenuated Human Parainfluenza Virus Type 1 Expressing Ebola Virus Glycoprotein GP Administered Intranasally Is Immunogenic in African Green Monkeys.

Science.gov (United States)

Lingemann, Matthias; Liu, Xueqiao; Surman, Sonja; Liang, Bo; Herbert, Richard; Hackenberg, Ashley D; Buchholz, Ursula J; Collins, Peter L; Munir, Shirin

2017-05-15

The recent 2014-2016 Ebola virus (EBOV) outbreak prompted increased efforts to develop vaccines against EBOV disease. We describe the development and preclinical evaluation of an attenuated recombinant human parainfluenza virus type 1 (rHPIV1) expressing the membrane-anchored form of EBOV glycoprotein GP, as an intranasal (i.n.) EBOV vaccine. GP was codon optimized and expressed either as a full-length protein or as an engineered chimeric form in which its transmembrane and cytoplasmic tail (TMCT) domains were replaced with those of the HPIV1 F protein in an effort to enhance packaging into the vector particle and immunogenicity. GP was inserted either preceding the N gene (pre-N) or between the N and P genes (N-P) of rHPIV1 bearing a stabilized attenuating mutation in the P/C gene (C Δ170 ). The constructs grew to high titers and efficiently and stably expressed GP. Viruses were attenuated, replicating at low titers over several days, in the respiratory tract of African green monkeys (AGMs). Two doses of candidates expressing GP from the pre-N position elicited higher GP neutralizing serum antibody titers than the N-P viruses, and unmodified GP induced higher levels than its TMCT counterpart. Unmodified EBOV GP was packaged into the HPIV1 particle, and the TMCT modification did not increase packaging or immunogenicity but rather reduced the stability of GP expression during in vivo replication. In conclusion, we identified an attenuated and immunogenic i.n. vaccine candidate expressing GP from the pre-N position. It is expected to be well tolerated in humans and is available for clinical evaluation. IMPORTANCE EBOV hemorrhagic fever is one of the most lethal viral infections and lacks a licensed vaccine. Contact of fluids from infected individuals, including droplets or aerosols, with mucosal surfaces is an important route of EBOV spread during a natural outbreak, and aerosols also might be exploited for intentional virus spread. Therefore, vaccines that protect

Involvement of viral envelope GP2 in Ebola virus entry into cells expressing the macrophage galactose-type C-type lectin

International Nuclear Information System (INIS)

Usami, Katsuaki; Matsuno, Keita; Igarashi, Manabu; Denda-Nagai, Kaori; Takada, Ayato; Irimura, Tatsuro

2011-01-01

Highlights: → Ebola virus infection is mediated by binding to and fusion with the target cells. → Structural feature of the viral glycoprotein determines the infectivity. → Surface C-type lectin, MGL, of macrophages and dendritic cells mediate the infection. → GP2, one of glycoprotein subunits, plays an essential role in MGL-mediated infection. → There is a critical amino acid residue involved in high infectivity. -- Abstract: Ebola virus (EBOV) infection is initiated by the interaction of the viral surface envelope glycoprotein (GP) with the binding sites on target cells. Differences in the mortality among different species of the Ebola viruses, i.e., Zaire ebolavirus (ZEBOV) and Reston ebolavirus (REBOV), correspond to the in vitro infectivity of the pseudo-typed virus constructed with the GPs in cells expressing macrophage galactose-type calcium-type lectin (MGL/CD301). Through mutagenesis of GP2, the transmembrane-anchored subunit of GP, we found that residues 502-527 of the GP2 sequence determined the different infectivity between VSV-ZEBOV GP and -REBOV GP in MGL/CD301-expressing cells and a histidine residue at position 516 of ZEBOV GP2 appeared essential in the differential infectivity. These findings may provide a clue to clarify a molecular basis of different pathogenicity among EBOV species.

Involvement of viral envelope GP2 in Ebola virus entry into cells expressing the macrophage galactose-type C-type lectin

Energy Technology Data Exchange (ETDEWEB)

Usami, Katsuaki [Laboratory of Cancer Biology and Molecular Immunology, Graduate School of Pharmaceutical Sciences, University of Tokyo, Tokyo 113-0033 (Japan); Matsuno, Keita; Igarashi, Manabu [Department of Global Epidemiology, Hokkaido University Research Center for Zoonosis Control, Sapporo 001-0020 (Japan); Denda-Nagai, Kaori [Laboratory of Cancer Biology and Molecular Immunology, Graduate School of Pharmaceutical Sciences, University of Tokyo, Tokyo 113-0033 (Japan); Takada, Ayato [Department of Global Epidemiology, Hokkaido University Research Center for Zoonosis Control, Sapporo 001-0020 (Japan); Irimura, Tatsuro, E-mail: irimura@mol.f.u-tokyo.ac.jp [Laboratory of Cancer Biology and Molecular Immunology, Graduate School of Pharmaceutical Sciences, University of Tokyo, Tokyo 113-0033 (Japan)

2011-04-01