Recovery of Dysphagia in Lateral Medullary Stroke

Science.gov (United States)

Gupta, Hitesh; Banerjee, Alakananda

2014-01-01

Lateral medullary stroke is typically associated with increased likelihood of occurrence of dysphagia and exhibits the most severe and persistent form. Worldwide little research exists on dysphagia in brainstem stroke. An estimated 15% of all patients admitted to stroke rehabilitation units experience a brainstem stroke out of which about 47% suffer from dysphagia. In India, a study showed that 22.3% of posterior circulation stroke patients develop dysphagia. Dearth of literature on dysphagia and its outcome in brainstem stroke particularly lateral medullary stroke motivated the author to present an actual case study of a patient who had dysphagia following a lateral medullary infarct. This paper documents the severity and management approach of dysphagia in brainstem stroke, with traditional dysphagia therapy and VitalStim therapy. Despite being diagnosed with a severe form of dysphagia followed by late treatment intervention, the patient had complete recovery of the swallowing function. PMID:25045555

Sex Differences in Stress Response Circuitry Activation Dependent on Female Hormonal Cycle

Science.gov (United States)

Goldstein, Jill M.; Jerram, Matthew; Abbs, Brandon; Whitfield-Gabrieli, Susan; Makris, Nikos

2010-01-01

Understanding sex differences in stress regulation has important implications for understanding basic physiological differences in the male and female brain and their impact on vulnerability to sex differences in chronic medical disorders associated with stress response circuitry. In this fMRI study, we demonstrated that significant sex differences in brain activity in stress response circuitry were dependent on women's menstrual cycle phase. Twelve healthy Caucasian premenopausal women were compared to a group of healthy men from the same population, based on age, ethnicity, education, and right-handedness. Subjects were scanned using negative valence/high arousal versus neutral visual stimuli that we demonstrated activated stress response circuitry (amygdala, hypothalamus, hippocampus, brainstem, orbitofrontal and medial prefrontal cortices (OFC and mPFC), and anterior cingulate gyrus (ACG). Women were scanned twice based on normal variation in menstrual cycle hormones (i.e., early follicular (EF) compared with late follicular-midcycle menstrual phases (LF/MC)). Using SPM8b, there were few significant differences in BOLD signal changes in men compared to EF women, except ventromedial (VMN) and lateral (LHA) hypothalamus, left amygdala, and ACG. In contrast, men exhibited significantly greater BOLD signal changes compared to LF/MC women on bilateral ACG and OFC, mPFC, LHA, VMN, hippocampus, and periaqueductal gray, with largest effect sizes in mPFC and OFC. Findings suggest that sex differences in stress response circuitry are hormonally regulated via the impact of subcortical brain activity on the cortical control of arousal, and demonstrate that females have been endowed with a natural hormonal capacity to regulate the stress response that differs from males. PMID:20071507

Quantification of deep medullary veins at 7 T brain MRI

Energy Technology Data Exchange (ETDEWEB)

Kuijf, Hugo J.; Viergever, Max A.; Vincken, Koen L. [University Medical Center Utrecht, Image Sciences Institute, Utrecht (Netherlands); Bouvy, Willem H.; Razoux Schultz, Tom B.; Biessels, Geert Jan [University Medical Center Utrecht, Department of Neurology, Brain Center Rudolf Magnus, Utrecht (Netherlands); Zwanenburg, Jaco J.M. [University Medical Center Utrecht, Image Sciences Institute, Utrecht (Netherlands); University Medical Center Utrecht, Department of Radiology, Utrecht (Netherlands)

2016-10-15

Deep medullary veins support the venous drainage of the brain and may display abnormalities in the context of different cerebrovascular diseases. We present and evaluate a method to automatically detect and quantify deep medullary veins at 7 T. Five participants were scanned twice, to assess the robustness and reproducibility of manual and automated vein detection. Additionally, the method was evaluated on 24 participants to demonstrate its application. Deep medullary veins were assessed within an automatically created region-of-interest around the lateral ventricles, defined such that all veins must intersect it. A combination of vesselness, tubular tracking, and hysteresis thresholding located individual veins, which were quantified by counting and computing (3-D) density maps. Visual assessment was time-consuming (2 h/scan), with an intra-/inter-observer agreement on absolute vein count of ICC = 0.76 and 0.60, respectively. The automated vein detection showed excellent inter-scan reproducibility before (ICC = 0.79) and after (ICC = 0.88) visually censoring false positives. It had a positive predictive value of 71.6 %. Imaging at 7 T allows visualization and quantification of deep medullary veins. The presented method offers fast and reliable automated assessment of deep medullary veins. (orig.)

Comparison of mammographic and sonographic findings in typical and atypical medullary carcinomas of the breast

International Nuclear Information System (INIS)

Yilmaz, E.; Lebe, B.; Balci, P.; Sal, S.; Canda, T.

2002-01-01

AIM: The aim of this study was to describe the contribution of mammographic and sonographic findings to the discrimination of typical and atypical histopathologic groups of medullary carcinomas of the breast. MATERIALS AND METHODS: Imaging findings were retrospectively assessed in 33 women with medullary carcinomas (15 typical medullary carcinomas and 18 atypical medullary carcinomas) identified during pre-operative mammography. Twenty-nine of these women also had ultrasound and these findings were reviewed. RESULTS: Mammography showed a well circumscribed mass in 10 of the 15 (67%) typical medullary carcinomas and in four of the 17 (24%) atypical medullary carcinomas (P < 0.02). One small tumour in a woman with atypical medullary carcinoma was missed on mammography and was shown only on sonography. Sonographically, an irregular margin surrounding the whole mass or part of it was seen in three out of 14 (21%) patients with typical medullary carcinoma and in nine out of 15 (60%) patients with atypical medullary carcinomas (P < 0.05). Posterior acoustic shadowing was more often observed in the typical medullary carcinoma group than in atypical medullary carcinoma and the difference was found to be statistically significant (P < 0.05). None of the other mammographic and sonographic findings were sufficiently characteristic to allow for a differentiation between two groups. CONCLUSION: When typical medullary carcinomas were compared with atypical medullary carcinomas according to imaging features, they tended to be well circumscribed masses on both mammography and sonography, and a posterior acoustic shadow was not found on sonography. However, the imaging findings in these two subgroups often resembled each other and histopathology will always be required to confirm the diagnosis. Yilmaz, E. et al. (2002)

Comparison of mammographic and sonographic findings in typical and atypical medullary carcinomas of the breast

Energy Technology Data Exchange (ETDEWEB)

Yilmaz, E.; Lebe, B.; Balci, P.; Sal, S.; Canda, T

2002-07-01

AIM: The aim of this study was to describe the contribution of mammographic and sonographic findings to the discrimination of typical and atypical histopathologic groups of medullary carcinomas of the breast. MATERIALS AND METHODS: Imaging findings were retrospectively assessed in 33 women with medullary carcinomas (15 typical medullary carcinomas and 18 atypical medullary carcinomas) identified during pre-operative mammography. Twenty-nine of these women also had ultrasound and these findings were reviewed. RESULTS: Mammography showed a well circumscribed mass in 10 of the 15 (67%) typical medullary carcinomas and in four of the 17 (24%) atypical medullary carcinomas (P < 0.02). One small tumour in a woman with atypical medullary carcinoma was missed on mammography and was shown only on sonography. Sonographically, an irregular margin surrounding the whole mass or part of it was seen in three out of 14 (21%) patients with typical medullary carcinoma and in nine out of 15 (60%) patients with atypical medullary carcinomas (P < 0.05). Posterior acoustic shadowing was more often observed in the typical medullary carcinoma group than in atypical medullary carcinoma and the difference was found to be statistically significant (P < 0.05). None of the other mammographic and sonographic findings were sufficiently characteristic to allow for a differentiation between two groups. CONCLUSION: When typical medullary carcinomas were compared with atypical medullary carcinomas according to imaging features, they tended to be well circumscribed masses on both mammography and sonography, and a posterior acoustic shadow was not found on sonography. However, the imaging findings in these two subgroups often resembled each other and histopathology will always be required to confirm the diagnosis. Yilmaz, E. et al. (2002)

Clinical study of 12 cases of medullary carcinoma of the breast

International Nuclear Information System (INIS)

Shibuya, Hitoshi; Sasaki, Kenichi; Yamamoto, Masaaki; Higaki, Nagato; Nakamura, Yukio

2006-01-01

Medullary carcinoma of the breast is a rare type breast cancer, and shows peculiar clinical features. In a series of 460 cases of breast cancer operated on at the hospital from 1975 to 2004, twelve (2.6%) cases were diagnosed as medullary carcinoma of the breast by postoperative pathological study. When the specimens from the twelve tumors were reevaluated according to the Ridolfi's subtype classification, six tumors were classified into typical medullary carcinoma (TMC) and the remaining six tumors into atypical medullary carcinoma (AMC). On mammography these tumors were visualized as homogeneously enhancing oval masses without calcification and the boundary was comparatively well-defined. US demonstrated well-defied masses with a heterogeneous, hypoechoic texture and with reinforcement of posterior echoes. The rate of lymph node metastasis was 33.3% in medullary carcinomas which was not significantly different from that of infiltrative ductal carcinomas experienced during the same period. The rate of a positivity of a hormone receptor was 8.3% in medullary carcinomas which was low in predominance in comparison with that of infiltrative ductal carcinomas. The positive rate for a HER2/neu (above2+) by the IHC method was 58%. An average observation period is 11 years, and all patients are alive. (author)

Introduction to European comments on "Medullary Thyroid Cancer

DEFF Research Database (Denmark)

Jarzab, Barbara; Feldt-Rasmussen, Ulla

2013-01-01

Guest Editors of Thyroid Research supplement devoted to medullary thyroid cancer present the history on how the discussion about "Medullary Thyroid Cancer: management guidelines of the American Thyroid Association" was initiated and subsequently widely commented before and during European Thyroid...... Association - Cancer Research Network Meeting in Lisbon. It is explained why it has been decided to publish the manuscripts within the supplement - to document voices from the discussion and popularize them....

Divergent projections of catecholaminergic neurons in the nucleus of the solitary tract to limbic forebrain and medullary autonomic brain regions.

Science.gov (United States)

Reyes, Beverly A S; Van Bockstaele, Elisabeth J

2006-10-30

The nucleus of the solitary tract (NTS) is a critical structure involved in coordinating autonomic and visceral activities. Previous independent studies have demonstrated efferent projections from the NTS to the nucleus paragigantocellularis (PGi) and the central nucleus of the amygdala (CNA) in rat brain. To further characterize the neural circuitry originating from the NTS with postsynaptic targets in the amygdala and medullary autonomic targets, distinct green or red fluorescent latex microspheres were injected into the PGi and the CNA, respectively, of the same rat. Thirty-micron thick tissue sections through the lower brainstem and forebrain were collected. Every fourth section through the NTS region was processed for immunocytochemical detection of tyrosine hydroxylase (TH), a marker of catecholaminergic neurons. Retrogradely labeled neurons from the PGi or CNA were distributed throughout the rostro-caudal segments of the NTS. However, the majority of neurons containing both retrograde tracers were distributed within the caudal third of the NTS. Cell counts revealed that approximately 27% of neurons projecting to the CNA in the NTS sent collateralized projections to the PGi while approximately 16% of neurons projecting to the PGi sent collateralized projections to the CNA. Interestingly, more than half of the PGi and CNA-projecting neurons in the NTS expressed TH immunoreactivity. These data indicate that catecholaminergic neurons in the NTS are poised to simultaneously coordinate activities in limbic and medullary autonomic brain regions.

Lateral medullary infarction with ipsilateral hemiparesis, lemniscal sensation loss and hypoglossal nerve palsy.

Science.gov (United States)

Li, Xiaodi; Wang, Yuzhou

2014-04-01

Here, we present a rare case of a lateral medullary infarction with ipsilateral hemiparesis, lemniscal sensation loss and hypoglossal nerve palsy. In this case, we proved Opalski's hypothesis by diffusion tensor tractography that ipsilateral hemiparesis in a medullary infarction is due to the involvement of the decussated corticospinal tract. We found that the clinical triad of ipsilateral hemiparesis, lemniscal sensation loss and hypoglossal nerve palsy, which had been regarded as a variant of medial medullary syndrome, turned out to be caused by lateral lower medullary infarction. Therefore, this clinical triad does not imply the involvement of the anteromedial part of medulla oblongata, when it is hard to distinguish a massive lateral medullary infarction from a hemimedullary infarction merely from MR images. At last, we suggest that hyperreflexia and Babinski's sign may not be indispensable to the diagnosis of Opalski's syndrome and we propose that "hemimedullary infarction with ipsilateral hemiparesis" is intrinsically a variant of lateral medullary infarction.

Medullary carcinoma of the thyroid - an unusual case of hyalinizing ...

African Journals Online (AJOL)

Medullary thyroid carcinoma is a neoplasm occurring in sporadic and familial patterns. A rare variant of medullary thyroid carcinoma shows microscopic features similar to hyalinizing trabecular adenoma of thyroid. Detection of this variant requires a high index of suspicion and immunohistochemical confirmation by ...

Medullary breast carcinoma: anatomo-radiological correlation

International Nuclear Information System (INIS)

Matheus, Valeria Soares; Canella, Ellyete de Oliveira; Djahjah, Maria Celia Resende; Koch, Hilton Augusto; Kestelman, Fabiola Procaci

2008-01-01

To evaluate radiological findings in patients submitted to surgical treatment for medullary breast cancer at Instituto Nacional de Cancer (INCa), Rio de Janeiro, RJ, Brazil, correlating them with histological results. A retrospective descriptive study was developed with patients submitted to surgery at INCa, in the period from January 1997 to December 2006, for identifying the presence of medullary breast carcinoma and analyzing radiological findings. Among 21,287 patients diagnosed with carcinoma, 76 (0.357%) had typical medullary breast carcinoma. The age range of these patients was 32-81 years (mean = 59.1 years). Mammography demonstrated lesions in 19 of these patients, 17 (89.5%) of them with masses, and 2 with focal asymmetry. Among the patients with masses, 15 (88.1%) presented with high density and 2 (11.9%) with isodensity. Twelve patients presented sonographic findings, 11 (91.6%) of them with hypoechoic masses, and one with an anechoic mass with areas of cystic degeneration. Nodular mass was the predominant radiological finding (89.5%), 88.1% of them corresponding to masses with high density and circumscribed margins. Despite the radiological characteristics of benignity, a solid, fast growing, highly dense mass with circumscribed margins should be further investigated to confirm the diagnosis. (author)

Medullary breast carcinoma: anatomo-radiological correlation

Energy Technology Data Exchange (ETDEWEB)

Matheus, Valeria Soares; Canella, Ellyete de Oliveira; Djahjah, Maria Celia Resende; Koch, Hilton Augusto [Instituto Nacional de Cancer (INCa), Rio de Janeiro, RJ (Brazil); Kestelman, Fabiola Procaci [Universidade Federal do Rio de Janeiro (UFRJ), Rio de Janeiro, RJ (Brazil); Instituto Nacional de Cancer (INCa), Rio de Janeiro, RJ (Brazil)]. E-mail: msavaleria@yahoo.com

2008-11-15

To evaluate radiological findings in patients submitted to surgical treatment for medullary breast cancer at Instituto Nacional de Cancer (INCa), Rio de Janeiro, RJ, Brazil, correlating them with histological results. A retrospective descriptive study was developed with patients submitted to surgery at INCa, in the period from January 1997 to December 2006, for identifying the presence of medullary breast carcinoma and analyzing radiological findings. Among 21,287 patients diagnosed with carcinoma, 76 (0.357%) had typical medullary breast carcinoma. The age range of these patients was 32-81 years (mean = 59.1 years). Mammography demonstrated lesions in 19 of these patients, 17 (89.5%) of them with masses, and 2 with focal asymmetry. Among the patients with masses, 15 (88.1%) presented with high density and 2 (11.9%) with isodensity. Twelve patients presented sonographic findings, 11 (91.6%) of them with hypoechoic masses, and one with an anechoic mass with areas of cystic degeneration. Nodular mass was the predominant radiological finding (89.5%), 88.1% of them corresponding to masses with high density and circumscribed margins. Despite the radiological characteristics of benignity, a solid, fast growing, highly dense mass with circumscribed margins should be further investigated to confirm the diagnosis. (author)

Basolateral P2X receptors mediate inhibition of NaCl transport in mouse medullary thick ascending limb (mTAL)

DEFF Research Database (Denmark)

Marques, Rita D; de Bruijn, Pauline I.A.; Sørensen, Mads Vaarby

2012-01-01

Extracellular nucleotides regulate epithelial transport via luminal and basolateral P2 receptors. Renal epithelia express multiple P2 receptors, which mediate significant inhibition of solute absorption. Recently, we identified several P2 receptors in the medullary thick ascending limb (m...

MR imaging of medullary streaks in osteosclerosis: a case report

International Nuclear Information System (INIS)

Lee, Hak Soo; Joo, Kyung Bin; Park, Tae Soo; Song, Ho Taek; Kim, Yong Soo; Park, Dong Woo; Park, Choong Ki

2000-01-01

We present a case of medullary sclerosis of the appendicular skeleton in a patient with chronic renal insufficiency for whom MR imaging findings were characteristic. T1- and T2-weighted MR images showed multiple vertical lines (medullary streaks) of low signal intensity in the metaphyses and diaphyses of the distal femur and proximal tibia

Medullary cystic disease of the kidney: report of a case diagnosed by ultrasonography and computed tomography examinations

International Nuclear Information System (INIS)

Carvalho, Tarcisio Nunes; Araujo Junior, Cyrillo Rodrigues de; Fraguas Filho, Sergio Roberto; Costa, Marlos Augusto Bittencourt; Teixeira, Kim-Ir-Sen Santos; Ribeiro, Flavia Aparecida de Souza

2003-01-01

The terms medullary cystic disease, juvenile nephronophthisis or medullary cystic disease complex refer to a group of similar diseases in which the basic pathological abnormality is progressive renal tubular atrophy with secondary glomerular sclerosis and medullary cystic formation. Medullary cystic disease is an important cause of renal failure in adolescent patients. Imaging methods play a primary role in the diagnosis of these diseases. Cysts are characteristically seen in the renal medulla and cortico medullary junction whereas kidneys may be of normal to small size. In this article we present the ultrasonography and computed tomography findings of a female adolescent patient with characteristic clinical picture of medullary cystic disease. (author)

The Development of Micromachined Gyroscope Structure and Circuitry Technology

Directory of Open Access Journals (Sweden)

Dunzhu Xia

2014-01-01

Full Text Available This review surveys micromachined gyroscope structure and circuitry technology. The principle of micromachined gyroscopes is first introduced. Then, different kinds of MEMS gyroscope structures, materials and fabrication technologies are illustrated. Micromachined gyroscopes are mainly categorized into micromachined vibrating gyroscopes (MVGs, piezoelectric vibrating gyroscopes (PVGs, surface acoustic wave (SAW gyroscopes, bulk acoustic wave (BAW gyroscopes, micromachined electrostatically suspended gyroscopes (MESGs, magnetically suspended gyroscopes (MSGs, micro fiber optic gyroscopes (MFOGs, micro fluid gyroscopes (MFGs, micro atom gyroscopes (MAGs, and special micromachined gyroscopes. Next, the control electronics of micromachined gyroscopes are analyzed. The control circuits are categorized into typical circuitry and special circuitry technologies. The typical circuitry technologies include typical analog circuitry and digital circuitry, while the special circuitry consists of sigma delta, mode matching, temperature/quadrature compensation and novel special technologies. Finally, the characteristics of various typical gyroscopes and their development tendency are discussed and investigated in detail.

Recurrent intramedullary epidermoid cyst of conus medullaris.

LENUS (Irish Health Repository)

Fleming, Christina

2011-01-01

Spinal intramedullary epidermoid cyst is a rare condition. Recurrent epidermoid cyst in the spine cord is known to occur. The authors describe a case of recurrent conus medullaris epidermoid cyst in a 24-year-old female. She initially presented at 7 years of age with bladder disturbance in the form of diurnal enuresis and recurrent urinary tract infection. MRI lumbar spine revealed a 4 cm conus medullaris epidermoid cyst. Since the initial presentation, the cyst had recurred seven times in the same location and she underwent surgical intervention in the form of exploration and debulking. This benign condition, owing to its anatomical location, has posed a surgical and overall management challenge. This occurrence is better managed in a tertiary-care centre requiring multi-disciplinary treatment approach.

Mutant HABP2 Causes Non-Medullary Thyroid Cancer | Center for Cancer Research

Science.gov (United States)

The thyroid is a butterfly-shaped gland that lies at the base of the throat in front of the windpipe. A member of the endocrine system, the thyroid secretes hormones to regulate heart rate, blood pressure, temperature, and metabolism. Cancer of the thyroid is the most common endocrine cancer and the eighth most common cancer in the U.S. An estimated 63,450 Americans will be diagnosed with thyroid cancer this year. The vast majority is of follicular cell origin, and the remaining cancer originates from parafollicular cells, so called medullary thyroid cancer.

Synaptic plasticity in drug reward circuitry.

Science.gov (United States)

Winder, Danny G; Egli, Regula E; Schramm, Nicole L; Matthews, Robert T

2002-11-01

Drug addiction is a major public health issue worldwide. The persistence of drug craving coupled with the known recruitment of learning and memory centers in the brain has led investigators to hypothesize that the alterations in glutamatergic synaptic efficacy brought on by synaptic plasticity may play key roles in the addiction process. Here we review the present literature, examining the properties of synaptic plasticity within drug reward circuitry, and the effects that drugs of abuse have on these forms of plasticity. Interestingly, multiple forms of synaptic plasticity can be induced at glutamatergic synapses within the dorsal striatum, its ventral extension the nucleus accumbens, and the ventral tegmental area, and at least some of these forms of plasticity are regulated by behaviorally meaningful administration of cocaine and/or amphetamine. Thus, the present data suggest that regulation of synaptic plasticity in reward circuits is a tractable candidate mechanism underlying aspects of addiction.

Neural control of adrenal medullary and cortical blood flow during hemorrhage

International Nuclear Information System (INIS)

Breslow, M.J.; Jordan, D.A.; Thellman, S.T.; Traystman, R.J.

1987-01-01

Hemorrhagic hypotension produces an increase in adrenal medullary blood flow and a decrease in adrenal cortical blood flow. To determine whether changes in adrenal blood flow during hemorrhage are neurally mediated, the authors compared blood flow responses following adrenal denervation (splanchnic nerve section) with changes in the contralateral, neurally intact adrenal. Carbonized microspheres labeled with 153 Gd, 114 In, 113 Sn, 103 Ru, 95 Nb or 46 Se were used. Blood pressure was reduced and maintained at 60 mmHg for 25 min by hemorrhage into a pressurized bottle system. Adrenal cortical blood flow decreased to 50% of control with hemorrhage in both the intact and denervated adrenal. Adrenal medullary blood flow increased to four times control levels at 15 and 25 min posthemorrhage in the intact adrenal, but was reduced to 50% of control at 3, 5, and 10 min posthemorrhage in the denervated adrenal. In a separate group of dogs, the greater splanchnic nerve on one side was electrically stimulated at 2, 5, or 15 Hz for 40 min. Adrenal medullary blood flow increased 5- to 10-fold in the stimulated adrenal but was unchanged in the contralateral, nonstimulated adrenal. Adrenal cortical blood flow was not affected by nerve stimulation. They conclude that activity of the splanchnic nerve profoundly affects adrenal medullary vessels but not adrenal cortical vessels and mediates the observed increase in adrenal medullary blood flow during hemorrhagic hypotension

Lighting up the brain's reward circuitry.

Science.gov (United States)

Lobo, Mary Kay

2012-07-01

The brain's reward circuit is critical for mediating natural reward behaviors including food, sex, and social interaction. Drugs of abuse take over this circuit and produce persistent molecular and cellular alterations in the brain regions and their neural circuitry that make up the reward pathway. Recent use of optogenetic technologies has provided novel insights into the functional and molecular role of the circuitry and cell subtypes within these circuits that constitute this pathway. This perspective will address the current and future use of light-activated proteins, including those involved in modulating neuronal activity, cellular signaling, and molecular properties in the neural circuitry mediating rewarding stimuli and maladaptive responses to drugs of abuse. © 2012 New York Academy of Sciences.

Brainstem circuitry regulating phasic activation of trigeminal motoneurons during REM sleep.

Directory of Open Access Journals (Sweden)

Christelle Anaclet

2010-01-01

Full Text Available Rapid eye movement sleep (REMS is characterized by activation of the cortical and hippocampal electroencephalogram (EEG and atonia of non-respiratory muscles with superimposed phasic activity or twitching, particularly of cranial muscles such as those of the eye, tongue, face and jaw. While phasic activity is a characteristic feature of REMS, the neural substrates driving this activity remain unresolved. Here we investigated the neural circuits underlying masseter (jaw phasic activity during REMS. The trigeminal motor nucleus (Mo5, which controls masseter motor function, receives glutamatergic inputs mainly from the parvocellular reticular formation (PCRt, but also from the adjacent paramedian reticular area (PMnR. On the other hand, the Mo5 and PCRt do not receive direct input from the sublaterodorsal (SLD nucleus, a brainstem region critical for REMS atonia of postural muscles. We hypothesized that the PCRt-PMnR, but not the SLD, regulates masseter phasic activity during REMS.To test our hypothesis, we measured masseter electromyogram (EMG, neck muscle EMG, electrooculogram (EOG and EEG in rats with cell-body specific lesions of the SLD, PMnR, and PCRt. Bilateral lesions of the PMnR and rostral PCRt (rPCRt, but not the caudal PCRt or SLD, reduced and eliminated REMS phasic activity of the masseter, respectively. Lesions of the PMnR and rPCRt did not, however, alter the neck EMG or EOG. To determine if rPCRt neurons use glutamate to control masseter phasic movements, we selectively blocked glutamate release by rPCRt neurons using a Cre-lox mouse system. Genetic disruption of glutamate neurotransmission by rPCRt neurons blocked masseter phasic activity during REMS.These results indicate that (1 premotor glutamatergic neurons in the medullary rPCRt and PMnR are involved in generating phasic activity in the masseter muscles, but not phasic eye movements, during REMS; and (2 separate brainstem neural circuits control postural and cranial muscle

A critical appraisal of neuroimaging studies of bipolar disorder: toward a new conceptualization of underlying neural circuitry and roadmap for future research

Science.gov (United States)

Phillips, Mary L; Swartz, Holly A.

2014-01-01

Objective This critical review appraises neuroimaging findings in bipolar disorder in emotion processing, emotion regulation, and reward processing neural circuitry, to synthesize current knowledge of the neural underpinnings of bipolar disorder, and provide a neuroimaging research “roadmap” for future studies. Method We examined findings from all major studies in bipolar disorder that used fMRI, volumetric analyses, diffusion imaging, and resting state techniques, to inform current conceptual models of larger-scale neural circuitry abnormalities in bipolar disorder Results Bipolar disorder can be conceptualized in neural circuitry terms as parallel dysfunction in bilateral prefrontal cortical (especially ventrolateral prefrontal cortical)-hippocampal-amygdala emotion processing and emotion regulation neural circuitries, together with an “overactive” left-sided ventral striatal-ventrolateral and orbitofrontal cortical reward processing circuitry, that result in characteristic behavioral abnormalities associated with bipolar disorder: emotional lability, emotional dysregulation and heightened reward sensitivity. A potential structural basis for these functional abnormalities are gray matter decreases in prefrontal and temporal cortices, amygdala and hippocampus, and fractional anisotropy decreases in white matter tracts connecting prefrontal and subcortical regions. Conclusion Neuroimaging studies of bipolar disorder clearly demonstrate abnormalities in neural circuitries supporting emotion processing, emotion regulation and reward processing, although there are several limitations to these studies. Future neuroimaging research in bipolar disorder should include studies adopting dimensional approaches; larger studies examining neurodevelopmental trajectories in bipolar disorder and at-risk youth; multimodal neuroimaging studies using integrated systems approaches; and studies using pattern recognition approaches to provide clinically useful, individual

Corticostriatal circuitry in regulating diseases characterized by intrusive thinking.

Science.gov (United States)

Kalivas, Benjamin C; Kalivas, Peter W

2016-03-01

Intrusive thinking triggers clinical symptoms in many neuropsychiatric disorders. Using drug addiction as an exemplar disorder sustained in part by intrusive thinking, we explore studies demonstrating that impairments in corticostriatal circuitry strongly contribute to intrusive thinking. Neuroimaging studies have long implicated this projection in cue-induced craving to use drugs, and preclinical models show that marked changes are produced at corticostriatal synapses in the nucleus accumbens during a relapse episode. We delineate an accumbens microcircuit that mediates cue-induced drug seeking becoming an intrusive event. This microcircuit harbors many potential therapeutic targets. We focus on preclinical and clinical studies, showing that administering N-acetylcysteine restores uptake of synaptic glutamate by astroglial glutamate transporters and thereby inhibits intrusive thinking. We posit that because intrusive thinking is a shared endophenotype in many disorders, N-acetylcysteine has positive effects in clinical trials for a variety of neuropsychiatric disorders, including drug addiction, gambling, trichotillomania, and depression.

Two-dimensional Fourier analysis of the spongy medullary keratin of structurally coloured feather barbs

Science.gov (United States)

Prum, R. O.; Torres, R.; Williamson, S.; Dyck, J.

1999-01-01

We conducted two-dimensional (2D) discrete Fourier analyses of the spatial variation in refractive index of the spongy medullary keratin from four different colours of structurally coloured feather barbs from three species of bird: the rose-faced lovebird, Agapornis roseicollis (Psittacidae), the budgerigar, Melopsittacus undulatus (Psittacidae), and the Gouldian finch, Poephila guttata (Estrildidae). These results indicate that the spongy medullary keratin is a nanostructured tissue that functions as an array of coherent scatterers. The nanostructure of the medullary keratin is nearly uniform in all directions. The largest Fourier components of spatial variation in refractive index in the tissue are of the appropriate size to produce the observed colours by constructive interference alone. The peaks of the predicted reflectance spectra calculated from the 2D Fourier power spectra are congruent with the reflectance spectra measured by using microspectrophotometry. The alternative physical models for the production of these colours, the Rayleigh and Mie theories, hypothesize that medullary keratin is an incoherent array and that scattered waves are independent in phase. This assumption is falsified by the ring-like Fourier power spectra of these feathers, and the spacing of the scattering air vacuoles in the medullary keratin. Structural colours of avian feather barbs are produced by constructive interference of coherently scattered light waves from the optically heterogeneous matrix of keratin and air in the spongy medullary layer.

Nanocantilever based mass sensor integrated with cmos circuitry

DEFF Research Database (Denmark)

Davis, Zachary James; Abadal, G.; Campabadal, F.

2003-01-01

We have demonstrated the successful integration of a cantilever based mass detector with standard CMOS circuitry. The purpose of the circuitry is to facilitate the readout of the cantilever's deflection in order to measure resonant frequency shifts of the cantilever. The principle and design...... of the mass detector are presented showing that miniaturization of such cantilever based resonant devices leads to highly sensitive mass sensors, which have the potential to detect single molecules. The design of the readout circuitry used for the first electrical characterization of an integrated cantilever...... with CMOS circuitry is demonstrated. The electrical characterization of the device shows that the resonant behavior of the cantilever depends on the applied voltages, which corresponds to theory....

PKC signaling regulates drug resistance of the fungal pathogen Candida albicans via circuitry comprised of Mkc1, calcineurin, and Hsp90.

Directory of Open Access Journals (Sweden)

Shantelle L LaFayette

2010-08-01

Full Text Available Fungal pathogens exploit diverse mechanisms to survive exposure to antifungal drugs. This poses concern given the limited number of clinically useful antifungals and the growing population of immunocompromised individuals vulnerable to life-threatening fungal infection. To identify molecules that abrogate resistance to the most widely deployed class of antifungals, the azoles, we conducted a screen of 1,280 pharmacologically active compounds. Three out of seven hits that abolished azole resistance of a resistant mutant of the model yeast Saccharomyces cerevisiae and a clinical isolate of the leading human fungal pathogen Candida albicans were inhibitors of protein kinase C (PKC, which regulates cell wall integrity during growth, morphogenesis, and response to cell wall stress. Pharmacological or genetic impairment of Pkc1 conferred hypersensitivity to multiple drugs that target synthesis of the key cell membrane sterol ergosterol, including azoles, allylamines, and morpholines. Pkc1 enabled survival of cell membrane stress at least in part via the mitogen activated protein kinase (MAPK cascade in both species, though through distinct downstream effectors. Strikingly, inhibition of Pkc1 phenocopied inhibition of the molecular chaperone Hsp90 or its client protein calcineurin. PKC signaling was required for calcineurin activation in response to drug exposure in S. cerevisiae. In contrast, Pkc1 and calcineurin independently regulate drug resistance via a common target in C. albicans. We identified an additional level of regulatory control in the C. albicans circuitry linking PKC signaling, Hsp90, and calcineurin as genetic reduction of Hsp90 led to depletion of the terminal MAPK, Mkc1. Deletion of C. albicans PKC1 rendered fungistatic ergosterol biosynthesis inhibitors fungicidal and attenuated virulence in a murine model of systemic candidiasis. This work establishes a new role for PKC signaling in drug resistance, novel circuitry through which

Neurobrucellosis presenting as an intra-medullary spinal cord abscess

Directory of Open Access Journals (Sweden)

Patil Chidanand S

2005-09-01

Full Text Available Abstract Background Of the diverse presentation of neurobrucellosis, intra-medullary spinal cord abscess is extremely rare. Only four other cases have been reported so far. We present a case of spinal cord intra-medullary abscess due to Brucella melitensis. Case presentation A forty-year-old female presented with progressive weakness of both lower limb with urinary incontinence of 6 months duration. She was febrile. Neurological examination revealed flaccid areflexic paraplegia with T10 below sensory impairment including perianal region. An intramedullary mass was diagnosed on Magnetic Resonance Image (MRI scan extending from T12 to L2. At surgery, a large abscess was encountered at the conus medullaris, from which Brucella melitensis was grown on culture. She was started on streptomycin and doxycycline for 1 month, followed by rifampicin and doxycycline for 1 month. At 2-year follow-up, she had recovered only partially and continued to have impaired bladder function. Conclusion Neurobrucellosis, if not treated early, can result in severe neurological morbidity and sequale, which may be irreversible. Hence it is important to consider the possibility of neurobrucellosis in endemic region and treat aggressively.

Somatostatin Receptor Scintigraphy in Medullary Thyroid Cancer

NARCIS (Netherlands)

van der Horst-Schrivers, Anouk N. A.; Brouwers, Adrienne; Links, Thera; Hubalewska‐Dydejczyk, Alicja; Signore, Alberto; de Jong, Marion; Dierckx, Rudi A.; Buscombe, John; Van de Wiele, Christophe

2015-01-01

Medullary thyroid cancer (MTC) is a neuroendocrine tumor originating from the calcitonin‐secreting C cells. Surgery, consisting of a total thyroidectomy and an extensive lymph node dissection, is the only effective treatment in MTC; however, metastases are frequently found in the regional cervical

A 9 years boy with MEN-2B variant of medullary thyroid carcinoma.

Science.gov (United States)

Sattar, M A; Hadi, H I; Ekramuddoula, F M; Hasanuzzaman, S M

2013-04-01

To highlight a rare disease like multiple endocrine neoplasia (MEN)-2B variant of medullary thyroid carcinoma and to optimize the management option in such cases, we present a nine year old boy with thyroid swelling, cervical lymphadenopathy and thick lips. His calcitonin level was raised. Investigation's results of the boy were as following fine needle aspiration cytology (FNAC) was medullary carcinoma of thyroid, preoperative calcitonin was >2000pg/ml, post operative histopathological report was medullary carcinoma. Total thyroidectomy with aggressive initial neck surgery may reduce the recurrence and increase better prognosis and survival rate. Calcitonin is used as diagnostic and follow-up marker.

Radionuclide bone scanning of medullary chondrosarcoma

International Nuclear Information System (INIS)

Hudson, T.M.; Chew, F.S.; Manaster, B.J.

1982-01-01

Technetium-99m methylene diphosphonate bone scans of 18 medullary chondrosarcomas of bone were correlated with pathologic macrosections of the resected tumors. There was increased scan intake by all 18 tumors, and the uptake in 15 scans corresponded accurately to the anatomic extent of the tumors. Only three scans displayed increased uptake beyond the true tumor margins; thus, the ''extended pattern of uptake'' beyond the true tumor extent is much less common in medullary chondrosarcomas than in many other primary bone tumors. Therefore, increased uptake beyond the apparent radiographic margin of the tumor suggests possible occult tumor spread. Pathologically, there was intense reactive new bone formation and hyperemia around the periphery of all 18 tumors, and there were foci of enchondral ossification, hyperemia, or calcification within the tumor itself in nearly every tumor. Three scans displayed less uptake in the center of the tumors than around their peripheries. One of these tumors was necrotic in the center, but the other two were pathologically no different from tumors that displayed homogenous uptake on the scan

Radionuclide bone scanning of medullary chondrosarcoma

International Nuclear Information System (INIS)

Hudson, T.M.; Chew, F.S.; Manaster, B.J.

1982-01-01

/sup 99m/Tc methylene diphosphonate bone scans of 18 medullary chondrosarcomas of bone were correlated with pathologic macrosections of the resected tumors. There was increased scan uptake by all 18 tumors, and the uptake in 15 scans corresponded accurately to the anatomic extent of the tumors. Only three scans displayed increased uptake beyond the true tumor margins; thus, the extended pattern of uptake beyond the true tumor extent is much less common in medullary chondrosarcomas than in many other primary bone tumors. Therefore, increased uptake beyond the apparent radiographic margin of the tumor suggests possible occult tumor spread. Pathologically, there was intense reactive new bone formation and hyperemia around the periphery of all 18 tumors, and there were foci of enchondral ossification, hyperemia, or calcification within the tumor itself in nearly every tumor. Three scans displayed less uptake in the center of the tumors than around their peripheries. One of these tumors was necrotic in the center, but the other two were pathologically no different from tumors that displayed homogeneous uptake on the scan

Schwannosis induced medullary compression in VACTERL syndrome.

LENUS (Irish Health Repository)

Treacy, A

2011-10-21

A 7-year-old boy with a history of VACTERL syndrome was found collapsed in bed. MRI had shown basilar invagination of the skull base and narrowing of the foramen magnum. Angulation, swelling and abnormal high signal at the cervicomedullary junction were felt to be secondary to compression of the medulla. Neuropathologic examination showed bilateral replacement of the medullary tegmentum by an irregularly circumscribed cellular lesion which was composed of elongated GFAP\\/S 100-positive cells with spindled nuclei and minimal atypia. The pathologic findings were interpreted as intramedullary schwannosis with mass effect. Schwannosis, is observed in traumatized spinal cords where its presence may represent attempted, albeit aberrant, repair by inwardly migrating Schwann cells ofperipheral origin. In our view the compressive effect of the basilar invagination on this boy\\'s medulla was of sufficient magnitude to have caused tumoral medullary schwannosis with resultant intermittent respiratory compromise leading to reflex anoxic seizures.

Packaging and interconnection for superconductive circuitry

International Nuclear Information System (INIS)

Anacker, W.

1976-01-01

A three dimensional microelectronic module packaged for reduced signal propagation delay times including a plurality of circuit carrying means, which may comprise unbacked chips, with integrated superconductive circuitry thereon is described. The circuit carrying means are supported on their edges and have contact lands in the vicinity of, or at, the edges to provide for interconnecting circuitry. The circuit carrying means are supported by supporting means which include slots to provide a path for interconnection wiring to contact the lands of the circuit carrying means. Further interconnecting wiring may take the form of integrated circuit wiring on the reverse side of the supporting means. The low heat dissipation of the superconductive circuitry allows the circuit carrying means to be spaced approximately no less than 30 mils apart. The three dimensional arrangement provides lower random propagation delays than would a planar array of circuits

Is thyroidectomy necessary in RET mutations carriers of the familial medullary thyroid carcinoma syndrome?

DEFF Research Database (Denmark)

Hansen, H S; Torring, H; Godballe, C

2000-01-01

BACKGROUND: The results and consequences of genetic testing in a family with familial medullary thyroid carcinoma (FMTC) are described. METHODS: In the screening of relatives, serum calcitonin is replaced by RET mutation analysis that was performed in families suspected of hereditary medullary th...

Reducing Ripple In A Switching Voltage Regulator

Science.gov (United States)

Paulkovich, John; Rodriguez, G. Ernest

1994-01-01

Ripple voltage in output of switching voltage regulator reduced substantially by simple additional circuitry adding little to overall weight and size of regulator. Heretofore, additional filtering circuitry needed to obtain comparable reductions in ripple typically as large and heavy as original regulator. Current opposing ripple current injected into filter capacitor.

VAC Therapy Direct to the Medullary Cavity for Chronic Tibial Osteomyelitis.

Science.gov (United States)

Miyamura, Satoshi; Tsuji, Shigeyoshi; Iwai, Takao; Hamada, Masayuki

2016-06-01

Vacuum-assisted wound closure (VAC) is useful for difficult wound beds, although sites where bleeding or infection is expected are usually regarded as problematic for this therapy. This report outlines the treatment of chronic tibial osteomyelitis (Cierny- Mader type III) due to mixed infection with Nocardia spp and Bacteroi- des fragilis by postoperative VAC therapy direct to the medullary cavity, followed by wound coverage with a gastrocnemius myocutaneous skin flap. A 64-year-old man developed chronic left tibial os- teomyelitis after a work injury. The nonviable tissues were debrided, including a sequestrum. Nocardia spp and B. fragilis were isolated from surgical bone specimens, and chronic tibial osteomyelitis due to mixed infection was diagnosed. Postoperatively, VAC therapy was performed directly to the open medullary cavity of the tibia and sub- sequently covered the residual soft tissue defect with a gastrocnemius myocutaneous flap. The authors could not find any English literature on VAC therapy direct to the medullary cavity combined with transplantation of a myocutaneous flap for osteomyelitis. Nocardia spp can cause a variety of infections, among which osteomyelitis occupies a relatively small percentage. This case raises the possibil- ity of treating chronic tibial osteomyelitis caused by mixed infection with Nocardia spp and B. fragilis by applying postoperative VAC ther- apy directly to the medullary cavity and covering the residual wound with a gastrocnemius myocutaneous flap.

Direction-selective circuitry in rat retina develops independently of GABAergic, cholinergic and action potential activity.

Directory of Open Access Journals (Sweden)

Le Sun

Full Text Available The ON-OFF direction selective ganglion cells (DSGCs in the mammalian retina code image motion by responding much more strongly to movement in one direction. They do so by receiving inhibitory inputs selectively from a particular sector of processes of the overlapping starburst amacrine cells, a type of retinal interneuron. The mechanisms of establishment and regulation of this selective connection are unknown. Here, we report that in the rat retina, the morphology, physiology of the ON-OFF DSGCs and the circuitry for coding motion directions develop normally with pharmacological blockade of GABAergic, cholinergic activity and/or action potentials for over two weeks from birth. With recent results demonstrating light independent formation of the retinal DS circuitry, our results strongly suggest the formation of the circuitry, i.e., the connections between the second and third order neurons in the visual system, can be genetically programmed, although emergence of direction selectivity in the visual cortex appears to require visual experience.

Successful intraosseous infusion in the critically ill patient does not require a medullary cavity.

LENUS (Irish Health Repository)

McCarthy, Gerard

2012-02-03

OBJECTIVES: To demonstrate that successful intraosseous infusion in critically ill patients does not require bone that contains a medullary cavity. DESIGN: Infusion of methyl green dye via standard intraosseous needles into bones without medullary cavity-in this case calcaneus and radial styloid-in cadaveric specimens. SETTING: University department of anatomy. PARTICIPANTS: Two adult cadaveric specimens. MAIN OUTCOME MEASURES: Observation of methyl green dye in peripheral veins of the limb in which the intraosseous infusion was performed. RESULTS: Methyl green dye was observed in peripheral veins of the chosen limb in five out of eight intraosseous infusions into bones without medullary cavity-calcaneus and radial styloid. CONCLUSIONS: Successful intraosseous infusion does not always require injection into a bone with a medullary cavity. Practitioners attempting intraosseous access on critically ill patients in the emergency department or prehospital setting need not restrict themselves to such bones. Calcaneus and radial styloid are both an acceptable alternative to traditional recommended sites.

Bladder urine oxygen tension for assessing renal medullary oxygenation in rabbits: experimental and modeling studies

Science.gov (United States)

Sgouralis, Ioannis; Kett, Michelle M.; Ow, Connie P. C.; Abdelkader, Amany; Layton, Anita T.; Gardiner, Bruce S.; Smith, David W.; Lankadeva, Yugeesh R.

2016-01-01

Oxygen tension (Po2) of urine in the bladder could be used to monitor risk of acute kidney injury if it varies with medullary Po2. Therefore, we examined this relationship and characterized oxygen diffusion across walls of the ureter and bladder in anesthetized rabbits. A computational model was then developed to predict medullary Po2 from bladder urine Po2. Both intravenous infusion of [Phe2,Ile3,Orn8]-vasopressin and infusion of NG-nitro-l-arginine reduced urinary Po2 and medullary Po2 (8–17%), yet had opposite effects on renal blood flow and urine flow. Changes in bladder urine Po2 during these stimuli correlated strongly with changes in medullary Po2 (within-rabbit r2 = 0.87–0.90). Differences in the Po2 of saline infused into the ureter close to the kidney could be detected in the bladder, although this was diminished at lesser ureteric flow. Diffusion of oxygen across the wall of the bladder was very slow, so it was not considered in the computational model. The model predicts Po2 in the pelvic ureter (presumed to reflect medullary Po2) from known values of bladder urine Po2, urine flow, and arterial Po2. Simulations suggest that, across a physiological range of urine flow in anesthetized rabbits (0.1–0.5 ml/min for a single kidney), a change in bladder urine Po2 explains 10–50% of the change in pelvic urine/medullary Po2. Thus, it is possible to infer changes in medullary Po2 from changes in urinary Po2, so urinary Po2 may have utility as a real-time biomarker of risk of acute kidney injury. PMID:27385734

Bladder urine oxygen tension for assessing renal medullary oxygenation in rabbits: experimental and modeling studies

OpenAIRE

Sgouralis, Ioannis; Kett, Michelle M.; Ow, Connie P. C.; Abdelkader, Amany; Layton, Anita T.; Gardiner, Bruce S.; Smith, David W.; Lankadeva, Yugeesh R.; Evans, Roger G.

2016-01-01

Oxygen tension (Po2) of urine in the bladder could be used to monitor risk of acute kidney injury if it varies with medullary Po2. Therefore, we examined this relationship and characterized oxygen diffusion across walls of the ureter and bladder in anesthetized rabbits. A computational model was then developed to predict medullary Po2 from bladder urine Po2. Both intravenous infusion of [Phe2,Ile3,Orn8]-vasopressin and infusion of NG-nitro-l-arginine reduced urinary Po2 and medullary Po2 (8–1...

How plastic are human spinal cord motor circuitries?

DEFF Research Database (Denmark)

Christiansen, Lasse; Lundbye-Jensen, Jesper; Perez, Monica A

2017-01-01

Human and animal studies have documented that neural circuitries in the spinal cord show adaptive changes caused by altered supraspinal and/or afferent input to the spinal circuitry in relation to learning, immobilization, injury and neurorehabilitation. Reversible adaptations following, e.g. the...

Reward Circuitry in Addiction.

Science.gov (United States)

Cooper, Sarah; Robison, A J; Mazei-Robison, Michelle S

2017-07-01

Understanding the brain circuitry that underlies reward is critical to improve treatment for many common health issues, including obesity, depression, and addiction. Here we focus on insights into the organization and function of reward circuitry and its synaptic and structural adaptations in response to cocaine exposure. While the importance of certain circuits, such as the mesocorticolimbic dopamine pathway, are well established in drug reward, recent studies using genetics-based tools have revealed functional changes throughout the reward circuitry that contribute to different facets of addiction, such as relapse and craving. The ability to observe and manipulate neuronal activity within specific cell types and circuits has led to new insight into not only the basic connections between brain regions, but also the molecular changes within these specific microcircuits, such as neurotrophic factor and GTPase signaling or α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptor function, that underlie synaptic and structural plasticity evoked by drugs of abuse. Excitingly, these insights from preclinical rodent work are now being translated into the clinic, where transcranial magnetic simulation and deep brain stimulation therapies are being piloted in human cocaine dependence. Thus, this review seeks to summarize current understanding of the major brain regions implicated in drug-related behaviors and the molecular mechanisms that contribute to altered connectivity between these regions, with the postulation that increased knowledge of the plasticity within the drug reward circuit will lead to new and improved treatments for addiction.

Role of nitric oxide and prostaglandin in the maintenance of cortical and renal medullary blood flow

Directory of Open Access Journals (Sweden)

S.I Gomez

2008-02-01

Full Text Available This study was undertaken in anesthetized dogs to evaluate the relative participation of prostaglandins (PGs and nitric oxide (NO in the maintenance of total renal blood flow (TRBF, and renal medullary blood flow (RMBF. It was hypothesized that the inhibition of NO should impair cortical and medullary circulation because of the synthesis of this compound in the endothelial cells of these two territories. In contrast, under normal conditions of perfusion pressure PG synthesis is confined to the renal medulla. Hence PG inhibition should predominantly impair the medullary circulation. The initial administration of 25 µM kg-1 min-1 NG-nitro-L-arginine methyl ester produced a significant 26% decrease in TRBF and a concomitant 34% fall in RMBF, while the subsequent inhibition of PGs with 5 mg/kg meclofenamate further reduced TRBF by 33% and RMBF by 89%. In contrast, the initial administration of meclofenamate failed to change TRBF, while decreasing RMBF by 49%. The subsequent blockade of NO decreased TRBF by 35% without further altering RMBF. These results indicate that initial PG synthesis inhibition predominantly alters the medullary circulation, whereas NO inhibition decreases both cortical and medullary flow. This latter change induced by NO renders cortical and RMBF susceptible to a further decrease by PG inhibition. However, the decrease in medullary circulation produced by NO inhibition is not further enhanced by subsequent PG inhibition.

Central dopaminergic circuitry controlling food intake and reward: implications for the regulation of obesity.

Science.gov (United States)

Vucetic, Zivjena; Reyes, Teresa M

2010-01-01

Prevalence of obesity in the general population has increased in the past 15 years from 15% to 35%. With increasing obesity, the coincident medical and social consequences are becoming more alarming. Control over food intake is crucial for the maintenance of body weight and represents an important target for the treatment of obesity. Central nervous system mechanisms responsible for control of food intake have evolved to sense the nutrient and energy levels in the organism and to coordinate appropriate responses to adjust energy intake and expenditure. This homeostatic system is crucial for maintenance of stable body weight over long periods of time of uneven energy availability. However, not only the caloric and nutritional value of food but also hedonic and emotional aspects of feeding affect food intake. In modern society, the increased availability of highly palatable and rewarding (fat, sweet) food can significantly affect homeostatic balance, resulting in dysregulated food intake. This review will focus on the role of hypothalamic and mesolimbic/mesocortical dopaminergic (DA) circuitry in coding homeostatic and hedonic signals for the regulation of food intake and maintenance of caloric balance. The interaction of dopamine with peripheral and central indices of nutritional status (e.g., leptin, ghrelin, neuropeptide Y), and the susceptibility of the dopamine system to prenatal insults will be discussed. Additionally, the importance of alterations in dopamine signaling that occur coincidently with obesity will be addressed.

Caenorhabditis elegans Male Copulation Circuitry Incorporates Sex-Shared Defecation Components To Promote Intromission and Sperm Transfer

Science.gov (United States)

LeBoeuf, Brigitte; Garcia, L. Rene

2016-01-01

Sexual dimorphism can be achieved using a variety of mechanisms, including sex-specific circuits and sex-specific function of shared circuits, though how these work together to produce sexually dimorphic behaviors requires further investigation. Here, we explore how components of the sex-shared defecation circuitry are incorporated into the sex-specific male mating circuitry in Caenorhabditis elegans to produce successful copulation. Using behavioral studies, calcium imaging, and genetic manipulation, we show that aspects of the defecation system are coopted by the male copulatory circuitry to facilitate intromission and ejaculation. Similar to hermaphrodites, male defecation is initiated by an intestinal calcium wave, but circuit activity is coordinated differently during mating. In hermaphrodites, the tail neuron DVB promotes expulsion of gut contents through the release of the neurotransmitter GABA onto the anal depressor muscle. However, in the male, both neuron and muscle take on modified functions to promote successful copulation. Males require calcium-dependent activator protein for secretion (CAPS)/unc-31, a dense core vesicle exocytosis activator protein, in the DVB to regulate copulatory spicule insertion, while the anal depressor is remodeled to promote release of sperm into the hermaphrodite. This work shows how sex-shared circuitry is modified in multiple ways to contribute to sex-specific mating. PMID:28031243

Signal conditioning circuitry design for instrumentation systems.

Energy Technology Data Exchange (ETDEWEB)

Larsen, Cory A.

2012-01-01

This report details the current progress in the design, implementation, and validation of the signal conditioning circuitry used in a measurement instrumentation system. The purpose of this text is to document the current progress of a particular design in signal conditioning circuitry in an instrumentation system. The input of the signal conditioning circuitry comes from a piezoresistive transducer and the output will be fed to a 250 ksps, 12-bit analog-to-digital converter (ADC) with an input range of 0-5 V. It is assumed that the maximum differential voltage amplitude input from the sensor is 20 mV with an unknown, but presumably high, sensor bandwidth. This text focuses on a specific design; however, the theory is presented in such a way that this text can be used as a basis for future designs.

Transitional circuitry for studying the properties of DNA

Science.gov (United States)

Trubochkina, N.

2018-01-01

The article is devoted to a new view of the structure of DNA as an intellectual scheme possessing the properties of logic and memory. The theory of transient circuitry, developed by the author for optimal computer circuits, revealed an amazing structural similarity between mathematical models of transition silicon elements and logic and memory circuits of solid state transient circuitry and atomic models of parts of DNA.

Wallenberg's lateral medullary syndrome: diffusion-weighted imaging findings

Energy Technology Data Exchange (ETDEWEB)

Kitis, O.; Calli, C.; Yunten, N.; Kocaman, A.; Sirin, H. [Ege Univ., Izmir (Turkey). Dept. of Radiology

2004-02-01

To investigate the efficacy of diffusion-weighted imaging in patients with Wallenberg's lateral medullary syndrome. Thirteen patients with Wallenberg's lateral medullary syndrome were examined with conventional and echoplanar diffusion-weighted magnetic resonance (MR) imaging in a 1.5 T magnetic resonance unit. MR examinations were obtained in the acute or subacute stage of clinical syndrome, and diffusion-weighted imaging (DWI) was considered to be positive for infarction when an increase in signal was seen on b = 1000 s/mm2 images in the posterolateral medullary localization. DWIs were positive in 12 patients in the acute or subacute stages of this clinical syndrome. A false-negative result was obtained in only one patient examined within the first day, 10 h after onset of the symptoms. In the visual evaluation of the DWI, the contrast between normal and infarcted brainstem area was better in the high b-value images than in the apparent diffusion coefficient map images. DWI is a valuable technique for examining patients presenting with the signs and symptoms of Wallenberg's syndrome and high b-value images can provide complementary data to T2-weighted images. However, because most of our case group were in either the acute or subacute stage, true sensitivity of the method in the hyperacute stage of the syndrome remains unclear.

Medullary thyroid cancer: RET testing of an archival material

DEFF Research Database (Denmark)

Godballe, Christian; Jørgensen, Gita; Gerdes, Anne-Marie Axø

2010-01-01

Medullary thyroid carcinoma (MTC) might be sporadic (75%) or hereditary (25%). Until the mid nineties the diagnosis of hereditary MTC was based on family history, clinical evaluation, histological detection of C-cell hyperplasia and tumor multifocality. Patients and families with hereditary MTC...

Medullary thyroid cancer: RET testing of an archival material

DEFF Research Database (Denmark)

Godballe, Christian; Jørgensen, Gita; Gerdes, Anne-Marie

2009-01-01

Medullary thyroid carcinoma (MTC) might be sporadic (75%) or hereditary (25%). Until the mid nineties the diagnosis of hereditary MTC was based on family history, clinical evaluation, histological detection of C-cell hyperplasia and tumor multifocality. Patients and families with hereditary MTC...

Proximal Tubular Injury in Medullary Rays Is an Early Sign of Acute Tacrolimus Nephrotoxicity

Directory of Open Access Journals (Sweden)

Diane Cosner

2015-01-01

Full Text Available Tacrolimus (FK506 is one of the principal immunosuppressive agents used after solid organ transplantations to prevent allograft rejection. Chronic renal injury induced by tacrolimus is characterized by linear fibrosis in the medullary rays; however, the early morphologic findings of acute tacrolimus nephrotoxicity are not well characterized. Kidney injury molecule-1 (KIM-1 is a specific injury biomarker that has been proven to be useful in the diagnosis of mild to severe acute tubular injury on renal biopsies. This study was motivated by a patient with acute kidney injury associated with elevated serum tacrolimus levels in whom KIM-1 staining was present only in proximal tubules located in the medullary rays in the setting of otherwise normal light, immunofluorescent, and electron microscopy. We subsequently evaluated KIM-1 expression in 45 protocol and 39 indicated renal transplant biopsies to determine whether higher serum levels of tacrolimus were associated with acute segment specific injury to the proximal tubule, as reflected by KIM-1 staining in the proximal tubules of the cortical medullary rays. The data suggest that tacrolimus toxicity preferentially affects proximal tubules in medullary rays and that this targeted injury is a precursor lesion for the linear fibrosis seen in chronic tacrolimus toxicity.

A Developmental Shift from Positive to Negative Connectivity in Human Amygdala-Prefrontal Circuitry

Science.gov (United States)

Gee, Dylan G.; Humphreys, Kathryn L.; Flannery, Jessica; Goff, Bonnie; Telzer, Eva H.; Shapiro, Mor; Hare, Todd A.; Bookheimer, Susan Y.; Tottenham, Nim

2013-01-01

Recent human imaging and animal studies highlight the importance of frontoamygdala circuitry in the regulation of emotional behavior and its disruption in anxiety-related disorders. While tracing studies have suggested changes in amygdala-cortical connectivity through the adolescent period in rodents, less is known about the reciprocal connections within this circuitry across human development, when these circuits are being fine-tuned and substantial changes in emotional control are observed. The present study examined developmental changes in amygdala-prefrontal circuitry across the ages of 4 to 22 years using task-based functional magnetic resonance imaging (fMRI). Results suggest positive amygdala-prefrontal connectivity in early childhood that switches to negative functional connectivity during the transition to adolescence. Amygdala-mPFC functional connectivity was significantly positive (greater than zero) among participants younger than ten, whereas functional connectivity was significantly negative (less than zero) among participants ten years and older, over and above the effect of amygdala reactivity. The developmental switch in functional connectivity was paralleled by a steady decline in amygdala reactivity. Moreover, the valence switch might explain age-related improvement in task performance and a developmentally normative decline in anxiety. Initial positive connectivity followed by a valence shift to negative connectivity provides a neurobiological basis for regulatory development and may present novel insight into a more general process of developing regulatory connections. PMID:23467374

Lateral medullary infarction with cardiovascular autonomic dysfunction: an unusual presentation with review of the literature.

Science.gov (United States)

Huynh, Tridu R; Decker, Barbara; Fries, Timothy J; Tunguturi, Ajay

2018-01-24

We report an unusual case of lateral medullary infarction presenting with orthostatic hypotension with pre-syncope without vertigo or Horner's syndrome. Case report with review of the literature. A 67-year-old man presented with pre-syncope and ataxia without vertigo. Initial brain CT and MRI were normal. Neurological evaluation revealed right-beating nystagmus with left gaze, vertical binocular diplopia, right upper-extremity dysmetria, truncal ataxia with right axial lateropulsion, and right-facial and lower extremity hypoesthesia. Bedside blood pressure measurements disclosed orthostatic hypotension. He had normal sinus rhythm on telemetry and normal ejection fraction on echocardiogram. A repeat brain MRI disclosed an acute right dorsolateral medullary infarct. Autonomic testing showed reduced heart rate variability during paced deep breathing, attenuated late phase II and phase IV overshoot on Valsalva maneuver, and a fall of 25 mmHg of blood pressure at the end of a 10-min head-up tilt with no significant change in heart rate. These results were consistent with impaired sympathetic and parasympathetic cardiovascular reflexes. He was discharged to acute rehabilitation a week later with residual right dysmetria and ataxia. Lateral medullary infarctions are usually reported as partial presentations of classical lateral medullary syndrome with accompanying unusual symptoms ranging from trigeminal neuralgias to hiccups. Pre-syncope from orthostatic hypotension is a rare presentation. In the first 3-4 days, absence of early DWI MRI findings is possible in small, dorsolateral medullary infarcts with sensory disturbances. Physicians should be aware of this presentation, as early diagnosis and optimal therapy are associated with good prognosis.

Frequency of Cushing's syndrome due to ACTH-secreting adrenal medullary lesions: a retrospective study over 10 years from a single center.

Science.gov (United States)

Falhammar, Henrik; Calissendorff, Jan; Höybye, Charlotte

2017-01-01

Cushing's syndrome due to ectopic adrenocorticotropic hormone production from adrenal medullary lesions has occasionally been described. We retrospectively reviewed all 164 cases of Cushing's syndrome and 77 cases of pheochromocytomas during 10 years. Of all cases with Cushing's syndrome, only two cases (1.2 %) were due to ectopic adrenocorticotropic hormone production from adrenal medullary lesions (one case of pheochromocytoma and one case of adrenal medullary hyperplasia). Of all pheochromocytomas only the above-mentioned case (1.3 %) also gave rise to an ectopic adrenocorticotropic hormone syndrome. The clinical presentation of adrenocorticotropic hormone-secreting pheochromocytoma and adrenal medullary hyperplasia can be anything from mild to dramatic. These are rare conditions important to bear in mind in the workup of a patient with Cushing's syndrome or with pheochromocytoma. The identification of ectopic adrenocorticotropic hormone secretion from adrenal medullary lesions can be life-saving.

Experimental selective elevation of renal medullary blood flow in hypertensive rats: evidence against short-term hypotensive effect.

Science.gov (United States)

Bądzyńska, B; Sadowski, J

2012-08-01

Renal medullary blood flow (MBF) can be selectively increased by intrarenal or systemic infusion of bradykinin (Bk) in anaesthetized normotensive rats. We reproduced this effect in a number of rat models of arterial hypertension and examined whether increased perfusion of the renal medulla can cause a short-term decrease in blood pressure (BP) that is not mediated by increased renal excretion and depletion of body fluids. In uninephrectomized Sprague-Dawley rats, BP was elevated to approx. 145 mmHg by acute i.v. infusion of noradrenaline (NA) or angiotensin II (Ang II) (groups 1, 2), 2-week exposure to high-salt diet (3), high-salt diet + chronic low-dose infusion of Ang II using osmotic minipumps (4) or chronic high-dose Ang II infusion on normal diet (5). Uninephrectomized spontaneous hypertensive rats (SHR) were also examined (6,7). To selectively increase medullary perfusion, in anaesthetized rats, bradykinin was infused during 30-75 min into the renal medullary interstitium or intravenously. Bradykinin increased outer- and inner-medullary blood flow (laser-Doppler fluxes) by 10-20% in groups (1, 2), by 30-50% in groups (3, 4, 5) and approx. 20% in SHR (6, 7). The concurrent increase in total renal blood flow (Transonic probe) was < 3%. A minor (<3%) decrease in BP was seen only in rats acutely rendered hypertensive by NA or Ang II infusions; however, the decreases in BP and increases in medullary perfusion were not correlated. Thus, there was no evidence that in hypertensive rats, substantial selective increases in medullary perfusion can cause a short-term decrease in BP. © 2012 The Authors Acta Physiologica © 2012 Scandinavian Physiological Society.

Intraoperative neurophysiology of the conus medullaris and cauda equina.

Science.gov (United States)

Kothbauer, Karl F; Deletis, Vedran

2010-02-01

Intraoperative neurophysiological techniques are becoming routine tools for neurosurgical practice. Procedures affecting the lumbosacral nervous system are frequent in adult and pediatric neurosurgery. This review provides an overview of the techniques utilized in cauda and conus operations. Two basic methodologies of intraoperative neurophysiological testing are utilized during surgery in the lumbosacral spinal canal. Mapping techniques help identify functional neural structures, namely, nerve roots and their respective spinal levels. Monitoring is referred to as the technology to continuously assess the functional integrity of pathways and reflex circuits. For mapping direct electrical stimulation of a structure within the surgical field and recording at a distant site, usually a muscle is the most commonly used setup. Sensory nerve roots or spinal cord areas can be mapped by stimulation of a distant sensory nerve or skin area and recording from a structure within the surgical field. Continuous monitoring of the motor system is done with motor evoked potentials. These are evoked by transcranial electrical stimulation and recorded from lower extremity and sphincter muscles. Presence or absence of muscle responses are the monitored parameters. To monitor the sensory pathways, sensory potentials evoked by tibial, peroneal, or pudendal nerve stimulation and recorded from the dorsal columns with a spinal electrode or as cortical responses from scalp electrodes are used. Amplitudes and latencies of these responses are measured for interpretation. The bulbocavernosus reflex, with stimulation of the pudendal nerve and recording from the external anal sphincter, is used for continuous monitoring of the reflex circuitry. The presence of absence of this response is the pertinent parameter monitored. Stimulation of individual dorsal nerve roots is used to identify those segments that generate spastic activity and which may be cut during selective dorsal rhizotomy

Recovery of Dysphagia in Lateral Medullary Stroke

OpenAIRE

Gupta, Hitesh; Banerjee, Alakananda

2014-01-01

Lateral medullary stroke is typically associated with increased likelihood of occurrence of dysphagia and exhibits the most severe and persistent form. Worldwide little research exists on dysphagia in brainstem stroke. An estimated 15% of all patients admitted to stroke rehabilitation units experience a brainstem stroke out of which about 47% suffer from dysphagia. In India, a study showed that 22.3% of posterior circulation stroke patients develop dysphagia. Dearth of literature on dysphagia...

The potential value of somatostatin receptor scintigraphy in medullary thyroid carcinoma

Energy Technology Data Exchange (ETDEWEB)

Doerr, U.; Bihl, H. (Katharinenhospital, Stuttgart (Germany). Dept. of Nuclear Medicine); Frank-Raue, K.; Raue, F. (Heidelberg Univ. (Germany). Dept. of Internal Medicine); Sautter-Bihl, M.L.; Buhr, H.J. (Staedt. Klinikum, Karlsruhe (Germany). Dept. of Radiooncology and Nuclear Medicine); Guzman, G. (Katherinenhospital, Stuttgart (Germany). Dept. of Nuclear Medicine Inst. de Neurocirugia, Investigationes Cerebrales ' Dr Asenjo' Santiago (Chile). Dept. de Medicina Nuclear)

1993-06-01

In a prospective study, ten patients with recurrent medullary thyroid carcinoma (markedly elevated calcitonin levels) were investigated by means of somatostatin receptor scintigraphy (SRS) with [sup 111]In-pentetreotide. Scintigraphically, 30 sites of pathological uptake were found, mostly located in the neck and upper mediastinum. So far, 18 suspected tumour sites underwent histological examination and 14 of them could be verified as metastases of medullary thyroid carcinoma (MTC). The remaining four putative tumour lesions turned out to be false positive scintigraphic findings caused by chronic inflammation and somatostatin receptor positive tumours other than MTC. We conclude that SRS is a promising imaging modality for localization of MTC recurrence and may thus make a contribution to better management of this patient group. (Author).

The potential value of somatostatin receptor scintigraphy in medullary thyroid carcinoma

International Nuclear Information System (INIS)

Doerr, U.; Bihl, H.; Frank-Raue, K.; Raue, F.; Sautter-Bihl, M.L.; Buhr, H.J.; Guzman, G.; Inst. de Neurocirugia, Investigationes Cerebrales 'Dr Asenjo' Santiago

1993-01-01

In a prospective study, ten patients with recurrent medullary thyroid carcinoma (markedly elevated calcitonin levels) were investigated by means of somatostatin receptor scintigraphy (SRS) with 111 In-pentetreotide. Scintigraphically, 30 sites of pathological uptake were found, mostly located in the neck and upper mediastinum. So far, 18 suspected tumour sites underwent histological examination and 14 of them could be verified as metastases of medullary thyroid carcinoma (MTC). The remaining four putative tumour lesions turned out to be false positive scintigraphic findings caused by chronic inflammation and somatostatin receptor positive tumours other than MTC. We conclude that SRS is a promising imaging modality for localization of MTC recurrence and may thus make a contribution to better management of this patient group. (Author)

Urinary acidification and urinary excretion of calcium and citrate in women with bilateral medullary sponge kidney

DEFF Research Database (Denmark)

Osther, P J; Mathiasen, Helle; Hansen, A B

1994-01-01

Urinary acidification ability, acid-base status and urinary excretion of calcium and citrate were evaluated in 10 women with bilateral medullary sponge kidney (MSK) and in 10 healthy women. Patients with MSK had higher fasting urine pH compared to normal controls (p ... in the mechanism of hypercalciuria and hypocitraturia in patients with medullary sponge kidney.(ABSTRACT TRUNCATED AT 250 WORDS)...

Biochemical markers in the follow-up of medullary thyroid cancer

NARCIS (Netherlands)

de Groot, Jan Willem B.; Kema, Ido P.; Breukelman, Henk; van der Veer, Eveline; Wiggers, Theo; Plukker, John T. M.; Wolffenbuttel, Bruce H. R.; Links, Thera P.

2006-01-01

Medullary thyroid cancer (MTC) shares biochemical features with other neuroendocrine tumors but the particular characteristics are largely unexplored. We investigated the biochemical neuroendocrine profile of MTC and whether specific markers could be useful in follow-up. In addition to the standard

Microsatellite instability in medullary carcinoma of the colon

Directory of Open Access Journals (Sweden)

Mario Martinotti

2017-03-01

Full Text Available Medullary carcinoma (MC of the large intestine is a relatively new histological type of adenocarcinoma characterized by poor glandular differentiation and an intraepithelial lymphocytic infiltrate. MC can be associated to a defective mechanism for DNA mismatch repair, caused by the so-called microsatellite instability (MSI. We present the case of a 44 years old Caucasian woman, who referred to the Emergency Room with symptoms mimicking an acute appendicitis. Computed tomography and colonoscopy demonstrated an ulcerated and stenotic lesion of the caecum without signs of metastasis and peritoneal carcinosis. Patient underwent a laparoscopic right colectomy. The final pathologic findings provided the diagnosis of medullary carcinoma with MSI. Patient then underwent adjuvant chemotherapy according to the FOLFOX- 4 protocol (association of 5-Fluorouracil, Leucovorin, and Oxaliplatin for twelve cycles. At two-years follow-up, patient is disease free. MC in association with MSI is a non-frequent tumor of the colon characterized by a better prognosis compared to other types of poorly differentiated adenocarcinoma. In the observed case, 24 months after the surgical operation, the patient is in good health and there is no evidence of metastasis or relapse.

Impacts of nitric oxide and superoxide on renal medullary oxygen transport and urine concentration

Science.gov (United States)

Edwards, Aurélie; Layton, Anita T.

2015-01-01

The goal of this study was to investigate the reciprocal interactions among oxygen (O2), nitric oxide (NO), and superoxide (O2−) and their effects on medullary oxygenation and urinary output. To accomplish that goal, we developed a detailed mathematical model of solute transport in the renal medulla of the rat kidney. The model represents the radial organization of the renal tubules and vessels, which centers around the vascular bundles in the outer medulla and around clusters of collecting ducts in the inner medulla. Model simulations yield significant radial gradients in interstitial fluid oxygen tension (Po2) and NO and O2− concentration in the OM and upper IM. In the deep inner medulla, interstitial fluid concentrations become much more homogeneous, as the radial organization of tubules and vessels is not distinguishable. The model further predicts that due to the nonlinear interactions among O2, NO, and O2−, the effects of NO and O2− on sodium transport, osmolality, and medullary oxygenation cannot be gleaned by considering each solute's effect in isolation. An additional simulation suggests that a sufficiently large reduction in tubular transport efficiency may be the key contributing factor, more so than oxidative stress alone, to hypertension-induced medullary hypoxia. Moreover, model predictions suggest that urine Po2 could serve as a biomarker for medullary hypoxia and a predictor of the risk for hospital-acquired acute kidney injury. PMID:25651567

Ondine's Curse in a Patient with Unilateral Medullary and Bilateral Cerebellar Infarctions

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Hui-Tzu Ho

2005-11-01

Full Text Available Central sleep apnea (CSA, also known as Ondine's curse (OC, is a phenomenon characterized by episodes of repeated apnea during sleep due to disorders of the central nervous system. We report a patient with CSA/OC due to right dorsolateral medullary and bilateral cerebellar infarctions that occurred in the clinical setting of right vertebral artery stenosis. Polysomnography (PSG showed repeated episodes of absence of nasal cannula flow accompanying cessation of thoracic and abdominal respiratory movements and a decline in blood oxygen saturation. The duration of apnea was as long as 12 seconds. Brain magnetic resonance (MR images showed acute infarctions involving the right dorsolateral medulla, bilateral cerebellar vermis and paramedian cerebellar hemispheres. MR angiography showed nonvisualization of the right vertebral artery. Transcranial Doppler sonography showed a high resistance flow profile in the right vertebral artery and normal flow patterns in the basilar artery and left vertebral artery. These findings suggest that the medullary and bilateral cerebellar infarcts were caused by stenosis/pseudo-occlusion of the right vertebral artery. Reduced respiratory afferent inputs to the dorsal respiratory group of medullary neurons, the nucleus tractus solitarius and reduced “automatic” components of the respiratory drive may play a role in the development of CSA/OC.

MR imaging of medullary compression due to vertebral metastases

International Nuclear Information System (INIS)

Dooms, G.C.; Mathurin, P.; Maldague, B.; Cornelis, G.; Malghem, J.; Demeure, R.

1987-01-01

A prospective study was performed to assess the value of MR imaging for demonstrating medullary compression due to vertebral metastases in cancer patients clinically suspected of presenting with that complication. Twenty-five consecutive unselected patients were studied, and the MR imaging findings were confirmed by myelography, CT, and/or surgical and autopsy findings for each patient. The MR examinations were performed with a superconducting magnet (Philips Gyroscan S15) operating at 0.5-T. MR imaging demonstrated the metastases (single or multiple) mainly on T1- weighted images (TR = 0.45 sec and TE = 20 msec). Soft-tissue tumoral mass and/or deformity of a vertebral body secondary to metastasis, compressing the spinal cord, was equally demonstrated on T1- and heavily T2-weighted images (TR = 1.65 sec and TE = 100 msec). In the sagittal plane, MR imaging demonstrated the exact level of the compression (one or multiple levels) and its full extent. In conclusion, MR is the first imaging modality for studying cancer patients with clinically suspected medullary compression and obviates the need for more invasive procedures

The origin of behavioral bursts in decision-making circuitry.

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Amanda Sorribes

2011-06-01

Full Text Available From ants to humans, the timing of many animal behaviors comes in bursts of activity separated by long periods of inactivity. Recently, mathematical modeling has shown that simple algorithms of priority-driven behavioral choice can result in bursty behavior. To experimentally test this link between decision-making circuitry and bursty dynamics, we have turned to Drosophila melanogaster. We have found that the statistics of intervals between activity periods in endogenous activity-rest switches of wild-type Drosophila are very well described by the Weibull distribution, a common distribution of bursty dynamics in complex systems. The bursty dynamics of wild-type Drosophila walking activity are shown to be determined by this inter-event distribution alone and not by memory effects, thus resembling human dynamics. Further, using mutant flies that disrupt dopaminergic signaling or the mushroom body, circuitry implicated in decision-making, we show that the degree of behavioral burstiness can be modified. These results are thus consistent with the proposed link between decision-making circuitry and bursty dynamics, and highlight the importance of using simple experimental systems to test general theoretical models of behavior. The findings further suggest that analysis of bursts could prove useful for the study and evaluation of decision-making circuitry.

Lateral medullary syndrome after a scorpion sting

Directory of Open Access Journals (Sweden)

Vineeth Varghese Thomas

2017-01-01

Full Text Available Scorpion bites are a common problem in Southern parts of India. The sting of Mesobuthus tamulus belonging to the Buthidae family is known for being fatal. The toxidrome of scorpion sting is known for its effect on the cardiovascular system, and there have been rare reports of cerebrovascular accidents as well. We describe a case of lateral medullary syndrome secondary to scorpion sting. As per the knowledge of the authors, this is the first case report of the same.

Epidermoid cyst of the conus medullaris: atypical MRI and angiographic features

International Nuclear Information System (INIS)

Debray, M.P.; Gaston, A.

1996-01-01

We report a 50-year-old man with an epidermoid cyst of the conus medullaris which showed a nodular gadolinium enhancement on MRI and a blush on angiography. These radiological features are compared with pathological examination. (orig.)

Is renal medullary carcinoma the seventh nephropathy in sickle cell ...

African Journals Online (AJOL)

Introduction: Previous studies had enlisted renal medullary carcinoma (RMC) as the seventh nephropathy in sickle cell disease (SCD). Clinical experience has contradicted this claim and this study is targeted at refuting or supporting this assumption. Objective: To estimate the prevalence of RMC and describe other renal ...

Cysticercosis of conus medullaris: A case report and literature review

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Saurabh K Verma

2014-01-01

Full Text Available "Neurocysticercosis" - involvement of the central nervous system (CNS by taenia solium, is one of the most common parasitic diseases of the CNS. However, spinal involvement by neurocysticercosis is uncommon. Spinal intramedullary cysticercosis involving the conus medullaris is an uncommon clinical condition, which may mimic an intramedullary tumor and can lead to irreversible neurological deficits if untreated. Here, we report a 31-year-old male patient with cysticercosis in the conus medullaris of the spinal cord. Magnetic resonance imaging revealed a well-defined round intramedullary lesion at D12-L1 vertebral levels, which was homogeneously hypointense on T1WI and hyperintense on T2WI with peripheral edema. Since the patient had progressive neurological deficits, surgery was performed to decompress the spinal cord. Histopathology examination of the removed lesion proved it to be cysticercosis. In this report, we also discuss the principles of diagnosis and treatment of intramedullary cysticercosis in combination with literature review.

Regulation of the neural circuitry of emotion by compassion meditation: effects of meditative expertise.

Directory of Open Access Journals (Sweden)

Antoine Lutz

2008-03-01

Full Text Available Recent brain imaging studies using functional magnetic resonance imaging (fMRI have implicated insula and anterior cingulate cortices in the empathic response to another's pain. However, virtually nothing is known about the impact of the voluntary generation of compassion on this network. To investigate these questions we assessed brain activity using fMRI while novice and expert meditation practitioners generated a loving-kindness-compassion meditation state. To probe affective reactivity, we presented emotional and neutral sounds during the meditation and comparison periods. Our main hypothesis was that the concern for others cultivated during this form of meditation enhances affective processing, in particular in response to sounds of distress, and that this response to emotional sounds is modulated by the degree of meditation training. The presentation of the emotional sounds was associated with increased pupil diameter and activation of limbic regions (insula and cingulate cortices during meditation (versus rest. During meditation, activation in insula was greater during presentation of negative sounds than positive or neutral sounds in expert than it was in novice meditators. The strength of activation in insula was also associated with self-reported intensity of the meditation for both groups. These results support the role of the limbic circuitry in emotion sharing. The comparison between meditation vs. rest states between experts and novices also showed increased activation in amygdala, right temporo-parietal junction (TPJ, and right posterior superior temporal sulcus (pSTS in response to all sounds, suggesting, greater detection of the emotional sounds, and enhanced mentation in response to emotional human vocalizations for experts than novices during meditation. Together these data indicate that the mental expertise to cultivate positive emotion alters the activation of circuitries previously linked to empathy and theory of mind in

Kidney Involvement in Systemic Calcitonin Amyloidosis Associated With Medullary Thyroid Carcinoma

NARCIS (Netherlands)

Koopman, Timco; Niedlich-den Herder, Cindy; Stegeman, Coen A.; Links, Thera P.; Bijzet, Johan; Hazenberg, Bouke P. C.; Diepstra, Arjan

A 52-year-old woman with widely disseminated medullary thyroid carcinoma developed nephrotic syndrome and slowly decreasing kidney function. A kidney biopsy was performed to differentiate between malignancy-associated membranous glomerulopathy and tyrosine kinase inhibitor-induced focal segmental

Nodular Graves' disease with medullary thyroid cancer.

Science.gov (United States)

Khan, Shoukat Hussain; Rather, Tanveer Ahmed; Makhdoomi, Rumana; Malik, Dharmender

2015-01-01

Co-existence of thyroid nodules with Graves' disease has been reported in various studies. 10-15% of such nodules harbor thyroid cancer with papillary thyroid cancer being the commonest. Medullary thyroid cancer (MTC) in nodules associated with Graves' disease is rare. On literature survey, we came across 11 such cases reported so far. We report a 62-year-old female with Graves' disease who also had a thyroid nodule that on fine-needle aspiration cytology and the subsequent postthyroidectomy histopathological examination was reported to be MTC.

Development and aging of human spinal cord circuitries

DEFF Research Database (Denmark)

Geertsen, Svend Sparre; Willerslev-Olsen, Maria; Lorentzen, Jakob

2017-01-01

development and to what extent they are shaped according to the demands of the body that they control and the environment that the body has to interact with. We also discuss how ageing processes and physiological changes in our body are reflected in adaptations of activity in the spinal cord motor circuitries....... The complex, multi-facetted connectivity of the spinal cord motor circuitries allow that they can be used to generate vastly different movements and that their activity can be adapted to meet new challenges imposed by bodily changes or a changing environment. There are thus plenty of possibilities...

Role of basal ganglia in sleep-wake regulation: neural circuitry and clinical significance

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Ramalingam Vetrivelan

2010-11-01

Full Text Available Researchers over the last decade have made substantial progress towards understanding the roles of dopamine and the basal ganglia in the control of sleep-wake behavior. In this review, we outline recent advancements regarding dopaminergic modulation of sleep through the basal ganglia (BG and extra-BG sites. Our main hypothesis is that dopamine promotes sleep by its action on the D2 receptors in the BG and promotes wakefulness by its action on D1 and D2 receptors in the extra-BG sites. This hypothesis implicates dopamine depletion in the BG (such as in Parkinson’s disease in causing frequent nighttime arousal and overall insomnia. Furthermore, the arousal effects of psychostimulants (methamphetamine, cocaine and modafinil may be linked to the ventral periaquductal grey (vPAG dopaminergic circuitry targeting the extra-BG sleep-wake network.

Vascular endothelial growth factor signaling is necessary for expansion of medullary microvessels during postnatal kidney development

DEFF Research Database (Denmark)

Robdrup Tinning, Anne; Jensen, Boye L; Johnsen, Iben

2016-01-01

Postnatal inhibition or deletion of angiotensin II (ANG II) AT1 receptors impairs renal medullary mircrovascular development through a mechanism that may include vascular endothelial growth factor (VEGF). The present study was designed to test if VEGF/VEGF receptor signaling is necessary....... In human fetal kidney tissue, immature vascular bundles appeared early in the third trimester (GA27-28) and expanded in size until term. Rat pups treated with the VEGF receptor-2 (VEGFR2) inhibitor vandetanib (100 mg·kg(-1)·day(-1)) from P7 to P12 or P10 to P16 displayed growth retardation and proteinuria...... for the development of the renal medullary microcirculation. Endothelial cell-specific immunolabeling of kidney sections from rats showed immature vascular bundles at postnatal day (P) 10 with subsequent expansion of bundles until P21. Medullary VEGF protein abundance coincided with vasa recta bundle formation...

Mapping the Brain’s Metaphor Circuitry:Is Abstract Thought Metaphorical Thought?

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George eLakoff

2014-12-01

Full Text Available An overview of the basics of metaphorical thought and language from the perspective of Neurocognition, the integrated interdisciplinary study of how conceptual thought and language work in the brain. The paper outlines a theory of metaphor circuitry and discusses how everyday reason makes use of embodied metaphor circuitry.

Deciphering the transcriptional circuitry of microRNA genes expressed during human monocytic differentiation

KAUST Repository

Schmeier, Sebastian; MacPherson, Cameron R; Essack, Magbubah; Kaur, Mandeep; Schaefer, Ulf; Suzuki, Harukazu; Hayashizaki, Yoshihide; Bajic, Vladimir B.

2009-01-01

Background: Macrophages are immune cells involved in various biological processes including host defence, homeostasis, differentiation, and organogenesis. Disruption of macrophage biology has been linked to increased pathogen infection, inflammation and malignant diseases. Differential gene expression observed in monocytic differentiation is primarily regulated by interacting transcription factors (TFs). Current research suggests that microRNAs (miRNAs) degrade and repress translation of mRNA, but also may target genes involved in differentiation. We focus on getting insights into the transcriptional circuitry regulating miRNA genes expressed during monocytic differentiation. Results: We computationally analysed the transcriptional circuitry of miRNA genes during monocytic differentiation using in vitro time-course expression data for TFs and miRNAs. A set of TF?miRNA associations was derived from predicted TF binding sites in promoter regions of miRNA genes. Time-lagged expression correlation analysis was utilised to evaluate the TF?miRNA associations. Our analysis identified 12 TFs that potentially play a central role in regulating miRNAs throughout the differentiation process. Six of these 12 TFs (ATF2, E2F3, HOXA4, NFE2L1, SP3, and YY1) have not previously been described to be important for monocytic differentiation. The remaining six TFs are CEBPB, CREB1, ELK1, NFE2L2, RUNX1, and USF2. For several miRNAs (miR-21, miR-155, miR-424, and miR-17-92), we show how their inferred transcriptional regulation impacts monocytic differentiation. Conclusions: The study demonstrates that miRNAs and their transcriptional regulatory control are integral molecular mechanisms during differentiation. Furthermore, it is the first study to decipher on a large-scale, how miRNAs are controlled by TFs during human monocytic differentiation. Subsequently, we have identified 12 candidate key controllers of miRNAs during this differentiation process. 2009 Schmeier et al; licensee Bio

Deciphering the transcriptional circuitry of microRNA genes expressed during human monocytic differentiation

KAUST Repository

Schmeier, Sebastian

2009-12-10

Background: Macrophages are immune cells involved in various biological processes including host defence, homeostasis, differentiation, and organogenesis. Disruption of macrophage biology has been linked to increased pathogen infection, inflammation and malignant diseases. Differential gene expression observed in monocytic differentiation is primarily regulated by interacting transcription factors (TFs). Current research suggests that microRNAs (miRNAs) degrade and repress translation of mRNA, but also may target genes involved in differentiation. We focus on getting insights into the transcriptional circuitry regulating miRNA genes expressed during monocytic differentiation. Results: We computationally analysed the transcriptional circuitry of miRNA genes during monocytic differentiation using in vitro time-course expression data for TFs and miRNAs. A set of TF?miRNA associations was derived from predicted TF binding sites in promoter regions of miRNA genes. Time-lagged expression correlation analysis was utilised to evaluate the TF?miRNA associations. Our analysis identified 12 TFs that potentially play a central role in regulating miRNAs throughout the differentiation process. Six of these 12 TFs (ATF2, E2F3, HOXA4, NFE2L1, SP3, and YY1) have not previously been described to be important for monocytic differentiation. The remaining six TFs are CEBPB, CREB1, ELK1, NFE2L2, RUNX1, and USF2. For several miRNAs (miR-21, miR-155, miR-424, and miR-17-92), we show how their inferred transcriptional regulation impacts monocytic differentiation. Conclusions: The study demonstrates that miRNAs and their transcriptional regulatory control are integral molecular mechanisms during differentiation. Furthermore, it is the first study to decipher on a large-scale, how miRNAs are controlled by TFs during human monocytic differentiation. Subsequently, we have identified 12 candidate key controllers of miRNAs during this differentiation process. 2009 Schmeier et al; licensee Bio

Medullary carcinoma of the thyroid

International Nuclear Information System (INIS)

Samuel, A.M.; Pradhan, S.A.; D'Cruz, A.; Shah, D.H.

1999-01-01

Medullary thyroid carcinoma is a biologically distinct form of thyroid cancer and accounts for 5-10% of all thyroid neoplasms. Twenty percent of MTC can occur in a familial setting either by itself or as part of the multiple endocrine neoplasm syndromes. A disciplined approach is necessary in the work-up of these patients to rule out coexistent endocrine tumors (pheochromocytomas and parathyroid). Cacitonin is a sensitive tumor marker secreted by MTC that is of prognostic value and important in the follow-up of patients. Surgery is the mainstay of treatment with a total thyroidectomy and centre compartment clearance being the minimum for patients without cervical adenopathy. Radiotherapy has a limited role and is only indicated as a palliative measure in patients with advanced/metastatic disease not amenable to surgery

Screening for sporadic or familial medullary thyroid carcinoma. Scintiscan s and radio-immunotherapy

International Nuclear Information System (INIS)

Rhmer, V.; Murat, A.

2000-01-01

The screening for sporadic medullary thyroid carcinoma relies upon calcitoninemia level, basal or during pentagastrine stimulation test. MEN2 are associated with nearly the third of medullary thyroid carcinoma. In these cases, prognosis of thyroid carcinoma is mainly driven by the tumor status at the time of surgery. Up to date, diagnosis relies upon the genetic screening. Prophylactic thyroidectomy indication may take account of calcitoninemia. Most of the molecules that have been suggested for scintiscan lack of accuracy and large use cannot be recommended. Promising results have been obtained with monoclonal antibodies anti-CEA, particularly with dual targeting antiCEA antiDTPA. This last technique may also be used for radio-guided surgery. Its use for radio-immunotherapy is under investigation. (authors)

Vandetanib in advanced medullary thyroid cancer: review of adverse event management strategies

DEFF Research Database (Denmark)

Grande, Enrique; Kreissl, Michael C; Filetti, Sebastiano

2013-01-01

Vandetanib has recently demonstrated clinically meaningful benefits in patients with unresectable, locally advanced or metastatic medullary thyroid cancer (MTC). Given the potential for long-term vandetanib therapy in this setting, in addition to treatment for disease-related symptoms, effective...

Medullary and papillary carcinoma of the thyroid gland occurring as a collision tumor with lymph node metastasis: A case report

Directory of Open Access Journals (Sweden)

Sadat Alavi Mehr

2011-12-01

Full Text Available Abstract Introduction Papillary thyroid carcinoma and medullary thyroid carcinoma are two different thyroid neoplasia. The simultaneous occurrence of medullary thyroid carcinoma and papillary thyroid carcinoma as a collison tumor with metastases from both lesions in the regional lymph nodes is a rare phenomenon. Case presentation A 32-year-old Iranian man presented with a fixed anterior neck mass. Ultrasonography revealed two separate thyroid nodules as well as a suspicious neck mass that appeared to be a metastatic lesion. The results of thyroid function tests were normal, but the preoperative calcitonin serum value was elevated. Our patient underwent a total thyroidectomy with neck exploration. Two separate and ill-defined solid lesions grossly in the right lobe were noticed. Histological and immunohistochemical studies of these lesions suggested the presence of medullary thyroid carcinoma and papillary thyroid carcinoma. The lymph nodes isolated from a neck dissection specimen showed metastases from both lesions. Conclusions The concomitant occurrence of papillary thyroid carcinoma and medullary thyroid carcinoma and the exact diagnosis of this uncommon event are important. The treatment strategy should be reconsidered in such cases, and genetic screening to exclude multiple endocrine neoplasia 2 syndromes should be performed. For papillary thyroid carcinoma, radioiodine therapy and thyroid-stimulating hormone suppressive therapy are performed. However, the treatment of medullary thyroid carcinoma is mostly radical surgery with no effective adjuvant therapy.

Renal cortical and medullary blood flow during modest saline loading in humans

DEFF Research Database (Denmark)

Damkjær, M; Vafaee, M; Braad, P E

2012-01-01

Renal medullary blood flow (RMBF) is considered an important element of sodium homeostasis, but the experimental evidence is incongruent. Studies in anaesthetized animals generally support the concept in contrast to measurements in conscious animals. We hypothesized that saline-induced natriuresis...

Unusual metastasis of medullary thyroid carcinoma to the breast: A cytological and histopathological correlation

Directory of Open Access Journals (Sweden)

Parul Tanwar

2018-01-01

Full Text Available Breast metastases are a relatively rare condition and account for approximately 0.5–2% of all breast tumors. Recognition of metastatic tumors in the breast is important because it would prevent unnecessary mutilating surgery and would lead to appropriate treatment of the primary tumor. Breast metastases from medullary thyroid cancer (MTC are very rare with only 21 reported cases in the literature. Some MTCs mimic primary invasive lobular carcinoma of the breast histopathologically and radiologically, making the distinction between the two diagnostically challenging. We present the case of a 45-year-old female presenting with a lump breast, which was later found out to be metastasis from medullary carcinoma thyroid.

Progress toward the maintenance and repair of degenerating retinal circuitry.

Science.gov (United States)

Vugler, Anthony A

2010-01-01

Retinal diseases such as age-related macular degeneration and retinitis pigmentosa remain major causes of severe vision loss in humans. Clinical trials for treatment of retinal degenerations are underway and advancements in our understanding of retinal biology in health/disease have implications for novel therapies. A review of retinal biology is used to inform a discussion of current strategies to maintain/repair neural circuitry in age-related macular degeneration, retinitis pigmentosa, and Type 2 Leber congenital amaurosis. In age-related macular degeneration/retinitis pigmentosa, a progressive loss of rods/cones results in corruption of bipolar cell circuitry, although retinal output neurons/photoreceptive melanopsin cells survive. Visual function can be stabilized/enhanced after treatment in age-related macular degeneration, but in advanced degenerations, reorganization of retinal circuitry may preclude attempts to restore cone function. In Type 2 Leber congenital amaurosis, useful vision can be restored by gene therapy where central cones survive. Remarkable progress has been made in restoring vision to rodents using light-responsive ion channels inserted into bipolar cells/retinal ganglion cells. Advances in genetic, cellular, and prosthetic therapies show varying degrees of promise for treating retinal degenerations. While functional benefits can be obtained after early therapeutic interventions, efforts should be made to minimize circuitry changes as soon as possible after rod/cone loss. Advances in retinal anatomy/physiology and genetic technologies should allow refinement of future reparative strategies.

SMARCB1/INI1 inactivation in renal medullary carcinoma.

Science.gov (United States)

Calderaro, Julien; Moroch, Julien; Pierron, Gaelle; Pedeutour, Florence; Grison, Camille; Maillé, Pascale; Soyeux, Pascale; de la Taille, Alexandre; Couturier, Jérome; Vieillefond, Annick; Rousselet, Marie Christine; Delattre, Olivier; Allory, Yves

2012-09-01

Renal medullary carcinoma (RMC), a rare and highly aggressive tumour which occurs in patients with sickle-cell disease, shares many clinicopathological features with collecting duct carcinoma (CDC). The molecular mechanisms underlying RMC and CDC are mainly unknown, and there is ongoing debate about their status as distinct entities. Loss of expression of SMARCB1/INI1, a chromatin remodelling regulator and repressor of cyclin D1 transcription, has been reported recently in RMC. The aim of our study was to investigate if such loss of expression is specific for RMC. SMARCB1/INI1 genetic alterations and cyclin D1 expression were also studied. Using immunochemistry, neoplastic cells showed complete loss of SMARCB1/INI1 expression in all six cases of RMC but in only one of 22 cases of CDC. In two RMC cases investigated, comparative genomic hybridization demonstrated complete loss of one SMARCB1/INI1 allele, with no other genomic imbalances, and no mutations were found on the remaining allele. Cyclin D1 was expressed in all RMCs, suggesting that SMARCB1/INI1 inactivation may result in increased cyclin D1 transcription. The specific SMARCB1/INI1 inactivation observed in RMCs suggests that RMC and CDC are different entities. © 2012 Blackwell Publishing Ltd.

Signal processing circuitry for CMOS-based SAW gas sensors with low power and area

International Nuclear Information System (INIS)

Mohd-Yasin, F.; Tye, K.F.; Reaz, M.B.I.

2009-06-01

The design and development of interface circuitries for CMOS-based SAW gas sensor is presented in this paper. The SAW gas sensor devices typically run at RF, requiring most designs to have complex signal conditioning circuitry. The proposed approach attempts to design a simple architecture with reduced power consumption. The SAW gas sensors operate at 354MHz. Simulation data show that the interface circuitries are ten times smaller with lower power supply, comparing to existing work. (author)

Cortico-medullary continuity in bizarre parosteal osteochondromatous proliferation mimicking osteochondroma on imaging

International Nuclear Information System (INIS)

Rybak, Leon D.; Abramovici, Luigia; Steiner, German C.; Kenan, Samuel; Posner, Martin A.; Bonar, Fiona

2007-01-01

Bizarre parosteal osteochondromatous proliferation (BPOP), or Nora's lesion, is an unusual surface-based lesion of bone found most commonly in the hands and feet. In the original description of the lesion and in all publications that followed, one of the key imaging characteristics used to define this entity was the lack of cortico-medullary continuity with the underlying bone. The authors present 4 unique cases of pathologically proven BPOP in which cortico-medullary continuity with the underlying bone was demonstrated on imaging. It is believed that florid reactive periostitis, BPOP and turret osteochondroma may reflect points along the same continuum with trauma the likely inciting event. The authors suggest that, given this continuum, it may be possible to have BPOP lesions demonstrating overlapping imaging features with osteochondroma. If this is the case, strict adherence to the standard imaging criterion of lack of continuity between the lesion and the underlying bone may lead to misdiagnosis of these unusual cases of BPOP as osteochondromas. (orig.)

Enhanced statistical damage identification using frequency-shift information with tunable piezoelectric transducer circuitry

International Nuclear Information System (INIS)

Zhao, J; Tang, J; Wang, K W

2008-01-01

The frequency-shift-based damage detection method entertains advantages such as global detection capability and easy implementation, but also suffers from drawbacks that include low detection accuracy and sensitivity and the difficulty in identifying damage using a small number of measurable frequencies. Moreover, the damage detection/identification performance is inevitably affected by the uncertainty/variations in the baseline model. In this research, we investigate an enhanced statistical damage identification method using the tunable piezoelectric transducer circuitry. The tunable piezoelectric transducer circuitry can lead to much enriched information on frequency shift (before and after damage occurrence). The circuitry elements, meanwhile, can be directly and accurately measured and thus can be considered uncertainty-free. A statistical damage identification algorithm is formulated which can identify both the mean and variance of the elemental property change. Our analysis indicates that the integration of the tunable piezoelectric transducer circuitry can significantly enhance the robustness of the frequency-shift-based damage identification approach under uncertainty and noise

The unique organization of filamentous actin in the medullary canal of the medulla oblongata.

Science.gov (United States)

Tan, Bai-Hong; Guo, Chun-Yan; Xiong, Tian-Qing; Chen, Ling-Meng; Li, Yan-Chao

2017-04-01

In the central canal, F-actin is predominantly localized in the apical region, forming a ring-like structure around the circumference of the lumen. However, an exception is found in the medulla oblongata, where the apical F-actin becomes interrupted in the ventral aspect of the canal. To clarify the precise localization of F-actin, the fluorescence signals for F-actin were converted to the peroxidase/DAB reaction products in this study by a phalloidin-based ultrastructural technique, which demonstrated that F-actin is located mainly in the microvilli and terminal webs in the ependymocytes. It is because the ventrally oriented ependymocytes do not possess well-developed microvilli or terminal web that led to a discontinuous labeling of F-actin in the medullary canal. Since spinal motions can change the shape and size of the central canal, we next examined the cytoskeletons in the medullary canal in both rats and monkeys, because these two kinds of animals show different kinematics at the atlanto-occipital articulation. Our results first demonstrated that the apical F-actin in the medullary canal is differently organized in the animals with different head-neck kinemics, which suggests that the mechanic stretching of spinal motions is capable of inducing F-actin reorganization and the subsequent cell-shape changes in the central canal. Copyright © 2017 Elsevier Ltd. All rights reserved.

The influence of age on positions of the conus medullaris, Tuffier's line, dural sac, and sacrococcygeal membrane in infants, children, adolescents, and young adults.

Science.gov (United States)

Jung, Ji-Yun; Kim, Eun-Hee; Song, In-Kyung; Lee, Ji-Hyun; Kim, Hee-Soo; Kim, Jin-Tae

2016-12-01

The purpose of this study was to analyze the distances between the conus medullaris and the Tuffier's line, and between the dural sac and the sacrococcygeal membrane (SCM) in the same pediatric population. Spinal magnetic resonance images and simple X-ray images of 350 patients aged from 1 month to 20 years were reviewed. Positions of the conus medullaris, Tuffier's line, the dural sac, and the SCM were identified. Each position was recorded in relation to the corresponding vertebral body segments. The distances between the conus medullaris and Tuffier's line, and between the dural sac and the SCM, were measured and then assessed according to age using an analysis of variance and a linear regression analysis. The median levels of the conus medullaris and Tuffier's line were in the lower third of L1 [the first lumbar vertebral body] and the middle third of L5, respectively. The levels of the conus medullaris and Tuffier's line were lower in younger populations. The distance between the conus medullaris and Tuffier's line ranged from 1.5 to 4.75 vertebral body height. However, a narrow range of 1.5-2.5 vertebral height was observed only in children younger than 2 years. The level of the dural sac did not differ greatly by age, but the upper limit of the SCM was lower in older populations. The distance between the dural sac and the upper limit of the SCM increased with age. In children, there is a distance of 1.5-4.75 vertebral body height between the conus medullaris and the Tuffier's line. However, these distances were narrower among younger populations. The distance between the dural sac and the upper limit of the SCM increased with age. © 2016 John Wiley & Sons Ltd.

The role of hemosorption detoxication in the modification of medullary hemoroisis caused by acute irradiation injury

International Nuclear Information System (INIS)

Nikolaev, V.G.; Rodionova, N.K.; Petrenko, S.V.; Bychkova, N.P.; Pinchouk, L.B.

2003-01-01

Using the model of a medullar form of acute radiation disease in dogs, we have shown that early detoxification through extracorporal hemosorption in various modifications is of high efficiency. On the basis of results of experimental research, a high efficiency of detoxification therapy of the medullary form of acute radiation diseases is established. It is revealed that the toxicity of liquid media of the body is reduced after the application of various modifications of extracorporal extracorporal hemosorption. The main indicators of the efficiency of these methods are the considerable relief of the medullary syndrome severity, lower level of clinical symptoms, and high survival rate of animals

Renal cortical and medullary blood flow responses to altered NO availability in humans

DEFF Research Database (Denmark)

Damkjær, Mads; Vafaee, Manoucher; Møller, Michael L

2010-01-01

The objective of this study was to quantify regional renal blood flow in humans. In nine young volunteers on a controlled diet, the lower abdomen was CT-scanned, and regional renal blood flow was determined by positron emission tomography (PET) scanning using H(2)(15)O as tracer. Measurements were......-NMMA injection to 1.57 ± 0.17 ml·g tissue(-1)·min(-1) (P blood flow was 4.67 ± 0.31 ml·g tissue(-1)·min(-1) during control, unchanged by glyceryl nitrate, and decreased after L-NMMA [3.48 ± 0.23 ml·(g·min)(-1), P renal medullary region in which...... the measured blood flow is 1) low, 2) independent of reduction in the VOI, and 3) reactive to changes in systemic NO supply. The technique seems to provide indices of renal medullary blood flow in humans....

Diagnosis of medullary thyroid cancer and prognostic factors of disease aggressiveness

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D O Gazizova

2013-12-01

Full Text Available In the study were enrolled 137 patients with medullary thyroid cancer (MTC. Low 35%-sensitivity of FNAC and high accuracy of basal calcitonin in MTC diagnostics were found. Mutation analysis of the RET pro- tooncogene in familial and sporadic MTC, RAS -gene in sporadic MTC were done. The correlation between type of the mutation and disease aggressiveness was found.

Prominent deep medullary veins: a predictive biomarker for stroke risk from transient ischemic attack?

Science.gov (United States)

Duan, Yang; Xu, Zhihua; Li, Hongyi; Cai, Xiaonan; Chang, Cancan; Yang, Benqiang

2018-05-01

Background Deep medullary veins (DMVs) are a biomarker of severity and prognosis in patients with acute cerebral infarction. However, their clinical significance remains unclear in patients with transient ischemic attack (TIA). Purpose To determine whether prominent deep medullary veins (PDMVs) are a predictive biomarker for stroke risk after TIA. Material and Methods Clinical and imaging data of 49 patients with TIA and 49 sex- and age-matched controls were studied. PDMVs were defined as DMVs with a score of 3 (TDMVs) or asymmetric DMVs (ADMVs), and the relationship between PDMVs and clinical features was analyzed. The DMV score based on susceptibility weighted imaging (SWI) ranged from 0 (not visible) to 3 (very prominent) and was calculated for both hemispheres separately. A different score in each hemisphere was defined as ADMVs and an equal score was defined as symmetric DMVs. The asymmetry and score of DMVs were compared between the two groups and with respect to the time from TIA onset to imaging analysis. Results Agreement between neuroradiologists for the DMV asymmetry/score on SWI was excellent. The frequency of ADMVs and TDMVs was significantly higher in patients with TIA than controls ( P  0.05); PDMVs were not correlated with age, blood pressure, or diabetes. However, PDMVs were associated with the ABCD2 score (≥4), clinical symptoms, and duration of TIA (≥10 min). Conclusion Prominent deep medullary veins is a predictive biomarker for the risk of stroke in many patients having suffered from TIA.

Effectiveness of Neuromuscular Electrical Stimulation on Patients With Dysphagia With Medullary Infarction.

Science.gov (United States)

Zhang, Ming; Tao, Tao; Zhang, Zhao-Bo; Zhu, Xiao; Fan, Wen-Guo; Pu, Li-Jun; Chu, Lei; Yue, Shou-Wei

2016-03-01

To evaluate and compare the effects of neuromuscular electrical stimulation (NMES) acting on the sensory input or motor muscle in treating patients with dysphagia with medullary infarction. Prospective randomized controlled study. Department of physical medicine and rehabilitation. Patients with dysphagia with medullary infarction (N=82). Participants were randomized over 3 intervention groups: traditional swallowing therapy, sensory approach combined with traditional swallowing therapy, and motor approach combined with traditional swallowing therapy. Electrical stimulation sessions were for 20 minutes, twice a day, for 5d/wk, over a 4-week period. Swallowing function was evaluated by the water swallow test and Standardized Swallowing Assessment, oral intake was evaluated by the Functional Oral Intake Scale, quality of life was evaluated by the Swallowing-Related Quality of Life (SWAL-QOL) Scale, and cognition was evaluated by the Mini-Mental State Examination (MMSE). There were no statistically significant differences between the groups in age, sex, duration, MMSE score, or severity of the swallowing disorder (P>.05). All groups showed improved swallowing function (P≤.01); the sensory approach combined with traditional swallowing therapy group showed significantly greater improvement than the other 2 groups, and the motor approach combined with traditional swallowing therapy group showed greater improvement than the traditional swallowing therapy group (Ptherapy and motor approach combined with traditional swallowing therapy groups than in the traditional swallowing therapy group, and the sensory approach combined with traditional swallowing therapy and motor approach combined with traditional swallowing therapy groups showed statistically significant differences (P=.04). NMES that targets either sensory input or motor muscle coupled with traditional therapy is conducive to recovery from dysphagia and improves quality of life for patients with dysphagia with

Bilateral Medial Medullary Stroke: A Challenge in Early Diagnosis

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Amir M. Torabi

2013-01-01

Full Text Available Bilateral medial medullary stroke is a very rare type of stroke, with catastrophic consequences. Early diagnosis is crucial. Here, I present a young patient with acute vertigo, progressive generalized weakness, dysarthria, and respiratory failure, who initially was misdiagnosed with acute vestibular syndrome. Initial brain magnetic resonance imaging (MRI that was done in the acute phase was read as normal. Other possibilities were excluded by lumbar puncture and MRI of cervical spine. MR of C-spine showed lesion at medial medulla; therefore a second MRI of brain was requested, showed characteristic “heart appearance” shape at diffusion weighted (DWI, and confirmed bilateral medial medullary stroke. Retrospectively, a vague-defined hyperintense linear DWI signal at midline was noted in the first brain MRI. Because of the symmetric and midline pattern of this abnormal signal and similarity to an artifact, some radiologists or neurologists may miss this type of stroke. Radiologists and neurologists must recognize clinical and MRI findings of this rare type of stroke, which early treatment could make a difference in patient outcome. The abnormal DWI signal in early stages of this type of stroke may not be a typical “heart appearance” shape, and other variants such as small dot or linear DWI signal at midline must be recognized as early signs of stroke. Also, MRI of cervical spine may be helpful if there is attention to brainstem as well.

Medullary sponge kidney and isolated hemihyperplasia

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P S Priyamvada

2014-01-01

Full Text Available The term hemihyperplasia refers to an enlargement of body parts beyond the normal asymmetry. Hemihyperplasia can be isolated or associated with various well-described malformation syndromes. Medullary sponge kidney (MSK has been described with isolated and syndromic hemihyperplasia; the actual prevalence is not known The hemi hypertrophy can be so subtle that it may be easily overlooked. MSK need not be limited to the side of hemihyperplasia - most often it is bilateral. Around 33 cases has been reported from different parts of the world of which 15 cases are isolated hemi hyperplasia (IHH, the remaining occurring in the context of various malformation syndromes So far only one case has been reported from India. We report a case of IHH involving right side of the body, recurrent renal stones, incomplete distal renal tubular acidosis hypercalciuria and imaging showing bilateral MSKs.

Bilateral Medial Medullary Infarction with Nondominant Vertebral Artery Occlusion.

Science.gov (United States)

Zhang, Lei; Zhang, Gui-lian; Du, Ju-mei; Ma, Zhu-lin

2015-09-01

Bilateral medial medullary infarction (MMI) is a rare stroke subtype. Here, we report a case with bilateral MMI caused by nondominant vertebral artery occlusion confirmed by brain digital subtraction angiography and magnetic resonance imaging basi-parallel-anatomical-scanning. We highlight that anterior spinal arteries could originate from a unilateral vertebral artery (VA). Radiologists and neurologists should pay attention to the nondominant VA as bilateral MMI may be induced by occlusion of nondominant VA that supplies the bilateral anteromedial territories of the medulla. Copyright © 2015 National Stroke Association. Published by Elsevier Inc. All rights reserved.

DNA-decorated carbon-nanotube-based chemical sensors on complementary metal oxide semiconductor circuitry

International Nuclear Information System (INIS)

Chen, Chia-Ling; Yang, Chih-Feng; Dokmeci, Mehmet R; Agarwal, Vinay; Sonkusale, Sameer; Kim, Taehoon; Busnaina, Ahmed; Chen, Michelle

2010-01-01

We present integration of single-stranded DNA (ss-DNA)-decorated single-walled carbon nanotubes (SWNTs) onto complementary metal oxide semiconductor (CMOS) circuitry as nanoscale chemical sensors. SWNTs were assembled onto CMOS circuitry via a low voltage dielectrophoretic (DEP) process. Besides, bare SWNTs are reported to be sensitive to various chemicals, and functionalization of SWNTs with biomolecular complexes further enhances the sensing specificity and sensitivity. After decorating ss-DNA on SWNTs, we have found that the sensing response of the gas sensor was enhanced (up to ∼ 300% and ∼ 250% for methanol vapor and isopropanol alcohol vapor, respectively) compared with bare SWNTs. The SWNTs coupled with ss-DNA and their integration on CMOS circuitry demonstrates a step towards realizing ultra-sensitive electronic nose applications.

Bilateral paramedian medullary infarction presenting subacute tetraplegia 14 years after irradiation for suprapharyngeal cancer. A case report

International Nuclear Information System (INIS)

Doi, Hikaru; Shigeto, Hiroshi; Kawano, Yuji; Ohyagi, Yasumasa; Kira, Jun-ichi

2007-01-01

A 52-year-old man presenting with progressive tetraplegia and dysesthsia over a period of 2 weeks was initially diagnosed as cervical myelitis. However, MRI taken 10 days later revealed bilateral paramedian medullary infarction. CT angiography showed calcification of bilateral vertebral arteries located within the field irradiated for superior pharyngeal cancer 14 years previously. Radiation therapy can facilitate atherosclerotic changes and the incidences of cerebral infarction increase after head and neck irradiation. Clinicians need to be aware that bilateral paramedian medullary infarction can occur after irradiation of the head and neck. Clinical manifestations can be similar to cervical myelitis with subacute progressive course. (author)

Extramedullary plasmacytoma of thyroid - a mimicker of medullary carcinoma at fine needle aspiration cytology: A case report

Directory of Open Access Journals (Sweden)

Vidya Bhat

2014-01-01

Full Text Available A rare case of extra medullary plasmacytoma (EMP of thyroid gland in a 60 year old male, occurring against a background of Hashimoto′s thyroiditis is reported. The fine needle aspiration cytology (FNAC initially done as an outpatient procedure, showed atypical epithelial cells on a background of amyloid. Considering these findings we gave a diagnosis of medullary carcinoma. Histology of the total thyroidectomy specimen showed an extensive infiltration of neoplastic plasma cells against a background of Hashimoto′s thyroiditis, with a bizarre Hurthle cell change. Immunohistochemistry on the histology sections confirmed the diagnosis of solitary plasmacytoma of thyroid against a background of Hashimoto′s thyroiditis.

Differential Activation of Medullary Vagal Nuclei Caused by Stimulation of Different Esophageal Mechanoreceptors

Science.gov (United States)

Lang, Ivan M.; Medda, Bidyut K.; Shaker, Reza

2010-01-01

Esophageal mechanorecptors, i.e. muscular slowly adapting tension receptors and mucosal rapidly adapting touch receptors, mediate different sets of reflexes. The aim of this study was to determine the medullary vagal nuclei involved in the reflex responses to activation of these receptors. Thirty-three cats were anesthetized with alpha-chloralose and the esophagus was stimulated by slow balloon or rapid air distension. The physiological effects of the stimuli (N=4) were identified by recording responses from the pharyngeal, laryngeal, and hyoid muscles, esophagus, and the lower esophageal sphincter (LES). The effects on the medullary vagal nuclei of the stimuli: slow distension (N=10), rapid distension (N=9), and in control animals (N=10) were identified using the immunohistochemical analysis of c-fos. The experimental groups were stimulated 3 times per minute for 3 hours. After the experiment, the brains were removed and processed for c-fos immunoreactivity or thioinin. We found that slow balloon distension activated the esophago-UES contractile reflex and esophago LES relaxation response, and rapid air injection activated the belch and its component reflexes. Slow balloon distension activated the NTSce, NTSdl, NTSvl, DMNc, DMNr and NAr; and rapid air injection primarily activated AP, NTScd, NTSim, NTSis, NTSdm, NTSvl, NAc and NAr. We concluded that different sets of medullary vagal nuclei mediate different reflexes of the esophagus activated from different sets of mechanoreceptors. The NTScd is the primary NTS subnucleus mediating reflexes from the mucosal rapidly adapting touch receptors, and the NTSce is the primary NTS subnucleus mediating reflexes from the muscular slowly adapting tension receptors. The AP may be involved in mediation of belching. PMID:20971087

Imaging of renal medullary carcinoma in children and young adults: a report from the Children's Oncology Group

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Sandberg, Jesse K.; Khanna, Geetika [Washington University School of Medicine, Mallinckrodt Institute of Radiology, St. Louis, MO (United States); Mullen, Elizabeth A. [Children' s Hospital Boston/Dana-Farber Cancer Institute, Department of Pediatric Oncology, Boston, MA (United States); Cajaiba, Mariana M.; Perlman, Elizabeth J. [Northwestern University Feinberg School of Medicine, Department of Pathology and Laboratory Medicine, Ann and Robert H. Lurie Children' s Hospital of Chicago, Chicago, IL (United States); Smith, Ethan A. [University of Michigan Health System, Section of Pediatric Radiology, C. S. Mott Children' s Hospital, Department of Radiology, Ann Arbor, MI (United States); Servaes, Sabah [Children' s Hospital of Philadelphia, Department of Radiology, Philadelphia, PA (United States); Geller, James I. [University of Cincinnati, Division of Pediatric Oncology, Cincinnati Children' s Hospital Medical Center, Cincinnati, OH (United States); Ehrlich, Peter F. [University of Michigan Health System, Section of Pediatric Surgery, C. S. Mott Children' s Hospital, Department of Surgery, Ann Arbor, MI (United States); Cost, Nicholas G. [University of Colorado School of Medicine, Division of Urology, Department of Surgery, Aurora, CO (United States); Dome, Jeffrey S. [Children' s National Medical Center, Division of Pediatric Oncology, Washington, DC (United States); Fernandez, Conrad V. [Dalhousie University and IWK Health Centre, Department of Pediatrics, Halifax, NS (Canada)

2017-11-15

Renal medullary carcinoma is a rare renal malignancy of childhood. There are no large series describing the imaging appearance of renal medullary carcinoma in children. To characterize the clinical and imaging features of pediatric renal medullary carcinoma at initial presentation. We retrospectively analyzed images of 25 pediatric patients with renal medullary carcinoma enrolled in the Children's Oncology Group renal tumors classification, biology and banking study (AREN03B2) from March 2006 to August 2016. Imaging findings of the primary mass, and patterns of locoregional and distant spread were evaluated in correlation with pathological and surgical findings. Median age at presentation was 13 years (range: 6-21 years), with a male predominance (3.2:1). The overall stage of disease at initial presentation was stage 1 in 1, stage 2 in 2 and stage 4 in 22. Maximum diameter of the primary renal mass ranged from 1.6 to 10.3 cm (mean: 6.6 cm) with a slight right side predilection (1.5:1). Enlarged (>1 cm short axis) retroperitoneal lymph nodes were identified at initial staging in 20/25 (80%) cases, 10 of which were histologically confirmed while the others did not undergo surgical sampling. Enlarged lymph nodes were also identified in the mediastinum (14/25; 56%) and supraclavicular regions (4/25; 16%). Metastatic disease was present in the lungs in 19/25 (76%) and liver in 6/25 (24%). The pattern of lung metastases was pulmonary lymphangitic carcinomatosis: 10 cases (9 bilateral, 1 unilateral), pulmonary nodules with indistinct margins: 6 cases, pulmonary nodules with distinct margins: 2 cases, while 1 case had pulmonary nodules with both indistinct and distinct margins. Pulmonary lymphangitic carcinomatosis was pathologically confirmed in 4/10 cases. All cases with pulmonary lymphangitic carcinomatosis had associated enlarged mediastinal lymph nodes. Renal medullary carcinoma in children and young adults presents at an advanced local and distant stage in the

Imaging of renal medullary carcinoma in children and young adults: a report from the Children's Oncology Group

International Nuclear Information System (INIS)

Sandberg, Jesse K.; Khanna, Geetika; Mullen, Elizabeth A.; Cajaiba, Mariana M.; Perlman, Elizabeth J.; Smith, Ethan A.; Servaes, Sabah; Geller, James I.; Ehrlich, Peter F.; Cost, Nicholas G.; Dome, Jeffrey S.; Fernandez, Conrad V.

2017-01-01

Renal medullary carcinoma is a rare renal malignancy of childhood. There are no large series describing the imaging appearance of renal medullary carcinoma in children. To characterize the clinical and imaging features of pediatric renal medullary carcinoma at initial presentation. We retrospectively analyzed images of 25 pediatric patients with renal medullary carcinoma enrolled in the Children's Oncology Group renal tumors classification, biology and banking study (AREN03B2) from March 2006 to August 2016. Imaging findings of the primary mass, and patterns of locoregional and distant spread were evaluated in correlation with pathological and surgical findings. Median age at presentation was 13 years (range: 6-21 years), with a male predominance (3.2:1). The overall stage of disease at initial presentation was stage 1 in 1, stage 2 in 2 and stage 4 in 22. Maximum diameter of the primary renal mass ranged from 1.6 to 10.3 cm (mean: 6.6 cm) with a slight right side predilection (1.5:1). Enlarged (>1 cm short axis) retroperitoneal lymph nodes were identified at initial staging in 20/25 (80%) cases, 10 of which were histologically confirmed while the others did not undergo surgical sampling. Enlarged lymph nodes were also identified in the mediastinum (14/25; 56%) and supraclavicular regions (4/25; 16%). Metastatic disease was present in the lungs in 19/25 (76%) and liver in 6/25 (24%). The pattern of lung metastases was pulmonary lymphangitic carcinomatosis: 10 cases (9 bilateral, 1 unilateral), pulmonary nodules with indistinct margins: 6 cases, pulmonary nodules with distinct margins: 2 cases, while 1 case had pulmonary nodules with both indistinct and distinct margins. Pulmonary lymphangitic carcinomatosis was pathologically confirmed in 4/10 cases. All cases with pulmonary lymphangitic carcinomatosis had associated enlarged mediastinal lymph nodes. Renal medullary carcinoma in children and young adults presents at an advanced local and distant stage in the

Singing modulates parvalbumin interneurons throughout songbird forebrain vocal control circuitry

Science.gov (United States)

Zengin-Toktas, Yildiz

2017-01-01

Across species, the performance of vocal signals can be modulated by the social environment. Zebra finches, for example, adjust their song performance when singing to females (‘female-directed’ or FD song) compared to when singing in isolation (‘undirected’ or UD song). These changes are salient, as females prefer the FD song over the UD song. Despite the importance of these performance changes, the neural mechanisms underlying this social modulation remain poorly understood. Previous work in finches has established that expression of the immediate early gene EGR1 is increased during singing and modulated by social context within the vocal control circuitry. Here, we examined whether particular neural subpopulations within those vocal control regions exhibit similar modulations of EGR1 expression. We compared EGR1 expression in neurons expressing parvalbumin (PV), a calcium buffer that modulates network plasticity and homeostasis, among males that performed FD song, males that produced UD song, or males that did not sing. We found that, overall, singing but not social context significantly affected EGR1 expression in PV neurons throughout the vocal control nuclei. We observed differences in EGR1 expression between two classes of PV interneurons in the basal ganglia nucleus Area X. Additionally, we found that singing altered the amount of PV expression in neurons in HVC and Area X and that distinct PV interneuron types in Area X exhibited different patterns of modulation by singing. These data indicate that throughout the vocal control circuitry the singing-related regulation of EGR1 expression in PV neurons may be less influenced by social context than in other neuron types and raise the possibility of cell-type specific differences in plasticity and calcium buffering. PMID:28235074

Circuitry for use with an ionizing-radiation detector

International Nuclear Information System (INIS)

Marshall, J.H. III; Harrington, T.M.

1976-01-01

An improved system of circuitry for use in combination with an ionizing-radiation detector over a wide range of radiation levels includes a current-to-frequency converter together with a digital data processor for respectively producing and measuring a pulse repetition frequency which is proportional to the output current of the ionizing-radiation detector, a dc-to-dc converter for providing closely regulated operating voltages from a rechargeable battery and a bias supply for providing high voltage to the ionization chamber. The ionizing-radiation detector operating as a part of this system produces a signal responsive to the level of ionizing radiation in the vicinity of the detector, and this signal is converted into a pulse frequency which will vary in direct proportion to such level of ionizing-radiation. The data processor, by counting the number of pulses from the converter over a selected integration interval, provides a digital indication of radiation dose rate, and by accumulating the total of all such pulses provides a digital indication of total integrated dose. Ordinary frequency-to-voltage conversion devices or digital display techniques can be used as a means for providing audible and visible indications of dose and dose-rate levels

Low Power/Low Voltage Interface Circuitry for Capacitive Sensors

DEFF Research Database (Denmark)

Furst, Claus Efdmann

This thesis focuses mainly on low power/low voltage interface circuits, implemented in CMOS, for capacitive sensors. A brief discussion of demands and possibilities for analog signal processing in the future is presented. Techniques for low power design is presented. This is done by analyzing power...... power consumption. It is shown that the Sigma-Delta modulator is advantageous when embedded in a feedback loop with a mechanical sensor. Here a micro mechanical capacitive microphone. Feedback and detection circuitry for a capacitive microphone is presented. Practical implementations of low power....../low voltage interface circuitry is presented. It is demonstrated that an amplifier optimized for a capacitive microphone implemented in a standard 0.7 micron CMOS technology competes well with a traditional JFET amplifier. Furthermore a low power/low voltage 3rd order Sigma-Delta modulator is presented...

Design and implementation of high-precision and low-jitter programmable delay circuitry

International Nuclear Information System (INIS)

Gao Yuan; Cui Ke; Zhang Hongfei; Luo Chunli; Yang Dongxu; Liang Hao; Wang Jian

2011-01-01

A programmable delay circuit design which has characteristics of high-precision, low-jitter, wide-programmable-range and low power is introduced. The delay circuitry uses the scheme which has two parts: the coarse delay and the fine delay that could be controlled separately. Using different coarse delay chip can reach different maximum programmable range. And the fine delay programmable chip has the minimum step which is down to 10 ps. The whole circuitry jitter will be less than 100 ps. The design has been successfully applied in Quantum Key Distribution experiment. (authors)

DNA-based random number generation in security circuitry.

Science.gov (United States)

Gearheart, Christy M; Arazi, Benjamin; Rouchka, Eric C

2010-06-01

DNA-based circuit design is an area of research in which traditional silicon-based technologies are replaced by naturally occurring phenomena taken from biochemistry and molecular biology. This research focuses on further developing DNA-based methodologies to mimic digital data manipulation. While exhibiting fundamental principles, this work was done in conjunction with the vision that DNA-based circuitry, when the technology matures, will form the basis for a tamper-proof security module, revolutionizing the meaning and concept of tamper-proofing and possibly preventing it altogether based on accurate scientific observations. A paramount part of such a solution would be self-generation of random numbers. A novel prototype schema employs solid phase synthesis of oligonucleotides for random construction of DNA sequences; temporary storage and retrieval is achieved through plasmid vectors. A discussion of how to evaluate sequence randomness is included, as well as how these techniques are applied to a simulation of the random number generation circuitry. Simulation results show generated sequences successfully pass three selected NIST random number generation tests specified for security applications.

AVP-stimulated nucleotide secretion in perfused mouse medullary thick ascending limb and cortical collecting duct

DEFF Research Database (Denmark)

Odgaard, Elvin V. P.; Prætorius, Helle; Leipziger, Jens Georg

2009-01-01

is stimulated remain elusive. Here, we investigate the phenomenon of nucleotide secretion in intact, perfused mouse medullary thick ascending limb (mTAL) and cortical collecting duct (CCD). The nucleotide secretion was monitored by a biosensor adapted to register nucleotides in the tubular outflow...

Functional Maps of Neocortical Local Circuitry

Science.gov (United States)

Thomson, Alex M.; Lamy, Christophe

2007-01-01

This review aims to summarize data obtained with different techniques to provide a functional map of the local circuit connections made by neocortical neurones, a reference for those interested in cortical circuitry and the numerical information required by those wishing to model the circuit. A brief description of the main techniques used to study circuitry is followed by outline descriptions of the major classes of neocortical excitatory and inhibitory neurones and the connections that each layer makes with other cortical and subcortical regions. Maps summarizing the projection patterns of each class of neurone within the local circuit and tables of the properties of these local circuit connections are provided. This review relies primarily on anatomical studies that have identified the classes of neurones and their local and long distance connections and on paired intracellular and whole-cell recordings which have documented the properties of the connections between them. A large number of different types of synaptic connections have been described, but for some there are only a few published examples and for others the details that can only be obtained with paired recordings and dye-filling are lacking. A further complication is provided by the range of species, technical approaches and age groups used in these studies. Wherever possible the range of available data are summarised and compared. To fill some of the more obvious gaps for the less well-documented cases, data obtained with other methods are also summarized. PMID:18982117

Primary medullary hemorrhage in a patient with coagulopathy due to alcoholic cirrhosis: A case report.

Science.gov (United States)

Shen, Guangxun; Gao, Yu; Lee, Kwee-Yum; Nan, Guangxian

2018-04-01

Mild-to-moderate alcoholic cirrhosis of the liver is related to spontaneous intracerebral hemorrhage (ICH). In terms of spontaneous brainstem hemorrhage, pontine is considered as the most common site in contrast to medulla oblongata where the hemorrhage is rarely seen. This rare primary medullary hemorrhage has been attributed so far to vascular malformation (VM), anticoagulants, hypertension, hemorrhagic transformation, and other undetermined factors. Herein, we describe a 53-year-old patient with 35-year history of alcohol abuse was admitted for acute-onset isolated hemianesthesia on the right side. He was normotensive on admission. A neurological examination revealed isolated hemihypoaesthesia on the right side. He had no history of hypertension, and viral hepatitis, and nil use of anticoagulants. Brain computed tomography (CT) image demonstrated hemorrhagic lesion in dorsal and medial medulla oblongata which was ruptured into the fourth ventricle. Brain magnetic resonance imaging (MRI), and magnetic resonance angiography (MRA) demonstrated no evidence of VM. The laboratory tests implied liver dysfunction, thrombocytopenia, and coagulation disorders. Abdominal ultrasound, and CT image showed a small, and nodular liver with splenomegaly, suggestive of moderate alcoholic cirrhosis. Liver protection therapy and the management of coagulation disorders. After 14 days, he was discharged with mild hemianesthesia but with more improved parameters in laboratory tests. At the 6-month follow-up, brain MRI, MRA, and non-contrast MRI showed no significant findings except for a malacic lesion. We conclude that the patient had alcoholic cirrhosis with coagulopathy, and this may have resulted in primary medullary hemorrhage. This is a first case to report alcoholic cirrhosis as etiology of primary medullary hemorrhage.

Diaphyseal medullary stenosis (sclerosis) with bone malignancy (malignant fibrous histiocytoma): hardcastle syndrome

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Norton, K.I. [Department of Radiology, Box 1234, Mount Sinai Hospital and Mount Sinai School of Medicine, City University of New York, One Gustave L. Levy Place, New York, NY 10029-6574 (United States)]|[Department of Pediatrics, Mount Sinai Hospital, New York, New York (United States); Wagreich, J.M. [Department of Radiology, Box 1234, Mount Sinai Hospital and Mount Sinai School of Medicine, City University of New York, One Gustave L. Levy Place, New York, NY 10029-6574 (United States); Granowetter, L. [Division of Pediatric Hematology-Oncology, Mount Sinai Hospital New York, New York (United States); Martignetti, J.A. [Department of Pediatrics, Mount Sinai Hospital, New York, New York (United States)

1996-09-01

Hardcastle syndrome is a rare, autosomally dominant inherited skeletal dysplasia, characterized by diaphyseal sclerosis, medullary stenosis, pathological fractures, bony infarction, and malignant transformation. A 19-year-old proband is presented and discussed, adding a fourth family to the world literature. Radiographic screening of family members is suggested from puberty onward. Thallium scanning is proposed as a more tumor-sensitive screening agent in affected individuals. (orig.). With 2 figs.

A resected case of medullary carcinoma of the ascending colon followed by infarction of the greater omentum mimicking anastomotic leakage

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Masaki Wakasugi

Full Text Available Introduction: Medullary carcinoma is a rare type of colorectal adenocarcinoma, and omental infarction is a rare cause of acute abdomen. Presentation of case: A 72-year-old woman underwent single-incision laparoscopic right hemicolectomy for ascending colon cancer. Pathological examination showed a medullary carcinoma (MC of T4aN0M0 Stage IIB. Her postoperative course was uneventful, and she was discharged on postoperative day (POD 6. From POD 7, she suffered from fever, and she returned to the hospital on POD 9. Plain computed tomography showed free air beside the anastomotic site around the elevated density of fat tissue and gallbladder wall thickening with a gallstone. Suspecting anastomotic leakage with acute cholecystitis, probe laparotomy was performed. Intraoperative observation confirmed omental infarction with acute cholecystitis, and no leakage was found at the anastomotic site. Therefore, the necrotic part of the greater omentum was resected, and cholecystectomy was performed. She has remained well, with no evidence of recurrent cancer during the 12 months of follow-up without chemotherapy after the surgery for MC of the ascending colon. Discussion: MC should be distinguished from other more aggressive, non-glandular tumors of the colon because MC appears to have a better survival outcome than undifferentiated colon adenocarcinoma. Omental infarction should be considered in the differential diagnosis of acute abdomen after surgery. Conclusion: A rare case of medullary carcinoma of the ascending colon followed by infarction of the greater omentum mimicking anastomotic leakage is presented. Keywords: Medullary carcinoma, Colon cancer, Omental infarction, Omental torsion

Direct effects of endogenous pyrogen on medullary temperature-responsive neurons in rabbits.

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Sakata, Y; Morimoto, A; Takase, Y; Murakami, N

1981-01-01

The effect of endogenous pyrogen (E.P.) injected directly into the tissue near the recording site were examined on the activities of the medullary temperature-responsive (TR) neurons in rabbits anesthetized with urethane. Endogenous pyrogen prepared from rabbit's whole blood was administered by a fine glass cannula (100-200 micrometer in diameter) in a fluid volume of 1 to 4 microliter. The cannula was fixed to the manipulator in parallel with a microelectrode and their tips were less than 0.05 mm apart. In rabbits with the intact preoptic/anterior hypothalamic (PO/AH) region, 4 warm-responsive neurons out of 7 were inhibited and 6 cold-responsive neuron out of 7 were excited by the direct administration of the E.P. In rabbits with lesions of the PO/AH, 5 warm-responsive neurons out of 9 were inhibited and 6 cold-responsive neurons out of 8 were facilitated by E.P. Antipyretics administered locally after the E.P. antagonized the pyretic effect, causing a return of the discharge of TR neuron to the control rate within 2.4 +/- 1.2 (mean +/- S.D.) min. The medullary TR neuron itself has the ability to respond to the E.P. and contributes to the development of fever.

Midbrain and medullary control of postinspiratory activity of the crural and costal diaphragm in vivo

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Subramanian, Hari H.; Holstege, Gert

Subramanian HH, Holstege G. Midbrain and medullary control of postinspiratory activity of the crural and costal diaphragm in vivo. J Neurophysiol 105: 2852-2862, 2011. First published March 30, 2011; doi:10.1152/jn.00168.2011.-Studies on brain stem respiratory neurons suggest that eupnea consists of

Epigenetic Regulation of Monocyte and Macrophage Function

NARCIS (Netherlands)

Hoeksema, Marten A.; de Winther, Menno P. J.

2016-01-01

Monocytes and macrophages are key players in tissue homeostasis and immune responses. Epigenetic processes tightly regulate cellular functioning in health and disease. Recent Advances: Recent technical developments have allowed detailed characterizations of the transcriptional circuitry underlying

Closing the medullary canal after retrograde nail removal using a bioabsorbable bone plug: technical tip

NARCIS (Netherlands)

Schepers, T.; Vogels, L. M. M.

2012-01-01

We describe a simple technique for closure of the intra-articular opening after the removal of a retrograde femur nail. With the use of a gelatine bioabsorbable bone plug the medullary canal is closed, reducing leakage of blood and cancellous bone particles from the bone into the knee joint

MR renography : An algorithm for calculation and correction of cortical volume averaging in medullary renographs

NARCIS (Netherlands)

de Priester, JA; den Boer, JA; Giele, ELW; Christiaans, MHL; Kessels, A; Hasman, A; van Engelshoven, JMA

We evaluated a mathematical algorithm for the generation of medullary signal from raw dynamic magnetic resonance (MR) data. Five healthy volunteers were studied. MR examination consisted of a run of 100 TI-weighted coronal scans (gradient echo: TR/TE 11/3.4 msec, flip angle 60 degrees; slice

Somatostatin receptor scintigraphy using (99m)Tc-EDDA/HYNIC-TOC in patients with medullary thyroid carcinoma

NARCIS (Netherlands)

Czepczynski, Rafal; Parisella, Maria Gemma; Kosowicz, Jerzy; Mikolajczak, Renata; Ziemnicka, Katarzyna; Gryczynska, Maria; Sowinski, Jerzy; Signore, Alberto

2007-01-01

Purpose Several new somatostatin analogues have been developed for the diagnosis and therapy of different tumours. Since somatostatin receptors are often over-expressed in medullary thyroid carcinoma (MTC), the aim of our study was to evaluate the utility of scintigraphy with the somatostatin

Ipsilateral hemiparesis in lateral medullary infarction: Clinical investigation of the lesion location on magnetic resonance imaging.

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Uemura, Masahiro; Naritomi, Hiroaki; Uno, Hisakazu; Umesaki, Arisa; Miyashita, Kotaro; Toyoda, Kazunori; Minematsu, Kazuo; Nagatsuka, Kazuyuki

2016-06-15

In 1946, Opalski reported two cases of Wallenberg syndrome with ipsilateral hemiparesis (IH). His hypothesis seems to be based on the view that IH is caused by post-decussating pyramidal tract damage. Afterwards, other researchers proposed a different hypothesis that ipsilateral sensory symptoms of limbs (ISSL) or ipsilateral limb ataxia (ILA) caused by lateral medullary infarction (LMI) might lead to ipsilateral motor weakness. The present study is aimed to clarify whether IH in LMI patients is attributable mainly to ISSL/ILA or disruption of ipsilateral post-decussating pyramidal tract. Thirty-two patients with acute LMI admitted during the last 13years were divided to IH Group (n=7) and Non-IH Group (n=25). Lesion location/distribution on MRI and neurological findings were compared between the two groups. LMI involved the lower medulla in all seven IH patients and 12 of 25 Non-IH patients. The lower medullary lesion extended to the cervico-medullary junction (CMJ) in four of seven IH patients and one of 12 Non-IH patients. Definitive extension to upper cervical cord (UCC) was confirmed in none of the patients. ISSL was found in two IH and three Non-IH patients all showing only superficial sensory impairments. ILA or hypotonia was observed in 57% of IH and 60% of Non-IH patients. IH in LMI appears to be due mainly to post-decussating pyramidal tract damage at the lower medulla instead of ILA or ISSL participation. Copyright © 2016 Elsevier B.V. All rights reserved.

Gastric Medullary Carcinoma with Sporadic Mismatch Repair Deficiency and a TP53 R273C Mutation: An Unusual Case with Wild-Type BRAF

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Brett M. Lowenthal

2017-01-01

Full Text Available Medullary carcinoma has long been recognized as a subtype of colorectal cancer associated with microsatellite instability and Lynch syndrome. Gastric medullary carcinoma is a very rare neoplasm. We report a 67-year-old male who presented with a solitary gastric mass. Total gastrectomy revealed a well-demarcated, poorly differentiated carcinoma with an organoid growth pattern, pushing borders, and abundant peritumoral lymphocytic response. The prior cytology was cellular with immunohistochemical panel consistent with upper gastrointestinal/pancreaticobiliary origin. Overall, the histopathologic findings were consistent with gastric medullary carcinoma. A mismatch repair panel revealed a mismatch repair protein deficient tumor with loss of MLH1 and PMS2 expression. BRAF V600E immunostain (VE1 and BRAF molecular testing were negative, indicating a wild-type gene. Tumor sequencing of MLH1 demonstrated a wild-type gene, while our molecular panel identified TP53 c.817C>T (p.R273C mutation. These findings were compatible with a sporadic tumor. Given that morphologically identical medullary tumors often occur in Lynch syndrome, it is possible that mismatch repair loss is an early event in sporadic tumors with p53 mutation being a late event. Despite having wild-type BRAF, this tumor is sporadic and unrelated to Lynch syndrome. This case report demonstrates that coordinate ancillary studies are needed to resolve sporadic versus hereditary rare tumors.

HV1 acts as a sodium sensor and promotes superoxide production in medullary thick ascending limb of Dahl salt-sensitive rats.

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Jin, Chunhua; Sun, Jingping; Stilphen, Carly A; Smith, Susan M E; Ocasio, Hiram; Bermingham, Brent; Darji, Sandip; Guha, Avirup; Patel, Roshan; Geurts, Aron M; Jacob, Howard J; Lambert, Nevin A; O'Connor, Paul M

2014-09-01

We previously characterized a H(+) transport pathway in medullary thick ascending limb nephron segments that when activated stimulated the production of superoxide by nicotinamide adenine dinucleotide phosphate oxidase. Importantly, the activity of this pathway was greater in Dahl salt-sensitive rats than salt-resistant (SS.13(BN)) rats, and superoxide production was enhanced in low Na(+) media. The goal of this study was to determine the molecular identity of this pathway and its relationship to Na(+). We hypothesized that the voltage-gated proton channel, HV1, was the source of superoxide-stimulating H(+) currents. To test this hypothesis, we developed HV1(-/-) null mutant rats on the Dahl salt-sensitive rat genetic background using zinc-finger nuclease gene targeting. HV1 could be detected in medullary thick limb from wild-type rats. Intracellular acidification using an NH4Cl prepulse in 0 sodium/BaCl2 containing media resulted in superoxide production in thick limb from wild-type but not HV1(-/-) rats (Pthick limb and peritoneal macrophages only when HV1 was present. When fed a high-salt diet, blood pressure, outer medullary renal injury (tubular casts), and oxidative stress (4-hydroxynonenal staining) were significantly reduced in HV1(-/-) rats compared with wild-type Dahl salt-sensitive rats. We conclude that HV1 is expressed in medullary thick ascending limb and promotes superoxide production in this segment when intracellular Na(+) is low. HV1 contributes to the development of hypertension and renal disease in Dahl salt-sensitive rats. © 2014 American Heart Association, Inc.

Medullary colonic carcinoma with microsatellite instability has lower survival compared with conventional colonic adenocarcinoma with microsatellite instability

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Miguel A. Gómez-Álvarez

2016-12-01

Full Text Available Introduction: Colorectal medullary carcinoma (MC is a rare subtype of poorly differentiated adenocarcinoma (PDA with unclear prognostic significance. Microsatellite instable (MSI colorectal carcinomas have demonstrated better prognosis in clinical stage II. Aim: To analyze the survival and clinicopathological characteristics of MCs versus PDAs with MSI in clinical stage III. Material and methods: We studied 22 cases of PDAs with MSI versus 10 MCs. Results : Of the 10 MCs, 7 patients were men; the mean age was 57.8 ±5.6 years. The mean tumor size was 9.6 ±4.1 cm, and the primary site was the right colon in 9; 7 patients showed lymph node metastases (LNM and lymphovascular invasion (LVI. Of the 22 PDA cases, 12 (54.5% were women with a mean age of 75 ±16.1 years. The mean tumor size was 6.4 ±3.2 cm. Twelve (54.5% presented in the right colon, 21 (95.5% showed LNM and 7 (31.8% LVI. Follow-up was 32 ±8 months, with a 5-year overall survival of 42.9% for MCs and 76.6% for PDAs (p = 0.048. Univariate analysis found local recurrence (p = 0.001 and medullary subtype (p = 0.043 associated with lower survival. Conclusions : Medullary carcinomas were of greater tumor size and associated with more LVI and worse survival versus PDAs with MSI in stage III.

Clinical relevance of18F-FDG PET and18F-DOPA PET in recurrent medullary thyroid carcinoma

NARCIS (Netherlands)

H.H.G. Verbeek (Hans H.); J.T. Plukker (John); K.P. Koopmans (Klaas Pieter); J. de Groot (Jan); R.M.W. Hofstra (Robert); A.C. Muller Kobold (Anneke); A.N.A. van der Horst-Schrivers (Anouk); A.H. Brouwers (A.); T.P. Links (Thera)

2012-01-01

textabstractThe transition from stable to progressive disease is unpredictable in patients with biochemical evidence of medullary thyroid carcinoma (MTC). Calcitonin and carcinoembryonic antigen (CEA) doubling times are currently the most reliable markers for progression, but for accurate

Statins Promote Long-Term Recovery after Ischemic Stroke by Reconnecting Noradrenergic Neuronal Circuitry

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Kyoung Joo Cho

2015-01-01

Full Text Available Inhibitors of HMG-CoA reductase (statins, widely used to lower cholesterol in coronary heart and vascular disease, are effective drugs in reducing the risk of stroke and improving its outcome in the long term. After ischemic stroke, cardiac autonomic dysfunction and psychological problems are common complications related to deficits in the noradrenergic (NA system. This study investigated the effects of statins on the recovery of NA neuron circuitry and its function after transient focal cerebral ischemia (tFCI. Using the wheat germ agglutinin (WGA transgene technique combined with the recombinant adenoviral vector system, NA-specific neuronal pathways were labeled, and were identified in the locus coeruleus (LC, where NA neurons originate. NA circuitry in the atorvastatin-treated group recovered faster than in the vehicle-treated group. The damaged NA circuitry was partly reorganized with the gradual recovery of autonomic dysfunction and neurobehavioral deficit. Newly proliferated cells might contribute to reorganizing NA neurons and lead anatomic and functional recovery of NA neurons. Statins may be implicated to play facilitating roles in the recovery of the NA neuron and its function.

Predictors for perioperative blood transfusion in elderly patients with extra capsular hip fractures treated with cephalo-medullary nailing.

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Fazal, M Ali; Bagley, Caroline; Garg, Parag

2018-02-01

The aim of our study was to determine predictive factors and requirement for perioperative blood transfusion in elderly patients with extra capsular hip fractures treated with cephalo-medullary device. Seventy-nine patients with extra capsular hip fractures treated with cephalo-medullary nailing were included in the study. Age, sex, ASA grade, timing of surgery, preoperative and postoperative haemoglobin, length of hospital stay, fracture type, number of units transfused and 30-day mortality were recorded. The mean age was 82.3 years. Forty-seven patients underwent a short nail and 32 patients a long nail; 53.4% patients required blood transfusion postoperatively. Transfusion was required in 71.8% of the long nails (p  0.05). Length of hospital stay in non-transfusion group was 13 days and in transfusion group was 19 days (p  0.05). Thirty-day mortality in patients needing blood transfusion was 5% and in non-transfusion group was 3.7% (p > 0.05). Patient age, ASA grade, preoperative haemoglobin and length of nail are reliable predictors for perioperative blood transfusion in extra capsular hip fractures in elderly patients treated with cephalo-medullary nailing and reinforce a selective transfusion policy. Copyright © 2017 Daping Hospital and the Research Institute of Surgery of the Third Military Medical University. Production and hosting by Elsevier B.V. All rights reserved.

Clinical Relevance of F-18-FDG PET and F-18-DOPA PET in Recurrent Medullary Thyroid Carcinoma

NARCIS (Netherlands)

Verbeek, Hans H. G.; Plukker, John T. M.; Koopmans, Klaas Pieter; de Groot, Jan Willem B.; Hofstra, Robert M. W.; Kobold, Anneke C. Muller; van der Horst-Schrivers, Anouk N. A.; Brouwers, Adrienne H.; Links, Thera P.

2012-01-01

The transition from stable to progressive disease is unpredictable in patients with biochemical evidence of medullary thyroid carcinoma (MTC). Calcitonin and carcinoembryonic antigen (CEA) doubling times are currently the most reliable markers for progression, but for accurate determination, serial

Reward Circuitry Function in Autism during Face Anticipation and Outcomes

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Dichter, Gabriel S.; Richey, J. Anthony; Rittenberg, Alison M.; Sabatino, Antoinette; Bodfish, James W.

2012-01-01

The aim of this study was to investigate reward circuitry responses in autism during reward anticipation and outcomes for monetary and social rewards. During monetary anticipation, participants with autism spectrum disorders (ASDs) showed hypoactivation in right nucleus accumbens and hyperactivation in right hippocampus, whereas during monetary…

Demographic, clinical, and genetic characteristics of patients with medullary thyroid cancer in the past 16 years in Castilla-La Mancha.

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Louhibi, Lynda; Marco, Amparo; Pinés, Pedro J; Padillo, José C; Gómez, Inés; Valero, Miguel A; Alramadán, Mubarak; Herranz, Sandra; Aguirre, Miguel; Hernández, Antonio

2014-10-01

Medullary thyroid cancer is a rare tumor that is more aggressive and has a worse prognosis than differentiated thyroid cancer. The purpose of this study was to report the demographic, clinical, and genetic characteristics of patients seen in the health care system of the community of Castilla-La Mancha over a 16-year period. Data were collected through a review of patients' medical records. The medical records of 58 patients (mean age at diagnosis, 51 years; range, 6-82 years; 63.8% women) were reviewed. Prevalence rate was 2.84 cases per 100,000 inhabitants, with a high variability between areas (range, 0-5.4 cases per 100,000 inhabitants). Familial cases accounted for 34.5% of all medullary thyroid cancers, and the most common mutation was C634Y. The condition was most commonly diagnosed following palpation of a cervical lump (70.6%). At diagnosis, 56 of 58 patients underwent ultrasound and 8 of 58 patients were tested for serum calcitonin. Tumor multicentricity was reported in 59 and 50% of patients with multiple endocrine neoplasia syndrome type 2A and 2B, respectively, and in no sporadic cases. Fifty-two percent of patients had an advanced stage (iii or iv) at diagnosis. Median follow-up was 36 months (interquartile range, 14-210); 11 patients were lost to follow-up. In Castilla-La Mancha, medullary thyroid cancer is diagnosed by cervical ultrasound, rather than calcitonin assay. There is a high prevalence of both familial and sporadic medullary thyroid cancer, and a significant variability in the type of proto-oncogen rearranged during transfection mutation as compared to the rest of the Spanish population. Copyright © 2013 SEEN. Published by Elsevier Espana. All rights reserved.

Neurobiological Programming of Early Life Stress: Functional Development of Amygdala-Prefrontal Circuitry and Vulnerability for Stress-Related Psychopathology.

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VanTieghem, Michelle R; Tottenham, Nim

2017-04-25

Early adverse experiences are associated with heighted vulnerability for stress-related psychopathology across the lifespan. While extensive work has investigated the effects of early adversity on neurobiology in adulthood, developmental approaches can provide further insight on the neurobiological mechanisms that link early experiences and long-term mental health outcomes. In the current review, we discuss the role of emotion regulation circuitry implicated in stress-related psychopathology from a developmental and transdiagnostic perspective. We highlight converging evidence suggesting that multiple forms of early adverse experiences impact the functional development of amygdala-prefrontal circuitry. Next, we discuss how adversity-induced alterations in amygdala-prefrontal development are associated with symptoms of emotion dysregulation and psychopathology. Additionally, we discuss potential mechanisms through which protective factors may buffer the effects of early adversity on amygdala-prefrontal development to confer more adaptive long-term outcomes. Finally, we consider limitations of the existing literature and make suggestions for future longitudinal and translational research that can better elucidate the mechanisms linking early adversity, neurobiology, and emotional phenotypes. Together, these findings may provide further insight into the neuro-developmental mechanisms underlying the emergence of adversity-related emotional disorders and facilitate the development of targeted interventions that can ameliorate risk for psychopathology in youth exposed to early life stress.

Incorporation of radioactive sulfate (Na235SO4) by mouse adrenal medullary cells as shown by radioautography

International Nuclear Information System (INIS)

Munhoz, C.O.G.; Merzel, J.

1977-01-01

Preliminary radioautographic results, observed in the adreno-medullary cells of mice injected with radiosulfate, suggested that the cells might synthetize sulfur-containing compounds. Only further studies could make-clear if sulfate groups are linked to carbohydrate molecules and/or chromaffin granules [pt

Use of the gamma probe and of 99mTc-DMSA (V) in the identification of the neck recurrence of medullary carcinoma thyroid

International Nuclear Information System (INIS)

Melo, Rosana Leite de; Kowalski, Luiz P.; Ubrich, Fabio F.; Lima, Eduardo N. Pereira; Torres, Ivone C.G.

2003-01-01

Medullary carcinoma of the thyroid, a malignant neoplasm of para follicular C cells, represent about 5-10% of thyroid tumors. The symptoms are related to local invasion and hormonal secretion. The clinical course is variable, from indolent cases to extremely aggressive. Many radionuclide imaging have been described to locate metastasis of medullary cancer. Tl-201 and Tc-99m (V)DMS A showed to be useful in the evaluation o persistent elevated serum calcitonin levels. On the other hand, the use of the 131 I-Mibg, that is the isotope more used, has not been demonstrating efficiency in identifying metastasis. Our objective is to report a case of a patient with medullary thyroid carcinoma in which the follow-up use DMS A(V) demonstrated a recurrence no identified for other methods. A 34-year-old man had a diagnosis of medullary thyroid carcinoma and has submitted a total thyroidectomy and neck lymph node dissection. He presented elevated serum calcitonin levels and DMS A(V) scintigraphy demonstrated focal area of pathologic uptake at the medline of the neck, but the surgical exploration was negative. He persisted with high calcitonin levels and it was used a new DMS A(V). On this occasion he was submitted to the radio-guided surgery that located the recurrence and it was confirmed with anatomo-pathologic exam. This case allowed to demonstrate that the use of radionuclide associated to the gamma-probe is promising, allowing a precise surgical approach. (author)

Differential Activation of Medullary Vagal Nuclei Caused by Stimulation of Different Esophageal Mechanoreceptors

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Lang, Ivan M.; Medda, Bidyut K.; Shaker, Reza

2010-01-01

Esophageal mechanorecptors, i.e. muscular slowly adapting tension receptors and mucosal rapidly adapting touch receptors, mediate different sets of reflexes. The aim of this study was to determine the medullary vagal nuclei involved in the reflex responses to activation of these receptors. Thirty-three cats were anesthetized with alpha-chloralose and the esophagus was stimulated by slow balloon or rapid air distension. The physiological effects of the stimuli (N=4) were identified by recordin...

Synaptic defects in the spinal and neuromuscular circuitry in a mouse model of spinal muscular atrophy.

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Karen K Y Ling

2010-11-01

Full Text Available Spinal muscular atrophy (SMA is a major genetic cause of death in childhood characterized by marked muscle weakness. To investigate mechanisms underlying motor impairment in SMA, we examined the spinal and neuromuscular circuitry governing hindlimb ambulatory behavior in SMA model mice (SMNΔ7. In the neuromuscular circuitry, we found that nearly all neuromuscular junctions (NMJs in hindlimb muscles of SMNΔ7 mice remained fully innervated at the disease end stage and were capable of eliciting muscle contraction, despite a modest reduction in quantal content. In the spinal circuitry, we observed a ∼28% loss of synapses onto spinal motoneurons in the lateral column of lumbar segments 3-5, and a significant reduction in proprioceptive sensory neurons, which may contribute to the 50% reduction in vesicular glutamate transporter 1(VGLUT1-positive synapses onto SMNΔ7 motoneurons. In addition, there was an increase in the association of activated microglia with SMNΔ7 motoneurons. Together, our results present a novel concept that synaptic defects occur at multiple levels of the spinal and neuromuscular circuitry in SMNΔ7 mice, and that proprioceptive spinal synapses could be a potential target for SMA therapy.

Adenocarcinoma of the prostate and metastatic medullary compression. A retrospective study of 22 patients

DEFF Research Database (Denmark)

Honnens de Lichtenberg, M; Kvist, E; Hjortberg, P

1992-01-01

A retrospective study of 709 patients with prostatic cancer was carried out. Twenty-two developed medullary cord compression (an incidence of 3%). All but two of the 22 patients were treated by radiation and 10 had additional hormonal treatment. Ten had some benefit from the treatment, but only 2...... of 19 regained their ability to walk. The need for immediate diagnosis and treatment is stressed....

Predictors for perioperative blood transfusion in elderly patients with extra capsular hip fractures treated with cephalo-medullary nailing

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M. Ali Fazal

2018-02-01

Conclusion: Patient age, ASA grade, preoperative haemoglobin and length of nail are reliable predictors for perioperative blood transfusion in extra capsular hip fractures in elderly patients treated with cephalo-medullary nailing and reinforce a selective transfusion policy.

[Medullary carcinoma experience in breast oncology unit of Hospital Juarez Mexico].

Science.gov (United States)

Jiménez-Villanueva, Xicoténcatl; Hernández-Rubio, Angela; García-Rodríguez, Francisco Mario; García, Rebeca Gil; Moreno-Eutimio, Mario; Herrera-Torre, Analy

2014-01-01

Medullary breast cancer is a rare type, considered of good prognosis. To know the epidemiological and clinical characteristics of the population attended in the Hospital Juarez de Mexico, to know if they are alike to described worldwide and if the treatments proposed internationally are applicable for this hospitable center. We performed a retrospective analysis. Reviewing the records with histopathologic diagnosis of medullary breast cancer from February 1993 to February 2011. Finding 41 patients in the oncology unit of the institution. We report an incidence of 3.04%, originating in 11 Mexican States, with a low to middle socioeconomic level in 39.02%. The average age at the time of diagnosis was 50 years. No family history was reported but some patients had medical history for type 2 diabetes, hypertension and previous breast cancer. 63.41% were menopausal. The average clinical size of the tumor was 58 mm. The 63% of the cases were located in the left breast. The 53.1% were clinical stages I and II, 46.3% were clinical stages III and in 9.6% of the cases primary tumor could not be assessed. Only 47% of the patients had positive axillary lynph nodes at diagnosis. The inmunohistochemestry was only reported in 14 of the 41 patients, according to the molecular classification of breast cancer: 8 were triple negative, 2 luminal A, 1 luminal B and 3 Her2neu. The Mexican population presents epidemiological and clinical characteristics similar to those patients described in other studies worldwide.

United in Diversity : A Physiological and Molecular Characterization of Subpopulations in the Basal Ganglia Circuitry

OpenAIRE

Viereckel, Thomas

2017-01-01

The Basal Ganglia consist of a number of different nuclei that form a diverse circuitry of GABAergic, dopaminergic and glutamatergic neurons. This complex network is further organized in subcircuits that govern limbic and motor functions in humans and other vertebrates. Due to the interconnection of the individual structures, dysfunction in one area or cell population can affect the entire network, leading to synaptic and molecular alterations in the circuitry as a whole. The studies in this ...

Plxnd1 expression in thymocytes regulates their intrathymic migration while that in thymic endothelium impacts medullary topology

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Young Il Choi

2013-11-01

Full Text Available An important role for plexinD1 in thymic development is inferred from studies of germline Plxnd1 knockout (KO mice where mislocalized CD69+ thymocytes as well as ectopic thymic subcapsular medullary structures were observed. Given embryonic lethality of the Plxnd1-/- genotype, fetal liver transplantation was employed in these prior analyses. Such embryonic hematopoietic reconstitution may have transferred Plxnd1 KO endothelial and/or epithelial stem cells in addition to Plxnd1 KO lymphoid progenitors, thereby contributing to that phenotype. Here we use Plxnd1flox/flox mice crossed to pLck-Cre, pKeratin14-Cre or pTek-Cre transgenic animals to create cell-type specific conditional knockout (CKO lines involving thymocytes (D1ThyCKO, thymic epithelium (D1EpCKO and thymic endothelium (D1EnCKO, respectively. These CKOs allowed us to directly assess the role of plexinD1 in each lineage. Loss of plexinD1 expression on double positive (DP thymocytes leads to their aberrant migration and cortical retention after TCR-mediated positive selection. In contrast, ectopic medulla formation is a consequence of loss of plexinD1 expression on endothelial cells, in turn linked to dysregulation of thymic angiogenesis. D1EpCKO thymi manifest neither abnormality. Collectively, our findings underscore the non-redundant roles for plexinD1 on thymocytes and endothelium, including the dynamic nature of medulla formation resulting from crosstalk between these thymic cellular components.

Disseminated medullary thyroid carcinoma despite early thyroid surgery in the multiple endocrine neoplasia-2A syndrome

NARCIS (Netherlands)

van Santen, H. M.; Aronson, D. C.; van Trotsenburg, A. S. P.; ten Kate, F. J. W.; van de Wetering, M. D.; Wiersinga, W. M.; de Vijlder, J. J. M.; Vulsma, T.

2005-01-01

A 5 1/2-year-old boy, with a family history of multiple endocrine neoplasia (MEN)-2A syndrome, was evaluated for presence of MEN-2A and medullary thyroid carcinoma (MTC). DNA diagnostics confirmed MEN-2A. Basal (360 ng/L) and pentagastrin stimulated (430 ng/L) calcitonin (CT) levels were slightly

Influence of Bisphosphonate Treatment on Medullary Macrophages and Osteoclasts: An Experimental Study

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Natalia Daniela Escudero

2012-01-01

Full Text Available Nitrogen-containing bisphosphonates are widely used for treating diverse bone pathologies. They are anticatabolic drugs that act on osteoclasts inhibiting bone resorption. It remains unknown whether the mechanism of action is by decreasing osteoclast number, impairing osteoclast function, or whether they continue to effectively inhibit bone resorption despite the increase in osteoclast number. There is increasing evidence that bisphosphonates also act on bone marrow cells like macrophages and monocytes. The present work sought to evaluate the dynamics of preosteoclast fusion and possible changes in medullary macrophage number in bisphosphonate-treated animals. Healthy female Wistar rats received olpadronate, alendronate, or vehicle during 5 weeks, and 5-bromo-2-deoxyuridine (BrdU on day 7, 28, or 34 of the experiment. Histomorphometric studies were performed to study femurs and evaluate: number of nuclei per osteoclast (N.Nu/Oc; number of BrdU-positive nuclei (N.Nu BrdU+/Oc; percentage of BrdU-positive nuclei per osteoclast (%Nu.BrdU+/Oc; medullary macrophage number (mac/mm2 and correlation between N.Nu/Oc and mac/mm2. Results showed bisphosphonate-treated animals exhibited increased N.Nu/Oc, caused by an increase in preosteoclast fusion rate and evidenced by higher N.Nu BrdU+/Oc, and significantly decreased mac/mm2. Considering the common origin of osteoclasts and macrophages, the increased demand for precursors of the osteoclast lineage may occur at the expense of macrophage lineage precursors.

Circuitry linking the Csr and stringent response global regulatory systems.

Science.gov (United States)

Edwards, Adrianne N; Patterson-Fortin, Laura M; Vakulskas, Christopher A; Mercante, Jeffrey W; Potrykus, Katarzyna; Vinella, Daniel; Camacho, Martha I; Fields, Joshua A; Thompson, Stuart A; Georgellis, Dimitris; Cashel, Michael; Babitzke, Paul; Romeo, Tony

2011-06-01

CsrA protein regulates important cellular processes by binding to target mRNAs and altering their translation and/or stability. In Escherichia coli, CsrA binds to sRNAs, CsrB and CsrC, which sequester CsrA and antagonize its activity. Here, mRNAs for relA, spoT and dksA of the stringent response system were found among 721 different transcripts that copurified with CsrA. Many of the transcripts that copurified with CsrA were previously determined to respond to ppGpp and/or DksA. We examined multiple regulatory interactions between the Csr and stringent response systems. Most importantly, DksA and ppGpp robustly activated csrB/C transcription (10-fold), while they modestly activated csrA expression. We propose that CsrA-mediated regulation is relieved during the stringent response. Gel shift assays confirmed high affinity binding of CsrA to relA mRNA leader and weaker interactions with dksA and spoT. Reporter fusions, qRT-PCR and immunoblotting showed that CsrA repressed relA expression, and (p)ppGpp accumulation during stringent response was enhanced in a csrA mutant. CsrA had modest to negligible effects on dksA and spoT expression. Transcription of dksA was negatively autoregulated via a feedback loop that tended to mask CsrA effects. We propose that the Csr system fine-tunes the stringent response and discuss biological implications of the composite circuitry. © Published 2011. This article is a US Government work and is in the public domain in the USA.

(18)F-Dihydroxyphenylalanine PET in patients with biochemical evidence of medullary thyroid cancer : Relation to tumor differentiation

NARCIS (Netherlands)

Koopmans, Klaas P.; de Groot, Jan Willem B.; Plukker, John T. M.; de Vries, Elisabeth G. E.; Kema, Ido P.; Sluiter, Wim J.; Jager, Pieter L.; Links, Thera P.

Curative treatment for recurrent medullary thyroid cancer (MTC), diagnosed by rising serum calcitonin, is surgery, but tumor localization is difficult. Therefore, the value of (18)F-dihy-droxyphenylanaline PET ((18)F-DOPA PET), (18)F-FDG PET, (99m)Tc-V-di-mercaptosulfuricacid (DMSA-V) scintigraphy,

The role of leptin in the regulation of energy balance and adiposity

NARCIS (Netherlands)

van Dijk, G

2001-01-01

Since its discovery, leptin (a 167-amino acid product of the OB gene) has quickly moved to the forefront as an important hormone for regulation of energy balance. It closes a feedback loop from adipose tissue to hypothalamic neuropeptide-containing neural circuitry involved in regulation of food

New method for identification of precentral and postcentral gyrus on CT and MR studies based on the medullary pattern of cerebral white matter

International Nuclear Information System (INIS)

Iwasaki, S.; Uchida, H.; Kichikawa, K.; Nakagawa, H.; Ohishi, H.; Kuru, Y.

1987-01-01

The authors proposed and verified a new method to identify the precentral and postcentral gyrus on the axial images of CT and MR. The method is founded on the pattern of medullary branches of white matter instead of sulci, which had been reported previously. The accuracy of this method was verified by fixed brains, normal CT analysis based on the pattern of sulci, and clinical cases analyzed by angiography. This method can be used even if there are space-occupying lesions. This will probably be widely used not only for CT but also for MR imaging, which depicts the medullary branch more clearly

Hematopoiesis stimulation test by interleukin 1α gene transfer in the Cynomolgus macaque: application to secondary medullary aplasia from an accidental irradiation

International Nuclear Information System (INIS)

De Revel, Th.

2002-12-01

After a description of the context of medullary aplasia (haematological radiobiology, radiation acute syndrome, therapeutic care), and an overview of knowledge about the interleukin-1 and medullary stroma cells, this research thesis aims at investigating therapeutic alternatives for radio-accidental aplasia. More precisely, it aims at defining means to get cytokines which are efficient for haematopoiesis. Interleukin-1 is chosen for its properties and tests are performed on a macaque with two approaches for gene transfer: an ex vivo transfer by retroviral vector enabling an integration in the target cell genome, and an in situ transfer by adeno-viral vector directly applied in the animal osseous medulla

Role of the Brain's Reward Circuitry in Depression: Transcriptional Mechanisms.

Science.gov (United States)

Nestler, Eric J

2015-01-01

Increasing evidence supports an important role for the brain's reward circuitry in controlling mood under normal conditions and contributing importantly to the pathophysiology and symptomatology of a range of mood disorders, such as depression. Here we focus on the nucleus accumbens (NAc), a critical component of the brain's reward circuitry, in depression and other stress-related disorders. The prominence of anhedonia, reduced motivation, and decreased energy level in most individuals with depression supports the involvement of the NAc in these conditions. We concentrate on several transcription factors (CREB, ΔFosB, SRF, NFκB, and β-catenin), which are altered in the NAc in rodent depression models--and in some cases in the NAc of depressed humans, and which produce robust depression- or antidepressant-like effects when manipulated in the NAc in animal models. These studies of the NAc have established novel approaches toward modeling key symptoms of depression in animals and could enable the development of antidepressant medications with fundamentally new mechanisms of action. © 2015 Elsevier Inc. All rights reserved.

Impact of F DOPA-PET on therapeutic decision in endocrine tumours: digestive tumours, medullary thyroid cancer or pheochromocytoma

International Nuclear Information System (INIS)

Montravers, F.; Grahek, D.; Kerrou, K.; Gutman, F.; Beco, V. de; Nataf, V.; Balard, M.; Talbot, J.N.

2006-01-01

FDOPA-PET has been proposed for a decade in oncology, in particular in endocrine tumours. To the best of our knowledge, only one impact rate has been reported: 31% in 17 patients with digestive carcinoid tumours. We did a questionnaire survey to evaluate this impact reported by the referring clinician in 87 patients who had FDOPA PET due to digestive carcinoid tumour or another type of digestive endocrine tumour or a medullary thyroid cancer or a pheochromocytoma. The response rate to the survey was 87%. The overall impact of FDOPA PET on patient's management was 36%. Its value was greater for digestive carcinoid tumour and for medullary thyroid cancer; the number of patients with pheochromocytoma is still limited. In the other digestive endocrine tumours, a change in patient management was less frequent and FDOPA PET should be performed when the other examinations are inconclusive. (author)

The heart of the matter: Acute quadriplegia with respiratory paralysis - bilateral medial medullary infarction

Directory of Open Access Journals (Sweden)

Bhaskara P Shelley

2017-01-01

Full Text Available The clinicoradiologic correlate of bilateral medial medullary infarction is described. This is a rare clinical entity of vertebrobasilar stroke syndrome with catastrophic consequences and a poor functional prognosis. Since the initial symptom is quadriplegia, the clinical diagnosis without neuroimaging can be challenging with a potential for misdiagnosis as Guillain–Barré syndrome or brainstem encephalitis in the early stages. The teaching neuroimage of the “heart appearance” sign is revisited.

Presence of a nail in the medullary canal; is it enough to prevent femoral neck shortening in trochanteric fracture?

Science.gov (United States)

Song, Hyung Keun; Yoon, Han Kuk; Yang, Kyu Hyun

2014-09-01

Presence of a cephalomedullary nail (CMN) in the medullary canal has been thought as advantageous in the control of femoral neck shortening (FNS) and lag screw sliding in trochanteric fracture compared to extramedullary fixation system. However, researches on the factors that influence the degree of FNS after cephalomedullary nailing are lacking. We observed 95 patients (mean age, 75±2.8 years) with trochanteric fractures who were treated with a CMN, and evaluated the relationship between FNS and patient factors including age, gender, fracture type (AO/OTA), bone mineral density, medullary canal diameter, canal occupancy ratio (COR=nail size/canal diameter), and tip-apex distance using initial, immediate postoperative, and follow-up radiography. Univariate regression analyses revealed that the degree of FNS was significantly correlated with fracture type (A1 versus A3, pfracture type (pfracture.

MR Imaging of Ventriculus Terminalis of The Conus Medullaris. A report of two operated patients and review of the literature

Energy Technology Data Exchange (ETDEWEB)

Dullerud, Reidar; Server, A. [Ullevaal Univ. Hospital, Oslo (Norway). Div. of Radiology; Berg-Johnsen, J. [The National Hospital, Oslo (Norway). Dept. of Neurosurgery

2003-07-01

We report on 2 patients in whom a cystic dilation of the conus medullaris was incidentally found at MR imaging carried out in the work-up for sciatica. The cysts were well circumscribed and had signal intensity identical to the CSF on both T1- and T2-weighted images. There was no evidence of contrast enhancement. None of the patients had specific symptoms related to the spinal cord. At surgery, no evidence of malignancy was seen in any of the patients. A benign cystic dilation, also called dilated ventriculus terminalis, occasionally can be seen in the conus medullaris as an incidental finding at thoracolumbar MR imaging. Unless the expansion per se indicates cyst drainage, these patients may be monitored by clinical and MR follow-up, avoiding surgery in a substantial number of cases.

MR Imaging of Ventriculus Terminalis of The Conus Medullaris. A report of two operated patients and review of the literature

International Nuclear Information System (INIS)

Dullerud, Reidar; Server, A.; Berg-Johnsen, J.

2003-01-01

We report on 2 patients in whom a cystic dilation of the conus medullaris was incidentally found at MR imaging carried out in the work-up for sciatica. The cysts were well circumscribed and had signal intensity identical to the CSF on both T1- and T2-weighted images. There was no evidence of contrast enhancement. None of the patients had specific symptoms related to the spinal cord. At surgery, no evidence of malignancy was seen in any of the patients. A benign cystic dilation, also called dilated ventriculus terminalis, occasionally can be seen in the conus medullaris as an incidental finding at thoracolumbar MR imaging. Unless the expansion per se indicates cyst drainage, these patients may be monitored by clinical and MR follow-up, avoiding surgery in a substantial number of cases

Medullary breast carcinoma: The role of radiotherapy as primary treatment

International Nuclear Information System (INIS)

Fourquet, A.; Vilcoq, J.R.; Zafrani, B.; Schlienger, P.; Campana, F.; Jullien, D.

1987-01-01

The results are reported of a selected series of 41 patients with medullary carcinoma of the breast, treated with primary radiotherapy with (24 patients) or without (17 patients) adjuvant chemotherapy. Complete responses to radiotherapy occurred with moderate doses (67% of the patients had a complete response after a dose of 55-60 Gy) and were increased by the addition of an irradiation boost. The 6-year actuarial free of local recurrence survival, metastase-free survival and survival rates were 86, 83, and 83%, respectively. The 6-year actuarial probability of living with breast preserved was 72%. Recurrences and survivals were not influenced by the tumor size or clinical axillary node status. Adjuvant chemotherapy had no effect on the rate of recurrence or survival. 14 refs.; 3 tabs

Conus medullaris syndrome due to an intradural disc herniation: A case report

Directory of Open Access Journals (Sweden)

Chaudhary Kshitij

2008-01-01

Full Text Available A 70-year-old male patient developed acute paraplegia due to conus medullaris compression secondary to extrusion of D12-L1 disc. After negative epidural examination intraoperatively, a durotomy was performed and an intradural disc fragment was excised. Patient did not regain ambulatory status at two-year follow-up. Intraoperative finding of negative extradural compression, tense swollen dura and CSF leak from ventral dura should alert the surgeon for the possibility of intradural disc herniation. A routine preoperative MRI is misleading and a high index of suspicion helps to avoid a missed diagnosis.

Reward circuitry dysfunction in psychiatric and neurodevelopmental disorders and genetic syndromes: animal models and clinical findings.

Science.gov (United States)

Dichter, Gabriel S; Damiano, Cara A; Allen, John A

2012-07-06

This review summarizes evidence of dysregulated reward circuitry function in a range of neurodevelopmental and psychiatric disorders and genetic syndromes. First, the contribution of identifying a core mechanistic process across disparate disorders to disease classification is discussed, followed by a review of the neurobiology of reward circuitry. We next consider preclinical animal models and clinical evidence of reward-pathway dysfunction in a range of disorders, including psychiatric disorders (i.e., substance-use disorders, affective disorders, eating disorders, and obsessive compulsive disorders), neurodevelopmental disorders (i.e., schizophrenia, attention-deficit/hyperactivity disorder, autism spectrum disorders, Tourette's syndrome, conduct disorder/oppositional defiant disorder), and genetic syndromes (i.e., Fragile X syndrome, Prader-Willi syndrome, Williams syndrome, Angelman syndrome, and Rett syndrome). We also provide brief overviews of effective psychopharmacologic agents that have an effect on the dopamine system in these disorders. This review concludes with methodological considerations for future research designed to more clearly probe reward-circuitry dysfunction, with the ultimate goal of improved intervention strategies.

Hippo-independent activation of YAP by the GNAQ uveal melanoma oncogene through a trio-regulated rho GTPase signaling circuitry.

Science.gov (United States)

Feng, Xiaodong; Degese, Maria Sol; Iglesias-Bartolome, Ramiro; Vaque, Jose P; Molinolo, Alfredo A; Rodrigues, Murilo; Zaidi, M Raza; Ksander, Bruce R; Merlino, Glenn; Sodhi, Akrit; Chen, Qianming; Gutkind, J Silvio

2014-06-16

Mutually exclusive activating mutations in the GNAQ and GNA11 oncogenes, encoding heterotrimeric Gαq family members, have been identified in ∼ 83% and ∼ 6% of uveal and skin melanomas, respectively. However, the molecular events underlying these GNAQ-driven malignancies are not yet defined, thus limiting the ability to develop cancer-targeted therapies. Here, we focused on the transcriptional coactivator YAP, a critical component of the Hippo signaling pathway that controls organ size. We found that Gαq stimulates YAP through a Trio-Rho/Rac signaling circuitry promoting actin polymerization, independently of phospholipase Cβ and the canonical Hippo pathway. Furthermore, we show that Gαq promotes the YAP-dependent growth of uveal melanoma cells, thereby identifying YAP as a suitable therapeutic target in uveal melanoma, a GNAQ/GNA11-initiated human malignancy. Copyright © 2014 Elsevier Inc. All rights reserved.

Regulation of body fat mass by the gut microbiota

DEFF Research Database (Denmark)

Schéle, Erik; Grahnemo, Louise; Anesten, Fredrik

2016-01-01

New insight suggests gut microbiota as a component in energy balance. However, the underlying mechanisms by which gut microbiota can impact metabolic regulation is unclear. A recent study from our lab shows, for the first time, a link between gut microbiota and energy balance circuitries...

Multiple Myeloma Presenting as Massive Amyloid Deposition in a Parathyroid Gland Associated with Amyloid Goiter: A Medullary Thyroid Carcinoma Mimic on Intra-operative Frozen Section.

Science.gov (United States)

Hill, Kirk; Diaz, Jason; Hagemann, Ian S; Chernock, Rebecca D

2018-06-01

Clinical examples of amyloid deposition in parathyroid glands are exceedingly rare and usually present as an incidental finding in a patient with amyloid goiter. Here, we present the first histologically documented case of parathyroid amyloid deposition that presented as a mass. The patient did not have hyperparathyroidism. The parathyroid gland was submitted for intra-operative frozen section and concern for medullary thyroid carcinoma was raised. An important histologic clue arguing against medullary thyroid carcinoma was the evenly dispersed nature of the amyloid. Histologic perinuclear clearing and parathyroid hormone immunohistochemistry confirmed parathyroid origin on permanent sections. The patient was also found to have associated amyloid goiter. Mass spectrometry of the amyloid showed it to be composed of kappa light chains. On further work-up, the patient was diagnosed with multiple myeloma. Awareness of parathyroid amyloid deposition is important as it is a histologic mimic of medullary thyroid carcinoma, especially on frozen section. Amyloid typing with evaluation for multiple myeloma in any patient with kappa or lambda light chain restriction is also important.

Adrenal medullary regulation of rat renal cortical adrenergic receptors

International Nuclear Information System (INIS)

Sundaresan, P.R.; Guarnaccia, M.M.; Izzo, J.L. Jr.

1987-01-01

The role of the adrenal medulla in the regulation of renal cortical adrenergic receptors was investigated in renal cortical particular fractions from control rats and rats 6 wk after adrenal demedullation. The specific binding of [ 3 H]prazosin, [ 3 H]rauwolscine, and [ 125 I]iodocyanopindolol were used to quantitate α 1 -, α 2 -, and β-adrenergic receptors, respectively. Adrenal demedullation increased the concentration of all three groups of renal adrenergic receptors; maximal number of binding sites (B max , per milligram membrane protein) for α 1 -, and α 2 -, and β-adrenergic receptors were increased by 22, 18.5, and 25%, respectively. No differences were found in the equilibrium dissociation constants (K D ) for any of the radioligands. Plasma corticosterone and plasma and renal norepinephrine levels were unchanged, whereas plasma epinephrine was decreased 72% by adrenal demedullation, renal cortical epinephrine was not detectable in control or demedullated animals. The results suggest that, in the physiological state, the adrenal medulla modulates the number of renal cortical adrenergic receptors, presumably through the actions of a circulating factor such as epinephrine

Interest of MIBG scintigraphy in screening for pheochromocytoma in patients with medullary thyroid carcinoma

International Nuclear Information System (INIS)

Bonnin, F.; Lumbroso, J.; Schlumberger, M.; Megnigbeto, A.; Tenenbaum, F.; Leclere, J.; Travagli, J.P.; Gardet, P.; Parmentier, C.

1995-01-01

Adrenal medullary disease (AMD) is clinically silent in most patients with medullary thyroid carcinoma (MTC). During 16 years, a series of 174 MTC patients was screened yearly for AMD. Metaiodobenzylguanidine (MIBG) scans were performed in 54 cases (21 at diagnosis and 33 during the follow up of MTC) either systematically (43 cases) or in patients with biological or ultrasonographic signs of AMD (11 cases). AMD was discovered in ten patients: five patients were already known to have a type II multiple endocrine neoplasia (MEN-2); in five patients previously considered as having either a sporadic (four cases) or a familial type of isolated MTC (one case), the occurrence of AMD led to diagnose a MEN-2 a syndrome. In three cases, AMD was bilateral. MIBG scan were performed in nine of the ten patients with AMD. No false positive MIBG scan was observed in the series. All patients with positive MIBG scan had either elevated excretion of catecholamines and derivates. MIBG scan had a sensitivity of 0.9 and specificity of 1. MIBG should not be used as a screening test. In particular, MIBG scan should not be performed systematically neither at diagnosis nor during follow-up. But, in cases with suspicion of AMD, it provides important complementary functional information. (authors). 15 refs., 3 tabs., 2 figs

Receptor stimulated formation of inositol phosphates in cultures of bovine adrenal medullary cells: the effects of bradykinin, bombesin and neurotensin.

Science.gov (United States)

Bunn, S J; Marley, P D; Livett, B G

1990-04-01

The ability of a number of drugs and neuropeptides to stimulate phosphoinositide metabolism in cultured bovine adrenal medullary cells has been assessed. Low concentrations (10 nM) of angiotensin II, bradykinin, histamine, arginine-vasopressin, and bombesin, and high (10 microM) concentrations of oxytocin, prostaglandins E1, and E2, beta-endorphin, and neurotensin stimulated significant accumulation of [3H]inositol phosphates in adrenal medullary cells preloaded with [3H)]inositol. Bradykinin stimulated a significant response at concentration as low as 10pM, with an EC50 of approximately 0.5 nM. The response was markedly inhibited by the bradykinin B2 antagonist [Thi5,8,D-Phe7] bradykinin but not the B1 antagonist [Des-Arg9,Leu8] bradykinin. Higher concentrations of bombesin and neurotensin were required to elicit a response (10 nM and 10 microM respectively). The bombesin response was sensitive to inhibition by the bombesin antagonist [D-Arg1,D-Pro2,D-Trp7,9Leu11]-substance P. In contrast, the neurotensin response was not reduced by the NT1 antagonist [D-Trp11]-neurotensin. These results indicate there are a number of agents that can stimulate phosphatidylinositide hydrolysis in the adrenal medullary cells by acting on different classes of receptors. Such a range of diverse agonists that stimulate inositol phosphate formation will facilitate further analysis of the phosphatidylinositide breakdown in chromaffin cell function.

Case report of severe Cushing's syndrome in medullary thyroid cancer complicated by functional diabetes insipidus, aortic dissection, jejunal intussusception, and paraneoplastic dysautonomia: remission with sorafenib without reduction in cortisol concentration.

Science.gov (United States)

Hammami, Muhammad M; Duaiji, Najla; Mutairi, Ghazi; Aklabi, Sabah; Qattan, Nasser; Abouzied, Mohei El-Din M; Sous, Mohamed W

2015-09-09

Normalization of cortisol concentration by multikinase inhibitors have been reported in three patients with medullary thyroid cancer-related Cushing's syndrome. Aortic dissection has been reported in three patients with Cushing's syndrome. Diabetes insipidus without intrasellar metastasis, intestinal intussusception, and paraneoplastic dysautonomia have not been reported in medullary thyroid cancer. An adult male with metastatic medullary thyroid cancer presented with hyperglycemia, hypernatremia, hypokalemia, hypertension, acne-like rash, and diabetes insipidus (urine volume >8 L/d, osmolality 190 mOsm/kg). Serum cortisol, adrenocorticoitropic hormone, dehydroepiandrostenedione sulfate, and urinary free cortisol were elevated 8, 20, 4.4, and 340 folds, respectively. Pituitary imaging was normal. Computed tomography scan revealed jejunal intussusception and incidental abdominal aortic dissection. Sorafenib treatment was associated with Cushing's syndrome remission, elevated progesterone (>10 fold), normalization of dehydroepiandrostenedione sulfate, but persistently elevated cortisol concentration. Newly-developed proximal lower limb weakness and decreased salivation were associated with elevated ganglionic neuronal acetylcholine receptor (alpha-3) and borderline P/Q type calcium channel antibodies. Extreme cortisol concentration may have contributed to aortic dissection and suppressed antidiuretic hormone secretion; which combined with hypokalemia due cortisol activation of mineralocorticoid receptors, manifested as diabetes insipidus. This is the first report of paraneoplastic dysautonomia and jejunal intussusception in medullary thyroid cancer, they may be related to medullary thyroid cancer's neuroendocrine origin and metastasis, respectively. Remission of Cushing's syndrome without measurable reduction in cortisol concentration suggests a novel cortisol-independent mechanism of action or assay cross-reactivity. Normalization of dehydroepiandrostenedione

Electro-active sensor, method for constructing the same; apparatus and circuitry for detection of electro-active species

Science.gov (United States)

Buehler, Martin (Inventor)

2009-01-01

An electro-active sensor includes a nonconductive platform with a first electrode set attached with a first side of a nonconductive platform. The first electrode set serves as an electrochemical cell that may be utilized to detect electro-active species in solution. A plurality of electrode sets and a variety of additional electrochemical cells and sensors may be attached with the nonconductive platform. The present invention also includes a method for constructing the aforementioned electro-active sensor. Additionally, an apparatus for detection and observation is disclosed, where the apparatus includes a sealable chamber for insertion of a portion of an electro-active sensor. The apparatus allows for monitoring and detection activities. Allowing for control of attached cells and sensors, a dual-mode circuitry is also disclosed. The dual-mode circuitry includes a switch, allowing the circuitry to be switched from a potentiostat to a galvanostat mode.

Modeling disease risk through analysis of physical interactions between genetic variants within chromatin regulatory circuitry.

Science.gov (United States)

Corradin, Olivia; Cohen, Andrea J; Luppino, Jennifer M; Bayles, Ian M; Schumacher, Fredrick R; Scacheri, Peter C

2016-11-01

SNPs associated with disease susceptibility often reside in enhancer clusters, or super-enhancers. Constituents of these enhancer clusters cooperate to regulate target genes and often extend beyond the linkage disequilibrium (LD) blocks containing risk SNPs identified in genome-wide association studies (GWAS). We identified 'outside variants', defined as SNPs in weak LD with GWAS risk SNPs that physically interact with risk SNPs as part of a target gene's regulatory circuitry. These outside variants further explain variation in target gene expression beyond that explained by GWAS-associated SNPs. Additionally, the clinical risk associated with GWAS SNPs is considerably modified by the genotype of outside variants. Collectively, these findings suggest a potential model in which outside variants and GWAS SNPs that physically interact in 3D chromatin collude to influence target transcript levels as well as clinical risk. This model offers an additional hypothesis for the source of missing heritability for complex traits.

Sonographic assessment of normal renal parenchymal and medullary pyramid thicknesses among children in Enugu, Southeast, Nigeria

International Nuclear Information System (INIS)

Eze, C.U.; Akpan, V.P.; Nwadike, I.U.

2016-01-01

Background: Renal parenchymal thickness (RPT) and renal medullary pyramid thickness (MPT) are important renal size parameters. This study was aimed at establishing normograms for RPT and MPT with respect to age and somatometric parameters among children. Methods: This was a cross sectional study done in Enugu, Nigeria between May 2013 and April 2014. The subjects were 512 children aged 1–17 years scanned with ultrasound equipment with 3.5 MHz and 5 MHz curvilinear transducers. The RPT was measured perpendicularly to the long axis of the kidney from the medullary papilla to the renal capsule and MPT was measured from the apex to the base of the medullary pyramid on the same plane. The age and somatometric parameters of the subjects were recorded. Results: The mean ± SD of RPT and MPT for the right kidney were 12.62 ± 1.67 mm and 7.10 ± 0.92 mm and the left kidney were 12.81 ± 1.7 and 7.23 ± 0.94 mm respectively. There was a significant difference between the right and left RPT and MPT (p < 0.05). The right and left RPT correlated strongly with age, body surface area (BSA), height, and weight but moderately with body mass index (BMI). A moderate positive correlation was observed between MPT and age, BSA, height, and weight. However, a weak correlation was observed between MPT and BMI. Conclusion: Normograms of RPT and MPT in relation to age could be useful for grading hydronephrosis in children. - Highlights: • Sonography of RPT and MPT at the anterior longitudinal axis of the kidney is simple. • RPT and MPT Measurements are reliable within and between experienced sonographers. • No significant gender differences in RPT and MPT values exist in this study. • Significant differences exist between the right and left RPT and MPT measurements. • Normative values of RPT and MPT in relation to age in children are useful.

Ischaemia of the medullary cone after stent-graft implantation in a patient with abdominal aortic aneurysm - a case study.

Science.gov (United States)

Wachowski, Mariusz; Polguj, Michał; Ścibór, Janusz; Majos, Agata

2018-03-01

Preoperative visualization of the Adamkiewicz artery - the vessel which is to a great extent responsible for supplying blood to the medullary cone - is an important step which must be taken before initiating restorative procedures in the aorta. We present a case of a 67-year-old patient who underwent an intravascular stent-graft implantation procedure, due to clinical signs of abdominal aortic aneurysm. Routine pre-operative computed tomography examination failed to demonstrate the Adamkiewicz artery. On the second day after the surgery, as a result of unexpected clinical deterioration, an magnetic resonance imaging examination of the lumbar spine was carried out. Based on the magnetic resonance imaging images and clinical manifestations the diagnosis of ischaemia of the medullary cone was made. In our work we also present a deep analysis of the anatomy of small-sized vessels supplying blood to the spinal cord and discuss effective techniques which enable visualization of the Adamkiewicz artery.

Reward circuitry dysfunction in psychiatric and neurodevelopmental disorders and genetic syndromes: animal models and clinical findings

Directory of Open Access Journals (Sweden)

Dichter Gabriel S

2012-07-01

Full Text Available Abstract This review summarizes evidence of dysregulated reward circuitry function in a range of neurodevelopmental and psychiatric disorders and genetic syndromes. First, the contribution of identifying a core mechanistic process across disparate disorders to disease classification is discussed, followed by a review of the neurobiology of reward circuitry. We next consider preclinical animal models and clinical evidence of reward-pathway dysfunction in a range of disorders, including psychiatric disorders (i.e., substance-use disorders, affective disorders, eating disorders, and obsessive compulsive disorders, neurodevelopmental disorders (i.e., schizophrenia, attention-deficit/hyperactivity disorder, autism spectrum disorders, Tourette’s syndrome, conduct disorder/oppositional defiant disorder, and genetic syndromes (i.e., Fragile X syndrome, Prader–Willi syndrome, Williams syndrome, Angelman syndrome, and Rett syndrome. We also provide brief overviews of effective psychopharmacologic agents that have an effect on the dopamine system in these disorders. This review concludes with methodological considerations for future research designed to more clearly probe reward-circuitry dysfunction, with the ultimate goal of improved intervention strategies.

A rare case of concomitant sicca keratopathy and ipsilateral central facial palsy in Wallenberg’s dorsolateral medullary syndrome

Directory of Open Access Journals (Sweden)

De Bruyn, Deborah

2017-03-01

Full Text Available Objective: To describe a patient with a right-sided supranuclear facial palsy and concomitant sicca keratopathy of the right eye following right-sided dorsolateral medullary infarction. Methods: Our patient underwent a complete ophthalmologic and neurologic examination including biomicroscopy, fundus examination, cranial nerve examination, Shirmer I test, and magnetic resonance imaging of the brain.Results: A 61-year-old woman presented in emergency with a central facial nerve palsy on the right side and truncal ataxia. Neurologic assessment revealed a concurrent dysphagia, dysarthria, hypoesthesia of the right face, and weakness of the right upper limb. Magnetic resonance imaging of the brain showed an old left-sided cerebellar infarction, but a recent ischemic infarction at the level of the right dorsolateral medulla oblongata was the cause of our patient’s current problems. One month after diagnosis of the right-sided dorsolateral medullary syndrome, there were complaints of ocular irritation and a diminished visual acuity in the right eye. Biomicroscopy showed a sicca keratopathy with nearly complete absence of tear secretion on the Shirmer I test, but with normal eye closure and preserved corneal reflexes and sensitivity.Conclusion: A dorsolateral medullary syndrome can have a variable expression in symptomatology. Our case is special because of the combination of an ipsilateral supranuclear facial palsy with normal upper facial muscle function together with an ipsilateral sicca keratopathy as a result of a nearly absent tear secretion. We hypothesized that the mechanism underlying the patient’s sicca keratopathy ipsilateral to the supranuclear facial palsy involved the superior salivatory nucleus, which is situated in the caudal pons inferiorly of the motor facial nucleus and is most probably affected by a superior extension of the infarcted area in the right medulla oblongata.

Clinical utility of vandetanib in the treatment of patients with advanced medullary thyroid cancer

Directory of Open Access Journals (Sweden)

Deshpande H

2011-12-01

Full Text Available Hari Deshpande1,3, Vicky Marler3, Julie Ann Sosa2,31Department of Medicine, 2Department of Surgery, Yale University School of Medicine, 3Yale Cancer Center, New Haven, CT, USAAbstract: Vandetanib (ZD6474 became the first systemic agent to be approved for the treatment of metastatic or locally advanced medullary thyroid cancer. It was a proof of principle, because it is an orally bioavailable medication that targets the growth factors felt to be important in the pathogenesis of this disease, ie, the rearranged during transfection proto-oncogene and vascular endothelial growth factor receptor. It was tested initially in two Phase II studies at doses of 100 mg and 300 mg daily. Although activity was seen at both doses, the higher dose was chosen for a randomized, placebo-controlled Phase II study. This trial, which accrued more than 300 patients, showed a statistically significant benefit for the group taking vandetanib compared with those taking placebo medication. Progression-free survival for the vandetanib arm has not been reached, compared with 19 months for the placebo arm. The main toxicity appears to be diarrhea, although some patients experienced significant side effects, including torsades de pointes and sudden cardiac death. Therefore, it is now necessary for practitioners to enroll in a Risk Evaluation Mitigation Strategy before being allowed to prescribe this medication, to reduce the risk of serious side effects occurring.Keywords: ZD6474, medullary thyroid cancer, vandetanib

Stress, trauma and PTSD: translational insights into the core synaptic circuitry and its modulation.

Science.gov (United States)

Bennett, Maxwell R; Hatton, Sean N; Lagopoulos, Jim

2016-06-01

Evidence is considered as to whether behavioral criteria for diagnosis of post-traumatic stress disorder (PTSD) are applicable to that of traumatized animals and whether the phenomena of acquisition, extinction and reactivation of fear behavior in animals are also successfully applicable to humans. This evidence suggests an affirmative answer in both cases. Furthermore, the deficits in gray matter found in PTSD, determined with magnetic resonance imaging, are also observed in traumatized animals, lending neuropsychological support to the use of animals to probe what has gone awry in PTSD. Such animal experiments indicate that the core synaptic circuitry mediating behavior following trauma consists of the amygdala, ventral-medial prefrontal cortex and hippocampus, all of which are modulated by the basal ganglia. It is not clear if this is the case in PTSD as the observations using fMRI are equivocal and open to technical objections. Nevertheless, the effects of the basal ganglia in controlling glutamatergic synaptic transmission through dopaminergic and serotonergic synaptic mechanisms in the core synaptic circuitry provides a ready explanation for why modifying these mechanisms delays extinction in animal models and predisposes towards PTSD. In addition, changes of brain-derived neurotrophic factor (BDNF) in the core synaptic circuitry have significant effects on acquisition and extinction in animal experiments with single nucleotide polymorphisms in the BDNF gene predisposing to PTSD.

Implementing size-optimal discrete neural networks require analog circuitry

Energy Technology Data Exchange (ETDEWEB)

Beiu, V.

1998-12-01

This paper starts by overviewing results dealing with the approximation capabilities of neural networks, as well as bounds on the size of threshold gate circuits. Based on a constructive solution for Kolmogorov`s superpositions the authors show that implementing Boolean functions can be done using neurons having an identity transfer function. Because in this case the size of the network is minimized, it follows that size-optimal solutions for implementing Boolean functions can be obtained using analog circuitry. Conclusions and several comments on the required precision are ending the paper.

Phase II study of safety and efficacy of motesanib in patients with progressive or symptomatic, advanced or metastatic medullary thyroid cancer

DEFF Research Database (Denmark)

Schlumberger, Martin J; Elisei, Rossella; Bastholt, Lars

2009-01-01

PURPOSE: This phase II study investigated the efficacy and tolerability of motesanib, an investigational, highly selective inhibitor of vascular endothelial growth factor receptors 1, 2, and 3; platelet-derived growth factor receptor; and Kit in advanced medullary thyroid cancer (MTC). PATIENTS A...

AgRP neurons regulate development of dopamine neuronal plasticity and nonfood-associated behaviors

Science.gov (United States)

Dietrich, Marcelo O; Bober, Jeremy; Ferreira, Jozélia G; Tellez, Luis A; Mineur, Yann S; Souza, Diogo O; Gao, Xiao-Bing; Picciotto, Marina R; Araújo, Ivan; Liu, Zhong-Wu; Horvath, Tamas L

2012-01-01

It is not known whether behaviors unrelated to feeding are affected by hypothalamic regulators of hunger. We found that impairment of Agouti-related protein (AgRP) circuitry by either Sirt1 knockdown in AgRP-expressing neurons or early postnatal ablation of these neurons increased exploratory behavior and enhanced responses to cocaine. In AgRP circuit–impaired mice, ventral tegmental dopamine neurons exhibited enhanced spike timing–dependent long-term potentiation, altered amplitude of miniature postsynaptic currents and elevated dopamine in basal forebrain. Thus, AgRP neurons determine the set point of the reward circuitry and associated behaviors. PMID:22729177

Regulation of chromatin states by drugs of abuse.

Science.gov (United States)

Walker, Deena M; Cates, Hannah M; Heller, Elizabeth A; Nestler, Eric J

2015-02-01

Drug addiction involves long-term behavioral abnormalities and gene expression changes throughout the mesolimbic dopamine system. Epigenetic mechanisms establish/maintain alterations in gene expression in the brain, providing the impetus for investigations characterizing how epigenetic processes mediate the effects of drugs of abuse. This review focuses on evidence that epigenetic events, specifically histone modifications, regulate gene expression changes throughout the reward circuitry. Drugs of abuse induce changes in histone modifications throughout the reward circuitry by altering histone-modifying enzymes, manipulation of which reveals a role for histone modification in addiction-related behaviors. There is a complex interplay between these enzymes, resulting in a histone signature of the addicted phenotype. Insights gained from these studies are key to identifying novel targets for diagnosis and therapy. Copyright © 2014 Elsevier Ltd. All rights reserved.

Oxytocin reduces neural activity in the pain circuitry when seeing pain in others

NARCIS (Netherlands)

Bos, P.A.; Montoya, E.R.; Hermans, E.; Keysers, C.; Honk, J. van

2015-01-01

Our empathetic abilities allow us to feel the pain of others. This phenomenon of vicarious feeling arises because the neural circuitry of feeling pain and seeing pain in others is shared. The neuropeptide oxytocin (OXT) is considered a robust facilitator of empathy, as intranasal OXT studies have

Oxytocin reduces neural activity in the pain circuitry when seeing pain in others

NARCIS (Netherlands)

Bos, Peter A; Montoya, Estrella R; Hermans, Erno J; Keysers, C.; van Honk, Jack

Our empathetic abilities allow us to feel the pain of others. This phenomenon of vicarious feeling arises because the neural circuitry of feeling pain and seeing pain in others is shared. The neuropeptide oxytocin (OXT) is considered a robust facilitator of empathy, as intranasal OXT studies have

Stitching Codeable Circuits: High School Students' Learning About Circuitry and Coding with Electronic Textiles

Science.gov (United States)

Litts, Breanne K.; Kafai, Yasmin B.; Lui, Debora A.; Walker, Justice T.; Widman, Sari A.

2017-10-01

Learning about circuitry by connecting a battery, light bulb, and wires is a common activity in many science classrooms. In this paper, we expand students' learning about circuitry with electronic textiles, which use conductive thread instead of wires and sewable LEDs instead of lightbulbs, by integrating programming sensor inputs and light outputs and examining how the two domains interact. We implemented an electronic textiles unit with 23 high school students ages 16-17 years who learned how to craft and code circuits with the LilyPad Arduino, an electronic textile construction kit. Our analyses not only confirm significant increases in students' understanding of functional circuits but also showcase students' ability in designing and remixing program code for controlling circuits. In our discussion, we address opportunities and challenges of introducing codeable circuit design for integrating maker activities that include engineering and computing into classrooms.

Easy to remember, difficult to forget: The development of fear regulation

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D.C. Johnson

2015-02-01

Full Text Available Fear extinction learning is a highly adaptive process that involves the integrity of frontolimbic circuitry. Its disruption has been associated with emotional dysregulation in stress and anxiety disorders. In this article we consider how age, genetics and experiences shape our capacity to regulate fear in cross-species studies. Evidence for adolescent-specific diminished fear extinction learning is presented in the context of immature frontolimbic circuitry. We also present evidence for less neural plasticity in fear regulation as a function of early-life stress and by genotype, focusing on the common brain derived neurotrophin factor (BDNF Val66Met polymorphism. Finally, we discuss this work in the context of exposure-based behavioral therapies for the treatment of anxiety and stress disorders that are based on principles of fear extinction. We conclude by speculating on how such therapies may be optimized for the individual based on the patient's age, genetic profile and personal history to move from standard treatment of care to personalized and precision medicine.

High voltage dc-dc converter with dynamic voltage regulation and decoupling during load-generated arcs

Science.gov (United States)

Shimer, Daniel W.; Lange, Arnold C.

1995-01-01

A high-power power supply produces a controllable, constant high voltage output under varying and arcing loads. The power supply includes a voltage regulator, an inductor, an inverter for producing a high frequency square wave current of alternating polarity, an improved inverter voltage clamping circuit, a step up transformer, an output rectifier for producing a dc voltage at the output of each module, and a current sensor for sensing output current. The power supply also provides dynamic response to varying loads by controlling the voltage regulator duty cycle and circuitry is provided for sensing incipient arc currents at the output of the power supply to simultaneously decouple the power supply circuitry from the arcing load. The power supply includes a plurality of discrete switching type dc--dc converter modules.

High voltage dc--dc converter with dynamic voltage regulation and decoupling during load-generated arcs

Science.gov (United States)

Shimer, D.W.; Lange, A.C.

1995-05-23

A high-power power supply produces a controllable, constant high voltage output under varying and arcing loads. The power supply includes a voltage regulator, an inductor, an inverter for producing a high frequency square wave current of alternating polarity, an improved inverter voltage clamping circuit, a step up transformer, an output rectifier for producing a dc voltage at the output of each module, and a current sensor for sensing output current. The power supply also provides dynamic response to varying loads by controlling the voltage regulator duty cycle and circuitry is provided for sensing incipient arc currents at the output of the power supply to simultaneously decouple the power supply circuitry from the arcing load. The power supply includes a plurality of discrete switching type dc--dc converter modules. 5 Figs.

Plasma levels of calcitonin in medullary thyroid carcinoma patients with and without the RET proto-oncogene mutations in exons 10 and 11

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Samira Ehyayi

2017-09-01

Conclusion: Routine measurement of calcitonin has been investigated as a screening method for the diagnosis of medullary thyroid carcinoma patients. Nevertheless, additional data are required to definitely support routine measurement of calcitonin due to the role of RET proto-oncogene.

Silent Synapse-Based Circuitry Remodeling in Drug Addiction.

Science.gov (United States)

Dong, Yan

2016-05-01

Exposure to cocaine, and likely other drugs of abuse, generates α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor-silent glutamatergic synapses in the nucleus accumbens. These immature synaptic contacts evolve after drug withdrawal to redefine the neurocircuital properties. These results raise at least three critical questions: (1) what are the molecular and cellular mechanisms that mediate drug-induced generation of silent synapses; (2) how are neurocircuits remodeled upon generation and evolution of drug-generated silent synapses; and (3) what behavioral consequences are produced by silent synapse-based circuitry remodeling? This short review analyzes related experimental results, and extends them to some speculations. © The Author 2015. Published by Oxford University Press on behalf of CINP.

Medullary sponge kidney on axial computed tomography

International Nuclear Information System (INIS)

Ginalski, J.-M.; Schnyder, Pierre; Portmann, Luc; Jaeger, Philippe

1991-01-01

To evaluate features of medullary sponge kidney (MSK) on computed tomography (CT), 4-mm-thick axial slices without intravenous contrast material were 1st made in 13 patients through 24 kidneys which showed images of MSK on excretory urograms. On CT, papillary calcifications were found in 11 kidneys. In 5 of these, the calcifications were not detectable on plain films. Some hyperdense papillae (attenuation value 55-70 Hounsfield units) without calcification were found in 4 other kidneys. 9 kidneys appeared normal. 10 of the 14 kidneys were reexamined by a 2nd series of 4-mm-thick axial slices, 5 min after intravenous injection of 50 ml of Urografin. Images suggesting possible ectasia of precaliceal tubules were found in only 4 kidneys. These images appear much less obvious and characteristic on CT than on excretory urogram and do nothing more than suggest the possibility of MSK. In conclusion, the sensitivity of CT in the detection of MSK is markedly lower than that of excretory urography. In the most florid cases of the disease, CT can only show images suggesting the possibility of MSK. On the other hand, CT appears much more sensitive than plain films and tomograms of excretory in the detection of papillary calcifications, the most frequent complication of MSK. (author). 13 refs.; 3 figs

A CREB-Sirt1-Hes1 Circuitry Mediates Neural Stem Cell Response to Glucose Availability

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Salvatore Fusco

2016-02-01

Full Text Available Summary: Adult neurogenesis plays increasingly recognized roles in brain homeostasis and repair and is profoundly affected by energy balance and nutrients. We found that the expression of Hes-1 (hairy and enhancer of split 1 is modulated in neural stem and progenitor cells (NSCs by extracellular glucose through the coordinated action of CREB (cyclic AMP responsive element binding protein and Sirt-1 (Sirtuin 1, two cellular nutrient sensors. Excess glucose reduced CREB-activated Hes-1 expression and results in impaired cell proliferation. CREB-deficient NSCs expanded poorly in vitro and did not respond to glucose availability. Elevated glucose also promoted Sirt-1-dependent repression of the Hes-1 promoter. Conversely, in low glucose, CREB replaced Sirt-1 on the chromatin associated with the Hes-1 promoter enhancing Hes-1 expression and cell proliferation. Thus, the glucose-regulated antagonism between CREB and Sirt-1 for Hes-1 transcription participates in the metabolic regulation of neurogenesis. : Using a combination of in vitro and in vivo studies, Fusco et al. find that excess glucose impairs the self-renewal capacity of neural stem cells through a molecular circuit that involves the transcription factor CREB and Sirtuin 1. The authors suggest that this circuitry may link nutrient excess with neurodegeneration and brain aging. Keywords: neural stem cells, adult neurogenesis, CREB, Sirt-1, nutrients, metabolism, diabetes

Exposure to Glycolytic Carbon Sources Reveals a Novel Layer of Regulation for the MalT Regulon

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Sylvia A. Reimann

2011-01-01

Full Text Available Bacteria adapt to changing environments by means of tightly coordinated regulatory circuits. The use of synthetic lethality, a genetic phenomenon in which the combination of two nonlethal mutations causes cell death, facilitates identification and study of such circuitry. In this study, we show that the E. coli ompR malTcon double mutant exhibits a synthetic lethal phenotype that is environmentally conditional. MalTcon, the constitutively active form of the maltose system regulator MalT, causes elevated expression of the outer membrane porin LamB, which leads to death in the absence of the osmoregulator OmpR. However, the presence and metabolism of glycolytic carbon sources, such as sorbitol, promotes viability and unveils a novel layer of regulation within the complex circuitry that controls maltose transport and metabolism.

Renal cortical and medullary blood flow responses to altered NO availability in humans.

Science.gov (United States)

Damkjær, Mads; Vafaee, Manoucher; Møller, Michael L; Braad, Poul Erik; Petersen, Henrik; Høilund-Carlsen, Poul Flemming; Bie, Peter

2010-12-01

The objective of this study was to quantify regional renal blood flow in humans. In nine young volunteers on a controlled diet, the lower abdomen was CT-scanned, and regional renal blood flow was determined by positron emission tomography (PET) scanning using H(2)(15)O as tracer. Measurements were performed at baseline, during constant intravenous infusion of nitric oxide (NO) donor glyceryl nitrate and after intravenous injection of NO synthase inhibitor N(ω)-monomethyl-L-arginine (L-NMMA). Using the CT image, the kidney pole areas were delineated as volumes of interest (VOI). In the data analysis, tissue layers with a thickness of one voxel were eliminated stepwise from the external surface of the VOI (voxel peeling), and the blood flow subsequently was determined in each new, reduced VOI. Blood flow in the shrinking VOIs decreased as the number of cycles of voxel peeling increased. After 4-5 cycles, blood flow was not reduced further by additional voxel peeling. This volume-insensitive flow was measured to be 2.30 ± 0.17 ml·g tissue(-1)·min(-1) during the control period; it increased during infusion of glyceryl nitrate to 2.97 ± 0.18 ml·g tissue(-1)·min(-1) (P blood flow was 4.67 ± 0.31 ml·g tissue(-1)·min(-1) during control, unchanged by glyceryl nitrate, and decreased after L-NMMA [3.48 ± 0.23 ml·(g·min)(-1), P renal medullary region in which the measured blood flow is 1) low, 2) independent of reduction in the VOI, and 3) reactive to changes in systemic NO supply. The technique seems to provide indices of renal medullary blood flow in humans.

KCC2-mediated regulation of respiration-related rhythmic activity during postnatal development in mouse medulla oblongata.

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Okabe, Akihito; Shimizu-Okabe, Chigusa; Arata, Akiko; Konishi, Shiro; Fukuda, Atsuo; Takayama, Chitoshi

2015-03-19

GABA acts as inhibitory neurotransmitter in the adult central nervous system but as excitatory neurotransmitter during early postnatal development. This shift in GABA's action from excitation to inhibition is caused by a decrease in intracellular chloride concentration ([Cl(-)]i), which in turn is caused by changes in the relative expression levels of the K(+)-Cl(-) co-transporter (KCC2) and the Na(+), K(+)-2Cl(-) co-transporter (NKCC1) proteins. Previous studies have used slices containing the medullary pre-Bötzinger complex (pre-BötC) to record respiration-related rhythmic activity (RRA) from the hypoglossal nucleus (12 N). The role of GABAergic transmission in the regulation of medullary RRA neonatally, however, is yet to be determined. Here, we examined how GABA and chloride co-transporters contribute to RRA during development in the 12 N where inspiratory neurons reside. We recorded extracellular RRA in medullary slices obtained from postnatal day (P) 0-7 mice. RRA was induced by soaking slices in artificial cerebrospinal fluid (aCSF) containing 8mM-K(+). Application of GABA significantly increased the frequency of RRA after P3, whereas application of a KCC2 blocker (R (+)-[(2-n-butyl-6,7-dichloro-2-cyclopentyl-2,3-dihydro-1-oxo-1H-indenyl-5-yl)oxy]acetic acid (DIOA)) significantly decreased the frequency of RRA after P1. In addition, dense KCC2 immunolabeling was seen in the superior longitudinalis (SL) of the 12 N, which is responsible for retraction of the tongue, from P0 and P7. These results indicate that GABA administration can increase RRA frequency during the first week following birth. This in turn suggests that decreasing [Cl(-)]i levels caused by increasing KCC2 levels in the 12 N could play important roles in regulating the frequency of RRA during development. Copyright © 2015 Elsevier B.V. All rights reserved.

SpiCAD: Integrated environment for circuitry simulation with SPICE code

Energy Technology Data Exchange (ETDEWEB)

D' Amore, D; Padovini, G; Santomauro, M [Politecnico di Milano (Italy). Dip. di Elettronica

1991-11-01

SPICE is one of the most commonly used programs for the simulation of the behaviour of electronic circuits. This article describes in detail the key design characteristics and capabilities of a computer environment called SpiCAD which integrates all the different phases of SPICE based circuitry simulation on a personal computer, i.e., the tracing of the electronics scheme, simulation and visualization of the results so as to help define semiconductor device models, determine input signals, construct macro-models and convert design sketches into formats acceptable to graphic systems.

Immunohistochemical analysis of medullary breast carcinoma autoantigens in different histological types of breast carcinomas

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Kostianets Olga

2012-11-01

Full Text Available Abstract Background On the past decade a plethora of investigations were directed on identification of molecules involved in breast tumorogenesis, which could represent a powerful tool for monitoring, diagnostics and treatment of this disease. In current study we analyzed six previously identified medullary breast carcinoma autoantigens including LGALS3BP, RAD50, FAM50A, RBPJ, PABPC4, LRRFIP1 with cancer restricted serological profile in different histological types of breast cancer. Methods Semi-quantitative immunohistochemical analysis of 20 tissue samples including medullary breast carcinoma, invasive ductal carcinoma, invasive lobular carcinoma and non-cancerous tissues obtained from patients with fibrocystic disease (each of five was performed using specifically generated polyclonal antibodies. Differences in expression patterns were evaluated considering percent of positively stained cells, insensitivity of staining and subcellular localization in cells of all tissue samples. Results All 6 antigens predominantly expressed in the most cells of all histological types of breast tumors and non-cancerous tissues with slight differences in intensity of staining and subcellular localization. The most significant differences in expression pattern were revealed for RAD50 and LGALS3BP in different histological types of breast cancer and for PABPC4 and FAM50A antigens in immune cells infiltrating breast tumors. Conclusions This pilot study made possible to select 4 antigens LGALS3BP, RAD50, PABPC4, and FAM50A as promising candidates for more comprehensive research as potential molecular markers for breast cancer diagnostics and therapy. Virtual slides The virtual slides’ for this article can be found here: http://www.diagnosticpathology.diagnomx.eu/vs/1860649350796892

Targeted Therapy for Medullary Thyroid Cancer: A Review

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S. R. Priya

2017-10-01

Full Text Available Medullary thyroid cancers (MTCs constitute between 2 and 5% of all thyroid cancers. The 10-year overall survival (OS rate of patients with localized disease is around 95% while that of patients with regional stage disease is about 75%. Only 20% of patients with distant metastases at diagnosis survive 10 years which is significantly lower than for differentiated thyroid cancers. Cases with regional metastases at presentation have high recurrence rates. Adjuvant external radiation confers local control but not improved OS. The management of residual, recurrent, or metastatic disease till a few years ago was re-surgery with local measures such as radiation. Chemotherapy was used with marginal benefit. The development of targeted therapy has brought in a major advantage in management of such patients. Two drugs—vandetanib and cabozantinib—have been approved for use in progressive or metastatic MTC. In addition, several drugs acting on other steps of the molecular pathway are being investigated with promising results. Targeted radionuclide therapy also provides an effective treatment option with good quality of life. This review covers the rationale of targeted therapy for MTC, present treatment options, drugs and methods under investigation, as well as an outline of the adverse effects and their management.

Infarcts presenting with a combination of medial medullary and posterior inferior cerebellar artery syndromes.

Science.gov (United States)

Lee, Hyung; Baik, Seung Kug

2004-09-15

Cerebellar and medial medullary infarctions are well-known vertebrobasilar stroke syndromes. However, their development in a patient with distal vertebral artery occlusion has not been previously reported. A 49-year-old man with longstanding hypertension suddenly developed vertigo, right-sided Horner syndrome, and left-sided weakness. An MRI of the brain showed acute infarcts in the right inferior cerebellum (posterior inferior cerebellar artery territory) and the right upper medial medulla (direct penetrating branches of vertebral artery). Magnetic resonance angiogram showed occlusion of the distal vertebral artery on the right side. Atherothrombotic occlusion of the distal vertebral artery may cause this unusual combination of vertebrobasilar stroke.

Role of the medial medullary reticular formation in relaying vestibular signals to the diaphragm and abdominal muscles

Science.gov (United States)

Mori, R. L.; Bergsman, A. E.; Holmes, M. J.; Yates, B. J.

2001-01-01

Changes in posture can affect the resting length of respiratory muscles, requiring alterations in the activity of these muscles if ventilation is to be unaffected. Recent studies have shown that the vestibular system contributes to altering respiratory muscle activity during movement and changes in posture. Furthermore, anatomical studies have demonstrated that many bulbospinal neurons in the medial medullary reticular formation (MRF) provide inputs to phrenic and abdominal motoneurons; because this region of the reticular formation receives substantial vestibular and other movement-related input, it seems likely that medial medullary reticulospinal neurons could adjust the activity of respiratory motoneurons during postural alterations. The objective of the present study was to determine whether functional lesions of the MRF affect inspiratory and expiratory muscle responses to activation of the vestibular system. Lidocaine or muscimol injections into the MRF produced a large increase in diaphragm and abdominal muscle responses to vestibular stimulation. These vestibulo-respiratory responses were eliminated following subsequent chemical blockade of descending pathways in the lateral medulla. However, inactivation of pathways coursing through the lateral medulla eliminated excitatory, but not inhibitory, components of vestibulo-respiratory responses. The simplest explanation for these data is that MRF neurons that receive input from the vestibular nuclei make inhibitory connections with diaphragm and abdominal motoneurons, whereas a pathway that courses laterally in the caudal medulla provides excitatory vestibular inputs to these motoneurons.

Neurobiological circuits regulating attention, cognitive control, motivation, and emotion: disruptions in neurodevelopmental psychiatric disorders.

Science.gov (United States)

Arnsten, Amy F T; Rubia, Katya

2012-04-01

This article aims to review basic and clinical studies outlining the roles of prefrontal cortical (PFC) networks in the behavior and cognitive functions that are compromised in childhood neurodevelopmental disorders and how these map into the neuroimaging evidence of circuit abnormalities in these disorders. Studies of animals, normally developing children, and patients with neurodevelopmental disorders were reviewed, with focus on neuroimaging studies. The PFC provides "top-down" regulation of attention, inhibition/cognitive control, motivation, and emotion through connections with posterior cortical and subcortical structures. Dorsolateral and inferior PFC regulate attention and cognitive/inhibitory control, whereas orbital and ventromedial structures regulate motivation and affect. PFC circuitries are very sensitive to their neurochemical environment, and small changes in the underlying neurotransmitter systems, e.g. by medications, can produce large effects on mediated function. Neuroimaging studies of children with neurodevelopmental disorders show altered brain structure and function in distinctive circuits respecting this organization. Children with attention-deficit/hyperactivity disorder show prominent abnormalities in the inferior PFC and its connections to striatal, cerebellar, and parietal regions, whereas children with conduct disorder show alterations in the paralimbic system, comprising ventromedial, lateral orbitofrontal, and superior temporal cortices together with specific underlying limbic regions, regulating motivation and emotion control. Children with major depressive disorder show alterations in ventral orbital and limbic activity, particularly in the left hemisphere, mediating emotions. Finally, children with obsessive-compulsive disorder appear to have a dysregulation in orbito-fronto-striatal inhibitory control pathways, but also deficits in dorsolateral fronto-parietal systems of attention. Altogether, there is a good correspondence

A rare mutation in the RET-protooncogen associated with mixed medullary-follicular micro-carcinoma of the thyroid gland

Energy Technology Data Exchange (ETDEWEB)

Richter, K.; Huwe, A.; Boldt, H.; Dresel, S. [Nuklearmedizinische Klinik, HELIOS-Klinikum Berlin-Buch (Germany); Geipel, D. [St.-Hedwig-Krankenhaus, Bereich Endokrine Chirurgie (Germany); Mairinger, T. [Inst. fuer Pathologie, HELIOS-Klinikum Emil von Behring (Germany); Schwabe, M. [Inst. fuer Pathologie, Charite Berlin Campus Mitte (Germany)

2008-07-01

Medullary thyroid carcinoma (MTC) arises from parafollicular C-cells of the thyroid and accounts for 1% to 10% of all thyroid cancers (1). MTC can be sporadic or hereditary. Hereditary MTC represents 20% to 30% of all MTC with an autosomal dominant pattern of transmission and a high degree of penetrance (>90%). It can be transmitted as a single entity (sporadic), familial MTC (FMTC), or it can arise as part of a multiple endocrine neoplasia (MEN) syndrome type 2A or 2B. Both genders are equally affected. (1, 9) The identification of hereditary MTC has been facilitated in recent years by the direct analysis of germline point mutations of the RET(rearranged during transfection)-protooncogene, a 21 exon gene that encodes a plasma membrane-bound tyrosine kinase receptor, localised on chromosome 10q11.2, which is expressed in tissues derived from the neural crest. To date codon mutations in nine different exons were identified (7, 8, 16, 22, 29) causing MEN 2A (MTC in combination with pheochromocytoma and hyperparathyroidism, including rare variants with Hirschsprung's disease and cutaneous lichen amyloidosis), FMTC (MTC as a sole disease phenotype) and MEN 2B (MTC in combination with pheochromocytoma, multiple mucosa neuromas, and marfanoid habitus). The most common mutation, accounting for over 80% of all mutations associated with MEN 2A (or Sipple's) syndrome affects codon 634 in exon 11 of the RET-protooncogene. Other mutations affect codon 630 in exon 11, and codons 609, 611, 618, 620 in exon 10 - they also cause FMTC, although some have a classic MEN 2A syndrome. 5% to 10% of families with FMTC have mutations that affect codons 768, 790, 791 in exon 13: codons 804, 844 in exon 14, and codon 891 in exon 15 (3, 4, 10). The much more aggressive MEN 2B is caused by a single mutation converting a methionine into a threonine at codon 918 in exon 16, and has been identified in approximately 95% of patients with MEN 2B. Other rare mutations associated with MEN 2

Adipostatic regulation of motivation and emotion.

Science.gov (United States)

Davis, Jon F

2010-05-01

The proper maintenance of body weight and mood are two of the most prevalent health issues present in society today. Obese humans display higher levels of mood-related disorders and the causality of such an association is unknown. A common feature of obesity is the imbalance of regulatory hormones which normally act to maintain stable energy balance and body weight. The adiposity hormone leptin is one such signal elevated in obesity with the capacity to dampen feeding behavior through action on brain circuits which regulate appetite and metabolism. Recent evidence suggests that leptin may regulate motivation through its actions within brain reward circuitry. In addition, leptin signaling within central nervous system regions that regulate cognition and emotion elicits anti-depressant like effects. Together, these data indicate that leptin may regulate the decreased motivation and mood present in obesity and depression. This review describes the capacity of leptin to regulate motivation and depression through actions within brain circuits that modulate effort-based behavior and emotion, respectively.

In Vitro Restoration of an Amyloid-Beta Altered Network Circuitry in a 'Mutated Biomimetic Acetylcholinesterase' Memristor/Memcapacitor Neural Prosthesis

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John THORNTON

2015-08-01

Full Text Available Many diseases involve the ysregulation of acetylcholinesterase (ACHE causing inappropriate production of the neurotransmitter acetylcholine (ACH. Study of how the ACH actually restores a life threatening neural circuitry damage will provide valuable information for study Alzhermer’s disease. An artificial neuronal device was developed with nanostructured biomimetic mutated ACHE gorge membrane on gold chips having memristor/memcapacitor’s characteristics, served as a model for damaged brain circuitry prosthesis, compared before and after ACH treatments, for in vitro evaluation of the memory restoration in the presence of Amyloid-beta (Ab under the conditions of free from tracers and antibodies in NIST human serum. The results are presented in three categories in “Energy-Sensory” images. Before ACH treatments, images showed four stages of circuitry damages from non symptomatic to life threatening. After a 15 nM ACH treatment, the circuitry was restored due to the ACH removed Pathological High Frequency Oscillation (pHFO center during Slow- Waving Sleeping (SWS. After the prosthesis increased hydrophobicity, the High Frequency Oscillation (HFO was created. Results were compared between the recovered and the “normal brain”: 0.14 vs. 0.47 pJ/bit/µm3 for long-term and 14.0 vs.7.0 aJ/bit/µm3 for short-term memory restoration, respectively. The ratio of Rmax/Rmin value is 6.3-fold higher after the treatment of ACH compared without the treatment in the presence of Ab and the reentry sensitivity increased by 613.8- fold.

Nuclear receptor/microRNA circuitry links muscle fiber type to energy metabolism.

Science.gov (United States)

Gan, Zhenji; Rumsey, John; Hazen, Bethany C; Lai, Ling; Leone, Teresa C; Vega, Rick B; Xie, Hui; Conley, Kevin E; Auwerx, Johan; Smith, Steven R; Olson, Eric N; Kralli, Anastasia; Kelly, Daniel P

2013-06-01

The mechanisms involved in the coordinate regulation of the metabolic and structural programs controlling muscle fitness and endurance are unknown. Recently, the nuclear receptor PPARβ/δ was shown to activate muscle endurance programs in transgenic mice. In contrast, muscle-specific transgenic overexpression of the related nuclear receptor, PPARα, results in reduced capacity for endurance exercise. We took advantage of the divergent actions of PPARβ/δ and PPARα to explore the downstream regulatory circuitry that orchestrates the programs linking muscle fiber type with energy metabolism. Our results indicate that, in addition to the well-established role in transcriptional control of muscle metabolic genes, PPARβ/δ and PPARα participate in programs that exert opposing actions upon the type I fiber program through a distinct muscle microRNA (miRNA) network, dependent on the actions of another nuclear receptor, estrogen-related receptor γ (ERRγ). Gain-of-function and loss-of-function strategies in mice, together with assessment of muscle biopsies from humans, demonstrated that type I muscle fiber proportion is increased via the stimulatory actions of ERRγ on the expression of miR-499 and miR-208b. This nuclear receptor/miRNA regulatory circuit shows promise for the identification of therapeutic targets aimed at maintaining muscle fitness in a variety of chronic disease states, such as obesity, skeletal myopathies, and heart failure.

Epigenetics in Medullary Thyroid Cancer: From Pathogenesis to Targeted Therapy.

Science.gov (United States)

Vitale, Giovanni; Dicitore, Alessandra; Messina, Erika; Sciammarella, Concetta; Faggiano, Antongiulio; Colao, Annamaria

2016-01-01

Medullary thyroid carcinoma (MTC) originates from the parafollicular C cells of the thyroid gland. Mutations of the RET proto-oncogene are implicated in the pathogenesis of MTC. Germline activating mutations of this gene have been reported in about 88-98% of familial MTCs, while somatic mutations of RET gene have been detected in about 23-70% of sporadic forms. Although these genetic events are well characterized, much less is known about the role of epigenetic abnormalities in MTC. The present review reports a detailed description of epigenetic abnormalities (DNA methylation, histone modifications and miRNA profile), probably involved in the pathogenesis and progression of MTC. A systematic review was performed using Pubmed and Google patents databases. We report the current understanding of epigenetic patterns in MTC and discuss the potential use of current knowledge in designing novel therapeutic strategies through epigenetic drugs, focusing on recent patents in this field. Taking into account the reversibility of epigenetic alterations and the recent development in this field, epigenetic therapy may emerge for clinical use in the near future for patients with advanced MTC.

Selective arterial chemoembolization for hepatic metastases from medullary thyroid carcinoma.

Science.gov (United States)

Lorenz, Kerstin; Brauckhoff, Michael; Behrmann, Curd; Sekulla, Carsten; Ukkat, Jörg; Brauckhoff, Katrin; Gimm, Oliver; Dralle, Henning

2005-12-01

Hepatic metastases from medullary thyroid carcinoma (MTC) may impair quality of life by hypercalcitonemia-associated diarrhea and pain. In this prospective study, the effect of selective arterial chemoembolization (SACE) was evaluated. Eleven patients with hepatic metastases from MTC received 1 to 9 courses of SACE using epirubicine. Symptomatic, biochemical, and morphologic responses on SACE were recorded. Symptomatic response was observed in all symptomatic patients. However, biochemical and radiologic response occurred only in 6 patients. Liver function was not affected by SACE. One patient with unexpected concurrent pheochromocytoma metastases died after the first course. Development of side effects in the course was observed in 8 patients but were only World Health Organization grade 1. Patients' satisfaction with SACE was excellent. Long-term follow-up found 7 patients alive (1-72 months). Three patients died with tumor 6, 12, and 24 months after SACE, respectively. SACE provided good symptom palliation for the majority of patients with hepatic metastases from MTC. However, transient remission or stabilization of hepatic metastases resulted in only 60%. Further studies using a randomized protocol are required.

NPR-9, a Galanin-Like G-Protein Coupled Receptor, and GLR-1 Regulate Interneuronal Circuitry Underlying Multisensory Integration of Environmental Cues in Caenorhabditis elegans.

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Jason C Campbell

2016-05-01

Full Text Available C. elegans inhabit environments that require detection of diverse stimuli to modulate locomotion in order to avoid unfavourable conditions. In a mammalian context, a failure to appropriately integrate environmental signals can lead to Parkinson's, Alzheimer's, and epilepsy. Provided that the circuitry underlying mammalian sensory integration can be prohibitively complex, we analyzed nematode behavioral responses in differing environmental contexts to evaluate the regulation of context dependent circuit reconfiguration and sensorimotor control. Our work has added to the complexity of a known parallel circuit, mediated by interneurons AVA and AIB, that integrates sensory cues and is responsible for the initiation of backwards locomotion. Our analysis of the galanin-like G-protein coupled receptor NPR-9 in C. elegans revealed that upregulation of galanin signaling impedes the integration of sensory evoked neuronal signals. Although the expression pattern of npr-9 is limited to AIB, upregulation of the receptor appears to impede AIB and AVA circuits to broadly prevent backwards locomotion, i.e. reversals, suggesting that these two pathways functionally interact. Galanin signaling similarly plays a broadly inhibitory role in mammalian models. Moreover, our identification of a mutant, which rarely initiates backwards movement, allowed us to interrogate locomotory mechanisms underlying chemotaxis. In support of the pirouette model of chemotaxis, organisms that did not exhibit reversal behavior were unable to navigate towards an attractant peak. We also assessed ionotropic glutamate receptor GLR-1 cell-specifically within AIB and determined that GLR-1 fine-tunes AIB activity to modify locomotion following reversal events. Our research highlights that signal integration underlying the initiation and fine-tuning of backwards locomotion is AIB and NPR-9 dependent, and has demonstrated the suitability of C. elegans for analysis of multisensory integration

Metal Chelation as a Powerful Strategy to Probe Cellular Circuitry Governing Fungal Drug Resistance and Morphogenesis.

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Elizabeth J Polvi

2016-10-01

Full Text Available Fungal pathogens have evolved diverse strategies to sense host-relevant cues and coordinate cellular responses, which enable virulence and drug resistance. Defining circuitry controlling these traits opens new opportunities for chemical diversity in therapeutics, as the cognate inhibitors are rarely explored by conventional screening approaches. This has great potential to address the pressing need for new therapeutic strategies for invasive fungal infections, which have a staggering impact on human health. To explore this approach, we focused on a leading human fungal pathogen, Candida albicans, and screened 1,280 pharmacologically active compounds to identify those that potentiate the activity of echinocandins, which are front-line therapeutics that target fungal cell wall synthesis. We identified 19 compounds that enhance activity of the echinocandin caspofungin against an echinocandin-resistant clinical isolate, with the broad-spectrum chelator DTPA demonstrating the greatest synergistic activity. We found that DTPA increases susceptibility to echinocandins via chelation of magnesium. Whole genome sequencing of mutants resistant to the combination of DTPA and caspofungin identified mutations in the histidine kinase gene NIK1 that confer resistance to the combination. Functional analyses demonstrated that DTPA activates the mitogen-activated protein kinase Hog1, and that NIK1 mutations block Hog1 activation in response to both caspofungin and DTPA. The combination has therapeutic relevance as DTPA enhanced the efficacy of caspofungin in a mouse model of echinocandin-resistant candidiasis. We found that DTPA not only reduces drug resistance but also modulates morphogenesis, a key virulence trait that is normally regulated by environmental cues. DTPA induced filamentation via depletion of zinc, in a manner that is contingent upon Ras1-PKA signaling, as well as the transcription factors Brg1 and Rob1. Thus, we establish a new mechanism by which

Analysis and simulation of the SLD WIC [Warm Iron Calorimeter] PADS hybrid preamplifier circuitry

International Nuclear Information System (INIS)

Fox, J.D.; Horelick, D.

1990-10-01

The SLD PADS electronics consist of over 9000 channels of charge-sensitive preamplifiers followed by integrated sample/hold data storage, digitizing, and readout circuitry. This paper uses computer simulation techniques to analyze critical performance parameters of the preamplifier hybrid including its interactions with the detector system. Simulation results are presented and verified with measured performance. 6 refs., 9 figs

Renal Medullary Carcinoma with an Aggressive Clinical Course: A Case Report and Review of the Literature

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Madhumati R. Kalavar

2017-01-01

Full Text Available Renal medullary carcinoma (RMC is a rare, yet aggressive malignancy of the kidney that is found predominantly in young patients with African descent and sickle cell hemoglobinopathies and most specifically sickle cell trait. Due to its aggressive nature, most cases have metastasis or local invasion at the time of diagnosis. Prognosis is extremely poor with survival less than 1 year after diagnosis. Here we present a case of metastatic RMC in a 29-year-old African female. Despite chemotherapy with cisplatin, gemcitabine, and paclitaxel, and initial shrinkage of the tumor, the patient died 5 months after diagnosis.

Adaptive Supply Voltage Management for Low Power Logic Circuitry Operating at Subthreshold

OpenAIRE

Rehan Ahmed

2015-01-01

With the rise in demand of portable hand held devices and with the rise in application of wireless sensor networks and RFID reduction of total power consumption has become a necessity. To save power we operate the logic circuitry of our devices at sub-threshold. In sub-threshold the drain current is exponentially dependent on the threshold voltage hence the threshold variation causes profound variation of ION and IOFF the ratio of which affect the speed of a circuit drastically. S...

Corticospinal tract insult alters GABAergic circuitry in the mammalian spinal cord

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Jeffrey B. Russ

2013-09-01

Full Text Available During perinatal development, corticospinal tract (CST projections into the spinal cord help refine spinal circuitry. Although the normal developmental processes that are controlled by the arrival of corticospinal input are becoming clear, little is known about how perinatal cortical damage impacts specific aspects of spinal circuit development, particularly the inhibitory microcircuitry that regulates spinal reflex circuits. In this study, we sought to determine how ischemic cortical damage impacts the synaptic attributes of a well-characterized population of inhibitory, GABAergic interneurons, called GABApre neurons, which modulates the efficiency of proprioceptive sensory terminals in the sensorimotor reflex circuit. We found that putative GABApre interneurons receive CST input and, using an established mouse model of perinatal stroke, that cortical ischemic injury results in a reduction of CST density within the intermediate region of the spinal cord, where these interneurons reside. Importantly, CST alterations were restricted to the side contralateral to the injury. Within the synaptic terminals of the GABApre interneurons, we observed a dramatic upregulation of the 65-isoform of the GABA synthetic enzyme glutamic acid decarboxylase (GAD65. In accordance with the CST density reduction, GAD65 was elevated on the side of the spinal cord contralateral to cortical injury. This effect was not seen for other GABApre synaptic markers or in animals that received sham surgery. Our data reveal a novel effect of perinatal stroke that involves severe deficits in the architecture of descending spinal pathways, which in turn appear to promote molecular alterations in a specific spinal GABAergic circuit.

A computational framework for ultrastructural mapping of neural circuitry.

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James R Anderson

2009-03-01

Full Text Available Circuitry mapping of metazoan neural systems is difficult because canonical neural regions (regions containing one or more copies of all components are large, regional borders are uncertain, neuronal diversity is high, and potential network topologies so numerous that only anatomical ground truth can resolve them. Complete mapping of a specific network requires synaptic resolution, canonical region coverage, and robust neuronal classification. Though transmission electron microscopy (TEM remains the optimal tool for network mapping, the process of building large serial section TEM (ssTEM image volumes is rendered difficult by the need to precisely mosaic distorted image tiles and register distorted mosaics. Moreover, most molecular neuronal class markers are poorly compatible with optimal TEM imaging. Our objective was to build a complete framework for ultrastructural circuitry mapping. This framework combines strong TEM-compliant small molecule profiling with automated image tile mosaicking, automated slice-to-slice image registration, and gigabyte-scale image browsing for volume annotation. Specifically we show how ultrathin molecular profiling datasets and their resultant classification maps can be embedded into ssTEM datasets and how scripted acquisition tools (SerialEM, mosaicking and registration (ir-tools, and large slice viewers (MosaicBuilder, Viking can be used to manage terabyte-scale volumes. These methods enable large-scale connectivity analyses of new and legacy data. In well-posed tasks (e.g., complete network mapping in retina, terabyte-scale image volumes that previously would require decades of assembly can now be completed in months. Perhaps more importantly, the fusion of molecular profiling, image acquisition by SerialEM, ir-tools volume assembly, and data viewers/annotators also allow ssTEM to be used as a prospective tool for discovery in nonneural systems and a practical screening methodology for neurogenetics. Finally

Marijuana and cannabinoid regulation of brain reward circuits.

Science.gov (United States)

Lupica, Carl R; Riegel, Arthur C; Hoffman, Alexander F

2004-09-01

The reward circuitry of the brain consists of neurons that synaptically connect a wide variety of nuclei. Of these brain regions, the ventral tegmental area (VTA) and the nucleus accumbens (NAc) play central roles in the processing of rewarding environmental stimuli and in drug addiction. The psychoactive properties of marijuana are mediated by the active constituent, Delta(9)-THC, interacting primarily with CB1 cannabinoid receptors in a large number of brain areas. However, it is the activation of these receptors located within the central brain reward circuits that is thought to play an important role in sustaining the self-administration of marijuana in humans, and in mediating the anxiolytic and pleasurable effects of the drug. Here we describe the cellular circuitry of the VTA and the NAc, define the sites within these areas at which cannabinoids alter synaptic processes, and discuss the relevance of these actions to the regulation of reinforcement and reward. In addition, we compare the effects of Delta(9)-THC with those of other commonly abused drugs on these reward circuits, and we discuss the roles that endogenous cannabinoids may play within these brain pathways, and their possible involvement in regulating ongoing brain function, independently of marijuana consumption. We conclude that, whereas Delta(9)-THC alters the activity of these central reward pathways in a manner that is consistent with other abused drugs, the cellular mechanism through which this occurs is likely different, relying upon the combined regulation of several afferent pathways to the VTA.

Testing the connections within face processing circuitry in Capgras delusion with diffusion imaging tractography

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Maria A. Bobes

2016-01-01

Full Text Available Although Capgras delusion (CD patients are capable of recognizing familiar faces, they present a delusional belief that some relatives have been replaced by impostors. CD has been explained as a selective disruption of a pathway processing affective values of familiar faces. To test the integrity of connections within face processing circuitry, diffusion tensor imaging was performed in a CD patient and 10 age-matched controls. Voxel-based morphometry indicated gray matter damage in right frontal areas. Tractography was used to examine two important tracts of the face processing circuitry: the inferior fronto-occipital fasciculus (IFOF and the inferior longitudinal (ILF. The superior longitudinal fasciculus (SLF and commissural tracts were also assessed. CD patient did not differ from controls in the commissural fibers, or the SLF. Right and left ILF, and right IFOF were also equivalent to those of controls. However, the left IFOF was significantly reduced respect to controls, also showing a significant dissociation with the ILF, which represents a selective impairment in the fiber-tract connecting occipital and frontal areas. This suggests a possible involvement of the IFOF in affective processing of faces in typical observers and in covert recognition in some cases with prosopagnosia.

Changes in neurochemicals within the ventrolateral medullary respiratory column in awake goats after carotid body denervation

Science.gov (United States)

Miller, Justin Robert; Neumueller, Suzanne; Muere, Clarissa; Olesiak, Samantha; Pan, Lawrence; Hodges, Matthew R.

2013-01-01

A current and major unanswered question is why the highly sensitive central CO2/H+ chemoreceptors do not prevent hypoventilation-induced hypercapnia following carotid body denervation (CBD). Because perturbations involving the carotid bodies affect central neuromodulator and/or neurotransmitter levels within the respiratory network, we tested the hypothesis that after CBD there is an increase in inhibitory and/or a decrease in excitatory neurochemicals within the ventrolateral medullary column (VMC) in awake goats. Microtubules for chronic use were implanted bilaterally in the VMC within or near the pre-Bötzinger Complex (preBötC) through which mock cerebrospinal fluid (mCSF) was dialyzed. Effluent mCSF was collected and analyzed for neurochemical content. The goats hypoventilated (peak +22.3 ± 3.4 mmHg PaCO2) and exhibited a reduced CO2 chemoreflex (nadir, 34.8 ± 7.4% of control ΔV̇E/ΔPaCO2) after CBD with significant but limited recovery over 30 days post-CBD. After CBD, GABA and glycine were above pre-CBD levels (266 ± 29% and 189 ± 25% of pre-CBD; P 0.05) different from control after CBD. Analyses of brainstem tissues collected 30 days after CBD exhibited 1) a midline raphe-specific reduction (P < 0.05) in the percentage of tryptophan hydroxylase–expressing neurons, and 2) a reduction (P < 0.05) in serotonin transporter density in five medullary respiratory nuclei. We conclude that after CBD, an increase in inhibitory neurotransmitters and a decrease in excitatory neuromodulation within the VMC/preBötC likely contribute to the hypoventilation and attenuated ventilatory CO2 chemoreflex. PMID:23869058

Microwave technology for waste management applications including disposition of electronic circuitry

International Nuclear Information System (INIS)

Wicks, G.G.; Clark, D.E.; Schulz, R.L.; Folz, D.C.

1995-01-01

Microwave technology is being developed nationally and internationally for a variety of environmental remediation purposes. These efforts include treatment and destruction of a vast array of gaseous, liquid and solid hazardous wastes as well as subsequent immobilization of selected components. Microwave technology provides an important contribution to an arsenal of existing remediation methods that are designed to protect the public and environment from undesirable consequences of hazardous materials. Applications of microwave energy for environmental remediation will be discussed. Emphasized will be a newly developed microwave process designed to treat discarded electronic circuitry and reclaim the precious metals within for reuse

Stimulation of entorhinal cortex-dentate gyrus circuitry is antidepressive.

Science.gov (United States)

Yun, Sanghee; Reynolds, Ryan P; Petrof, Iraklis; White, Alicia; Rivera, Phillip D; Segev, Amir; Gibson, Adam D; Suarez, Maiko; DeSalle, Matthew J; Ito, Naoki; Mukherjee, Shibani; Richardson, Devon R; Kang, Catherine E; Ahrens-Nicklas, Rebecca C; Soler, Ivan; Chetkovich, Dane M; Kourrich, Saïd; Coulter, Douglas A; Eisch, Amelia J

2018-04-16

Major depressive disorder (MDD) is considered a 'circuitopathy', and brain stimulation therapies hold promise for ameliorating MDD symptoms, including hippocampal dysfunction. It is unknown whether stimulation of upstream hippocampal circuitry, such as the entorhinal cortex (Ent), is antidepressive, although Ent stimulation improves learning and memory in mice and humans. Here we show that molecular targeting (Ent-specific knockdown of a psychosocial stress-induced protein) and chemogenetic stimulation of Ent neurons induce antidepressive-like effects in mice. Mechanistically, we show that Ent-stimulation-induced antidepressive-like behavior relies on the generation of new hippocampal neurons. Thus, controlled stimulation of Ent hippocampal afferents is antidepressive via increased hippocampal neurogenesis. These findings emphasize the power and potential of Ent glutamatergic afferent stimulation-previously well-known for its ability to influence learning and memory-for MDD treatment.

Medullary thyroid carcinoma: prognostic factors and treatment

International Nuclear Information System (INIS)

Rougier, P.; Parmentier, C.; Laplanche, A.; Lefevre, M.; Travagli, J.P.; Caillou, B.; Schlumberger, M.; Lacour, J.; Tubiana, M.

1983-01-01

Seventy-five patients with medullary thyroid carcinoma (MTC) have been treated at Institut Gustave-Roussy from 1932 to 1979. Of these, 13 patients had distant metastases and received palliative treatment, their median survival was 3 years. Sixty-two patients with MTC limited to the neck received curative treatment: 6 had exclusive external radiotherapy for inoperable disease and 56 were surgically treated: 23 by total thyroidectomy and 33 by partial thyroidectomy. After surgery 29 patients received external radiotherapy for cervical lymph node involvement (25/29) and/or incomplete surgical resection (12/27). The survival rate was 69% at 5 years and 48% at 10 years. The 29 patients who received post-operative cervical radiotherapy had initially more extensive local disease (p<0.05) than the 27 patients treated by surgery alone, nevertheless their survival was slightly higher. No difference in survival rate was observed between patients treated by total thyroidectomy or partial thyroidectomy, among whom only 4 local recurrences occurred. Three of the 6 patients treated with external radiotherapy alone experienced long survival (4, 7 and 10 years) and a fourth is still in clinical remission 4 years after treatment. The effectiveness of chemotherapy in patients with metastases was poor, only one patient out of 6 had a partial remission following a treatment by adriamycin. In the familial form and multiple endocrine neoplasia type II, total thyroidectomy appears to be indicated. In the sporadic cases, partial thyroidectomy is usually sufficient. External radiotherapy is effective in MTC and seems to be able to eradicate small foci of residual tumor; it is indicated when surgical excision is impossible or incomplete

Fully automatic segmentation of femurs with medullary canal definition in high and in low resolution CT scans.

Science.gov (United States)

Almeida, Diogo F; Ruben, Rui B; Folgado, João; Fernandes, Paulo R; Audenaert, Emmanuel; Verhegghe, Benedict; De Beule, Matthieu

2016-12-01

Femur segmentation can be an important tool in orthopedic surgical planning. However, in order to overcome the need of an experienced user with extensive knowledge on the techniques, segmentation should be fully automatic. In this paper a new fully automatic femur segmentation method for CT images is presented. This method is also able to define automatically the medullary canal and performs well even in low resolution CT scans. Fully automatic femoral segmentation was performed adapting a template mesh of the femoral volume to medical images. In order to achieve this, an adaptation of the active shape model (ASM) technique based on the statistical shape model (SSM) and local appearance model (LAM) of the femur with a novel initialization method was used, to drive the template mesh deformation in order to fit the in-image femoral shape in a time effective approach. With the proposed method a 98% convergence rate was achieved. For high resolution CT images group the average error is less than 1mm. For the low resolution image group the results are also accurate and the average error is less than 1.5mm. The proposed segmentation pipeline is accurate, robust and completely user free. The method is robust to patient orientation, image artifacts and poorly defined edges. The results excelled even in CT images with a significant slice thickness, i.e., above 5mm. Medullary canal segmentation increases the geometric information that can be used in orthopedic surgical planning or in finite element analysis. Copyright © 2016 IPEM. Published by Elsevier Ltd. All rights reserved.

[Role of centro-medullary nailing in fractures of the distal quarter of the leg: about 30 cases].

Science.gov (United States)

Margad, Omar; Boukhris, Jalal; Sallahi, Hicham; Azriouil, Ouahb; Daoudi, Mohamed; Koulali, Khalid

2017-01-01

The fractures of the distal quarter of the leg are characterized by fracture line located at the level of the lower quarter of the tibia, according to Gerard and Evrard definition [1]. They are serious and pose problems for consolidation, immobilization and stability. We here describe our experience in the Department of Orthopaedics and Traumatology at the Avicenne Military Hospital, Marrakech. We report 30 cases of closed fractures of the lower quarter of the leg treated with centro-medullary nailing over a period of 10 years (January 2001-December 2010). Locked nailing was performed in 80% of cases and simple nailing was performed in the other cases. The average age of patients was 36 years. There was a clear male predominance (27 men, 3 women). The average time for consolidation was 17 weeks and functional outcomes were satisfactory. A single case of infection occurred 6 months after surgery (3.3%) and no other complication was reported. Malunion was detected in 30% of patients. Our epidemiological data and results were almost identical to those in the literature. Angular results were significantly lower than those obtained with the series of plates. By contrast, data on infections called for caution and some nails produced excellent angular results when nail fixation was stable. In the light of these results, codified indications for locked centro-medullary nailing should be extended to the fractures of the lower quarter of the leg, provided that stable fixation using double screw distal locking and primary osteosynthesis of distal fibula fractures are performed.

CHARACTERIZATION OF OZONE EMISSIONS FROM AIR CLEANERS EQUIPPED WITH OZONE GENERATORS AND SENSOR AND FEEDBACK CONTROL CIRCUITRY

Science.gov (United States)

The paper give results of a characterization of ozone emissions from air cleaners equipped with ozone generators and sensor and feedback control circuitry. Ozone emission rates of several consumer appliances, marketed as indoor air treatment or air purification systems, were det...

Focusing on optic tectum circuitry through the lens of genetics

Directory of Open Access Journals (Sweden)

Nevin Linda M

2010-09-01

Full Text Available Abstract The visual pathway is tasked with processing incoming signals from the retina and converting this information into adaptive behavior. Recent studies of the larval zebrafish tectum have begun to clarify how the 'micro-circuitry' of this highly organized midbrain structure filters visual input, which arrives in the superficial layers and directs motor output through efferent projections from its deep layers. The new emphasis has been on the specific function of neuronal cell types, which can now be reproducibly labeled, imaged and manipulated using genetic and optical techniques. Here, we discuss recent advances and emerging experimental approaches for studying tectal circuits as models for visual processing and sensorimotor transformation by the vertebrate brain.

The role of the anterodorsal thalami nuclei in the regulation of adrenal medullary function, beta-adrenergic cardiac receptors and anxiety responses in maternally deprived rats under stressful conditions.

Science.gov (United States)

Suárez, M M; Rivarola, M A; Molina, S M; Levin, G M; Enders, J; Paglini, P

2004-09-01

Maternal separation can interfere with growth and development of the brain and represents a significant risk factor for adult psychopathology. In rodents, prolonged separation from the mother affects the behavioral and endocrine responses to stress for the lifetime of the animal. Limbic structures such as the anterodorsal thalamic nuclei (ADTN) play an important role in the control of neuroendocrine and sympathetic-adrenal function. In view of these findings we hypothesized that the function of the ADTN may be affected in an animal model of maternal deprivation. To test this hypothesis female rats were isolated 4.5 h daily, during the first 3 weeks of life and tested as adults. We evaluated plasma epinephrine (E) and norepinephrine (NE), cardiac adrenoreceptors and anxiety responses after maternal deprivation and variable chronic stress (VCS) in ADTN-lesioned rats. Thirty days after ADTN lesion, in non-maternally deprived rats basal plasma NE concentration was greater and cardiac beta-adrenoreceptor density was lower than that in the sham-lesioned group. Maternal deprivation induced a significant increase in basal plasma NE concentration, which was greater in lesioned rats, and cardiac beta-adrenoreceptor density was decreased in lesioned rats. After VCS plasma catecholamine concentration was much greater in non-maternally deprived rats than in maternally-deprived rats; cardiac beta-adrenoreceptor density was decreased by VCS in both maternally-deprived and non-deprived rats, but more so in non-deprived rats, and further decreased by the ADTN lesion. In the plus maze test, the number of open arm entries was greater in the maternally deprived and in the stressed rats. Thus, sympathetic-adrenal medullary activation produced by VCS was much greater in non-deprived rats, and was linked to a down regulation of myocardial beta-adrenoceptors. The ADTN are not responsible for the reduced catecholamine responses to stress in maternally-deprived rats. Maternal deprivation or

S1P lyase in thymic perivascular spaces promotes egress of mature thymocytes via up-regulation of S1P receptor 1.

Science.gov (United States)

Maeda, Yasuhiro; Yagi, Hideki; Takemoto, Kana; Utsumi, Hiroyuki; Fukunari, Atsushi; Sugahara, Kunio; Masuko, Takashi; Chiba, Kenji

2014-05-01

Sphingosine 1-phosphate (S1P) and S1P receptor 1 (S1P1) play an important role in the egress of mature CD4 or CD8 single-positive (SP) thymocytes from the thymus. Fingolimod hydrochloride (FTY720), an S1P1 functional antagonist, induced significant accumulation of CD62L(high)CD69(low) mature SP thymocytes in the thymic medulla. Immunohistochemical staining using anti-S1P1 antibody revealed that S1P1 is predominantly expressed on thymocytes in the thymic medulla and is strongly down-regulated even at 3h after FTY720 administration. 2-Acetyl-4-tetrahydroxybutylimidazole (THI), an S1P lyase inhibitor, also induced accumulation of mature SP thymocytes in the thymic medulla with an enlargement of the perivascular spaces (PVS). At 6h after THI administration, S1P1-expressing thymocytes reduced partially as if to form clusters and hardly existed in the proximity of CD31-expressing blood vessels in the thymic medulla, suggesting S1P lyase expression in the cells constructing thymic medullary PVS. To determine the cells expressing S1P lyase in the thymus, we newly established a mAb (YK19-2) specific for mouse S1P lyase. Immunohistochemical staining with YK19-2 revealed that S1P lyase is predominantly expressed in non-lymphoid thymic stromal cells in the thymic medulla. In the thymic medullary PVS, S1P lyase was expressed in ER-TR7-positive cells (reticular fibroblasts and pericytes) and CD31-positive vascular endothelial cells. Our findings suggest that S1P lyase expressed in the thymic medullary PVS keeps the tissue S1P concentration low around the vessels and promotes thymic egress via up-regulation of S1P1.

Neuron class-specific requirements for Fragile X Mental Retardation Protein in critical period development of calcium signaling in learning and memory circuitry.

Science.gov (United States)

Doll, Caleb A; Broadie, Kendal

2016-05-01

Neural circuit optimization occurs through sensory activity-dependent mechanisms that refine synaptic connectivity and information processing during early-use developmental critical periods. Fragile X Mental Retardation Protein (FMRP), the gene product lost in Fragile X syndrome (FXS), acts as an activity sensor during critical period development, both as an RNA-binding translation regulator and channel-binding excitability regulator. Here, we employ a Drosophila FXS disease model to assay calcium signaling dynamics with a targeted transgenic GCaMP reporter during critical period development of the mushroom body (MB) learning/memory circuit. We find FMRP regulates depolarization-induced calcium signaling in a neuron-specific manner within this circuit, suppressing activity-dependent calcium transients in excitatory cholinergic MB input projection neurons and enhancing calcium signals in inhibitory GABAergic MB output neurons. Both changes are restricted to the developmental critical period and rectified at maturity. Importantly, conditional genetic (dfmr1) rescue of null mutants during the critical period corrects calcium signaling defects in both neuron classes, indicating a temporally restricted FMRP requirement. Likewise, conditional dfmr1 knockdown (RNAi) during the critical period replicates constitutive null mutant defects in both neuron classes, confirming cell-autonomous requirements for FMRP in developmental regulation of calcium signaling dynamics. Optogenetic stimulation during the critical period enhances depolarization-induced calcium signaling in both neuron classes, but this developmental change is eliminated in dfmr1 null mutants, indicating the activity-dependent regulation requires FMRP. These results show FMRP shapes neuron class-specific calcium signaling in excitatory vs. inhibitory neurons in developing learning/memory circuitry, and that FMRP mediates activity-dependent regulation of calcium signaling specifically during the early

Interest of the SPECT-CT to D.M.S.A.-V images merging in the management of thyroid medullary carcinomas; Interets de la fusion d'image TEMP-TDM au DMSA-V dans la prise en charge des carcinomes medullaires de la thyroide

Energy Technology Data Exchange (ETDEWEB)

Menemani, A.; Mebarki, M.; Slama, A.; Khellil, N.; Meghelli, S.; Lachachi, B.; Krim, M.; Merad, S.; Berber, N. [CHU Tlemcen, Service de medecine nucleaire (Algeria)

2010-07-01

Purpose: hybrid imaging associating SPECT and CT, integers functional and anatomical data. The aim of this communication is to present the contribution of the SPECT coupled to CT with D.M.S.A. V. in our daily practice of the medullary thyroid carcinomas management. Conclusions: the SPECT/CT got by a system of images merging allows a better anatomical location and improves the management of thyroid medullary carcinomas. (N.C.)

Lessons from sleeping flies: insights from Drosophila melanogaster on the neuronal circuitry and importance of sleep.

Science.gov (United States)

Potdar, Sheetal; Sheeba, Vasu

2013-06-01

Sleep is a highly conserved behavior whose role is as yet unknown, although it is widely acknowledged as being important. Here we provide an overview of many vital questions regarding this behavior, that have been addressed in recent years using the genetically tractable model organism Drosophila melanogaster in several laboratories around the world. Rest in D. melanogaster has been compared to mammalian sleep and its homeostatic and circadian regulation have been shown to be controlled by intricate neuronal circuitry involving circadian clock neurons, mushroom bodies, and pars intercerebralis, although their exact roles are not entirely clear. We draw attention to the yet unanswered questions and contradictions regarding the nature of the interactions between the brain regions implicated in the control of sleep. Dopamine, octopamine, γ-aminobutyric acid (GABA), and serotonin are the chief neurotransmitters identified as functioning in different limbs of this circuit, either promoting arousal or sleep by modulating membrane excitability of underlying neurons. Some studies have suggested that certain brain areas may contribute towards both sleep and arousal depending on activation of specific subsets of neurons. Signaling pathways implicated in the sleep circuit include cyclic adenosine monophosphate (cAMP) and epidermal growth factor receptor-extracellular signal-regulated kinase (EGFR-ERK) signaling pathways that operate on different neural substrates. Thus, this field of research appears to be on the cusp of many new and exciting findings that may eventually help in understanding how this complex physiological phenomenon is modulated by various neuronal circuits in the brain. Finally, some efforts to approach the "Holy Grail" of why we sleep have been summarized.

Microwave Technology for Waste Management Applications Including Disposition of Electronic Circuitry

International Nuclear Information System (INIS)

Wicks, G.G.; Clark, D.E.; Schulz, R.L.

1998-01-01

Advanced microwave technology is being developed nationally and internationally for a variety of waste management and environmental remediation purposes. These efforts include treatment and destruction of a vast array of gaseous, liquid and solid hazardous wastes as well as subsequent immobilization of hazardous components into leach resistant forms. Microwave technology provides an important contribution to an arsenal of existing remediation methods that are designed to protect the public and environment from the undesirable consequences of hazardous materials. One application of special interest is the treatment of discarded electronic circuitry using a new hybrid microwave treatment process and subsequent reclamation of the precious metals within

Circuitry and plasticity of the dorsal horn--toward a better understanding of neuropathic pain.

Science.gov (United States)

West, S J; Bannister, K; Dickenson, A H; Bennett, D L

2015-08-06

Maladaptive plasticity within the dorsal horn (DH) of the spinal cord is a key substrate for development of neuropathic pain following peripheral nerve injury. Advances in genetic engineering, tracing techniques and opto-genetics are leading to a much better understanding of the complex circuitry of the spinal DH and the radical changes evoked in such circuitry by nerve injury. These changes can be viewed at multiple levels including: synaptic remodeling including enhanced excitatory and reduced inhibitory drive, morphological and electrophysiological changes which are observed both to primary afferent inputs as well as DH neurons, and ultimately circuit-level rewiring which leads to altered connectivity and aberrant processing of sensory inputs in the DH. The DH should not be seen in isolation but is subject to important descending modulation from the brainstem, which is further dysregulated by nerve injury. Understanding which changes relate to specific disease-states is essential, and recent work has aimed to stratify patient populations in a mechanistic fashion. In this review we will discuss how such pathophysiological mechanisms may lead to the distressing sensory phenomena experienced by patients suffering neuropathic pain, and the relationship of such mechanisms to current and potential future treatment modalities. Copyright © 2015 IBRO. Published by Elsevier Ltd. All rights reserved.

H+, Water and Urea Transport in the Inner Medullary Collecting Duct and Their Role in the Prevention and Pathogenesis of Renal Stone Disease

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Wall, Susan M.; Klein, Janet D.

2008-09-01

The inner medullary collecting duct (IMCD) is the final site within the kidney for the reabsorption of urea, water and electrolytes and for the secretion of H+ before the luminal fluid becomes the final urine. Transporters expressed in the IMCD contribute to the generation of the large ion gradients that exist between the interstitium and the collecting duct lumen. Thus, the luminal fluid within the human IMCD can reach an osmolality of 1200 mOsm/kg H2O and a pH of 4. This ability of the human nephron to concentrate and acidify the urine might predispose to stone formation. However, under treatment conditions that predispose to stone formation, such as during hypercalciuria, the kidney mitigates stone formation by reducing solute concentration by reducing H2O reabsorption. Moreover, the kidney attenuates stone formation by tightly controlling acid-base balance, which prevents the bone loss, hypocitraturia and hypercalciuria observed during metabolic acidosis by augmenting net H+ excretion by tightly regulating H+ transporter function and through luminal buffering, particularly with NH3. This article will review the ion transporters present in the mammalian IMCD and their role in the prevention and in the pathogenesis of renal stone formation.

First realization of a tracking detector for high energy physics experiments based on Josephson digital readout circuitry

CERN Document Server

Pagano, S; Esposito, A P; Mukhanov, O; Rylov, S

1999-01-01

We have designed and realized a prototype of a high energy particle microstrip detector with Josephson readout circuits. The key features of this device are: minimum ionizing particle sensitivity, due to the use of semiconductive sensors, fast speed and radiation hardness, due to the use of superconductive circuitry, and current discrimination, which allows the use of several types of semiconductors as detector (Si, GaAs, CVD-diamond) without loss in performances. The Josephson circuitry, made by a combination of RSFQ and latching logic gates, realizes an 8-bit current discriminator and parallel to serial converter and can be directly interfaced to room temperature electronics. This device, which is designed for application as vertex detector for the Compass and LHC-B accelerator experiments, has been tested with small radioactive sources acid will undergo to a test beam at the CERN SPS facility with 24 GeV/c protons. Current results and future perspectives will be reported. (11 refs).

The Neural Basis of and a Common Neural Circuitry in Different Types of Pro-social Behavior

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Jun Luo

2018-06-01

Full Text Available Pro-social behaviors are voluntary behaviors that benefit other people or society as a whole, such as charitable donations, cooperation, trust, altruistic punishment, and fairness. These behaviors have been widely described through non self-interest decision-making in behavioral experimental studies and are thought to be increased by social preference motives. Importantly, recent studies using a combination of neuroimaging and brain stimulation, designed to reveal the neural mechanisms of pro-social behaviors, have found that a wide range of brain areas, specifically the prefrontal cortex, anterior insula, anterior cingulate cortex, and amygdala, are correlated or causally related with pro-social behaviors. In this review, we summarize the research on the neural basis of various kinds of pro-social behaviors and describe a common shared neural circuitry of these pro-social behaviors. We introduce several general ways in which experimental economics and neuroscience can be combined to develop important contributions to understanding social decision-making and pro-social behaviors. Future research should attempt to explore the neural circuitry between the frontal lobes and deeper brain areas.

Advances and controversies in the management of medullary thyroid carcinoma.

Science.gov (United States)

Maia, Ana Luiza; Wajner, Simone Magagnin; Vargas, Carla Vaz Ferreira

2017-01-01

Medullary thyroid carcinoma (MTC) comprises approximately 4% of all malignant thyroid neoplasms. Although the majority of patients have a good prognosis, a subgroup of patients develops progressive disease and requires systemic therapy. Here, we focused on the current MTC therapeutic approaches and discussed the advantages and disadvantages of molecular targeted therapies. Targeted molecular therapies that inhibit RET and other tyrosine kinase receptors involved in angiogenesis have been shown to improve progression-free survival in patients with advanced MTC. Two drugs, vandetanib and cabozantinib, have been approved for the treatment of progressive or symptomatic MTC, and several others have exhibited variable efficacy. No tyrosine kinase inhibitor has been shown to improve survival. Although no definitive recommendation can currently be made, cumulative data indicate that knowledge of the tumor mutational profile may facilitate improvements in targeted therapy for MTC. Tyrosine kinase inhibitors are effective therapeutic agents for the treatment of progressive MTC. Nevertheless, it is not clear who will benefit the most from therapy, and the decision regarding when and how to initiate the treatment should be made based on the patient's medical history and tumor behavior. Hopefully, in the near future, molecular profiling of MTC can be used to determine the most effective molecular therapeutic target.

Circuitry for monitoring a high direct current voltage supply for an ionization chamber

International Nuclear Information System (INIS)

1981-01-01

An arrangement to measure the voltage of the supply and a switching means controlled by this is described. The voltage measurer consists of first and second signal coupling means, the input of the second (connected to the voltage supply) is connected in series with the output of the first. An ionization chamber with this circuitry may be used to monitor the radiation output of a particle accelerator more accurately. Faulty measurements of the dose output, caused by voltages in the earth circuit, are avoided. (U.K.)

Age and gender modulate the neural circuitry supporting facial emotion processing in adults with major depressive disorder.

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Briceño, Emily M; Rapport, Lisa J; Kassel, Michelle T; Bieliauskas, Linas A; Zubieta, Jon-Kar; Weisenbach, Sara L; Langenecker, Scott A

2015-03-01

Emotion processing, supported by frontolimbic circuitry known to be sensitive to the effects of aging, is a relatively understudied cognitive-emotional domain in geriatric depression. Some evidence suggests that the neurophysiological disruption observed in emotion processing among adults with major depressive disorder (MDD) may be modulated by both gender and age. Therefore, the present study investigated the effects of gender and age on the neural circuitry supporting emotion processing in MDD. Cross-sectional comparison of fMRI signal during performance of an emotion processing task. Outpatient university setting. One hundred adults recruited by MDD status, gender, and age. Participants underwent fMRI while completing the Facial Emotion Perception Test. They viewed photographs of faces and categorized the emotion perceived. Contrast for fMRI was of face perception minus animal identification blocks. Effects of depression were observed in precuneus and effects of age in a number of frontolimbic regions. Three-way interactions were present between MDD status, gender, and age in regions pertinent to emotion processing, including frontal, limbic, and basal ganglia. Young women with MDD and older men with MDD exhibited hyperactivation in these regions compared with their respective same-gender healthy comparison (HC) counterparts. In contrast, older women and younger men with MDD exhibited hypoactivation compared to their respective same-gender HC counterparts. This the first study to report gender- and age-specific differences in emotion processing circuitry in MDD. Gender-differential mechanisms may underlie cognitive-emotional disruption in older adults with MDD. The present findings have implications for improved probes into the heterogeneity of the MDD syndrome. Copyright © 2015 American Association for Geriatric Psychiatry. Published by Elsevier Inc. All rights reserved.

Neuroanatomical circuitry between kidney and rostral elements of brain: a virally mediated transsynaptic tracing study in mice.

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Zhou, Ye-Ting; He, Zhi-Gang; Liu, Tao-Tao; Feng, Mao-Hui; Zhang, Ding-Yu; Xiang, Hong-Bing

2017-02-01

The identity of higher-order neurons and circuits playing an associative role to control renal function is not well understood. We identified specific neural populations of rostral elements of brain regions that project multisynaptically to the kidneys in 3-6 days after injecting a retrograde tracer pseudorabies virus (PRV)-614 into kidney of 13 adult male C57BL/6J strain mice. PRV-614 infected neurons were detected in a number of mesencephalic (e.g. central amygdala nucleus), telencephalic regions and motor cortex. These divisions included the preoptic area (POA), dorsomedial hypothalamus (DMH), lateral hypothalamus, arcuate nucleus (Arc), suprachiasmatic nucleus (SCN), periventricular hypothalamus (PeH), and rostral and caudal subdivision of the paraventricular nucleus of the hypothalamus (PVN). PRV-614/Tyrosine hydroxylase (TH) double-labeled cells were found within DMH, Arc, SCN, PeH, PVN, the anterodorsal and medial POA. A subset of neurons in PVN that participated in regulating sympathetic outflow to kidney was catecholaminergic or serotonergic. PRV-614 infected neurons within the PVN also contained arginine vasopressin or oxytocin. These data demonstrate the rostral elements of brain innervate the kidney by the neuroanatomical circuitry.

Isolated, extra-articular neck and shaft fractures of the 4th and 5th metacarpals: a comparison of transverse and bouquet (intra-medullary) pinning in 67 patients.

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Sletten, I N; Nordsletten, L; Husby, T; Ødegaard, R A; Hellund, J C; Kvernmo, H D

2012-06-01

Although extra-articular metacarpal fractures are common, there is no consensus on the mode of treatment. We evaluated the outcome in 67 patients operated for isolated, extra-articular fractures in the neck or shaft of the ulnar two metacarpals 28 months post-operatively. There were 22 bouquet (intra-medullary) pinnings and 45 transverse pinnings; 11 were lost to follow-up. Overall, hand function was good, and no difference was detected between the two methods (QuickDASH, grip strength, range of motion, VAS pain and VAS satisfaction). Many patients suffered complications: 12% had a superficial infection (all treated with transverse pinning with wires left exposed); 39% had some impairment in skin sensation; 29% reported cold intolerance; and 10% had other complications. Due to the potential risk of a secondary fracture of the neighbouring metacarpal after transverse pinning, we recommend bouquet (intra-medullary) pinning. We also recommend burying wires beneath the skin surface to avoid infection.

Cellular Signaling Pathway Alterations and Potential Targeted Therapies for Medullary Thyroid Carcinoma

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Serena Giunti

2013-01-01

Full Text Available Parafollicular C-cell-derived medullary thyroid cancer (MTC comprises 3% to 4% of all thyroid cancers. While cytotoxic treatments have been shown to have limited efficacy, targeted molecular therapies that inhibit rearranged during transfection (RET and other tyrosine kinase receptors that are mainly involved in angiogenesis have shown great promise in the treatment of metastatic or locally advanced MTC. Multi-tyrosine kinase inhibitors such as vandetanib, which is already approved for the treatment of progressive MTC, and cabozantinib have shown distinct advantages with regard to rates of disease response and control. However, these types of tyrosine kinase inhibitor compounds are able to concurrently block several types of targets, which limits the understanding of RET as a specific target. Moreover, important resistances to tyrosine kinase inhibitors can occur, which limit the long-term efficacy of these treatments. Deregulated cellular signaling pathways and genetic alterations in MTC, particularly the activation of the RAS/mammalian target of rapamycin (mTOR cascades and RET crosstalk signaling, are now emerging as novel and potentially promising therapeutic treatments for aggressive MTC.

Comparison of 99Tcm(V)-DMSA and 99Tcm-MIBI scintigraphy in medullary thyroid carcinoma

International Nuclear Information System (INIS)

Deng Bo; Xiao Huan; Chen Xiaofeng; Chen Huaming

2004-01-01

SPECT scintigraphy is used in 62 patients with medullary thyroid carcinoma (MTC), which are divided into two groups: 32 patients by 99 Tc m (V)-DMSA and 30 patients by 99 Tc m -MIBI. The qualitative analysis and half quantitative analysis are performed to the early and delayed images. Comparing the results with two groups, there is no difference in the masculine rate of MTC primary focus, but the results of 99 Tc m (V)-DMSA scintigraphy is obviously larger than 99 Tc m -MIBI by half quantitative analysis. The results show that the 99 Tc m (V)-DMSA scintigraphy is more predominant than the 99 Tc m -(V)-DMSA scintigraphy may be superior to 99 Tc m -MIBI in MTC primary focus and metastasis focus before surging for MTC patients. (authors)

Regulation of hippocampus-dependent memory by the zinc finger protein Zbtb20 in mature CA1 neurons.

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Ren, Anjing; Zhang, Huan; Xie, Zhifang; Ma, Xianhua; Ji, Wenli; He, David Z Z; Yuan, Wenjun; Ding, Yu-Qiang; Zhang, Xiao-Hui; Zhang, Weiping J

2012-10-01

The mammalian hippocampus harbours neural circuitry that is crucial for associative learning and memory. The mechanisms that underlie the development and regulation of this complex circuitry are not fully understood. Our previous study established an essential role for the zinc finger protein Zbtb20 in the specification of CA1 field identity in the developing hippocampus. Here, we show that conditionally deleting Zbtb20 specifically in mature CA1 pyramidal neurons impaired hippocampus-dependent memory formation, without affecting hippocampal architecture or the survival, identity and basal excitatory synaptic activity of CA1 pyramidal neurons. We demonstrate that mature CA1-specific Zbtb20 knockout mice exhibited reductions in long-term potentiation (LTP) and NMDA receptor (NMDAR)-mediated excitatory post-synaptic currents. Furthermore, we show that activity-induced phosphorylation of ERK and CREB is impaired in the hippocampal CA1 of Zbtb20 mutant mice. Collectively, these results indicate that Zbtb20 in mature CA1 plays an important role in LTP and memory by regulating NMDAR activity, and activation of ERK and CREB.

Heterogeneity of neuroblastoma cell identity defined by transcriptional circuitries.

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Boeva, Valentina; Louis-Brennetot, Caroline; Peltier, Agathe; Durand, Simon; Pierre-Eugène, Cécile; Raynal, Virginie; Etchevers, Heather C; Thomas, Sophie; Lermine, Alban; Daudigeos-Dubus, Estelle; Geoerger, Birgit; Orth, Martin F; Grünewald, Thomas G P; Diaz, Elise; Ducos, Bertrand; Surdez, Didier; Carcaboso, Angel M; Medvedeva, Irina; Deller, Thomas; Combaret, Valérie; Lapouble, Eve; Pierron, Gaelle; Grossetête-Lalami, Sandrine; Baulande, Sylvain; Schleiermacher, Gudrun; Barillot, Emmanuel; Rohrer, Hermann; Delattre, Olivier; Janoueix-Lerosey, Isabelle

2017-09-01

Neuroblastoma is a tumor of the peripheral sympathetic nervous system, derived from multipotent neural crest cells (NCCs). To define core regulatory circuitries (CRCs) controlling the gene expression program of neuroblastoma, we established and analyzed the neuroblastoma super-enhancer landscape. We discovered three types of identity in neuroblastoma cell lines: a sympathetic noradrenergic identity, defined by a CRC module including the PHOX2B, HAND2 and GATA3 transcription factors (TFs); an NCC-like identity, driven by a CRC module containing AP-1 TFs; and a mixed type, further deconvoluted at the single-cell level. Treatment of the mixed type with chemotherapeutic agents resulted in enrichment of NCC-like cells. The noradrenergic module was validated by ChIP-seq. Functional studies demonstrated dependency of neuroblastoma with noradrenergic identity on PHOX2B, evocative of lineage addiction. Most neuroblastoma primary tumors express TFs from the noradrenergic and NCC-like modules. Our data demonstrate a previously unknown aspect of tumor heterogeneity relevant for neuroblastoma treatment strategies.

Thin Film Transistor Control Circuitry for MEMS Acoustic Transducers

Science.gov (United States)

Daugherty, Robin

This work seeks to develop a practical solution for short range ultrasonic communications and produce an integrated array of acoustic transmitters on a flexible substrate. This is done using flexible thin film transistor (TFT) and micro electromechanical systems (MEMS). The goal is to develop a flexible system capable of communicating in the ultrasonic frequency range at a distance of 10-100 meters. This requires a great deal of innovation on the part of the FDC team developing the TFT driving circuitry and the MEMS team adapting the technology for fabrication on a flexible substrate. The technologies required for this research are independently developed. The TFT development is driven primarily by research into flexible displays. The MEMS development is driving by research in biosensors and micro actuators. This project involves the integration of TFT flexible circuit capabilities with MEMS micro actuators in the novel area of flexible acoustic transmitter arrays. This thesis focuses on the design, testing and analysis of the circuit components required for this project.

Molt performance and bone density of cortical, medullary, and cancellous bone in laying hens during feed restriction or alfalfa-based feed molt.

Science.gov (United States)

Kim, W K; Donalson, L M; Bloomfield, S A; Hogan, H A; Kubena, L F; Nisbet, D J; Ricke, S C

2007-09-01

A study was conducted to evaluate the effects of alfalfa-based molt diets on molting performance and bone qualities. A total of 36 Single Comb White Leghorn hens were used for the study. There were 6 treatments: pretrial control (PC), fully fed (FF), feed withdrawal (FW), 90% alfalfa:10% layer ration (A90), 80% alfalfa:20% layer ration (A80), and 70% alfalfa:30% layer ration (A70). For the PC treatment, hens were euthanized by CO(2) gas, and bones were collected before molt was initiated. At the end of the 9-d molt period, hens were euthanized, and femurs and tibias were collected to evaluate bone qualities by peripheral quantitative computed tomography, mechanical testing, and conventional ash weights. The hens fed alfalfa-based molt diets and FW stopped laying eggs within 5 d after molt started, and all hens in these groups had reduced ovary weights compared with those of the FF hens. In the FW and A90 groups, total femur volumetric bone mineral densities (vBMD) at the midshaft were significantly lower, but those of the A80 and A70 groups were not significantly different from the values for the PC and FF hens. In cortical bone density, the midshaft tibial vBMD were significantly higher for FF and A70 hens than for PC hens. The medullary bone densities at the midshaft femur or tibia of the FW, A90, A80, and A70 hens were reduced compared with those of the PC hens. Femur cancellous densities at the distal femur for the FW and A90 hens were significantly reduced compared with those of the PC and FF hens. The FW, A80, and A70 hens yielded significantly higher elastic moduli, and the A80 hens had higher ultimate stress compared with the PC hens, suggesting that the mechanical integrity of the midshaft bone was maintained even though the medullary vBMD was reduced. These results suggest that alfalfa-based molt diets exhibit molt performance similar to FW, that medullary and cancellous bones are labile bone compartments during molting, and that alfalfa-based molt diets

Long-term potentiation in hilar circuitry modulates gating by the dentate gyrus.

Science.gov (United States)

Wright, Brandon J; Jackson, Meyer B

2014-07-16

The dentate gyrus serves as a gateway to the hippocampus, filtering and processing sensory inputs as an animal explores its environment. The hilus occupies a strategic position within the dentate gyrus from which it can play a pivotal role in these functions. Inputs from dentate granule cells converge on the hilus, and excitatory hilar mossy cells redistribute these signals back to granule cells to transform a pattern of cortical input into a new pattern of output to the hippocampal CA3 region. Using voltage-sensitive dye to image electrical activity in rat hippocampal slices, we explored how long-term potentiation (LTP) of different excitatory synapses modifies the flow of information. Theta burst stimulation of the perforant path potentiated responses throughout the molecular layer, but left responses in the CA3 region unchanged. By contrast, theta burst stimulation of the granule cell layer potentiated responses throughout the molecular layer, as well as in the CA3 region. Theta burst stimulation of the granule cell layer potentiated CA3 responses not only to granule cell layer stimulation but also to perforant path stimulation. Potentiation of responses in the CA3 region reflected NMDA receptor-dependent LTP of upstream synapses between granule cells and mossy cells, with no detectable contribution from NMDA receptor-independent LTP of local CA3 mossy fiber synapses. Potentiation of transmission to the CA3 region required LTP in both granule cell→mossy cell and mossy cell→granule cell synapses. This bidirectional plasticity enables hilar circuitry to regulate the flow of information through the dentate gyrus and on to the hippocampus. Copyright © 2014 the authors 0270-6474/14/349743-11$15.00/0.

Disrupted Structural and Functional Connectivity in Prefrontal-Hippocampus Circuitry in First-Episode Medication-Naïve Adolescent Depression.

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Haiyang Geng

Full Text Available Evidence implicates abnormalities in prefrontal-hippocampus neural circuitry in major depressive disorder (MDD. This study investigates the potential disruptions in prefrontal-hippocampus structural and functional connectivity, as well as their relationship in first-episode medication-naïve adolescents with MDD in order to investigate the early stage of the illness without confounds of illness course and medication exposure.Diffusion tensor imaging and resting-state functional magnetic resonance imaging (rs-fMRI data were acquired from 26 first-episode medication-naïve MDD adolescents and 31 healthy controls (HC. Fractional anisotropy (FA values of the fornix and the prefrontal-hippocampus functional connectivity was compared between MDD and HC groups. The correlation between the FA value of fornix and the strength of the functional connectivity in the prefrontal cortex (PFC region showing significant differences between the two groups was identified.Compared with the HC group, adolescent MDD group had significant lower FA values in the fornix, as well as decreased functional connectivity in four PFC regions. Significant negative correlations were observed between fornix FA values and functional connectivity from hippocampus to PFC within the HC group. There was no significant correlation between the fornix FA and the strength of functional connectivity within the adolescent MDD group.First-episode medication-naïve adolescent MDD showed decreased structural and functional connectivity as well as deficits of the association between structural and functional connectivity shown in HC in the PFC-hippocampus neural circuitry. These findings suggest that abnormal PFC-hippocampus neural circuitry may present in the early onset of MDD and play an important role in the neuropathophysiology of MDD.

Synaptic reorganization of inhibitory hilar interneuron circuitry after traumatic brain injury in mice

Science.gov (United States)

Hunt, Robert F.; Scheff, Stephen W.; Smith, Bret N.

2011-01-01

Functional plasticity of synaptic networks in the dentate gyrus has been implicated in the development of posttraumatic epilepsy and in cognitive dysfunction after traumatic brain injury, but little is known about potentially pathogenic changes in inhibitory circuits. We examined synaptic inhibition of dentate granule cells and excitability of surviving GABAergic hilar interneurons 8–13 weeks after cortical contusion brain injury in transgenic mice that express enhanced green fluorescent protein in a subpopulation of inhibitory neurons. Whole-cell voltage-clamp recordings in granule cells revealed a reduction in spontaneous and miniature IPSC frequency after head injury; no concurrent change in paired-pulse ratio was found in granule cells after paired electrical stimulation of the hilus. Despite reduced inhibitory input to granule cells, action potential and EPSC frequencies were increased in hilar GABA neurons from slices ipsilateral to the injury, versus those from control or contralateral slices. Further, increased excitatory synaptic activity was detected in hilar GABA neurons ipsilateral to the injury after glutamate photostimulation of either the granule cell or CA3 pyramidal cell layers. Together, these findings suggest that excitatory drive to surviving hilar GABA neurons is enhanced by convergent input from both pyramidal and granule cells, but synaptic inhibition of granule cells is not fully restored after injury. This rewiring of circuitry regulating hilar inhibitory neurons may reflect an important compensatory mechanism, but it may also contribute to network destabilization by increasing the relative impact of surviving individual interneurons in controlling granule cell excitability in the posttraumatic dentate gyrus. PMID:21543618

Neural alterations of fronto-striatal circuitry during reward anticipation in euthymic bipolar disorder.

Science.gov (United States)

Schreiter, S; Spengler, S; Willert, A; Mohnke, S; Herold, D; Erk, S; Romanczuk-Seiferth, N; Quinlivan, E; Hindi-Attar, C; Banzhaf, C; Wackerhagen, C; Romund, L; Garbusow, M; Stamm, T; Heinz, A; Walter, H; Bermpohl, F

2016-11-01

Bipolar disorder (BD), with the hallmark symptoms of elevated and depressed mood, is thought to be characterized by underlying alterations in reward-processing networks. However, to date the neural circuitry underlying abnormal responses during reward processing in BD remains largely unexplored. The aim of this study was to investigate whether euthymic BD is characterized by aberrant ventral striatal (VS) activation patterns and altered connectivity with the prefrontal cortex in response to monetary gains and losses. During functional magnetic resonance imaging 20 euthymic BD patients and 20 age-, gender- and intelligence quotient-matched healthy controls completed a monetary incentive delay paradigm, to examine neural processing of reward and loss anticipation. A priori defined regions of interest (ROIs) included the VS and the anterior prefrontal cortex (aPFC). Psychophysiological interactions (PPIs) between these ROIs were estimated and tested for group differences for reward and loss anticipation separately. BD participants, relative to healthy controls, displayed decreased activation selectively in the left and right VS during anticipation of reward, but not during loss anticipation. PPI analyses showed decreased functional connectivity between the left VS and aPFC in BD patients compared with healthy controls during reward anticipation. This is the first study showing decreased VS activity and aberrant connectivity in the reward-processing circuitry in euthymic, medicated BD patients during reward anticipation. Our findings contrast with research supporting a reward hypersensitivity model of BD, and add to the body of literature suggesting that blunted activation of reward processing circuits may be a vulnerability factor for mood disorders.

Invasive medullary thymoma associated with myasthenia gravis: an unusual case Miastenia gravis em um paciente com timoma medular invasivo: relato de caso

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JORGE S. REIS FILHO

2000-12-01

Full Text Available Thymomas are tumors characterized by a remarkable morphological heterogeneity and variable clinical behavior. This tumor has unique clinical associations, most notably with hematological abnormalities and myasthenia gravis. According with the Müller-Hermelink criteria, there are significant differences between the histological types of thymomas and the association with myasthenia gravis. Among the different histological types, medullary thymoma is the least frequent variant associated with this autoimmune disease. In this report we describe a case of medullary thymoma presenting in a 71-year- old woman with a myasthenic syndrome.Os timomas são tumores caracterizados por grande heterogeneidade morfológica e comportamento clínico variável. Este tumor apresenta associações clínicas singulares, principalmente com doenças hematológicas e com a miastenia gravis. De acordo com a classificação de Müller-Hermelink, existem diferenças significativas entre as variedades histológicas dos timomas e sua associação com a miastenia gravis. Entre os diferentes tipos histológicos, o timoma medular é a variante menos frequentemente associada com esta doença autoimune. Neste relato, nós descrevemos caso de timoma medular em uma paciente de 71 anos de idade com síndrome miastênica.

Circulation of the medullary cerebrospinal fluid. Comparative study of various tracers

International Nuclear Information System (INIS)

Bok, B.; Thebault, B.; Cavailloles, F.; Aboulker, J.

Gammamyelography is used to study the circulation of the cerebrospinal fluid in the perimedullary sub-arachoid spaces. Many radioactive preparations have been proposed for this examination which is designed to show up all dynamic perturbations of the CSF flux. Of the criteria governing the choice of tracer some importance given has been to the molecular diffusion constant of the preparation, iodinated albumine seeming the most suitable in this respect. An attempt was made to estimate the influence of molecular weight on the tracer kinetics by comparing three preparations injected simultaneously: indium 111-labelled siderophilline of M.W. above 100,000; iodine 131-labelled human serum albumine of MW around 70,000; sup(99m)Tc-labelled DTPA, a chelate of low molecular weight. The results showed no detectable influence of the molecular weight of these preparations on their intraspinal kinetics in the time taken for the examination. In practice this work justifies the use of the preparation most convenient and least harmful from the dosimetric viewpoint for the isotope and from the antigenic toxicological viewpoint for the tracer, which means that the replacement of iodinated albumine by indium-111 DTPA for example should be possible at least at the medullary level [fr

UCP2 Regulates Mitochondrial Fission and Ventromedial Nucleus Control of Glucose Responsiveness.

Science.gov (United States)

Toda, Chitoku; Kim, Jung Dae; Impellizzeri, Daniela; Cuzzocrea, Salvatore; Liu, Zhong-Wu; Diano, Sabrina

2016-02-25

The ventromedial nucleus of the hypothalamus (VMH) plays a critical role in regulating systemic glucose homeostasis. How neurons in this brain area adapt to the changing metabolic environment to regulate circulating glucose levels is ill defined. Here, we show that glucose load results in mitochondrial fission and reduced reactive oxygen species in VMH neurons mediated by dynamin-related peptide 1 (DRP1) under the control of uncoupling protein 2 (UCP2). Probed by genetic manipulations and chemical-genetic control of VMH neuronal circuitry, we unmasked that this mitochondrial adaptation determines the size of the pool of glucose-excited neurons in the VMH and that this process regulates systemic glucose homeostasis. Thus, our data unmasked a critical cellular biological process controlled by mitochondrial dynamics in VMH regulation of systemic glucose homeostasis. Copyright © 2016 Elsevier Inc. All rights reserved.

Medullary Venous Hypertension Secondary to a Petrous Apex Dural Arteriovenous Fistula: A Case Report

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Meghan Murphy

2012-11-01

Full Text Available Background: Dural arteriovenous fistulae (dAVF are common intracranial vascular lesions typically becoming symptomatic with cortical venous hypertension and possible hemorrhage. Here, we present a case illustration of a petrous apex dAVF with marked medullary venous hypertension and a unique clinical presentation. Methods: Case report. Results: A 72-year-old female, whose clinical progression was significant for altered mental status and progressive weakness, presented with diplopia, right leg paresis, and ataxia. Magnetic resonance imaging revealed edema involving the medulla. On digital subtraction cerebral angiogram, the patient was found to have a petrous apex dAVF, Cognard type IV. Following treatment with Onyx embolization, her symptoms rapidly improved, with complete resolution of diplopia and drastic improvement of her ataxia. Conclusion: The importance of this case is in the presentation and deterioration of the clinical exam, resembling an acute ischemic event. Further, this case illustrates that dAVF may cause venous hypertension with rapid onset of focal neurologic symptoms not exclusive to cortical locations.

microRNAs as regulators of adipogenic differentiation of mesenchymal stem cells.

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Hamam, Dana; Ali, Dalia; Kassem, Moustapha; Aldahmash, Abdullah; Alajez, Nehad M

2015-02-15

microRNAs (miRNAs) constitute complex regulatory network, fine tuning the expression of a myriad of genes involved in different biological and physiological processes, including stem cell differentiation. Mesenchymal stem cells (MSCs) are multipotent stem cells present in the bone marrow stroma, and the stroma of many other tissues, and can give rise to a number of mesoderm-type cells including adipocytes and osteoblasts, which form medullary fat and bone tissues, respectively. The role of bone marrow fat in bone mass homeostasis is an area of intensive investigation with the aim of developing novel approaches for enhancing osteoblastic bone formation through inhibition of bone marrow fat formation. A number of recent studies have reported several miRNAs that enhance or inhibit adipogenic differentiation of MSCs and with potential use in microRNA-based therapy to regulate adipogenesis in the context of treating bone diseases and metabolic disorders. The current review focuses on miRNAs and their role in regulating adipogenic differentiation of MSCs.

Targeting Lumbar Spinal Neural Circuitry by Epidural Stimulation to Restore Motor Function After Spinal Cord Injury

OpenAIRE

Minassian, Karen; McKay, W. Barry; Binder, Heinrich; Hofstoetter, Ursula S.

2016-01-01

Epidural spinal cord stimulation has a long history of application for improving motor control in spinal cord injury. This review focuses on its resurgence following the progress made in understanding the underlying neurophysiological mechanisms and on recent reports of its augmentative effects upon otherwise subfunctional volitional motor control. Early work revealed that the spinal circuitry involved in lower-limb motor control can be accessed by stimulating through electrodes placed epidur...

Renal medullary AA amyloidosis, hepatocyte dissociation and multinucleated hepatocytes in a 14-year-old free-ranging lioness (Panthera leo

Directory of Open Access Journals (Sweden)

J.H. Williams

2005-06-01

Full Text Available A 14-year-old lioness, originating from Etosha in Namibia, and a member of a pride in Pilanesberg National Park since translocation in 1994, was euthanased due to fight-related vertebral fracture and spinal injury, incurred approximately 6-8 weeks previously. Blood specimens collected at the time of death showed mild anaemia and a leukogram reflecting stress and chronic infection. Necropsy conducted within 2 hours of death was on a dehydrated, emaciated animal with hindquarter wasting and chronic traumatic friction injuries from dragging her hindlegs. There was cellulitis in the region of bite-wounds adjacent to the thoraco-lumbar vertebral fracture, at which site there was spinal cord compression, and there was marked intestinal helminthiasis. The outer renal medullae appeared pale and waxy and the liver was macroscopically unremarkable. Histopathology and electron microscopy of the kidneys revealed multifocal to coalescing deposits of proximal medullary interstitial amyloid, which fluoresced strongly with thioflavine T, and was sensitive to potassium permanganate treatment prior to Congo Red staining, thus indicating inflammatory (AA origin. There was diffuse hepatocyte dissociation, as well as numerous binucleated and scattered multinucleated (up to 8 nuclei/cell hepatocytes, with swollen hepatocyte mitochondria, in liver examined light microscopically. Ultrastructurally, the mono-, bi- and multinucleated hepatocytes contained multifocal irregular membrane-bound accumulations of finely-granular, amorphous material both intra-cytoplasmically and intra-nuclearly, as well as evidence of irreversible mitochondrial injury. The incidence and relevance in cats and other species of amyloidosis, particularly with renal medullary distribution, as well as of hepatocyte dissociation and multinucleation, as reported in selected literature, is briefly overviewed and their occurrence in this lioness is discussed.

Use of intra-medullary stacked nailing in the reduction of proximal plastic deformity in a pediatric Monteggia fracture: a case report

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Huntley James S

2011-04-01

Full Text Available Abstract Introduction In a Monteggia fracture dislocation, it is important to reduce the ulnar fracture completely. Extensive plastic deformation of the proximal ulna may make reduction by closed manipulation impossible. Case presentation We report the case of a four-year-old Caucasian boy in whom the plastic deformation of the proximal ulna was reduced, and this reduction was maintained, using intra-medullary stacked nailing. Conclusion The technique of stacked nailing is a useful addition to the armamentarium in the management of the potentially awkward Monteggia fracture.

Tone and call responses of units in the auditory nerve and dorsal medullary nucleus of Xenopus laevis

DEFF Research Database (Denmark)

Elliott, Taffeta M.; Christensen-Dalsgaard, Jakob; Kelley, Darcy B.

2007-01-01

The clawed frog Xenopus laevis produces vocalizations consisting of distinct patterns of clicks. This study provides the first description of spontaneous, pure-tone and communication-signal evoked discharge properties of auditory nerve (n.VIII) fibers and dorsal medullary nucleus (DMN) cells...... in an obligatorily aquatic anuran. Responses of 297 n.VIII and 253 DMN units are analyzed for spontaneous rates (SR), frequency tuning, rate-intensity functions, and firing rate adaptation, with a view to how these basic characteristics shape responses to recorded call stimuli. Response properties generally resemble......Hz with approximately 500 Hz in 3 dB bandwidth. SRs range from 0 to 80 (n.VIII) and 0 to 73 spikes/s (DMN). Nerve and DMN units of all CFs follow click rates in natural calls,

NF-κB–YY1–miR-29 Regulatory Circuitry in Skeletal Myogenesis and Rhabdomyosarcoma

Science.gov (United States)

Wang, Huating; Garzon, Ramiro; Sun, Hao; Ladner, Katherine J.; Singh, Ravi; Dahlman, Jason; Cheng, Alfred; Hall, Brett M.; Qualman, Stephen J.; Chandler, Dawn S.; Croce, Carlo M.; Guttridge, Denis C.

2008-01-01

SUMMARY Studies support the importance of microRNAs in physiological and pathological processes. Here we describe the regulation and function of miR-29 in myogenesis and Rhabdomyosarcoma (RMS). Results demonstrate that in myoblasts miR-29 is repressed by NF-κB acting through YY1 and the Polycomb. During myogenesis, NF-κB and YY1 downregulation causes derepression of miR-29, which in turn accelerates differentiation by targeting its repressor YY1. However, in RMS cells and primary tumors that possess impaired differentiation, miR-29 is epigenetically silenced by an activated NF-κB-YY1 pathway. Reconstitution of miR-29 in RMS in mice inhibits tumor growth and stimulates differentiation, suggesting that miR-29 acts as a tumor suppressor through its pro-myogenic function. Together, results identify a NF-κB–YY1–miR-29 regulatory circuit whose disruption may contribute to RMS. SIGNIFICANCE MicroRNAs regulate skeletal myogenesis, but their impact in muscle diseases is not well understood. Here we describe miR-29 as an enhancer of myogenic differentiation and a suppressor of RMS. We find that miR-29 exists in a regulatory circuit involving NF-κB and YY1. In myoblasts NF-B acts through YY1 to epigenetically suppress miR-29, while during differentiation miR-29 is induced to facilitate myogenesis by a negative feedback on YY1. Significantly, RMS tumors lose miR-29 due to an elevation in NF-B and YY1, and readjustment of miR-29 levels in RMS stimulates differentiation. Thus, myogenesis is dependent on NF-κB–YY1–miR-29 circuitry whose dysfunction may contribute to RMS pathogenesis. Such findings offer potential avenues for the diagnosis and treatment of muscle relevant cancers. PMID:18977326

New Drug Candidate Targeting the 4A1 Orphan Nuclear Receptor for Medullary Thyroid Cancer Therapy

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Lei Zhang

2018-03-01

Full Text Available Medullary thyroid cancer (MTC is a relatively rare thyroid cancer responsible for a substantial fraction of thyroid cancer mortality. More effective therapeutic drugs with low toxicity for MTC are urgently needed. Orphan nuclear receptor 4A1 (NR4A1 plays a pivotal role in regulating the proliferation and apoptosis of a variety of tumor cells. Based on the NR4A1 protein structure, 2-imino-6-methoxy-2H-chromene-3-carbothioamide (IMCA was identified from the Specs compounds database using the protein structure-guided virtual screening approach. Computationally-based molecular modeling studies suggested that IMCA has a high affinity for the ligand binding pocket of NR4A1. MTT [3-(4,5-dimethyl-2-thiazolyl-2,5-diphenyl-2-H-tetrazolium bromide] and apoptosis assays demonstrated that IMCA resulted in significant thyroid cancer cell death. Immunofluorescence assays showed that IMCA induced NR4A1 translocation from the nucleus to the cytoplasm in thyroid cancer cell lines, which may be involved in the cell apoptotic process. In this study, the quantitative polymerase chain reaction results showed that the IMCA-induced upregulation of sestrin1 and sestrin2 was dose-dependent in thyroid cancer cell lines. Western blot showed that IMCA increased phosphorylation of adenosine 5′-monophosphate-activated protein kinase (AMPK and decreased phosphorylation of ribosomal protein S6 kinase (p70S6K, which is the key enzyme in the mammalian target of rapamycin (mTOR pathway. The experimental results suggest that IMCA is a drug candidate for MTC therapy and may work by increasing the nuclear export of NR4A1 to the cytoplasm and the tumor protein 53 (p53-sestrins-AMPK-mTOR signaling pathway.

New Drug Candidate Targeting the 4A1 Orphan Nuclear Receptor for Medullary Thyroid Cancer Therapy.

Science.gov (United States)

Zhang, Lei; Liu, Wen; Wang, Qun; Li, Qinpei; Wang, Huijuan; Wang, Jun; Teng, Tieshan; Chen, Mingliang; Ji, Ailing; Li, Yanzhang

2018-03-02

Medullary thyroid cancer (MTC) is a relatively rare thyroid cancer responsible for a substantial fraction of thyroid cancer mortality. More effective therapeutic drugs with low toxicity for MTC are urgently needed. Orphan nuclear receptor 4A1 (NR4A1) plays a pivotal role in regulating the proliferation and apoptosis of a variety of tumor cells. Based on the NR4A1 protein structure, 2-imino-6-methoxy-2H-chromene-3-carbothioamide (IMCA) was identified from the Specs compounds database using the protein structure-guided virtual screening approach. Computationally-based molecular modeling studies suggested that IMCA has a high affinity for the ligand binding pocket of NR4A1. MTT [3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2-H-tetrazolium bromide] and apoptosis assays demonstrated that IMCA resulted in significant thyroid cancer cell death. Immunofluorescence assays showed that IMCA induced NR4A1 translocation from the nucleus to the cytoplasm in thyroid cancer cell lines, which may be involved in the cell apoptotic process. In this study, the quantitative polymerase chain reaction results showed that the IMCA-induced upregulation of sestrin1 and sestrin2 was dose-dependent in thyroid cancer cell lines. Western blot showed that IMCA increased phosphorylation of adenosine 5'-monophosphate-activated protein kinase (AMPK) and decreased phosphorylation of ribosomal protein S6 kinase (p70S6K), which is the key enzyme in the mammalian target of rapamycin (mTOR) pathway. The experimental results suggest that IMCA is a drug candidate for MTC therapy and may work by increasing the nuclear export of NR4A1 to the cytoplasm and the tumor protein 53 (p53)-sestrins-AMPK-mTOR signaling pathway.

The affection of APA microcapsulation on catecholamine and leucine-enkephalin secretion from the bovine adrenal medullary chromaffin cells

International Nuclear Information System (INIS)

Guo Shuilong; Cui Xin; Luo Yun; Xue Yilong

2002-01-01

The affection of alginate-polylysine-alginate (APA) microcapsulation on catecholamine (CA) and leucine-enkephalin (L-EK) secretion from bovine adrenal medullary chromaffin cells was analysed. Encapsulating BCCs with the APA microcapsulation, the secretion of CA and L-EK in encapsulated BCCs was detected by high-performance liquid chromatography-electrochemical assay and radioimmunoassay, respectively. There is little difference between the encapsulated BCCs and the non-encapsulated BCCs in the secretion of epinephrine (E) and noradrenaline (NE) but the secretion of dopamine (DA) and L-EK in several points decline. The studies indicated that APA microcapsulation of BCCs didn't affect the secretion of E and NE, but did the secretion DA and L-EK in forepart

Post-translational regulation of Oct4 transcriptional activity.

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Jonathan P Saxe

Full Text Available Oct4 is a key component of the molecular circuitry which regulates embryonic stem cell proliferation and differentiation. It is essential for maintenance of undifferentiated, pluripotent cell populations, and accomplishes these tasks by binding DNA in multiple heterodimer and homodimer configurations. Very little is known about how formation of these complexes is regulated, or the mechanisms through which Oct4 proteins respond to complex extracellular stimuli which regulate pluripotency. Here, we provide evidence for a phosphorylation-based mechanism which regulates specific Oct4 homodimer conformations. Point mutations of a putative phosphorylation site can specifically abrogate transcriptional activity of a specific homodimer assembly, with little effect on other configurations. Moreover, we performed bioinformatic predictions to identify a subset of Oct4 target genes which may be regulated by this specific assembly, and show that altering Oct4 protein levels affects transcription of Oct4 target genes which are regulated by this assembly but not others. Finally, we identified several signaling pathways which may mediate this phosphorylation and act in combination to regulate Oct4 transcriptional activity and protein stability. These results provide a mechanism for rapid and reversible alteration of Oct4 transactivation potential in response to extracellular signals.

Targeting Lumbar Spinal Neural Circuitry by Epidural Stimulation to Restore Motor Function After Spinal Cord Injury.

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Minassian, Karen; McKay, W Barry; Binder, Heinrich; Hofstoetter, Ursula S

2016-04-01

Epidural spinal cord stimulation has a long history of application for improving motor control in spinal cord injury. This review focuses on its resurgence following the progress made in understanding the underlying neurophysiological mechanisms and on recent reports of its augmentative effects upon otherwise subfunctional volitional motor control. Early work revealed that the spinal circuitry involved in lower-limb motor control can be accessed by stimulating through electrodes placed epidurally over the posterior aspect of the lumbar spinal cord below a paralyzing injury. Current understanding is that such stimulation activates large-to-medium-diameter sensory fibers within the posterior roots. Those fibers then trans-synaptically activate various spinal reflex circuits and plurisegmentally organized interneuronal networks that control more complex contraction and relaxation patterns involving multiple muscles. The induced change in responsiveness of this spinal motor circuitry to any residual supraspinal input via clinically silent translesional neural connections that have survived the injury may be a likely explanation for rudimentary volitional control enabled by epidural stimulation in otherwise paralyzed muscles. Technological developments that allow dynamic control of stimulation parameters and the potential for activity-dependent beneficial plasticity may further unveil the remarkable capacity of spinal motor processing that remains even after severe spinal cord injuries.

A novel germ-line point mutation in RET exon 8 (Gly(533)Cys) in a large kindred with familial medullary thyroid carcinoma

OpenAIRE

Silva, Adriana Madeira Alvares da [UNIFESP; Maciel, Rui Monteiro de Barros [UNIFESP; Dias-da-Silva, Magnus Régios [UNIFESP; Toledo, Silvia Regina Caminada de [UNIFESP; De Carvalho, Marcos B.; Cerutti, Janete Maria [UNIFESP

2003-01-01

Familial medullary thyroid carcinoma is related to germ-line mutations in the RET oncogene, mainly in cysteine codon 10 or 11, whereas noncysteine mutations in codons 13 - 15 are rare. We now report a new missense point mutation in exon 8 of the RET gene (1597G-->T) corresponding to a Gly(533)Cys substitution in the cystein-rich domain of RET protein in 76 patients from a 6-generation Brazilian family with 229 subjects, with ascendants from Spain. It is likely that the mutation causes familia...

Use of the gamma probe and of 99mTc-DMSA (V) in the identification of the neck recurrence of medullary carcinoma thyroid; Uso do gama probe e do 99mTc-DMSA (V) na identificacao de recorrencias cervicais de carcinoma medular de tireoide

Energy Technology Data Exchange (ETDEWEB)

Melo, Rosana Leite de; Kowalski, Luiz P.; Ubrich, Fabio F. [Hospital do Cancer A.C. Camargo, Sao Paulo, SP (Brazil). Centro de Tratamento e Pesquisa. Dept. de Cirurgia de Cabeca e Pescoco e Otorrinolaringologia; Lima, Eduardo N. Pereira; Torres, Ivone C.G. [Hospital do Cancer A.C. Camargo, Sao Paulo, SP (Brazil). Centro de Tratamento e Pesquisa. Dept. de Medicina Nuclear

2003-03-01

Medullary carcinoma of the thyroid, a malignant neoplasm of para follicular C cells, represent about 5-10% of thyroid tumors. The symptoms are related to local invasion and hormonal secretion. The clinical course is variable, from indolent cases to extremely aggressive. Many radionuclide imaging have been described to locate metastasis of medullary cancer. Tl-201 and Tc-99m (V)DMS A showed to be useful in the evaluation o persistent elevated serum calcitonin levels. On the other hand, the use of the 131 I-Mibg, that is the isotope more used, has not been demonstrating efficiency in identifying metastasis. Our objective is to report a case of a patient with medullary thyroid carcinoma in which the follow-up use DMS A(V) demonstrated a recurrence no identified for other methods. A 34-year-old man had a diagnosis of medullary thyroid carcinoma and has submitted a total thyroidectomy and neck lymph node dissection. He presented elevated serum calcitonin levels and DMS A(V) scintigraphy demonstrated focal area of pathologic uptake at the medline of the neck, but the surgical exploration was negative. He persisted with high calcitonin levels and it was used a new DMS A(V). On this occasion he was submitted to the radio-guided surgery that located the recurrence and it was confirmed with anatomo-pathologic exam. This case allowed to demonstrate that the use of radionuclide associated to the gamma-probe is promising, allowing a precise surgical approach. (author)

Radiation-Hardened Circuitry Using Mask-Programmable Analog Arrays. Final Report

Energy Technology Data Exchange (ETDEWEB)

Britton, Jr., Charles L. [Oak Ridge National Lab. (ORNL), Oak Ridge, TN (United States); Ericson, Milton Nance [Oak Ridge National Lab. (ORNL), Oak Ridge, TN (United States); Bobrek, Miljko [Oak Ridge National Lab. (ORNL), Oak Ridge, TN (United States); Blalock, Benjamin [Univ. of Tennessee, Knoxville, TN (United States)

2015-12-01

As the recent accident at Fukushima Daiichi so vividly demonstrated, telerobotic technologies capable of withstanding high radiation environments need to be readily available to enable operations, repair, and recovery under severe accident scenarios where human entry is extremely dangerous or not possible. Telerobotic technologies that enable remote operation in high dose rate environments have undergone revolutionary improvement over the past few decades. However, much of this technology cannot be employed in nuclear power environments due the radiation sensitivity of the electronics and the organic insulator materials currently in use. This is the final report of the activities involving the NEET 2 project Radiation Hardened Circuitry Using Mask-Programmable Analog Arrays. We present a detailed functional block diagram of the proposed data acquisition system, the thought process leading to technical decisions, the implemented system, and the tested results from the systems. This system will be capable of monitoring at least three parameters of importance to nuclear reactor monitoring: temperature, radiation level, and pressure.

Results of Screening in Familial Non-Medullary Thyroid Cancer.

Science.gov (United States)

Klubo-Gwiezdzinska, Joanna; Yang, Lily; Merkel, Roxanne; Patel, Dhaval; Nilubol, Naris; Merino, Maria J; Skarulis, Monica; Sadowski, Samira M; Kebebew, Electron

2017-08-01

Although a family history of thyroid cancer is one of the main risk factors for thyroid cancer, the benefit of screening individuals with a family history of thyroid cancer is not known. A prospective cohort study was performed with yearly screening using neck ultrasound and fine-needle aspiration biopsy of thyroid nodule(s) >0.5 cm in at-risk individuals whose relatives were diagnosed with familial non-medullary thyroid cancer (FNMTC). The eligibility criteria were the presence of thyroid cancer in two or more first-degree relatives and being older than seven years of age. Twenty-five kindred were enrolled in the study (12 families with two members affected, and 13 with three or more members affected at enrollment). Thyroid cancer was detected by screening in 4.6% (2/43) of at-risk individuals from families with two members affected, and in 22.7% (15/66) of at-risk members from families with three or more patients affected (p = 0.01). FNMTC detected by screening was characterized by a smaller tumor size (0.7 ± 0.5 cm vs. 1.5 ± 1.1 cm; p = 0.006), a lower rate of central neck lymph node metastases (17.6% vs. 51.1%; p = 0.02), less extensive surgery (hemithyroidectomy 23.5% vs. 0%; p = 0.002), and a lower rate of radioactive iodine therapy (23.5% vs. 79%; p thyroid ultrasound should be considered in kindred with three or more family members affected by FNMTC. Since active screening might be associated with the risk of overtreatment, it should be implemented with caution, specifically in elderly individuals.

Neuroanatomical circuitry associated with exploratory eye movement in schizophrenia: a voxel-based morphometric study.

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Linlin Qiu

Full Text Available Schizophrenic patients present abnormalities in a variety of eye movement tasks. Exploratory eye movement (EEM dysfunction appears to be particularly specific to schizophrenia. However, the underlying mechanisms of EEM dysfunction in schizophrenia are not clearly understood. To assess the potential neuroanatomical substrates of EEM, we recorded EEM performance and conducted a voxel-based morphometric analysis of gray matter in 33 schizophrenic patients and 29 well matched healthy controls. In schizophrenic patients, decreased responsive search score (RSS and widespread gray matter density (GMD reductions were observed. Moreover, the RSS was positively correlated with GMD in distributed brain regions in schizophrenic patients. Furthermore, in schizophrenic patients, some brain regions with neuroanatomical deficits overlapped with some ones associated with RSS. These brain regions constituted an occipito-tempro-frontal circuitry involved in visual information processing and eye movement control, including the left calcarine cortex [Brodmann area (BA 17], the left cuneus (BA 18, the left superior occipital cortex (BA 18/19, the left superior frontal gyrus (BA 6, the left cerebellum, the right lingual cortex (BA 17/18, the right middle occipital cortex (BA19, the right inferior temporal cortex (BA 37, the right dorsolateral prefrontal cortex (BA 46 and bilateral precentral gyri (BA 6 extending to the frontal eye fields (FEF, BA 8. To our knowledge, we firstly reported empirical evidence that gray matter loss in the occipito-tempro-frontal neuroanatomical circuitry of visual processing system was associated with EEM performance in schizophrenia, which may be helpful for the future effort to reveal the underlying neural mechanisms for EEM disturbances in schizophrenia.

Sixth Warren K. Sinclair keynote address: The role of a strong regulator in safe and secure nuclear energy.

Science.gov (United States)

Lyons, Peter B

2011-01-01

The history of nuclear regulation is briefly reviewed to underscore the early recognition that independence of the regulator was essential in achieving and maintaining public credibility. The current licensing process is reviewed along with the status of applications. Challenges faced by both the NRC and the industry are reviewed, such as new construction techniques involving modular construction, digital controls replacing analog circuitry, globalization of the entire supply chain, and increased security requirements. The vital area of safety culture is discussed in some detail, and its importance is emphasized. Copyright © 2010 Health Physics Society

Motor and non-motor circuitry activation induced by subthalamic nucleus deep brain stimulation (STN DBS) in Parkinson’s disease patients: Intraoperative fMRI for DBS

Science.gov (United States)

Knight, Emily J.; Testini, Paola; Min, Hoon-Ki; Gibson, William S.; Gorny, Krzysztof R.; Favazza, Christopher P.; Felmlee, Joel P.; Kim, Inyong; Welker, Kirk M.; Clayton, Daniel A.; Klassen, Bryan T.; Chang, Su-youne; Lee, Kendall H.

2015-01-01

Objective To test the hypothesis suggested by previous studies that subthalamic nucleus (STN) deep brain stimulation (DBS) in patients with PD would affect the activity of both motor and non-motor networks, we applied intraoperative fMRI to patients receiving DBS. Patients and Methods Ten patients receiving STN DBS for PD underwent intraoperative 1.5T fMRI during high frequency stimulation delivered via an external pulse generator. The study was conducted between the dates of January 1, 2013 and September 30, 2014. Results We observed blood oxygen level dependent (BOLD) signal changes (FDR<.001) in the motor circuitry, including primary motor, premotor, and supplementary motor cortices, thalamus, pedunculopontine nucleus (PPN), and cerebellum, as well as in the limbic circuitry, including cingulate and insular cortices. Activation of the motor network was observed also after applying a Bonferroni correction (p<.001) to our dataset, suggesting that, across subjects, BOLD changes in the motor circuitry are more consistent compared to those occurring in the non-motor network. Conclusions These findings support the modulatory role of STN DBS on the activity of motor and non-motor networks, and suggest complex mechanisms at the basis of the efficacy of this treatment modality. Furthermore, these results suggest that, across subjects, BOLD changes in the motor circuitry are more consistent compared to those occurring in the non-motor network. With further studies combining the use of real time intraoperative fMRI with clinical outcomes in patients treated with DBS, functional imaging techniques have the potential not only to elucidate the mechanisms of DBS functioning, but also to guide and assist in the surgical treatment of patients affected by movement and neuropsychiatric disorders. PMID:26046412

Cytologic aspects of an interesting case of medullary thyroid carcinoma coexisting with Hashimoto′s thyroiditis

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Bidish K Patel

2016-01-01

Full Text Available Among primary thyroid neoplasms, papillary thyroid carcinoma (PTC and primary thyroid lymphoma (PTL are known to coexist and are pathogenetically linked with Hashimoto′s thyroiditis (HT. However, HT occurring in association with medullary thyroid carcinoma (MTC is rarely documented. We report here an interesting case. A 34-year-old female with a solitary thyroid nodule underwent fine needle aspiration cytology (FNAC that was interpreted as "MTC with admixed reactive lymphoid cells, derived possibly from a pretracheal lymph node." Total thyroidectomy specimen showed "MTC with coexisting HT." At a later stage, a follow-up FNAC from the recurrent thyroid swelling showed features consistent with HT. As an academic exercise, the initial smears on which a diagnosis of MTC was offered were reviewed to look for evidence of coexisting HT that showed scanty and patchy aggregates of reactive lymphoid cells without Hόrthle cells. Our case highlights an unusual instance of MTC in concurrence with HT that can create a tricky situation for cytopathologists.

Localization of hepatic metastases by radiolabelled anti-carcino-embryonic antigen antibody and meta-iodobenzylguanidine in a patient with medullary thyroid carcinoma

International Nuclear Information System (INIS)

Liewendahl, K.; Vaelimaeki, M.; Taavitsainen, M.

1993-01-01

Sonography, computed tomography and magnetic resonance imaging examinations did not detect recurrence or metastases of medullary thyroid carcinoma (MTC) in a patient with a rapidly rising serum calcitonin concentration after total thyroidectomy. Scintigraphy with technetium-99m labelled anti-carcinoembryonic antigen antibody, 99m Tc-colloid and iodine-131 metaiodobenzylguanidine indicated liver metastases. The three scintigrams were to some extent discrepant but from the combined information the diagnosis of hepatic metastases could be established; it was subsequently verified by sonography and aspiration biopsy. This case demonstrates the usefulness of applying nuclear medicine imaging methods for the localization of hepatic MTC metastases. (orig.)

Three-dimensional cytomorphology in fine needle aspiration biopsy of medullary thyroid carcinoma.

Science.gov (United States)

Chang, T C; Lai, S M; Wen, C Y; Hsiao, Y L; Huang, S H

2001-01-01

To elucidate three-dimensional (3-D) cytomorphology in fine needle aspiration biopsy (FNAB) of medullary thyroid carcinoma (MTC). ENAB was performed on tumors from five patients with MTC. The aspirate was stained and observed under a light microscope (LM). The aspirate was also fixed, dehydrated, critical point dried, spattered with gold ions and observed with a scanning electron microscope (SEM). For transmission electron microscopy (TEM), the specimen was fixed, dehydrated, embedded in an Epon mixture, cut with an ultramicrotome, mounted on copper grids, electron doubly stained with uranium acetate and lead citrate, and observed with TEM. Findings under SEM were correlated with those under LM and TEM. Under SEM, 3-D cytomorphology of MTC displayed a disorganized cellular arrangement with indistinct cell borders in three cases. The cell surface was uneven and had granular protrusions that corresponded to secretory granules observed under TEM. In one case with multiple endocrine neoplasia type IIB, there were abundant granules on the cell surface. In one case of sporadic MTC with multinucleated tumor giant cells and small cells, granular protrusions also were noted on the cell surface. Granular protrusion was a characteristic finding in FNAB of MTC tinder SEM and might be helpful in the differential diagnosis.

Lateral hypothalamus, nucleus accumbens, and ventral pallidum roles in eating and hunger: interactions between homeostatic and reward circuitry

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Daniel Charles Castro

2015-06-01

Full Text Available The study of the neural bases of eating behavior, hunger, and reward has consistently implicated the lateral hypothalamus (LH and its interactions with mesocorticolimbic circuitry, such as mesolimbic dopamine projections to nucleus accumbens (NAc and ventral pallidum (VP, in controlling motivation to eat. The NAc and VP play special roles in mediating the hedonic impact (‘liking’ and motivational incentive salience (‘wanting’ of food rewards, and their interactions with LH help permit regulatory hunger/satiety modulation of food motivation and reward. Here, we review some progress that has been made regarding this circuitry and its functions: the identification of localized anatomical hedonic hotspots within NAc and VP for enhancing hedonic impact; interactions of NAc/VP hedonic hotspots with specific LH signals such as orexin; an anterior-posterior gradient of sites in NAc shell for producing intense appetitive eating versus intense fearful reactions; and anatomically distributed appetitive functions of dopamine and mu opioid signals in NAc shell and related structures. Such findings help improve our understanding of NAc, VP, and LH interactions in mediating affective and motivation functions, including ‘liking’ and ‘wanting’ for food rewards.

False positive results using calcitonin as a screening method for medullary thyroid carcinoma

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Rafael Loch Batista

2013-01-01

Full Text Available The role of serum calcitonin as part of the evaluation of thyroid nodules has been widely discussed in literature. However there still is no consensus of measurement of calcitonin in the initial evaluation of a patient with thyroid nodule. Problems concerning cost-benefit, lab methods, false positive and low prevalence of medullary thyroid carcinoma (MTC are factors that limit this approach. We have illustrated two cases where serum calcitonin was used in the evaluation of thyroid nodule and rates proved to be high. A stimulation test was performed, using calcium as secretagogue, and calcitonin hyper-stimulation was confirmed, but anatomopathologic examination did not evidence medullar neoplasia. Anatomopathologic diagnosis detected Hashimoto thyroiditis in one case and adenomatous goiter plus an occult papillary thyroid carcinoma in the other one. Recommendation for routine use of serum calcitonin in the initial diagnostic evaluation of a thyroid nodule, followed by a confirming stimulation test if basal serum calcitonin is showed to be high, is the most currently recommended approach, but questions concerning cost-benefit and possibility of diagnosis error make the validity of this recommendation discussible.

Second messenger production in avian medullary nephron segments in response to peptide hormones.

Science.gov (United States)

Goldstein, D L; Reddy, V; Plaga, K

1999-03-01

We examined the sites of peptide hormone activation within medullary nephron segments of the house sparrow (Passer domesticus) kidney by measuring rates of hormone-induced generation of cyclic nucleotide second messenger. Thin descending limbs, thick ascending limbs, and collecting ducts had baseline activity of adenylyl cyclase that resulted in cAMP accumulation of 207 +/- 56, 147 +/- 31, and 151 +/- 41 fmol. mm-1. 30 min-1, respectively. In all segments, this activity increased 10- to 20-fold in response to forskolin. Activity of adenylyl cyclase in the thin descending limb was stimulated approximately twofold by parathyroid hormone (PTH) but not by any of the other hormones tested [arginine vasotocin (AVT), glucagon, atrial natriuretic peptide (ANP), or isoproterenol, each at 10(-6) M]. Thick ascending limb was stimulated two- to threefold by both AVT and PTH; however, glucagon and isoproterenol had no effect, and ANP stimulated neither cAMP nor cGMP accumulation. Adenylyl cyclase activity in the collecting duct was stimulated fourfold by AVT but not by the other hormones; likewise, ANP did not stimulate cGMP accumulation in this segment. These data support a tubular action of AVT and PTH in the avian renal medulla.

Engineering nucleic acid structures for programmable molecular circuitry and intracellular biocomputation

Science.gov (United States)

Li, Jiang; Green, Alexander A.; Yan, Hao; Fan, Chunhai

2017-11-01

Nucleic acids have attracted widespread attention due to the simplicity with which they can be designed to form discrete structures and programmed to perform specific functions at the nanoscale. The advantages of DNA/RNA nanotechnology offer numerous opportunities for in-cell and in-vivo applications, and the technology holds great promise to advance the growing field of synthetic biology. Many elegant examples have revealed the potential in integrating nucleic acid nanostructures in cells and in vivo where they can perform important physiological functions. In this Review, we summarize the current abilities of DNA/RNA nanotechnology to realize applications in live cells and then discuss the key problems that must be solved to fully exploit the useful properties of nanostructures. Finally, we provide viewpoints on how to integrate the tools provided by DNA/RNA nanotechnology and related new technologies to construct nucleic acid nanostructure-based molecular circuitry for synthetic biology.

An evolution-based strategy for engineering allosteric regulation

Science.gov (United States)

Pincus, David; Resnekov, Orna; Reynolds, Kimberly A.

2017-04-01

Allosteric regulation provides a way to control protein activity at the time scale of milliseconds to seconds inside the cell. An ability to engineer synthetic allosteric systems would be of practical utility for the development of novel biosensors, creation of synthetic cell signaling pathways, and design of small molecule pharmaceuticals with regulatory impact. To this end, we outline a general approach—termed rational engineering of allostery at conserved hotspots (REACH)—to introduce novel regulation into a protein of interest by exploiting latent allostery that has been hard-wired by evolution into its structure. REACH entails the use of statistical coupling analysis (SCA) to identify ‘allosteric hotspots’ on protein surfaces, the development and implementation of experimental assays to test hotspots for functionality, and a toolkit of allosteric modulators to impinge on endogenous cellular circuitry. REACH can be broadly applied to rewire cellular processes to respond to novel inputs.

Trigeminal-Rostral Ventromedial Medulla circuitry is involved in orofacial hyperalgesia contralateral to tissue injury

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Chai Bryan

2012-10-01

Full Text Available Abstract Background Our previous studies have shown that complete Freund’s adjuvant (CFA-induced masseter inflammation and microinjection of the pro-inflammatory cytokine interleukin-1β (IL-1β into the subnucleus interpolaris/subnucleus caudalis transition zone of the spinal trigeminal nucleus (Vi/Vc can induce contralateral orofacial hyperalgesia in rat models. We have also shown that contralateral hyperalgesia is attenuated with a lesion of the rostral ventromedial medulla (RVM, a critical site of descending pain modulation. Here we investigated the involvement of the RVM-Vi/Vc circuitry in mediating contralateral orofacial hyperalgesia after an injection of CFA into the masseter muscle. Results Microinjection of the IL-1 receptor antagonist (5 nmol, n=6 into the ipsilateral Vi/Vc attenuated the CFA-induced contralateral hyperalgesia but not the ipsilateral hyperalgesia. Intra-RVM post-treatment injection of the NK1 receptor antagonists, RP67580 (0.5-11.4 nmol and L-733,060 (0.5-11.4 nmol, attenuated CFA-induced bilateral hyperalgesia and IL-1β induced bilateral hyperalgesia. Serotonin depletion in RVM neurons prior to intra-masseter CFA injection prevented the development of contralateral hyperalgesia 1–3 days after CFA injection. Inhibition of 5-HT3 receptors in the contralateral Vi/Vc with direct microinjection of the select 5-HT3 receptor antagonist, Y-25130 (2.6-12.9 nmol, attenuated CFA-induced contralateral hyperalgesia. Lesions to the ipsilateral Vc prevented the development of ipsilateral hyperalgesia but did not prevent the development of contralateral hyperalgesia. Conclusions These results suggest that the development of CFA-induced contralateral orofacial hyperalgesia is mediated through descending facilitatory mechanisms of the RVM-Vi/Vc circuitry.

Survival improvement in patients with disseminated medullary thyroid carcinoma treated with 131I-MIBG therapy

International Nuclear Information System (INIS)

Mihaljevic, I.; Topuzovi, N.; Snajder, D.

2015-01-01

Full text of publication follows. Introduction and aim: The aim of this paper is to present our experience of 131 I-MIBG therapy in the cases of aggressive form of medullary thyroid carcinoma (MTC) with local and distant metastases. MTC is an uncommon thyroid tumor, accounting from 3-5% of all thyroid malignancies, and arises from para-follicular C cells which produce calcitonin (CT). Prognosis of MTC is related to tumor extension at disease detection, but long-term survival in patients with disseminated MTC is still unsatisfactory. Methods: 4 female patients with metastatic MTC (63, 69 and 2 patients aged 73 years), which already underwent total thyroidectomy and selective neck dissection, received therapy with 100 mCi 131 I-MIBG in our Institute. Patients had widespread disease with neck recurrences (all 4 cases), liver and bone metastases (2 cases) and lung metastases (1 case). All those patients received the therapy twice, second one 3 months up to 1 year after the first cycle. After therapy, whole body scintigraphy was performed; tumor marker levels (CT, carcinoembryonic antigen - CEA, neuron specific enolase - NSE, chromogranin A - CgA and pro-gastrin releasing peptide - pro-GRP) were measured before and after therapy. Results: in one patient we observed a slight decrease in CT level after first MIBG therapy, in another one a slight decrease in CEA serum level, and no lung metastases were visible on whole body scan after second 131 I-MIBG therapy. In one of the two remaining cases there was a significant decrease in CT serum level only after neck dissection. In all cases the patients reported an improvement in subjective symptom reduction. Conclusion: 131 I-MIBG therapy could provide additional benefit to patients with MTC and could improve overall survival, but more patient should be treated in order to define the true potential of the therapy. The aim of this paper is to present our experience of 131 I-MIBG therapy in the cases of aggressive form of

Low stored energy 100 kV regulator for ion sources at LANSCE

International Nuclear Information System (INIS)

Jacobson, E.G.; Haffner, R.L.; Ingalls, W.B.; Meyer, B.J.; Stelzer, J.E.

1998-01-01

To minimize accelerating column damage caused by uncontrolled energy release during arc-downs, it is desirable to minimize the available stored electrical energy. For the Los Alamos Neutron Science Center (LANSCE) H - ion sources, the stored energy includes, in addition to the charge in the power supply output capacitance, the charge on the electronics racks. They are supported and insulated from ground by PVC pipe and have a capacitance to ground of approximately 900 pf. In 1988 (LANSCE) personnel designed a high-voltage current source using a low-stored-energy power supply and planar triode with the goal of eliminating uncontrolled release of charge stored in the power supply. Construction and testing were performed intermittently as resources permitted until 1993. When work on the Short Pulse Spallation Source (SPSS) started on the LANSCE Ion Source Test Stand (ISTS) it was recognized that a higher current power supply would be needed and work resumed on the regulator circuitry. A 120 kV power supply having low output capacitance, and a planar triode have been used to supply 40 mA, 120 Hz, 12% duty-factor current for the ISTS beam. The triode's cathode current is controlled by circuitry operating both at power-supply voltage level and at ground level via a fiber optic link. Voltage droop is approximately 600 V during the 1 ms beam pulse. The authors present the status of the regulator and its special challenges

Renal Medullary and Cortical Correlates in Fibrosis, Epithelial Mass, Microvascularity, and Microanatomy Using Whole Slide Image Analysis Morphometry.

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Alton B Farris

Full Text Available Renal tubulointerstitial injury often leads to interstitial fibrosis and tubular atrophy (IF/TA. IF/TA is typically assessed in the renal cortex and can be objectively quantitated with computerized image analysis (IA. However, the human medulla accounts for a substantial proportion of the nephron; therefore, medullary scarring will have important cortical consequences and may parallel overall chronic renal injury. Trichrome, periodic acid-Schiff (PAS, and collagen III immunohistochemistry (IHC were visually examined and quantitated on scanned whole slide images (WSIs (N = 67 cases. When tuned to measure fibrosis, IA of trichrome and Trichrome-PAS (T-P WSIs correlated for all anatomic compartments (among cortex, medulla, and entire tissue, r = 0.84 to 0.89, P all <0.0001; and collagen III deposition correlated between compartments (r = 0.69 to 0.89, P <0.0001 to 0.0002; however, trichrome and T-P measures did not correlate with collagen deposition, suggesting heterogeneous contributions to extracellular matrix deposition. Epithelial cell mass (EPCM correlated between cortex and medulla when measured with cytokeratin IHC and with the trichrome red portion (r = 0.85 and 0.66, respectively, all P < 0.0001. Visual assessment also correlated between compartments for fibrosis and EPCM. Correlations were found between increasing medullary inner stripe (IS width and fibrosis in all of the tissue and the medulla by trichrome morphometry (r = 0.56, P < 0.0001, and r = 0.48, P = 0.00008, respectively. Weak correlations were found between increasing IS width and decreasing visual assessment of all tissue EPCM. Microvessel density (MVD and microvessel area (MVA measured using a MVD algorithm applied to CD34 IHC correlated significantly between all compartments (r = 0.76 to 0.87 for MVD and 0.71 to 0.87 for MVA, P all < 0.0001. Overall, these findings demonstrate the interrelatedness of the cortex and medulla and the importance of considering the renal

P2Y2 receptor knock-out mice display normal NaCl absorption in medullary thick ascending limb

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Rita Delgado Marques

2013-10-01

Full Text Available Local purinergic signals modulate renal tubular transport. Acute activation of renal epithelial P2 receptors causes inhibition of epithelial transport and thus, should favor increased water and salt excretion by the kidney. So far only a few studies have addressed the effects of extracellular nucleotides on ion transport in the thick ascending limb. In the medullary thick ascending limb (mTAL, basolateral P2X receptors markedly (~25% inhibit NaCl absorption. Although this segment does express both apical and basolateral P2Y2 receptors, acute activation of the basolateral P2Y2 receptors had no apparent effect on transepithelial ion transport. Here we studied, if the absence of the P2Y2 receptor causes chronic alterations in mTAL NaCl absorption by comparing basal and AVP-stimulated transepithelial transport rates. We used perfused mouse mTALs to electrically measure NaCl absorption in juvenile (35 days male mice. Using microelectrodes, we determined the transepithelial voltage (Vte and the transepithelial resistance (Rte and thus, transepithelial NaCl absorption (equivalent short circuit current, I’sc.We find that mTALs from adult wild type (WT mice have significantly lower NaCl absorption rates when compared to mTALs from juvenile WT mice. This could be attributed to significantly higher Rte values in mTALs from adult WT mice. This pattern was not observed in mTALs from P2Y2 receptor knockout (KO mice. In addition, adult P2Y2 receptor KO mTALs have significantly lower Vte values compared to the juvenile. No difference in absolute I´sc was observed when comparing mTALs from WT and KO mice. AVP stimulated the mTALs to similar increases of NaCl absorption irrespective of the absence of the P2Y2 receptor. No difference was observed in the medullary expression level of NKCC2 in between the genotypes.These data indicate that the lack of P2Y2 receptors does not cause substantial differences in resting and AVP-stimulated NaCl absorption in

Genomic Circuitry Underlying Immunological Response to Pediatric Acute Respiratory Infection.

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Henrickson, Sarah E; Manne, Sasikanth; Dolfi, Douglas V; Mansfield, Kathleen D; Parkhouse, Kaela; Mistry, Rakesh D; Alpern, Elizabeth R; Hensley, Scott E; Sullivan, Kathleen E; Coffin, Susan E; Wherry, E John

2018-01-09

Acute respiratory tract viral infections (ARTIs) cause significant morbidity and mortality. CD8 T cells are fundamental to host responses, but transcriptional alterations underlying anti-viral mechanisms and links to clinical characteristics remain unclear. CD8 T cell transcriptional circuitry in acutely ill pediatric patients with influenza-like illness was distinct for different viral pathogens. Although changes included expected upregulation of interferon-stimulated genes (ISGs), transcriptional downregulation was prominent upon exposure to innate immune signals in early IFV infection. Network analysis linked changes to severity of infection, asthma, sex, and age. An influenza pediatric signature (IPS) distinguished acute influenza from other ARTIs and outperformed other influenza prediction gene lists. The IPS allowed a deeper investigation of the connection between transcriptional alterations and clinical characteristics of acute illness, including age-based differences in circuits connecting the STAT1/2 pathway to ISGs. A CD8 T cell-focused systems immunology approach in pediatrics identified age-based alterations in ARTI host response pathways. Copyright © 2017 The Author(s). Published by Elsevier Inc. All rights reserved.

Identification of genes with altered expression in medullary breast cancer vs. ductal breast cancer and normal breast epithelia

DEFF Research Database (Denmark)

Gjerstorff, Morten; Benoit, Vivian; Laenkholm, Anne-Vibeke

2006-01-01

to both immunological and endogenous cellular factors, although little is known about the distinct biology of MCB that may contribute to the improved outcome of MCB patients. To identify candidate genes, we performed gene array expression analysis of cell lines of MCB, ductal breast cancer and normal......Medullary breast cancer (MCB) is a morphologically and biologically distinct subtype that, despite cytologically highly malignant characteristics, has a favorable prognosis compared to the more common infiltrating ductal breast carcinoma. MCB metastasizes less frequently, which has been attributed...... breast epithelia, and the differential expression of a panel of candidate genes was further validated by quantitative PCR and immunohistochemical analysis of cell lines and tumor biopsies. A limited number of genes, including several members of the GAGE and insulin growth factor binding protein (IGFBP...

Circuitry Linking the Catabolite Repression and Csr Global Regulatory Systems of Escherichia coli.

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Pannuri, Archana; Vakulskas, Christopher A; Zere, Tesfalem; McGibbon, Louise C; Edwards, Adrianne N; Georgellis, Dimitris; Babitzke, Paul; Romeo, Tony

2016-11-01

Cyclic AMP (cAMP) and the cAMP receptor protein (cAMP-CRP) and CsrA are the principal regulators of the catabolite repression and carbon storage global regulatory systems, respectively. cAMP-CRP controls the transcription of genes for carbohydrate metabolism and other processes in response to carbon nutritional status, while CsrA binds to diverse mRNAs and regulates translation, RNA stability, and/or transcription elongation. CsrA also binds to the regulatory small RNAs (sRNAs) CsrB and CsrC, which antagonize its activity. The BarA-UvrY two-component signal transduction system (TCS) directly activates csrB and csrC (csrB/C) transcription, while CsrA does so indirectly. We show that cAMP-CRP inhibits csrB/C transcription without negatively regulating phosphorylated UvrY (P-UvrY) or CsrA levels. A crp deletion caused an elevation in CsrB/C levels in the stationary phase of growth and increased the expression of csrB-lacZ and csrC-lacZ transcriptional fusions, although modest stimulation of CsrB/C turnover by the crp deletion partially masked the former effects. DNase I footprinting and other studies demonstrated that cAMP-CRP bound specifically to three sites located upstream from the csrC promoter, two of which overlapped the P-UvrY binding site. These two proteins competed for binding at the overlapping sites. In vitro transcription-translation experiments confirmed direct repression of csrC-lacZ expression by cAMP-CRP. In contrast, cAMP-CRP effects on csrB transcription may be mediated indirectly, as it bound nonspecifically to csrB DNA. In the reciprocal direction, CsrA bound to crp mRNA with high affinity and specificity and yet exhibited only modest, conditional effects on expression. Our findings are incorporated into an emerging model for the response of Csr circuitry to carbon nutritional status. Csr (Rsm) noncoding small RNAs (sRNAs) CsrB and CsrC of Escherichia coli use molecular mimicry to sequester the RNA binding protein CsrA (RsmA) away from lower

Roles of Akt and SGK1 in the Regulation of Renal Tubular Transport

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Nobuhiko Satoh

2015-01-01

Full Text Available A serine/threonine kinase Akt is a key mediator in various signaling pathways including regulation of renal tubular transport. In proximal tubules, Akt mediates insulin signaling via insulin receptor substrate 2 (IRS2 and stimulates sodium-bicarbonate cotransporter (NBCe1, resulting in increased sodium reabsorption. In insulin resistance, the IRS2 in kidney cortex is exceptionally preserved and may mediate the stimulatory effect of insulin on NBCe1 to cause hypertension in diabetes via sodium retention. Likewise, in distal convoluted tubules and cortical collecting ducts, insulin-induced Akt phosphorylation mediates several hormonal signals to enhance sodium-chloride cotransporter (NCC and epithelial sodium channel (ENaC activities, resulting in increased sodium reabsorption. Serum- and glucocorticoid-inducible kinase 1 (SGK1 mediates aldosterone signaling. Insulin can stimulate SGK1 to exert various effects on renal transporters. In renal cortical collecting ducts, SGK1 regulates the expression level of ENaC through inhibition of its degradation. In addition, SGK1 and Akt cooperatively regulate potassium secretion by renal outer medullary potassium channel (ROMK. Moreover, sodium-proton exchanger 3 (NHE3 in proximal tubules is possibly activated by SGK1. This review focuses on recent advances in understanding of the roles of Akt and SGK1 in the regulation of renal tubular transport.

Motor and Nonmotor Circuitry Activation Induced by Subthalamic Nucleus Deep Brain Stimulation in Patients With Parkinson Disease: Intraoperative Functional Magnetic Resonance Imaging for Deep Brain Stimulation.

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Knight, Emily J; Testini, Paola; Min, Hoon-Ki; Gibson, William S; Gorny, Krzysztof R; Favazza, Christopher P; Felmlee, Joel P; Kim, Inyong; Welker, Kirk M; Clayton, Daniel A; Klassen, Bryan T; Chang, Su-youne; Lee, Kendall H

2015-06-01

To test the hypothesis suggested by previous studies that subthalamic nucleus (STN) deep brain stimulation (DBS) in patients with Parkinson disease would affect the activity of motor and nonmotor networks, we applied intraoperative functional magnetic resonance imaging (fMRI) to patients receiving DBS. Ten patients receiving STN DBS for Parkinson disease underwent intraoperative 1.5-T fMRI during high-frequency stimulation delivered via an external pulse generator. The study was conducted between January 1, 2013, and September 30, 2014. We observed blood oxygen level-dependent (BOLD) signal changes (false discovery rate <0.001) in the motor circuitry (including the primary motor, premotor, and supplementary motor cortices; thalamus; pedunculopontine nucleus; and cerebellum) and in the limbic circuitry (including the cingulate and insular cortices). Activation of the motor network was observed also after applying a Bonferroni correction (P<.001) to the data set, suggesting that across patients, BOLD changes in the motor circuitry are more consistent compared with those occurring in the nonmotor network. These findings support the modulatory role of STN DBS on the activity of motor and nonmotor networks and suggest complex mechanisms as the basis of the efficacy of this treatment modality. Furthermore, these results suggest that across patients, BOLD changes in the motor circuitry are more consistent than those in the nonmotor network. With further studies combining the use of real-time intraoperative fMRI with clinical outcomes in patients treated with DBS, functional imaging techniques have the potential not only to elucidate the mechanisms of DBS functioning but also to guide and assist in the surgical treatment of patients affected by movement and neuropsychiatric disorders. clinicaltrials.gov Identifier: NCT01809613. Copyright © 2015 Mayo Foundation for Medical Education and Research. Published by Elsevier Inc. All rights reserved.

Bidirectional regulation of bakuchiol, an estrogenic-like compound, on catecholamine secretion

International Nuclear Information System (INIS)

Mao, Haoping; Wang, Hong; Ma, Shangwei; Xu, Yantong; Zhang, Han; Wang, Yuefei; Niu, Zichang; Fan, Guanwei; Zhu, Yan; Gao, Xiu Mei

2014-01-01

Excess or deficiency of catecholamine (CA) secretion was related with several diseases. Recently, estrogen and phytoestrogens were reported to regulate the activity of CA system. Bakuchiol is a phytoestrogen isolated from the seeds of Psoralea corylifolia L. (Leguminosae) which has been used in Traditional Chinese medicine as a tonic or aphrodisiac. In the present study, bovine adrenal medullary cells were employed to investigate the effects and mechanisms of bakuchiol on the regulation of CA secretion. Further, its anti-depressant like and anti-stress effects were evaluated by using behavioral despair and chronic immobilization stress models. Our results indicated that bakuchiol showed bidirectional regulation on CA secretion. It stimulated basal CA secretion in a concentration dependent manner (p + (p + induced CA secretion was related with reduction of intracellular calcium rise. In vivo experiments, we found that bakuchiol significantly reduced immobilization time in behavioral despair mouse (p < 0.05 or 0.01), and plasma epinephrine (E) and norepinephrine (NE) levels in chronic immobilization stress (p < 0.05). Overall, these results present a bidirectional regulation of bakuchiol on CA secretion which indicated that bakuchiol may exert anti-stress and the potential anti-depressant-like effects. - Highlights: • Bakuchiol stimulated basal catecholamine secretion. • Bakuchiol inhibited various secretagogues induced catecholamine secretion. • Bakuchiol may have anti-stress and the potential anti-depression-like effects

Risperidone and Divalproex Differentially Engage the Fronto-Striato-Temporal Circuitry in Pediatric Mania: A Pharmacological Functional Magnetic Resonance Imaging Study

Science.gov (United States)

Pavuluri, Mani N.; Passarotti, Alessandra M.; Fitzgerald, Jacklynn M.; Wegbreit, Ezra; Sweeney, John A.

2012-01-01

Objective: The current study examined the impact of risperidone and divalproex on affective and working memory circuitry in patients with pediatric bipolar disorder (PBD). Method: This was a six-week, double-blind, randomized trial of risperidone plus placebo versus divalproex plus placebo for patients with mania (n = 21; 13.6 [plus or minus] 2.5…

Regulation of glycogenesis in bone marrow of irradiated body

Energy Technology Data Exchange (ETDEWEB)

Barkalaya, A I

1976-02-01

In connection with a stimulating effect of insulin on postradiation restoration of medullary hemopoiesis the authors studied the influence of insulin on glycogenesis of bone marrow in comparison with glycogenesis of the liver under the conditions of irradiation. As a result the experiment made on white mice the authors established that the level of glycogen in both tissues on the first two days after irradiation (750 R) increased. Later, the decrease of glycogen concentration was observed and its exhaustion was more marked. Insulin protected bone marrow and the liver from exhaustion of glycogen reserves and ensured a higher level of glycogen in the liver. It is supposed that the regulation mechanisms by means of insulin of glycogenesis in the bone marrow and the liver are mainly of the same type. The influence of insulin on carbohydrate metabolism in the bone marrow is likely to be of significance for postradiation hemopoiesis.

Left-right asymmetry defect in the hippocampal circuitry impairs spatial learning and working memory in iv mice.

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Kazuhiro Goto

Full Text Available Although left-right (L-R asymmetry is a fundamental feature of higher-order brain function, little is known about how asymmetry defects of the brain affect animal behavior. Previously, we identified structural and functional asymmetries in the circuitry of the mouse hippocampus resulting from the asymmetrical distribution of NMDA receptor GluR ε2 (NR2B subunits. We further examined the ε2 asymmetry in the inversus viscerum (iv mouse, which has randomized laterality of internal organs, and found that the iv mouse hippocampus exhibits right isomerism (bilateral right-sidedness in the synaptic distribution of the ε2 subunit, irrespective of the laterality of visceral organs. To investigate the effects of hippocampal laterality defects on higher-order brain functions, we examined the capacity of reference and working memories of iv mice using a dry maze and a delayed nonmatching-to-position (DNMTP task, respectively. The iv mice improved dry maze performance more slowly than control mice during acquisition, whereas the asymptotic level of performance was similar between the two groups. In the DNMTP task, the iv mice showed poorer accuracy than control mice as the retention interval became longer. These results suggest that the L-R asymmetry of hippocampal circuitry is critical for the acquisition of reference memory and the retention of working memory.

Management of treatment-related toxicities in advanced medullary thyroid cancer.

Science.gov (United States)

Brose, Marcia S; Bible, Keith C; Chow, Laura Q M; Gilbert, Jill; Grande, Carolyn; Worden, Francis; Haddad, Robert

2018-04-22

Progress in the treatment of advanced medullary thyroid cancer (MTC) has resulted from the approval of 2 drugs within the past 5 years, vandetanib and cabozantinib. These multikinase inhibitors (MKIs) possess overlapping specificities for multiple kinase targets implicated in the progression of MTC. Both drugs are associated with toxicities, including hypertension, hemorrhage/perforation, diarrhea and other gastrointestinal events, several dermatologic events, and hypothyroidism. In addition, vandetanib is uniquely associated with QTc prolongation through interaction with myocardial potassium channels, and cabozantinib is uniquely associated with hand-foot skin reaction. Treatment-related toxicities occur frequently and can be severe or life-threatening, and patients undergoing long-term treatment will likely experience adverse events (AEs). Here we offer specific practical recommendations for managing AEs commonly occurring with vandetanib and cabozantinib. The recommended approach relies on early recognition and palliation of symptoms, dose interruption, and dose reduction as necessary in order for the patient to maintain the highest tolerable dose for as long as possible and optimal quality of life. Treatment guidelines do not specify a recommended sequence for treating with vandetanib and cabozantinib; however, most patients will receive both drugs during their lifetime. The choice for first-line therapy is individualized after a risk-benefit assessment and depends on physician preference and patient-related factors, such as comorbid conditions. Because most generalist practices may not be familiar with the intricacies of agents such as vandetanib and cabozantinib, we commend that patients with advanced MTC be managed and treated by a thyroid cancer specialist with coordination of care within a multidisciplinary team. Copyright © 2018. Published by Elsevier Ltd.

Changes of medullary hemopoiesis produced by chronic exposure to tritium oxide and external γ-radiation

International Nuclear Information System (INIS)

Murzina, L.D.; Muksinova, K.N.

1982-01-01

A comparative study of a chronic effect of tritium oxide ( 3 HOH) and external γ-radiation by 137 Cs on medullary hemopoiesis was conducted in experiments on Wistar rats. 3 HOH was administered for 3mos., 37x10 4 Bk per lg per of body mass daily (the absorbed dose 10.8 Gy), external irradiation was given in correlated values of dose rates and integral doses. Bone marrow depopulation was 1.9 times as deeper in rats exposed to 3 HOH as compared to that in irradiated rats. This difference is caused by early and stable inhibition of erythropoiesis with the administration of the radionuclide. The integral index showing the injuring effect of tritium on erythropoiesis was 4 times as high as compared to that of external γ-irradiation by 137 Cs. The time course of value of the proliferative pool of bone marrow granulocytes with the exposure to 2 types of radiation was monotypic. Differences in maturing and functioning granulocytic pools were marked in early time of the experiment

Cost-benefit decision circuitry: proposed modulatory role for acetylcholine.

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Fobbs, Wambura C; Mizumori, Sheri J Y

2014-01-01

In order to select which action should be taken, an animal must weigh the costs and benefits of possible outcomes associate with each action. Such decisions, called cost-benefit decisions, likely involve several cognitive processes (including memory) and a vast neural circuitry. Rodent models have allowed research to begin to probe the neural basis of three forms of cost-benefit decision making: effort-, delay-, and risk-based decision making. In this review, we detail the current understanding of the functional circuits that subserve each form of decision making. We highlight the extensive literature by detailing the ability of dopamine to influence decisions by modulating structures within these circuits. Since acetylcholine projects to all of the same important structures, we propose several ways in which the cholinergic system may play a local modulatory role that will allow it to shape these behaviors. A greater understanding of the contribution of the cholinergic system to cost-benefit decisions will permit us to better link the decision and memory processes, and this will help us to better understand and/or treat individuals with deficits in a number of higher cognitive functions including decision making, learning, memory, and language. © 2014 Elsevier Inc. All rights reserved.

Mild to moderate increase of serum calcitonin levels only in presence of large medullary thyroid cancer deposits.

Science.gov (United States)

Pelizzo, M R; Torresan, F; Da Roit, A; Merante Boschin, I; Chondrogiannis, S; Rampin, L; Colletti, P M; Vinjamury, S; Perkins, A J; Rubello, D

2015-01-01

Many open questions remain to be elucidated about the diagnosis, treatment and prognosis of medullary thyroid cancer (MTC). The most intriguing concerns the outcome of MTC patients after surgery. Great importance is usually given to serum calcitonin (Ct) and carcinoembryonic (CEA) levels. It is commonly believed that the higher are the levels of these tumor markers and their kinetics (double time and velocity of markers levels) the worst is the prognosis. However, this is not the rule, as there are huge MTC metastatic deposits characterized by low serum Ct and CEA levels, and this condition is not closely related to the outcome of the disease during post-surgical follow-up. A series is reported here of patients who have these characteristics, as well as a description of their prognosis and clinical outcome. Copyright © 2015 Elsevier España, S.L.U. and SEMNIM. All rights reserved.

Disrupted Working Memory Circuitry in Adolescent Psychosis

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Ariel Eckfeld

2017-08-01

Full Text Available Individuals with schizophrenia (SZ consistently show deficits in spatial working memory (WM and associated atypical patterns of neural activity within key WM regions, including the dorsolateral prefrontal cortex (dlPFC and parietal cortices. However, little research has focused on adolescent psychosis (AP and potential age-associated disruptions of WM circuitry that may occur in youth with this severe form of illness. Here we utilized each subject’s individual spatial WM capacity to investigate task-based neural dysfunction in 17 patients with AP (16.58 ± 2.60 years old as compared to 17 typically developing, demographically comparable adolescents (18.07 ± 3.26 years old. AP patients showed lower behavioral performance at higher WM loads and lower overall WM capacity compared to healthy controls. Whole-brain activation analyses revealed greater bilateral precentral and right postcentral activity in controls relative to AP patients, when controlling for individual WM capacity. Seed-based psychophysiological interaction (PPI analyses revealed significantly greater co-activation between the left dlPFC and left frontal pole in controls relative to AP patients. Significant group-by-age interactions were observed in both whole-brain and PPI analyses, with AP patients showing atypically greater neural activity and stronger coupling between WM task activated brain regions as a function of increasing age. Additionally, AP patients demonstrated positive relationships between right dlPFC neural activity and task performance, but unlike healthy controls, failed to show associations between neural activity and out-of-scanner neurocognitive performance. Collectively, these findings are consistent with atypical WM-related functioning and disrupted developmental processes in youth with AP.

The prognostic value of tumor markers doubling times in medullary thyroid carcinoma - preliminary report

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Gawlik Tomasz

2010-11-01

Full Text Available Abstract Introduction Calcitonin (Ct and carcinoembrional antigen (CEA are widely used as tumor markers for the post-operative follow-up of patients with medullary thyroid carcinoma (MTC. In patients with elevated serum Ct and CEA their dynamics can be described by calculating the doubling time (DT - the time, they need to double the serum concentration. Previous reports concluded that the Ct and CEA DT have prognostic value in MTC patients. Patients and methods We retrospectively analyzed data of 70 MTC patients with elevated serum Ct or CEA. In total, doubling times were calculated and the DT of the less favorable marker was used to stratify the patients into the low- and high-risk group with the cut-off value of 2 years. The survival analysis was performed using Cox proportional hazard method. Results The doubling time Conclusions The calcitonin and carcinembrional antigen doubling times of less than two years are negative prognostic factors for MTC recurrence-free and total survival in patients with persistent or recurrent disease. They may be used as predictive factors for more intensive search of disease localization in asymptomatic hypercalcitoninemia and for therapy choice in symptomatic disease.

NeuronBank: a tool for cataloging neuronal circuitry

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Paul S Katz

2010-04-01

Full Text Available The basic unit of any nervous system is the neuron. Therefore, understanding the operation of nervous systems ultimately requires an inventory of their constituent neurons and synaptic connectivity, which form neural circuits. The presence of uniquely identifiable neurons or classes of neurons in many invertebrates has facilitated the construction of cellular-level connectivity diagrams that can be generalized across individuals within a species. Homologous neurons can also be recognized across species. Here we describe NeuronBank.org, a web-based tool that we are developing for cataloging, searching, and analyzing neuronal circuitry within and across species. Information from a single species is represented in an individual branch of NeuronBank. Users can search within a branch or perform queries across branches to look for similarities in neuronal circuits across species. The branches allow for an extensible ontology so that additional characteristics can be added as knowledge grows. Each entry in NeuronBank generates a unique accession ID, allowing it to be easily cited. There is also an automatic link to a Wiki page allowing an encyclopedic explanation of the entry. All of the 44 previously published neurons plus one previously unpublished neuron from the mollusc, Tritonia diomedea, have been entered into a branch of NeuronBank as have 4 previously published neurons from the mollusc, Melibe leonina. The ability to organize information about neuronal circuits will make this information more accessible, ultimately aiding research on these important models.

Carcinoma medular da mama: correlação anátomo-radiológica Medullary breast carcinoma: anatomo-radiological correlation

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Valéria Soares Matheus

2008-12-01

Full Text Available OBJETIVO: Avaliar as características radiológicas do câncer de mama medular em pacientes submetidas a tratamento cirúrgico no Instituto Nacional de Câncer (INCA - Ministério da Saúde, Rio de Janeiro, RJ, correlacionando os achados com estudo histopatológico. MATERIAIS E MÉTODOS: Foi realizado estudo descritivo retrospectivo de mulheres submetidas a tratamento cirúrgico no INCA, no período de janeiro de 1997 a dezembro de 2006, para identificação das pacientes com carcinoma medular e análise dos achados radiológicos. RESULTADOS: Foram identificadas 21.287 pacientes com diagnóstico de carcinoma neste período, sendo 76 pacientes com diagnóstico de carcinoma medular típico (0,357%. Nessas pacientes selecionadas, a idade média foi de 51,9 anos (32 a 81 anos. Dezenove pacientes apresentavam lesão na mamografia, sendo 17 (89,5% nódulos e 2 assimetrias focais (10,5%. Entre as pacientes com nódulo, 15 (88,1% apresentavam alta densidade e 2 eram isodensos (11,9%. Doze pacientes apresentavam achados ultra-sonográficos e, destas, 11 (91,6% apresentavam nódulos hipoecóicos. Foi observada uma paciente com nódulo anecóico com áreas de degeneração cística. CONCLUSÃO: O nódulo foi o achado radiológico dominante (89,5%, dos quais 88,1% apresentaram nódulos com alta densidade e margens circunscritas. Apesar das características radiológicas de benignidade, um nódulo com alta densidade, sólido, margens circunscritas e crescimento rápido deve ser investigado para confirmar o diagnóstico.OBJECTIVE: To evaluate radiological findings in patients submitted to surgical treatment for medullary breast cancer at Instituto Nacional de Câncer (INCA, Rio de Janeiro, RJ, Brazil, correlating them with histological results. MATERIALS AND METHODS: A retrospective descriptive study was developed with patients submitted to surgery at INCA, in the period from January 1997 to December 2006, for identifying the presence of medullary breast

Emotion regulation reduces loss aversion and decreases amygdala responses to losses.

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Sokol-Hessner, Peter; Camerer, Colin F; Phelps, Elizabeth A

2013-03-01

Emotion regulation strategies can alter behavioral and physiological responses to emotional stimuli and the neural correlates of those responses in regions such as the amygdala or striatum. The current study investigates the brain systems engaged when using an emotion regulation technique during financial decisions. In decision making, regulating emotion with reappraisal-focused strategies that encourage taking a different perspective has been shown to reduce loss aversion as observed both in choices and in the relative arousal responses to actual loss and gain outcomes. In the current study, we find using fMRI that behavioral loss aversion correlates with amygdala activity in response to losses relative to gains. Success in regulating loss aversion also correlates with the reduction in amygdala responses to losses but not to gains. Furthermore, across both decisions and outcomes, we find the reappraisal strategy increases baseline activity in dorsolateral and ventromedial prefrontal cortex and the striatum. The similarity of the neural circuitry observed to that seen in emotion regulation, despite divergent tasks, serves as further evidence for a role of emotion in decision making, and for the power of reappraisal to change assessments of value and thereby choices.

Corticostriatal Regulation of Acute Pain

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Erik Martinez

2017-05-01

Full Text Available The mechanisms for acute pain regulation in the brain are not well understood. The prefrontal cortex (PFC provides top-down control of emotional processes, and it projects to the nucleus accumbens (NAc. This corticostriatal projection forms an important regulatory pathway within the brain’s reward system. Recently, this projection has been suggested to control both sensory and affective phenotypes specifically associated with chronic pain. As this projection is also known to play a role in the transition from acute to chronic pain, we hypothesized that this corticostriatal circuit can also exert a modulatory function in the acute pain state. Here, we used optogenetics to specifically target the projection from the PFC to the NAc. We tested sensory pain behaviors with Hargreaves’ test and mechanical allodynia, and aversive pain behaviors with conditioned place preference (CPP test. We found that the activation of this corticostriatal circuit gave rise to bilateral relief from peripheral nociceptive inputs. Activation of this circuit also provided important control for the aversive response to transient noxious stimulations. Hence, our results support a novel role for corticostriatal circuitry in acute pain regulation.

Shear wave elastography in medullary thyroid carcinoma diagnostics.

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Dobruch-Sobczak, Katarzyna; Gumińska, Anna; Bakuła-Zalewska, Elwira; Mlosek, Krzysztof; Słapa, Rafał Z; Wareluk, Paweł; Krauze, Agnieszka; Ziemiecka, Agnieszka; Migda, Bartosz; Jakubowski, Wiesław; Dedecjus, Marek

2015-12-01

Shear wave elastography (SWE) is a modern method for the assessment of tissue stiffness. There has been a growing interest in the use of this technique for characterizing thyroid focal lesions, including preoperative diagnostics. The aim of the study was to assess the clinical usefulness of SWE in medullary thyroid carcinoma (MTC) diagnostics. A total of 169 focal lesions were identified in the study group (139 patients), including 6 MTCs in 4 patients (mean age: 45 years). B-mode ultrasound and SWE were performed using Aixplorer (SuperSonic, Aix-en-Provence), with a 4-15 MHz linear probe. The ultrasound was performed to assess the echogenicity and echostructure of the lesions, their margin, the halo sign, the height/width ratio (H/W ratio), the presence of calcifications and the vascularization pattern. This was followed by an analysis of maximum and mean Young's (E) modulus values for MTC (EmaxLR, EmeanLR) and the surrounding thyroid tissues (EmaxSR, EmeanSR), as well as mean E-values (EmeanLRz) for 2 mm region of interest in the stiffest zone of the lesion. The lesions were subject to pathological and/or cytological evaluation. The B-mode assessment showed that all MTCs were hypoechogenic, with no halo sign, and they contained micro- and/ or macrocalcifications. Ill-defined lesion margin were found in 4 out of 6 cancers; 4 out of 6 cancers had a H/W ratio > 1. Heterogeneous echostructure and type III vascularity were found in 5 out of 6 lesions. In the SWE, the mean value of EmaxLR for all of the MTCs was 89.5 kPa and (the mean value of EmaxSR for all surrounding tissues was) 39.7 kPa Mean values of EmeanLR and EmeanSR were 34.7 kPa and 24.4 kPa, respectively. The mean value of EmeanLRz was 49.2 kPa. SWE showed MTCs as stiffer lesions compared to the surrounding tissues. The lesions were qualified for fine needle aspiration biopsy based on B-mode assessment. However, the diagnostic algorithm for MTC is based on the measurement of serum calcitonin levels, B

Understanding overbidding: using the neural circuitry of reward to design economic auctions.

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Delgado, Mauricio R; Schotter, Andrew; Ozbay, Erkut Y; Phelps, Elizabeth A

2008-09-26

We take advantage of our knowledge of the neural circuitry of reward to investigate a puzzling economic phenomenon: Why do people overbid in auctions? Using functional magnetic resonance imaging (fMRI), we observed that the social competition inherent in an auction results in a more pronounced blood oxygen level-dependent (BOLD) response to loss in the striatum, with greater overbidding correlated with the magnitude of this response. Leveraging these neuroimaging results, we design a behavioral experiment that demonstrates that framing an experimental auction to emphasize loss increases overbidding. These results highlight a role for the contemplation of loss in understanding the tendency to bid "too high." Current economic theories suggest overbidding may result from either "joy of winning" or risk aversion. By combining neuroeconomic and behavioral economic techniques, we find that another factor, namely loss contemplation in a social context, may mediate overbidding in auctions.

"Liking" and "wanting" linked to Reward Deficiency Syndrome (RDS): hypothesizing differential responsivity in brain reward circuitry.

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Blum, Kenneth; Gardner, Eliot; Oscar-Berman, Marlene; Gold, Mark

2012-01-01

In an attempt to resolve controversy regarding the causal contributions of mesolimbic dopamine (DA) systems to reward, we evaluate the three main competing explanatory categories: "liking,"learning," and "wanting" [1]. That is, DA may mediate (a) the hedonic impact of reward (liking), (b) learned predictions about rewarding effects (learning), or (c) the pursuit of rewards by attributing incentive salience to reward-related stimuli (wanting). We evaluate these hypotheses, especially as they relate to the Reward Deficiency Syndrome (RDS), and we find that the incentive salience or "wanting" hypothesis of DA function is supported by a majority of the evidence. Neuroimaging studies have shown that drugs of abuse, palatable foods, and anticipated behaviors such as sex and gaming affect brain regions involving reward circuitry, and may not be unidirectional. Drugs of abuse enhance DA signaling and sensitize mesolimbic mechanisms that evolved to attribute incentive salience to rewards. Addictive drugs have in common that they are voluntarily selfadministered, they enhance (directly or indirectly) dopaminergic synaptic function in the nucleus accumbens (NAC), and they stimulate the functioning of brain reward circuitry (producing the "high" that drug users seek). Although originally believed simply to encode the set point of hedonic tone, these circuits now are believed to be functionally more complex, also encoding attention, reward expectancy, disconfirmation of reward expectancy, and incentive motivation. Elevated stress levels, together with polymorphisms of dopaminergic genes and other neurotransmitter genetic variants, may have a cumulative effect on vulnerability to addiction. The RDS model of etiology holds very well for a variety of chemical and behavioral addictions.

The Advantages of Human Milk Recognize the Spatiotemporal Locations of Toxins and Intelligently Bypass Them by Forming a Hummingbird-Like Hovering Neural Network Circuitry Based on an Organic Biomimetic Choline Acetyltransferase Memristor/Memcapacitor Prosthesis

Directory of Open Access Journals (Sweden)

E. T. CHEN

2016-08-01

Full Text Available We have demonstrated a unique approach to study human milk’s advantage in promoting and protecting infant early brain cognitive development by recognizing toxins and intelligently bypassing the toxin by forming high frequency oscillation (HFO in the brain circuitry when compared with organic cow milk samples based on an organic memristor/memcapacitor biomimetic Choline Acetyltransferase (CHAT neural network circuitry prosthesis along with a 3D Energy-sensory dynamic mapping method under antibody- free, radiolabeling-free, and reagent-less conditions. We also demonstrated cow milk is unfit for infant cognitive development, and it is actually harmful in terms of mutating infant brain synapse circuitry conformation, current flow direction, and energy output that lead to multiple Pathological High Frequency Oscillation (pHFO formations, and further, it led to sudden infant death syndrome (SIDS based on our prediction.

Glycogen Synthase Kinase-3 Modulates Hyperosmotic-Induced Urea Transporter A1 Relocation in the Inner Medullary Collecting Duct Cells.

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Li, Yong-Xia; Huang, Yun; Liu, Song; Mao, Yan; Yuan, Cheng-Yan; Yang, Xiao; Yao, Li-Jun

2016-01-01

Glycogen synthase kinase 3 (GSK3) regulates urine concentration by mediating the vasopressin-induced aquaporin 2 expression and water permeability, although it is unknown whether GSK3 also mediates the accumulation of the urea transporter A1 (UT-A1). The aim of this study is to investigate the effect of GSK3 on UT-A1 distribution. Mouse inner medullary collecting duct 3 cells were transfected with UT-A1-GFP construct. The stable transfected cells were cultured under hypertonic conditions, treated with GSK3 inhibitor lithium chloride, GSK3 activator, lysosome or proteasome inhibitor. The expression levels of UT-A1, GSK3, and phospho-GSK3 were analyzed using western blot. The interaction between UT-A1 and the Golgi apparatus was examined using confocal immunofluorescence microscope. The UT-A1 trafficking was examined using the biotinylation of surface membranes. UT-A1 dissociated away from the Golgi apparatus and translocated to the plasma membrane under hypertonic-NaCl and NaCl plus urea stimulation. This movement was accompanied by the increased phosphorylation of GSK3 and its localization on the cellular membrane. Moreover, these results were duplicated by treating the cells with the GSK3 inhibitor, and by contrast, were partially reversed by the GSK3 activator. Treating cells with a lysosome or proteasome inhibitor failed to attenuate the effects of hypertonic stimulus, indicating that the loss of UT-A1 from the Golgi was not due to degradation. Our results suggest that GSK3 may in part modulate the hypertonic-induced intracellular UT-A1 redistribution and its accumulation on the plasma membrane, which may constitute another mechanism by which GSK3 modulates urine concentration. © 2016 S. Karger AG, Basel.

Activation of ion transport systems during cell volume regulation

International Nuclear Information System (INIS)

Eveloff, J.L.; Warnock, D.G.

1987-01-01

This review discusses the activation of transport pathways during volume regulation, including their characteristics, the possible biochemical pathways that may mediate the activation of transport pathways, and the relations between volume regulation and transepithelial transport in renal cells. Many cells regulate their volume when exposed to an anisotonic medium. The changes in cell volume are caused by activation of ion transport pathways, plus the accompanying osmotically driven water movement such that cell volume returns toward normal levels. The swelling of hypertonically shrunken cells is termed regulatory volume increase (RVI) and involves an influx of NaCl into the cell via either activation of Na-Cl, Na-K-2Cl cotransport systems, or Na + -H + and Cl - -HCO 3 - exchangers. The reshrinking of hypotonically swollen cells is termed regulatory volume decrease (RVD) and involves an efflux of KCl and water from the cell by activation of either separate K + and Cl - conductances, a K-Cl cotransport system, or parallel K + -H + and Cl - -HCO 3 - exchangers. The biochemical mechanisms involved in the activation of transport systems are largely unknown, however, the phosphoinositide pathway may be implicated in RVI; phorbol esters, cGMP, and Ca 2+ affect the process of volume regulation. Renal tubular cells, as well as the blood cells that transverse the medulla, are subjected to increasing osmotic gradients from the corticomedullary junction to the papillary tip, as well as changing interstitial and tubule fluid osmolarity, depending on the diuretic state of the animal. Medullary cells from the loop of Henle and the papilla can volume regulate by activating Na-K-2Cl cotransport or Na + -H + and Cl - -HCO 3 - exchange systems

Comparison of dysphagia outcomes between rostral and caudal lateral medullary infarct patients.

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Chun, Min Ho; Kim, Daeha; Chang, Min Cheol

2017-11-01

A detailed knowledge of dysphagia outcomes in lateral medullary infarct (LMI) patients would enable proper establishment of swallowing therapy goals and strategies. However, little is known about the impact of infarct location on dysphagia outcomes in patients with LMI. Twenty patients with rostral LMI (rostral group) and 20 patients with caudal LMI (caudal group) participated in the study. All patients underwent swallowing therapy, which included compensatory treatments and strengthening exercises, for >3 months. Dysphagia evaluation was performed twice (during the subacute stage and six months after stroke onset) using videofluoroscopic swallowing studies. Dysphagia degree was assessed using the functional dysphagia scale (FDS), the penetration-aspiration scale (PAS) and the American Speech-Language-Hearing Association (ASHA) National Outcome Measurement System (NOMS) swallowing scale. In the subacute stage, the rostral group had significantly higher FDS and PAS scores and a significantly lower ASHA NOMS score than the caudal group. Patients from both groups showed significant improvement from the initial evaluation to the six-month evaluation. There were no significant differences in these scale scores between the two groups at the six-month evaluation. In the subacute stage, patients in the rostral group had more severe dysphagia than those in the caudal group. Dysphagia improved in both groups after 3-6 months of swallowing therapy. At six months after onset, there were no significant differences in dysphagia severity between the two groups. Recovery from dysphagia after LMI was observed regardless of the infarct location.

Structure of a shear-thickening polysaccharide extracted from the New Zealand black tree fern, Cyathea medullaris.

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Wee, May S M; Matia-Merino, Lara; Carnachan, Susan M; Sims, Ian M; Goh, Kelvin K T

2014-09-01

A shear-thickening water-soluble polysaccharide was purified from mucilage extracted from the fronds of the New Zealand black tree fern (Cyathea medullaris or 'mamaku' in Māori) and its structure characterised. Constituent sugar analysis by three complementary methods, combined with linkage analysis (of carboxyl reduced samples) and 1H and 13C nuclear magnetic resonance spectroscopy (NMR) revealed a glucuronomannan comprising a backbone of 4-linked methylesterified glucopyranosyl uronic acid and 2-linked mannopyranosyl residues, branched at O-3 of 45% and at both O-3 and O-4 of 53% of the mannopyranosyl residues with side chains likely comprising terminal xylopyranosyl, terminal galactopyranosyl, non-methylesterified terminal glucopyranosyl uronic acid and 3-linked glucopyranosyl uronic acid residues. The weight-average molecular weight of the purified polysaccharide was ∼1.9×10(6) Da as determined by size-exclusion chromatography coupled with multi-angle laser light scattering (SEC-MALLS). The distinctive rheological properties of this polysaccharide are discussed in relation to its structure. Copyright © 2014 Elsevier B.V. All rights reserved.

A framework for the first-person internal sensation of visual perception in mammals and a comparable circuitry for olfactory perception in Drosophila.

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Vadakkan, Kunjumon I

2015-01-01

Perception is a first-person internal sensation induced within the nervous system at the time of arrival of sensory stimuli from objects in the environment. Lack of access to the first-person properties has limited viewing perception as an emergent property and it is currently being studied using third-person observed findings from various levels. One feasible approach to understand its mechanism is to build a hypothesis for the specific conditions and required circuit features of the nodal points where the mechanistic operation of perception take place for one type of sensation in one species and to verify it for the presence of comparable circuit properties for perceiving a different sensation in a different species. The present work explains visual perception in mammalian nervous system from a first-person frame of reference and provides explanations for the homogeneity of perception of visual stimuli above flicker fusion frequency, the perception of objects at locations different from their actual position, the smooth pursuit and saccadic eye movements, the perception of object borders, and perception of pressure phosphenes. Using results from temporal resolution studies and the known details of visual cortical circuitry, explanations are provided for (a) the perception of rapidly changing visual stimuli, (b) how the perception of objects occurs in the correct orientation even though, according to the third-person view, activity from the visual stimulus reaches the cortices in an inverted manner and (c) the functional significance of well-conserved columnar organization of the visual cortex. A comparable circuitry detected in a different nervous system in a remote species-the olfactory circuitry of the fruit fly Drosophila melanogaster-provides an opportunity to explore circuit functions using genetic manipulations, which, along with high-resolution microscopic techniques and lipid membrane interaction studies, will be able to verify the structure

Ghrelin and obestatin in thyroid gland - immunohistochemical expression in nodular goiter, papillary and medullary cancer.

Science.gov (United States)

Gurgul, Edyta; Kasprzak, Aldona; Blaszczyk, Agata; Biczysko, Maciej; Surdyk-Zasada, Joanna; Seraszek-Jaros, Agnieszka; Ruchala, Marek

2015-01-01

Previous studies analyzing ghrelin and obestatin expression in thyroid gland tissue are not unanimous and are mostly related to ghrelin. The role of ghrelin and obestatin in the thyroid gland appears very interesting due to their probable involvement in cell proliferation. Furthermore, since the thyroid gland is associated with the maintenance of energy balance, the relationship between ghrelin, obestatin and thyroid function is worthy of consideration. The aim of the study was to assess ghrelin and obestatin immunocytochemical expression in nodular goiter (NG), papillary cancer (PTC) and medullary cancer (MTC). Analyzed samples included 9 cases of NG, 8 cases of PTC and 11 cases of MTC. The analysis of ghrelin and obestatin expression was performed by use of the immunohistochemical (IHC) EnVision system and evaluated with filter HSV software (quantitative morphometric analysis). Quantitative ghrelin expression in MTC cells was higher than in NG (p = 0.013) and correlated negatively with the size of the tumor (r= -0.829, p thyroid cell proliferation. The differences between ghrelin and obestatin immunoreactivity in benign and malignant thyroid tumors could support the theory of alternative transcription of the preproghrelin gene and independent production of ghrelin and obestatin.

Shear wave elastography in medullary thyroid carcinoma diagnostics

Directory of Open Access Journals (Sweden)

Katarzyna Dobruch-Sobczak

2015-12-01

Full Text Available Shear wave elastography (SWE is a modern method for the assessment of tissue stiffness. There has been a growing interest in the use of this technique for characterizing thyroid focal lesions, including preoperative diagnostics. Aim: The aim of the study was to assess the clinical usefulness of SWE in medullary thyroid carcinoma (MTC diagnostics. Materials and methods: A total of 169 focal lesions were identifi ed in the study group (139 patients, including 6 MTCs in 4 patients (mean age: 45 years. B-mode ultrasound and SWE were performed using Aixplorer (SuperSonic, Aix-en-Provence, with a 4–15 MHz linear probe. The ultrasound was performed to assess the echogenicity and echostructure of the lesions, their margin, the halo sign, the height/width ratio (H/W ratio, the presence of calcifi cations and the vascularization pattern. This was followed by an analysis of maximum and mean Young’s (E modulus values for MTC (EmaxLR, EmeanLR and the surrounding thyroid tissues (EmaxSR, EmeanSR, as well as mean E-values (EmeanLRz for 2 mm region of interest in the stiffest zone of the lesion. The lesions were subject to pathological and/or cytological evaluation. Results: The B-mode assessment showed that all MTCs were hypoechogenic, with no halo sign, and they contained micro- and/ or macrocalcifi cations. Ill-defi ned lesion margin were found in 4 out of 6 cancers; 4 out of 6 cancers had a H/W ratio > 1. Heterogeneous echostructure and type III vascularity were found in 5 out of 6 lesions. In the SWE, the mean value of EmaxLR for all of the MTCs was 89.5 kPa and (the mean value of EmaxSR for all surrounding tissues was 39.7 kPa Mean values of EmeanLR and EmeanSR were 34.7 kPa and 24.4 kPa, respectively. The mean value of EmeanLRz was 49.2 kPa. Conclusions: SWE showed MTCs as stiffer lesions compared to the surrounding tissues. The lesions were qualifi ed for fi ne needle aspiration biopsy based on B-mode assessment. However, the diagnostic algorithm

Anatomical Recruitment of Spinal V2a Interneurons into Phrenic Motor Circuitry after High Cervical Spinal Cord Injury.

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Zholudeva, Lyandysha V; Karliner, Jordyn S; Dougherty, Kimberly J; Lane, Michael A

2017-11-01

More than half of all spinal cord injuries (SCIs) occur at the cervical level, often resulting in impaired respiration. Despite this devastating outcome, there is substantial evidence for endogenous neuroplasticity after cervical SCI. Spinal interneurons are widely recognized as being an essential anatomical component of this plasticity by contributing to novel neuronal pathways that can result in functional improvement. The identity of spinal interneurons involved with respiratory plasticity post-SCI, however, has remained largely unknown. Using a transgenic Chx10-eGFP mouse line (Strain 011391-UCD), the present study is the first to demonstrate the recruitment of excitatory interneurons into injured phrenic circuitry after a high cervical SCI. Diaphragm electromyography and anatomical analysis were used to confirm lesion-induced functional deficits and document extent of the lesion, respectively. Transneuronal tracing with pseudorabies virus (PRV) was used to identify interneurons within the phrenic circuitry. There was a robust increase in the number of PRV-labeled V2a interneurons ipsilateral to the C2 hemisection, demonstrating that significant numbers of these excitatory spinal interneurons were anatomically recruited into the phrenic motor pathway two weeks after injury, a time known to correspond with functional phrenic plasticity. Understanding this anatomical spinal plasticity and the neural substrates associated with functional compensation or recovery post-SCI in a controlled, experimental setting may help shed light onto possible cellular therapeutic candidates that can be targeted to enhance spontaneous recovery.

The interleukin-15 system suppresses T cell-mediated autoimmunity by regulating negative selection and nT(H)17 cell homeostasis in the thymus.

Science.gov (United States)

Hou, Mau-Sheng; Huang, Shih-Ting; Tsai, Ming-Han; Yen, Ching-Cheng; Lai, Yein-Gei; Liou, Yae-Huei; Lin, Chih-Kung; Liao, Nan-Shih

2015-01-01

The interleukin-15 (IL-15) system is important for regulating both innate and adaptive immune responses, however, its role in autoimmune disease remained unclear. Here we found that Il15(-/-) and Il15ra(-/-) mice spontaneously developed late-onset autoimmune phenotypes. CD4(+) T cells of the knockout mice showed elevated autoreactivity as demonstrated by the induction of lymphocyte infiltration in the lacrimal and salivary glands when transferred into nude mice. The antigen-presenting cells in the thymic medullary regions expressed IL-15 and IL-15Rα, whose deficiency resulted in insufficient negative selection and elevated number of natural IL-17A-producing CD4(+) thymocytes. These findings reveal previously unknown functions of the IL-15 system in thymocyte development, and thus a new layer of regulation in T cell-mediated autoimmunity. Copyright © 2014 Elsevier Ltd. All rights reserved.

Descending projections from the nucleus accumbens shell excite activity of taste-responsive neurons in the nucleus of the solitary tract in the hamster.

Science.gov (United States)

Li, Cheng-Shu; Lu, Da-Peng; Cho, Young K

2015-06-01

The nucleus of the solitary tract (NST) and the parabrachial nuclei (PbN) are the first and second relays in the rodent central taste pathway. A series of electrophysiological experiments revealed that spontaneous and taste-evoked activities of brain stem gustatory neurons are altered by descending input from multiple forebrain nuclei in the central taste pathway. The nucleus accumbens shell (NAcSh) is a key neural substrate of reward circuitry, but it has not been verified as a classical gustatory nucleus. A recent in vivo electrophysiological study demonstrated that the NAcSh modulates the spontaneous and gustatory activities of hamster pontine taste neurons. In the present study, we investigated whether activation of the NAcSh modulates gustatory responses of the NST neurons. Extracellular single-unit activity was recorded from medullary neurons in urethane-anesthetized hamsters. After taste response was confirmed by delivery of sucrose, NaCl, citric acid, and quinine hydrochloride to the anterior tongue, the NAcSh was stimulated bilaterally with concentric bipolar stimulating electrodes. Stimulation of the ipsilateral and contralateral NAcSh induced firings from 54 and 37 of 90 medullary taste neurons, respectively. Thirty cells were affected bilaterally. No inhibitory responses or antidromic invasion was observed after NAcSh activation. In the subset of taste cells tested, high-frequency electrical stimulation of the NAcSh during taste delivery enhanced taste-evoked neuronal firing. These results demonstrate that two-thirds of the medullary gustatory neurons are under excitatory descending influence from the NAcSh, which is a strong indication of communication between the gustatory pathway and the mesolimbic reward pathway. Copyright © 2015 the American Physiological Society.

Complex rheological properties of a water-soluble extract from the fronds of the black tree fern, Cyathea medullaris.

Science.gov (United States)

Goh, Kelvin K T; Matia-Merino, Lara; Hall, Christopher E; Moughan, Paul J; Singh, Harjinder

2007-11-01

A water-soluble extract was obtained from the fronds of a New Zealand native black tree fern (Cyathea medullaris or Mamaku in Māori). The extract exhibited complex rheological behavior. Newtonian, shear-thinning, shear-thickening, thixotropic, antithixotropic, and viscoelastic behaviors were observed depending on polymer concentration, shear rate, and shear history. The extract also displayed rod-climbing and self-siphoning properties typical of viscoelastic fluids. Such complex rheological properties have been reported in synthetic or chemically modified polymers but are less frequent in unmodified biopolymers. Although Mamaku extract obtained from the pith of the fern has been traditionally used by the Māori in New Zealand for treating wounds and diarrhea among other ailments, this material has never been characterized before. This study reports on the chemical composition of the extract and on its viscoelastic properties through rotational and oscillatory rheological measurements. Explanations of the mechanism behind the rheological properties were based on transient network models for associating polymers.

HIV-1 proteins dysregulate motivational processes and dopamine circuitry.

Science.gov (United States)

Bertrand, Sarah J; Mactutus, Charles F; Harrod, Steven B; Moran, Landhing M; Booze, Rosemarie M

2018-05-18

Motivational alterations, such as apathy, in HIV-1+ individuals are associated with decreased performance on tasks involving frontal-subcortical circuitry. We used the HIV-1 transgenic (Tg) rat to assess effect of long-term HIV-1 protein exposure on motivated behavior using sucrose (1-30%, w/v) and cocaine (0.01-1.0 mg/kg/infusion) maintained responding with fixed-ratio (FR) and progressive-ratio (PR) schedules of reinforcement. For sucrose-reinforced responding, HIV-1 Tg rats displayed no change in EC 50 relative to controls, suggesting no change in sucrose reinforcement but had a downward shifted concentration-response curves, suggesting a decrease in response vigor. Cocaine-maintained responding was attenuated in HIV-1 Tg rats (FR1 0.33 mg/kg/infusion and PR 1.0 mg/kg/infusion). Dose-response tests (PR) revealed that HIV-1 Tg animals responded significantly less than F344 control rats and failed to earn significantly more infusions of cocaine as the unit dose increased. When choosing between cocaine and sucrose, control rats initially chose sucrose but with time shifted to a cocaine preference. In contrast, HIV-1 disrupted choice behaviors. DAT function was altered in the striatum of HIV-1 Tg rats; however, prior cocaine self-administration produced a unique effect on dopamine homeostasis in the HIV-1 Tg striatum. These findings of altered goal directed behaviors may determine neurobiological mechanisms of apathy in HIV-1+ patients.

[The effects of anterio-posterior and dorso-ventral inversions of the lateral mesoblast of the neurula on the formation of the mesonephric, medullary, and adrenal anlage of the common toad, Bufo bufo L. (Amphibia, Anoura)].

Science.gov (United States)

Gipouloux, J D; Hakim, J

1975-10-13

The experimental results of cranio-caudal reversal and dorso-ventral reversal of the lateral mesoblast of the toad early neurula prove that, at this stage, the cranio-caudal polarity of this tissue is fixed but not the dorso-ventral one. External factors are responsible for the formation of mesonephric, adrenal and gonadal medullary anlage by the lateral mesoblast.

Benefit of measuring basal serum calcitonin to detect medullary thyroid carcinoma in a Danish population with a high prevalence of thyroid nodules

DEFF Research Database (Denmark)

Hasselgren, Martin; Hegedüs, Laszlo; Godballe, Christian

2009-01-01

; thyroidectomy was performed in 307 of these patients. RESULTS: Thirty-nine patients had elevated serum calcitonin; 6 of these patients had MTC detected by the initial diagnostic setup. No additional patient in the cohort was registered in the Danish Thyroid Cancer Database, reflecting that all patients with MTC......BACKGROUND: Routine measurement of serum calcitonin to detect medullary thyroid carcinoma (MTC) continues to be fiercely debated, although less attention has been paid to the positive predictive value (PPV) of this method. METHODS: We collected data from 959 patients with nontoxic nodular goiter....... The low PPV might lead to unnecessary thyroid surgery. Thus, the result of serum calcitonin measurement should always be interpreted in the context of other clinical variables. (c) 2009 Wiley Periodicals, Inc. Head Neck, 2009....

Identification of Stria Medullaris Fibers in the Massa Intermedia Using Diffusion Tensor Imaging.

Science.gov (United States)

Kochanski, Ryan B; Dawe, Robert; Kocak, Mehmet; Sani, Sepehr

2018-04-01

The massa intermedia (MI) or interthalamic adhesion is an inconsistent band spanning between bilateral medial thalami that is absent in up to 20%-30% of individuals. Little is known of its significance, especially in regard to functional pathways. Probabilistic diffusion tensor imaging (DTI) has recently been used to seed the lateral habenula and define its afferent white matter pathway, the stria medullaris thalami (SM). We sought to determine whether the MI serves as a conduit for crossing of limbic fibers such as the SM. Probabilistic DTI was performed on 10 subjects who had presence of a MI as visualized on magnetic resonance imaging. Tractography was also performed on 2 subjects without MI. Manual identification of the lateral habenula on axial T1-weighted magnetic resonance imaging was used for the initial seed region for tractography. In all subjects, the SM was reliably visualized. In 7 of the 10 subjects with MI, there was evidence of SM fibers that crossed to the ipsilateral hemisphere. Three subjects with small diameter MI did not have tractographic evidence of crossing SM fibers. Of the 7 subjects with crossing SM fibers within the MI, 5 showed predilection toward the right orbitofrontal cortex from both the left and right seed regions. Probabilistic DTI provides evidence of SM fibers within the MI. Given its anatomic location as a bridging pathway between thalami, further studies are necessary to assess its role within the limbic functional network. Copyright © 2018 Elsevier Inc. All rights reserved.

Correlation of RET somatic mutations with clinicopathological features in sporadic medullary thyroid carcinomas

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Moura, M M; Cavaco, B M; Pinto, A E; Domingues, R; Santos, J R; Cid, M O; Bugalho, M J; Leite, V

2009-01-01

Screening of REarranged during Transfection (RET) gene mutations has been carried out in different series of sporadic medullary thyroid carcinomas (MTC). RET-positive tumours seem to be associated to a worse clinical outcome. However, the correlation between the type of RET mutation and the patients' clinicopathological data has not been evaluated yet. We analysed RET exons 5, 8, 10–16 in fifty-one sporadic MTC, and found somatic mutations in thirty-three (64.7%) tumours. Among the RET-positive cases, exon 16 was the most frequently affected (60.6%). Two novel somatic mutations (Cys630Gly, c.1881del18) were identified. MTC patients were divided into three groups: group 1, with mutations in RET exons 15 and 16; group 2, with other RET mutations; group 3, having no RET mutations. Group 1 had higher prevalence (P=0.0051) and number of lymph node metastases (P=0.0017), and presented more often multifocal tumours (P=0.037) and persistent disease at last control (P=0.0242) than group 2. Detectable serum calcitonin levels at last screening (P=0.0119) and stage IV disease (P=0.0145) were more frequent in group 1, than in the other groups. Our results suggest that, among the sporadic MTC, cases with RET mutations in exons 15 and 16 are associated with the worst prognosis. Cases with other RET mutations have the most indolent course, and those with no RET mutations have an intermediate risk. PMID:19401695

Placebo neural systems: nitric oxide, morphine and the dopamine brain reward and motivation circuitries.

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Fricchione, Gregory; Stefano, George B

2005-05-01

Evidence suggests that the placebo response is related to the tonic effects of constitutive nitric oxide in neural, vascular and immune tissues. Constitutive nitric oxide levels play a role in the modulation of dopamine outflow in the nigrostriatal movement and the mesolimbic and mesocortical reward and motivation circuitries. Endogenous morphine, which stimulates constitutive nitric oxide, may be an important signal molecule working at mu receptors on gamma aminobutyric acid B interneurons to disinhibit nigral and tegmental dopamine output. We surmise that placebo induced belief will activate the prefrontal cortex with downstream stimulatory effects on these dopamine systems as well as on periaqueductal grey opioid output neurons. Placebo responses in Parkinson's disease, depression and pain disorder may result. In addition, mesolimbic/mesocortical control of the stress response systems may provide a way for the placebo response to benefit other medical conditions.

Molecular Regulation of Antibiotic Biosynthesis in Streptomyces

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Liu, Gang; Chandra, Govind; Niu, Guoqing

2013-01-01

SUMMARY Streptomycetes are the most abundant source of antibiotics. Typically, each species produces several antibiotics, with the profile being species specific. Streptomyces coelicolor, the model species, produces at least five different antibiotics. We review the regulation of antibiotic biosynthesis in S. coelicolor and other, nonmodel streptomycetes in the light of recent studies. The biosynthesis of each antibiotic is specified by a large gene cluster, usually including regulatory genes (cluster-situated regulators [CSRs]). These are the main point of connection with a plethora of generally conserved regulatory systems that monitor the organism's physiology, developmental state, population density, and environment to determine the onset and level of production of each antibiotic. Some CSRs may also be sensitive to the levels of different kinds of ligands, including products of the pathway itself, products of other antibiotic pathways in the same organism, and specialized regulatory small molecules such as gamma-butyrolactones. These interactions can result in self-reinforcing feed-forward circuitry and complex cross talk between pathways. The physiological signals and regulatory mechanisms may be of practical importance for the activation of the many cryptic secondary metabolic gene cluster pathways revealed by recent sequencing of numerous Streptomyces genomes. PMID:23471619

Examination of Csr regulatory circuitry using epistasis analysis with RNA-seq (Epi-seq) confirms that CsrD affects gene expression via CsrA, CsrB and CsrC.

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Potts, Anastasia H; Leng, Yuanyuan; Babitzke, Paul; Romeo, Tony

2018-03-29

The Csr global regulatory system coordinates gene expression in response to metabolic status. This system utilizes the RNA binding protein CsrA to regulate gene expression by binding to transcripts of structural and regulatory genes, thus affecting their structure, stability, translation, and/or transcription elongation. CsrA activity is controlled by sRNAs, CsrB and CsrC, which sequester CsrA away from other transcripts. CsrB/C levels are partly determined by their rates of turnover, which requires CsrD to render them susceptible to RNase E cleavage. Previous epistasis analysis suggested that CsrD affects gene expression through the other Csr components, CsrB/C and CsrA. However, those conclusions were based on a limited analysis of reporters. Here, we reassessed the global behavior of the Csr circuitry using epistasis analysis with RNA seq (Epi-seq). Because CsrD effects on mRNA levels were entirely lost in the csrA mutant and largely eliminated in a csrB/C mutant under our experimental conditions, while the majority of CsrA effects persisted in the absence of csrD, the original model accounts for the global behavior of the Csr system. Our present results also reflect a more nuanced role of CsrA as terminal regulator of the Csr system than has been recognized.

Do cognitive measures and brain circuitry predict outcomes of exercise in Parkinson Disease: a randomized clinical trial.

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King, L A; Peterson, D S; Mancini, M; Carlson-Kuhta, P; Fling, B W; Smulders, K; Nutt, J G; Dale, M; Carter, J; Winters-Stone, K M; Horak, F B

2015-10-24

There is emerging research detailing the relationship between balance/gait/falls and cognition. Imaging studies also suggest a link between structural and functional changes in the frontal lobe (a region commonly associated with cognitive function) and mobility. People with Parkinson's disease have important changes in cognitive function that may impact rehabilitation efficacy. Our underlying hypothesis is that cognitive function and frontal lobe connections with the basal ganglia and brainstem posture/locomotor centers are responsible for postural deficits in people with Parkinson's disease and play a role in rehabilitation efficacy. The purpose of this study is to 1) determine if people with Parkinson's disease can improve mobility and/or cognition after partaking in a cognitively challenging mobility exercise program and 2) determine if cognition and brain circuitry deficits predict responsiveness to exercise rehabilitation. This study is a randomized cross-over controlled intervention to take place at a University Balance Disorders Laboratory. The study participants will be people with Parkinson's disease who meet inclusion criteria for the study. The intervention will be 6 weeks of group exercise (case) and 6 weeks of group education (control). The exercise is a cognitively challenging program based on the Agility Boot Camp for people with PD. The education program is a 6-week program to teach people how to better live with a chronic disease. The primary outcome measure is the MiniBESTest and the secondary outcomes are measures of mobility, cognition and neural imaging. The results from this study will further our understanding of the relationship between cognition and mobility with a focus on brain circuitry as it relates to rehabilitation potential. This trial is registered at clinical trials.gov (NCT02231073).

The influence of emotion regulation on decision-making under risk.

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Martin, Laura N; Delgado, Mauricio R

2011-09-01

Cognitive strategies typically involved in regulating negative emotions have recently been shown to also be effective with positive emotions associated with monetary rewards. However, it is less clear how these strategies influence behavior, such as preferences expressed during decision-making under risk, and the underlying neural circuitry. That is, can the effective use of emotion regulation strategies during presentation of a reward-conditioned stimulus influence decision-making under risk and neural structures involved in reward processing such as the striatum? To investigate this question, we asked participants to engage in imagery-focused regulation strategies during the presentation of a cue that preceded a financial decision-making phase. During the decision phase, participants then made a choice between a risky and a safe monetary lottery. Participants who successfully used cognitive regulation, as assessed by subjective ratings about perceived success and facility in implementation of strategies, made fewer risky choices in comparison with trials where decisions were made in the absence of cognitive regulation. Additionally, BOLD responses in the striatum were attenuated during decision-making as a function of successful emotion regulation. These findings suggest that exerting cognitive control over emotional responses can modulate neural responses associated with reward processing (e.g., striatum) and promote more goal-directed decision-making (e.g., less risky choices), illustrating the potential importance of cognitive strategies in curbing risk-seeking behaviors before they become maladaptive (e.g., substance abuse).

The Influence of Emotion Regulation on Decision-making under Risk

Science.gov (United States)

Martin, Laura N.; Delgado, Mauricio R.

2011-01-01

Cognitive strategies typically involved in regulating negative emotions have recently been shown to also be effective with positive emotions associated with monetary rewards. However, it is less clear how these strategies influence behavior, such as preferences expressed during decision-making under risk, and the underlying neural circuitry. That is, can the effective use of emotion regulation strategies during presentation of a reward-conditioned stimulus influence decision-making under risk and neural structures involved in reward processing such as the striatum? To investigate this question, we asked participants to engage in imagery-focused regulation strategies during the presentation of a cue that preceded a financial decision-making phase. During the decision phase, participants then made a choice between a risky and a safe monetary lottery. Participants who successfully used cognitive regulation, as assessed by subjective ratings about perceived success and facility in implementation of strategies, made fewer risky choices in comparison to trials where decisions were made in the absence of cognitive regulation. Additionally, blood-oxygen-level-dependent (BOLD) responses in the striatum were attenuated during decision-making as a function of successful emotion regulation. These findings suggest that exerting cognitive control over emotional responses can modulate neural responses associated with reward processing (e.g., striatum), and promote more goal-directed decision-making (e.g., less risky choices), illustrating the potential importance of cognitive strategies in curbing risk-seeking behaviors before they become maladaptive (e.g., substance abuse). PMID:21254801

Somatostatin receptor scintigraphy and magnetic resonance imaging in recurrent medullary thyroid carcinoma: A comparative study

International Nuclear Information System (INIS)

Doerr, U.; Wuerstlin, S.; Frank-Raue, K.; Raue, F.; Hehrmann, R.; Iser, G.; Scholz, M.; Guhl, L.; Buhr, H.J.; Bihl, H.

1993-01-01

In a prospective study, 18 patients with recurrent medullary thyroid carcinoma (MTC) underwent magnetic resonance imaging (MRI) of the neck and mediastinum and somatostatin receptor scintigraphy (SRS) with 111 In-labeled pentetreotide. In nine patients with macroscopic MTC, 17 corresponding lesions were found on MRI and SRS; in addition, 13 suspicious lesions were seen on SRS only. Histological confirmation was available for 19 metastatic lesions, showing MRI to be true positive in 13 metastases, SRS in 18. In minimal residual disease (n=10), MRI and SRS were compared with the histological findings in three patients and with selective venous catheterization (SVC) in seven patients. Corresponding findings on MRI and SVC were seen in one of seven, whereas SRS and SVC showed concordant localization of tumor recurrence in five of seven. Histological examination demonstrated MTC tissue in one of three cases; MRI and SRS were false positive in one of three cases, while in the others the interpretation remained uncertain. In conclusion, SRS is a promising imaging modality for localization of MTC recurrence. MRI provides better spatial resolution and thus facilitates the planning of surgery for macroscopic metastases. In minimal residual disease, SRS turned out to be superior in detecting occult MTC recurrence, confirming SVC findings. (orig.)

Dentate Gyrus circuitry features improve performance of sparse approximation algorithms.

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Panagiotis C Petrantonakis

Full Text Available Memory-related activity in the Dentate Gyrus (DG is characterized by sparsity. Memory representations are seen as activated neuronal populations of granule cells, the main encoding cells in DG, which are estimated to engage 2-4% of the total population. This sparsity is assumed to enhance the ability of DG to perform pattern separation, one of the most valuable contributions of DG during memory formation. In this work, we investigate how features of the DG such as its excitatory and inhibitory connectivity diagram can be used to develop theoretical algorithms performing Sparse Approximation, a widely used strategy in the Signal Processing field. Sparse approximation stands for the algorithmic identification of few components from a dictionary that approximate a certain signal. The ability of DG to achieve pattern separation by sparsifing its representations is exploited here to improve the performance of the state of the art sparse approximation algorithm "Iterative Soft Thresholding" (IST by adding new algorithmic features inspired by the DG circuitry. Lateral inhibition of granule cells, either direct or indirect, via mossy cells, is shown to enhance the performance of the IST. Apart from revealing the potential of DG-inspired theoretical algorithms, this work presents new insights regarding the function of particular cell types in the pattern separation task of the DG.

Ketamine inhibits 45Ca influx and catecholamine secretion by inhibiting 22Na influx in cultured bovine adrenal medullary cells

International Nuclear Information System (INIS)

Takara, Hiroshi; Wada, Akihiko; Arita, Masahide; Izumi, Futoshi; Sumikawa, Koji

1986-01-01

The effects of ketamine, an intravenous anesthetic, on 22 Na influx, 45 Ca influx and catecholamine secretion were investigated in cultured bovine adrenal medullary cells. Ketamine inhibited carbachol-induced 45 Ca influx and catecholamine secretion in a concentration-dependent manner with a similar potency. Ketamine also reduced veratridine-induced 45 Ca influx and catecholamine secretion. The influx of 22 Na caused by carbachol or by veratridine was suppressed by ketamine with a concentration-inhibition curve similar to that of 45 Ca influx and catecholamine secretion. Inhibition by ketamine of the carbachol-induced influx of 22 Na, 45 Ca and secretion of catecholamines was not reversed by the increased concentrations of carbachol. These observations indicate that ketamine, at clinical concentrations, can inhibit nicotinic receptor-associated ionic channels and that the inhibition of Na influx via the receptor-associated ionic channels is responsible for the inhibition of carbachol-induced Ca influx and catecholamine secretion. (Auth.)

Childhood trauma exposure disrupts the automatic regulation of emotional processing.

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Marusak, Hilary A; Martin, Kayla R; Etkin, Amit; Thomason, Moriah E

2015-03-13

Early-life trauma is one of the strongest risk factors for later emotional psychopathology. Although research in adults highlights that childhood trauma predicts deficits in emotion regulation that persist decades later, it is unknown whether neural and behavioral changes that may precipitate illness are evident during formative, developmental years. This study examined whether automatic regulation of emotional conflict is perturbed in a high-risk urban sample of trauma-exposed children and adolescents. A total of 14 trauma-exposed and 16 age-, sex-, and IQ-matched comparison youth underwent functional MRI while performing an emotional conflict task that involved categorizing facial affect while ignoring an overlying emotion word. Engagement of the conflict regulation system was evaluated at neural and behavioral levels. Results showed that trauma-exposed youth failed to dampen dorsolateral prefrontal cortex activity and engage amygdala-pregenual cingulate inhibitory circuitry during the regulation of emotional conflict, and were less able to regulate emotional conflict. In addition, trauma-exposed youth showed greater conflict-related amygdala reactivity that was associated with diminished levels of trait reward sensitivity. These data point to a trauma-related deficit in automatic regulation of emotional processing, and increase in sensitivity to emotional conflict in neural systems implicated in threat detection. Aberrant amygdala response to emotional conflict was related to diminished reward sensitivity that is emerging as a critical stress-susceptibility trait that may contribute to the emergence of mental illness during adolescence. These results suggest that deficits in conflict regulation for emotional material may underlie heightened risk for psychopathology in individuals that endure early-life trauma.

Fighting food temptations: the modulating effects of short-term cognitive reappraisal, suppression and up-regulation on mesocorticolimbic activity related to appetitive motivation.

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Siep, Nicolette; Roefs, Anne; Roebroeck, Alard; Havermans, Remco; Bonte, Milene; Jansen, Anita

2012-03-01

The premise of cognitive therapy is that one can overcome the irresistible temptation of highly palatable foods by actively restructuring the way one thinks about food. Testing this idea, participants in the present study were instructed to passively view foods, up-regulate food palatability thoughts, apply cognitive reappraisal (e.g., thinking about health consequences), or suppress food palatability thoughts and cravings. We examined whether these strategies affect self-reported food craving and mesocorticolimbic activity as assessed by functional magnetic resonance imaging. It was hypothesized that cognitive reappraisal would most effectively inhibit the mesocorticolimbic activity and associated food craving as compared to suppression. In addition, it was hypothesized that suppression would lead to more prefrontal cortex activity, reflecting the use of more control resources, as compared to cognitive reappraisal. Self-report results indicated that up-regulation increased food craving compared to the other two conditions, but that there was no difference in craving between the suppression and cognitive reappraisal strategy. Corroborating self-report results, the neuroimaging results showed that up-regulation increased activity in important regions of the mesocorticolimbic circuitry, including the ventral tegmental area, ventral striatum, operculum, posterior insular gyrus, medial orbitofrontal cortex and ventromedial prefrontal cortex. Contrary to our hypothesis, suppression more effectively decreased activity in the core of the mesocorticolimbic circuitry (i.e., ventral tegmental area and ventral striatum) compared to cognitive reappraisal. Overall, the results support the contention that appetitive motivation can be modulated by the application of short-term cognitive control strategies. Copyright © 2012 Elsevier Inc. All rights reserved.

A Role for the Lateral Dorsal Tegmentum in Memory and Decision Neural Circuitry

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Redila, Van; Kinzel, Chantelle; Jo, Yong Sang; Puryear, Corey B.; Mizumori, Sheri J.Y.

2017-01-01

A role for the hippocampus in memory is clear, although the mechanism for its contribution remains a matter of debate. Converging evidence suggests that hippocampus evaluates the extent to which context-defining features of events occur as expected. The consequence of mismatches, or prediction error, signals from hippocampus is discussed in terms of its impact on neural circuitry that evaluates the significance of prediction errors: Ventral tegmental area (VTA) dopamine cells burst fire to rewards or cues that predict rewards (Schultz et al., 1997). Although the lateral dorsal tegmentum (LDTg) importantly controls dopamine cell burst firing (Lodge & Grace, 2006) the behavioral significance of the LDTg control is not known. Therefore, we evaluated LDTg functional activity as rats performed a spatial memory task that generates task-dependent reward codes in VTA (Jo et al., 2013; Puryear et al., 2010) and another VTA afferent, the pedunculopontine nucleus (PPTg, Norton et al., 2011). Reversible inactivation of the LDTg significantly impaired choice accuracy. LDTg neurons coded primarily egocentric information in the form of movement velocity, turning behaviors, and behaviors leading up to expected reward locations. A subset of the velocity-tuned LDTg cells also showed high frequency bursts shortly before or after reward encounters, after which they showed tonic elevated firing during consumption of small, but not large, rewards. Cells that fired before reward encounters showed stronger correlations with velocity as rats moved toward, rather than away from, rewarded sites. LDTg neural activity was more strongly regulated by egocentric behaviors than that observed for PPTg or VTA cells that were recorded by Puryear et al. and Norton et al. While PPTg activity was uniquely sensitive to ongoing sensory input, all three regions encoded reward magnitude (although in different ways), reward expectation, and reward encounters. Only VTA encoded reward prediction errors. LDTg

Cognitive enhancement therapy improves fronto-limbic regulation of emotion in alcohol and/or cannabis misusing schizophrenia: a preliminary study

Directory of Open Access Journals (Sweden)

Jessica Ann Wojtalik

2016-01-01

Full Text Available Individuals with schizophrenia who misuse substances are burdened with impairments in emotion regulation. Cognitive Enhancement Therapy (CET may address these problems by enhancing prefrontal brain function. A small sample of outpatients with schizophrenia and alcohol and/or cannabis substance use problems participating in an 18-month randomized trial of CET (n = 10 or usual care (n = 4 completed post-treatment functional neuroimaging using an emotion regulation task. General linear models explored CET effects on brain activity in emotional neurocircuitry. Individuals treated with CET had significantly greater activation in broad regions of the prefrontal cortex, limbic and striatal systems implicated in emotion regulation compared to usual care. Differential activation favoring CET in prefrontal regions and the insula mediated behavioral improvements in emotional processing. Our data lend preliminary support of CET effects on neuroplasticity in fronto-limbic and striatal circuitries which mediate emotion regulation in people with schizophrenia and comorbid substance misuse problems.

Changes in neural circuitry associated with depression at pre-clinical, pre-motor and early motor phases of Parkinson's disease.

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Borgonovo, Janina; Allende-Castro, Camilo; Laliena, Almudena; Guerrero, Néstor; Silva, Hernán; Concha, Miguel L

2017-02-01

Although Parkinson's Disease (PD) is mostly considered a motor disorder, it can present at early stages as a non-motor pathology. Among the non-motor clinical manifestations, depression shows a high prevalence and can be one of the first clinical signs to appear, even a decade before the onset of motor symptoms. Here, we review the evidence of early dysfunction in neural circuitry associated with depression in the context of PD, focusing on pre-clinical, pre-motor and early motor phases of the disease. In the pre-clinical phase, structural and functional changes in the substantia nigra, basal ganglia and limbic structures are already observed. Some of these changes are linked to motor compensation mechanisms while others correspond to pathological processes common to PD and depression and thus could underlie the appearance of depressive symptoms during the pre-motor phase. Studies of the early motor phase (less than five years post diagnosis) reveal an association between the extent of damage in different monoaminergic systems and the appearance of emotional disorders. We propose that the limbic loop of the basal ganglia and the lateral habenula play key roles in the early genesis of depression in PD. Alterations in the neural circuitry linked with emotional control might be sensitive markers of the ongoing neurodegenerative process and thus may serve to facilitate an early diagnosis of this disease. To take advantage of this, we need to improve the clinical criteria and develop biomarkers to identify depression, which could be used to determine individuals at risk to develop PD. Copyright © 2016 Elsevier Ltd. All rights reserved.

Application of Color Doppler Ultrasound in Renal Medullary Calcium%彩色多普勒超声在肾髓质钙质沉着症中的应用分析

Institute of Scientific and Technical Information of China (English)

金丽梅

2016-01-01

目的：分析彩色多普勒超声在肾髓质钙沉着症中的应用价值。方法回顾性分析2011—2015年期间在该院行彩色多普勒超声诊断肾髓质钙沉着症的68例患者的临床资料，观察患者的超声诊断特点以及血流动力学改变。结果68例行彩色多普勒超声诊断肾髓质钙沉着症的患者中，诊断阳性共65例，阴性3例，诊断的准确率为95.6%，65例肾髓质钙沉着症患者中包括皮质型30例，髓质型32例，混合型3例，患者的两侧肾脏大小正常，形态对称，包膜光滑，皮质和髓质界限较为清楚，肾脏的皮质厚度和回声均正常，在患者的髓质内，有密集点状的强回声，形态和椎体的形态基本一致，有一侧有弱声影。结论彩色多普勒超声在肾髓质钙沉着症中应用，准确率较高，可以有效的显示内部的形态、血流变化等指标，具有重要的临床诊断价值。%Objective To analyze the value of color Doppler ultrasound in the renal medulla of calcium applications. Methods Convenient selection a retrospective analysis of clinical data by color Doppler ultrasound diagnosis of renal medullary calcinosis disease 68 patients were retrospectively analyzed the period from 2011 to 2015, observed in patients with ultrasonic diagnostic characteristics and hemodynamic change. Results 68 patients with routine color Doppler ultra-sound diagnosis of renal medullary calcinosis disease, the diagnosis of a total of65 positive cases, negative in 3 cases, the diagnostic accuracy was 95.6%, 65 cases of renal medullary calcinosis patients included cortical 30 cases, 32 cases of medullary, mixed three cases, both sides of the patient's normal kidney size, shape symmetry, smooth coated, cortex and medulla boundaries more clearly, renal cortical thickness and echo were normal in patients within the medulla, a strong e-cho dense point-like, form and shape of the vertebral body are basically the same, there is one

Bone densitometry by gamma ray attenuation measurement. Development of an apparatus for use on medullary casualties

International Nuclear Information System (INIS)

Berard, E.J.-J.

1975-01-01

We proposed to follow changes in the bone mineral content of medullary damage cases by measuring the attenuation of a monoenergetic gamma ray according to the Cameron and Sorenson technique. Apart from their high cost, existing instruments are not designed for this bedside observation of patients. Our aim was therefore to design and develop an easily portable, inexpensive apparatus. The γ radiation is supplied by a sealed 125 I source fitted with a narrow collimator. The battery-operated scintillation detector is that used to detect post-operative phlebites after injection of radio-fibrinogen. The source-detector unit can move to allow a transverse bone mineral content measurement. Data from the detector are processed electronically and the results given: - either graphically on a tracing board which gives an area proportional to the bone mineral content, - or numerically by means of an integrator computing this area and supplying the linear bone density directly. Experiments carried out in vivo showed the apparatus to be sensitive and the measurements reproducible, the results obtained being comparable with those of other authors. Using pieces of embalmed bone moreover an excellent correlation was observed between the bone mineral content obtained after incineration and the results displayed by our apparatus, which can therefore be calibrated [fr

Medullary neurons in the core white matter of the olfactory bulb: a new cell type.

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Paredes, Raúl G; Larriva-Sahd, Jorge

2010-02-01

The structure of a new cell type, termed the medullary neuron (MN) because of its intimate association with the rostral migratory stream (RMS) in the bulbar core, is described in the adult rat olfactory bulb. The MN is a triangular or polygonal interneuron whose soma lies between the cellular clusters of the RMS or, less frequently, among the neuron progenitors therein. MNs are easily distinguished from adjacent cells by their large size and differentiated structure. Two MN subtypes have been categorized by the Golgi technique: spiny pyramidal neurons and aspiny neurons. Both MN subtypes bear a large dendritic field impinged upon by axons in the core bulbar white matter. A set of collaterals from the adjacent axons appears to terminate on the MN dendrites. The MN axon passes in close apposition to adjacent neuron progenitors in the RMS. MNs are immunoreactive with antisera raised against gamma-aminobutyric acid and glutamate decarboxylase 65/67. Electron-microscopic observations confirm that MNs correspond to fully differentiated, mature neurons. MNs seem to be highly conserved among macrosmatic species as they occur in Nissl-stained brain sections from mouse, guinea pig, and hedgehog. Although the functional role of MNs remains to be determined, we suggest that MNs represent a cellular interface between endogenous olfactory activity and the differentiation of new neurons generated during adulthood.

Sodium-bicarbonate cotransporter NBCn1 in the kidney medullary thick ascending limb cell line is upregulated under acidic conditions and enhances ammonium transport.

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Lee, Soojung; Lee, Hye Jeong; Yang, Han Soo; Thornell, Ian M; Bevensee, Mark O; Choi, Inyeong

2010-09-01

In this study, we examined the effect of bicarbonate transporters on ammonium/ammonia uptake in the medullary thick ascending limb cell line ST-1. Cells were treated with 1 mm ouabain and 0.2 mM bumetanide to minimize carrier-mediated NH(4)(+) transport, and the intracellular accumulation of (14)C-methylammonium/methylammonia ((14)C-MA) was determined. In CO(2)/HCO(3)(-)-free solution, cells at normal pH briefly accumulated (14)C-MA over 7 min and reached a plateau. In CO(2)/HCO(3)(-) solution, however, cells markedly accumulated (14)C-MA over the experimental period of 30 min. This CO(2)/HCO(3)(-)-dependent accumulation was reduced by the bicarbonate transporter blocker, 4,4-diisothiocyanatostilbene-2,2-disulfonate (DIDS; 0.5 mM). Replacing Cl(-) with gluconate reduced the accumulation, but the reduction was more substantial in the presence of DIDS. Incubation of cells at pH 6.8 (adjusted with NaHCO(3) in 5% CO(2)) for 24 h lowered the mean steady-state intracellular pH to 6.96, significantly lower than 7.28 for control cells. The presence of DIDS reduced (14)C-MA accumulation in control conditions but had no effect after acidic incubation. Immunoblotting showed that NBCn1 was upregulated after acidic incubation and in NH(4)Cl-containing media. The Cl(-)-HCO(3)(-) exchanger AE2 was present, but its expression remained unaffected by acidic incubation. Expressed in Xenopus oocytes, NBCn1 increased carrier-mediated (14)C-MA transport, which was abolished by replacing Na(+). Two-electrode voltage clamp of oocytes exhibited negligible current after NH(4)Cl application. These results suggest that DIDS-sensitive HCO(3)(-) extrusion normally governs NH(4)(+)/NH(3) uptake in the medullary thick ascending limb cells. We propose that, in acidic conditions, DIDS-sensitive HCO(3)(-) extrusion is inactivated, while NBCn1 is upregulated to stimulate NH(4)(+) transport.

Radioimmunoassay of human calcitonin in serum and tissue from healthy individuals and patients with medullary carcinoma of the thyroid gland

International Nuclear Information System (INIS)

Gautvik, K.M.; Normann, T.; Teig, V.; Wille, S.Oe.; Brennhovd, I.O.; Christensen, I.

1976-01-01

A specific radioimmunological method for measurement of immunoreactive calcitonin (iCT) in human serum and tissue is described. Of healthy individuals of both sexes, 85 % had measurable iCT in serum (mean, 0.23 ng/ml). Of 29 patients who had received treatment for medullary carcinoma of the thyroid gland (MCT), 19 had increased serum iCT (0-60 ng/ml to205 ng/ml). Elevated serum iCT was also found preoperatively in 2 MCT patients. Eleven of the patients with abnormal elevations of serum iCT were alive 4 to 13 years after the operation. Concentration of iCT in extracts from MCT varied from 0.5 to 540 ng/ml wet weight. The diagnostic value of this method and its importance for pre- and post-operative evaluation of these patients are improved by the use of selective venous catheterization in basal state and during stimulation of CT secretion. (Auth.)

Contribution of different scintigraphic techniques to the management of medullary thyroid carcinoma

International Nuclear Information System (INIS)

Sandrock, D.; Blossey, H.C.; Steinroeder, M.; Munz, D.L.

1989-01-01

We compared three different scintigraphic techniques for the localization of neck recurrences and metastases in seven patients with medullary thyroid carcinoma one month to eight years after the first surgical intervention. Three successive scintigraphic studies were performed in five patients (6 x 3 studies) within two weeks using 201Tl chloride, 111In-labeled F(ab')2 fragments of the anti-carcinoembryonic antigen (anti-CEA) monoclonal antibody (MoAb) BW 431/31, and 131I meta-iodo-benzylguanidine (MIBG). Additionally, 11 studies were performed with the 111In-labeled MoAb fragment BW 431/31 (seven studies) or the 99mTc-labeled intact anti-CEA MoAb BW 431/26 (four studies). The gold standards for classifying scintigraphic results were biopsy, histology, surgery, and cytology. Six regions were classified as positive or negative in each study: thyroid region, four quadrants (lymph node regions) around the thyroid, and the region of the upper mediastinum. Of 36 sites, 201Tl was true positive (TP) in seven sites, false-positive (FP) in one site, true negative (TN) in 22 sites, and false-negative (FN) in six sites, resulting in a sensitivity of 54% and a specificity of 96%. 131I MIBG was TP in four sites, FP in none of the sites, TN in 23 sites, and FN in nine sites, with a sensitivity of 31% and a specificity of 100%. Immunoscintigraphy (102 sites overall) was TP in 16 sites, FP in five sites, TN in 77 sites, and FN in four sites, resulting in a sensitivity of 80% and a specificity of 94%. Immunoscintigraphy with 111In/99mTc anti-CEA F(ab')2 fragment/intact antibody is superior to scintigraphy with 201Tl and 131I MIBG

THERMAL REGULATION OF THE BRAIN -AN ANATOMICAL AND PHYSIOLOGICAL REVIEW FOR CLINICAL NEUROSCIENTISTS

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Huan (John eWang

2016-01-01

Full Text Available Humans, like all mammals and birds, maintain a nearly constant core body temperature (36 -37.5°C over a wide range of environmental conditions and are thus referred to as endotherms. The evolution of the brain and its supporting structures in mammals and birds coincided with this development of endothermy. Despite the recognition that a more evolved and complicated brain with all of its temperature-dependent cerebral circuitry and neuronal processes would require more sophisticated thermal control mechanisms, the current understanding of brain temperature regulation remains limited. To optimize the development and maintenance of the brain in health and to accelerate its healing and restoration in illness, focused and committed efforts are much needed to advance the fundamental understanding of brain temperature. In order to effectively study and examine brain temperature regulation, it is critical to first understand the relevant anatomical and physiological properties in the head-neck regions.

Somatic VHL gene alterations in MEN2-associated medullary thyroid carcinoma

International Nuclear Information System (INIS)

Koch, Christian A; Brouwers, Frederieke M; Vortmeyer, Alexander O; Tannapfel, Andrea; Libutti, Steven K; Zhuang, Zhengping; Pacak, Karel; Neumann, Hartmut PH; Paschke, Ralf

2006-01-01

Germline mutations in RET are responsible for multiple endocrine neoplasia type 2 (MEN2), an autosomal dominantly inherited cancer syndrome that is characterized by medullary thyroid carcinoma (MTC), pheochromocytoma, and parathyroid hyperplasia/adenoma. Recent studies suggest a 'second hit' mechanism resulting in amplification of mutant RET. Somatic VHL gene alterations are implicated in the pathogenesis of MEN2 pheochromocytomas. We hypothesized that somatic VHL gene alterations are also important in the pathogenesis of MEN2-associated MTC. We analyzed 6 MTCs and 1 C-cell hyperplasia (CCH) specimen from 7 patients with MEN2A and RET germline mutations in codons 609, 618, 620, or 634, using microdissection, microsatellite analysis, phosphorimage densitometry, and VHL mutation analysis. First, we searched for allelic imbalance between mutant and wild-type RET by using the polymorphic markers D10S677, D10S1239, and RET on thyroid tissue from these patients. Evidence for RET amplification by this technique could be demonstrated in 3 of 6 MTCs. We then performed LOH analysis using D3S1038 and D3S1110 which map to the VHL gene locus at 3p25/26. VHL gene deletion was present in 3 MTCs. These 3 MTCs also had an allelic imbalance between mutant and wild-type RET. Mutation analysis of the VHL gene showed a somatic frameshift mutation in 1 MTC that also demonstrated LOH at 3p25/26. In the 2 other MTCs with allelic imbalance of RET and somatic VHL gene deletion, no somatic VHL mutation could be detected. The CCH specimen did neither reveal RET imbalance nor somatic VHL gene alterations. These data suggest that a RET germline mutation is necessary for development of CCH, that allelic imbalance between mutant and wild-type RET may set off tumorigenesis, and that somatic VHL gene alterations may not play a major role in tumorigenesis of MEN2A-associated MTC

MicroRNA, SND1, and alterations in translational regulation in colon carcinogenesis

International Nuclear Information System (INIS)

Tsuchiya, Naoto; Nakagama, Hitoshi

2010-01-01

Post-transcriptional regulation of gene expression by microRNA (miRNA) has recently attracted major interest in relation to its involvement in cancer development. miRNA is a member of small non-coding RNA, consists of 22-24 nucleotides and regulates expression of target mRNA species in a post-transcriptional manner by being incorporated with RNA-induced silencing complex (RISC). Staphylococcal nuclease homology domain containing 1 (SND1), a component of RISC, is frequently up-regulated in human colon cancers and also chemically induced colon cancers in animals. We here showed that SDN1 is involved in miRNA-mediated gene suppression and overexpression of SND1 in colon cancer cells causes down-regulation of APC without altering APC mRNA levels. As for the miRNA expression profile in human colon cancer, miR-34a was among the list of down-regulated miRNA. Expression of miR-34a is tightly regulated by p53, and ectopic expression of miR-34a in colon cancer cells causes remarkable reduction of cell proliferation and induces senescence-like phenotypes. MiR-34a also participates in the positive feedback loop of the p53 tumor suppressor network. This circuitry mechanism for p53 activation is of interest in understanding the tumor suppressive function of miR-34a in colon carcinogenesis. miRNA should also be considered as novel anti-cancer agents in tumor suppressive therapeutic applications.

Regulating prefrontal cortex activation: an emerging role for the 5-HT₂A serotonin receptor in the modulation of emotion-based actions?

Science.gov (United States)

Aznar, Susana; Klein, Anders B

2013-12-01

The prefrontal cortex (PFC) is involved in mediating important higher-order cognitive processes such as decision making, prompting thereby our actions. At the same time, PFC activation is strongly influenced by emotional reactions through its functional interaction with the amygdala and the striatal circuitry, areas involved in emotion and reward processing. The PFC, however, is able to modulate amygdala reactivity via a feedback loop to this area. A role for serotonin in adjusting for this circuitry of cognitive regulation of emotion has long been suggested based primarily on the positive pharmacological effect of elevating serotonin levels in anxiety regulation. Recent animal and human functional magnetic resonance studies have pointed to a specific involvement of the 5-hydroxytryptamine (5-HT)2A serotonin receptor in the PFC feedback regulatory projection onto the amygdala. This receptor is highly expressed in the prefrontal cortex areas, playing an important role in modulating cortical activity and neural oscillations (brain waves). This makes it an interesting potential pharmacological target for the treatment of neuropsychiatric modes characterized by lack of inhibitory control of emotion-based actions, such as addiction and other impulse-related behaviors. In this review, we give an overview of the 5-HT2A receptor distribution (neuronal, intracellular, and anatomical) along with its functional and physiological effect on PFC activation, and how that relates to more recent findings of a regulatory effect of the PFC on the emotional control of our actions.

The neural circuitry of visual artistic production and appreciation: A proposition

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Ambar Chakravarty

2012-01-01

Full Text Available The nondominant inferior parietal lobule is probably a major "store house" of artistic creativity. The ventromedial prefrontal lobe (VMPFL is supposed to be involved in creative cognition and the dorsolateral prefrontal lobe (DLPFL in creative output. The conceptual ventral and dorsal visual system pathways likely represent the inferior and superior longitudinal fasciculi. During artistic production, conceptualization is conceived in the VMPFL and the executive part is operated through the DLFPL. The latter transfers the concept to the visual brain through the superior longitudinal fasciculus (SLF, relaying on its path to the parietal cortex. The conceptualization at VMPFL is influenced by activity from the anterior temporal lobe through the uncinate fasciculus and limbic system pathways. The final visual image formed in the visual brain is subsequently transferred back to the DLPFL through the SLF and then handed over to the motor cortex for execution. During art appreciation, the image at the visual brain is transferred to the frontal lobe through the SLF and there it is matched with emotional and memory inputs from the anterior temporal lobe transmitted through the uncinate fasiculus. Beauty is perceived at the VMPFL and transferred through the uncinate fasciculus to the hippocampo-amygdaloid complex in the anterior temporal lobe. The limbic system (Papez circuit is activated and emotion of appreciation is evoked. It is postulated that in practice the entire circuitry is activated simultaneously.

Assessing Ink Transfer Performance of Gravure-Offset Fine-Line Circuitry Printing

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Cheng, Hsien-Chie; Chen, You-Wei; Chen, Wen-Hwa; Lu, Su-Tsai; Lin, Shih-Ming

2018-03-01

In this study, the printing mechanism and performance of gravure-offset fine-line circuitry printing technology are investigated in terms of key printing parameters through experimental and theoretical analyses. First, the contact angles of the ink deposited on different substrates, blankets, and gravure metal plates are experimentally determined; moreover, their temperature and solvent content dependences are analyzed. Next, the ink solvent absorption and evaporation behaviors of the blankets at different temperatures, times, and numbers of printing repetitions are characterized by conducting experiments. In addition, while printing repeatedly, the surface characteristics of the blankets, such as the contact angle, vary with the amount of absorbed ink solvent, further affecting the ink transfer performance (ratio) and printing quality. Accordingly, the surface effect of the blanket due to ink solvent absorption on the ink contact angle is analyzed. Furthermore, the amount of ink transferred from the gravure plate to the blanket in the "off process" and from the blanket to the substrate in the "set process" is evaluated by conducting a simplified plate-to-plate experiment. The influences of loading rate (printing velocity), temperature, and solvent content on the ink transfer performance are addressed. Finally, the ink transfer mechanism is theoretically analyzed for different solvent contents using Surface Evolver. The calculation results are compared with those of the experiment.

The neural circuitry of visual artistic production and appreciation: A proposition.

Science.gov (United States)

Chakravarty, Ambar

2012-04-01

The nondominant inferior parietal lobule is probably a major "store house" of artistic creativity. The ventromedial prefrontal lobe (VMPFL) is supposed to be involved in creative cognition and the dorsolateral prefrontal lobe (DLPFL) in creative output. The conceptual ventral and dorsal visual system pathways likely represent the inferior and superior longitudinal fasciculi. During artistic production, conceptualization is conceived in the VMPFL and the executive part is operated through the DLFPL. The latter transfers the concept to the visual brain through the superior longitudinal fasciculus (SLF), relaying on its path to the parietal cortex. The conceptualization at VMPFL is influenced by activity from the anterior temporal lobe through the uncinate fasciculus and limbic system pathways. The final visual image formed in the visual brain is subsequently transferred back to the DLPFL through the SLF and then handed over to the motor cortex for execution. During art appreciation, the image at the visual brain is transferred to the frontal lobe through the SLF and there it is matched with emotional and memory inputs from the anterior temporal lobe transmitted through the uncinate fasiculus. Beauty is perceived at the VMPFL and transferred through the uncinate fasciculus to the hippocampo-amygdaloid complex in the anterior temporal lobe. The limbic system (Papez circuit) is activated and emotion of appreciation is evoked. It is postulated that in practice the entire circuitry is activated simultaneously.

Rapid response of hypercortisolism to vandetanib treatment in a patient with advanced medullary thyroid cancer and ectopic Cushing syndrome

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Pitoia Fabian; Bueno, Fernanda; Schmidt, Angelica; Lucas, Sabrina; Cross, Graciela, E-mail: fpitoia@intramed.net [Division de Endocrinologia, Hospital de Clinicas, Universidad de Buenos Aires Buenos Aires (Argentina)

2015-08-15

Medullary thyroid carcinoma (MTC) may rarely present with paraneoplastic syndromes. Among the most frequent ones are the appearance of diarrhea and ectopic Cushing syndrome (ECS). The ECS in the context of MTC is usually present in patients with distant metastatic disease. The use of drugs such as ketoconazole, metyrapone, somatostatin analogs and etomidate have been ineffective alternatives to control hypercortisolism in these patients. Bilateral adrenalectomy is often required to manage this situation. Recently, the use of tyrosine kinase inhibitors has been shown to be a useful tool to achieve eucortisolism in patients with metastatic MTC and ECS. We present a patient with sporadic advanced persistent and progressive MTC with lymph node and liver metastases, which after 16 years of followup developed an ECS. After one month of 300 mg/day vandetanib treatment, a biochemical and clinical response of the ECS was achieved but it did not result in significant reduction of tumor burden. However the patient reached criteria for stable disease according to response evaluation criteria in solid tumors (RECIST 1.1) after 8 months of follow-up. (author)

Rapid response of hypercortisolism to vandetanib treatment in a patient with advanced medullary thyroid cancer and ectopic Cushing syndrome

International Nuclear Information System (INIS)

Pitoia Fabian; Bueno, Fernanda; Schmidt, Angelica; Lucas, Sabrina; Cross, Graciela

2015-01-01

Medullary thyroid carcinoma (MTC) may rarely present with paraneoplastic syndromes. Among the most frequent ones are the appearance of diarrhea and ectopic Cushing syndrome (ECS). The ECS in the context of MTC is usually present in patients with distant metastatic disease. The use of drugs such as ketoconazole, metyrapone, somatostatin analogs and etomidate have been ineffective alternatives to control hypercortisolism in these patients. Bilateral adrenalectomy is often required to manage this situation. Recently, the use of tyrosine kinase inhibitors has been shown to be a useful tool to achieve eucortisolism in patients with metastatic MTC and ECS. We present a patient with sporadic advanced persistent and progressive MTC with lymph node and liver metastases, which after 16 years of followup developed an ECS. After one month of 300 mg/day vandetanib treatment, a biochemical and clinical response of the ECS was achieved but it did not result in significant reduction of tumor burden. However the patient reached criteria for stable disease according to response evaluation criteria in solid tumors (RECIST 1.1) after 8 months of follow-up. (author)

99mTc-EDDA/HYNIC-TOC in the management of medullary thyroid carcinoma.

Science.gov (United States)

Parisella, Maria; D'Alessandria, Calogero; van de Bossche, Bieke; Chianelli, Marco; Ronga, Giuseppe; Papini, Enrico; Mikolajczak, Renata; Letizia, Claudio; De Toma, Giorgio; Veneziani, Augusto; Scopinaro, Francesco; Signore, Alberto

2004-04-01

An early diagnosis of distant metastases or local recurrences of medullary thyroid carcinoma (MTC) can be achieved by several conventional radiological modalities (e.g., ultrasonography, computed tomography [CT], and magnetic resonance imaging [MRI] as well as by radioisotopic procedures, such as positron emission tomography (PET), scintigraphy with different types of radiopharmaceuticals, and radiolabeled receptor-ligands in particular. The aim of this study was to evaluate the clinical utility of 99mTc-EDDA/HYNIC-TOC, a new octreotide derivative, to detect recurrences of disease or distant metastases in MTC. Images obtained of 5 patients with high levels of serum calcitonin were compared to findings obtained with other diagnostic procedures: 111In-octreotide, 99mTc-DMSA-V, 18F-flouro-D-deoxyglucose-PET, and CT/MRI. 99mTc-EDDA/HYNIC-TOC was positive in all patients and showed 15 areas of pathological uptake in the cervical and mediastinal regions. 111In-octreotide was positive in 3 of 3 patients and showed 4 areas, compared to 8 of 99mTc-EDDA/HYNIC-TOC. 99mTc-V-DMSA was positive in 3 of 4 patients but showed 6 pathological areas, compared to 13 of 99mTc-EDDA/HYNIC-TOC. 18F-FDG-PET was positive in 5 of 5 patients but showed only 11 areas, compared to 15 of 99mTc-EDDA/HYNIC-TOC. The CT scan was positive in only 2 patients. In conclusion, 99mTc-EDDA/HYNIC-TOC detected more sites of pathological uptake than other modalities, showed better imaging properties than 111In-octreotide, and might be the radiopharmaceutical of choice for providing a rationale for radioisotopic therapy.

Post-transcriptional regulation on a global scale: form and function of Csr/Rsm systems.

Science.gov (United States)

Romeo, Tony; Vakulskas, Christopher A; Babitzke, Paul

2013-02-01

Originally described as a repressor of gene expression in the stationary phase of growth, CsrA (RsmA) regulates primary and secondary metabolic pathways, biofilm formation, motility, virulence circuitry of pathogens, quorum sensing and stress response systems by binding to conserved sequences in its target mRNAs and altering their translation and/or turnover. While the binding of CsrA to RNA is understood at an atomic level, new mechanisms of gene activation and repression by this protein are still emerging. In the γ-proteobacteria, small non-coding RNAs (sRNAs) use molecular mimicry to sequester multiple CsrA dimers away from mRNA. In contrast, the FliW protein of Bacillus subtilis inhibits CsrA activity by binding to this protein, thereby establishing a checkpoint in flagellum morphogenesis. Turnover of CsrB and CsrC sRNAs in Escherichia coli requires a specificity protein of the GGDEF-EAL domain superfamily, CsrD, in addition to the housekeeping nucleases RNase E and PNPase. The Csr system of E. coli contains extensive autoregulatory circuitry, which governs the expression and activity of CsrA. Interaction of the Csr system with transcriptional regulatory networks results in a variety of complex response patterns. This minireview will highlight basic principles and new insights into the workings of these complex eubacterial regulatory systems. © 2012 Society for Applied Microbiology and Blackwell Publishing Ltd.

Innate Interferons Regulate CNS Inflammation

DEFF Research Database (Denmark)

Dieu, Ruthe; Khorooshi, Reza M. H.; Mariboe, Anne

Multiple sclerosis (MS) is a chronic inflammatory disease of the central nervous system (CNS) whose pathology is characterised by demyelination and axonal damage. This results from interplay between CNS-resident glia, infiltrating leukocytes and a plethora of cytokines and chemokines. Currently...... potential IFN-inducing receptor that signals through NF-kB. Receptor activator of NF-kB (RANK) belongs to the TNF-receptor superfamily and has been shown to induce IFN-beta in medullary thymic epithelial cells affecting autoimmune regulatory processes and osteoclast precursor cells in association to bone...

Dopaminergic circuitry and risk/reward decision making: implications for schizophrenia.

Science.gov (United States)

Stopper, Colin M; Floresco, Stan B

2015-01-01

Abnormal reinforcement learning and representations of reward value are present in schizophrenia, and these impairments can manifest as deficits in risk/reward decision making. These abnormalities may be due in part to dopaminergic dysfunction within cortico-limbic-striatal circuitry. Evidence from studies with laboratory animal have revealed that normal DA activity within different nodes of these circuits is critical for mediating dissociable processes that can refine decision biases. Moreover, both phasic and tonic dopamine transmission appear to play separate yet complementary roles in these processes. Tonic dopamine release within the prefrontal cortex and nucleus accumbens, serves as a "running rate-meter" of reward and reflects contextual information such as reward uncertainty and overt choice behavior. On the other hand, manipulations of outcome-related phasic dopamine bursts and dips suggest these signals provide rapid feedback to allow for quick adjustments in choice as reward contingencies change. The lateral habenula is a key input to the DA system that phasic signals is necessary for expressing subjective decision biases; as suppression of activity within this nucleus leads to catastrophic impairments in decision making and random patterns of choice behavior. As schizophrenia is characterized by impairments in using positive and negative feedback to appropriately guide decision making, these findings suggest that these deficits in these processes may be mediated, at least in part, by abnormalities in both tonic and phasic dopamine transmission. © The Author 2014. Published by Oxford University Press on behalf of the Maryland Psychiatric Research Center. All rights reserved. For permissions, please email: journals.permissions@oup.com.

Sex differences, hormones, and fMRI stress response circuitry deficits in psychoses.

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Goldstein, Jill M; Lancaster, Katie; Longenecker, Julia M; Abbs, Brandon; Holsen, Laura M; Cherkerzian, Sara; Whitfield-Gabrieli, Susan; Makris, Nicolas; Tsuang, Ming T; Buka, Stephen L; Seidman, Larry J; Klibanski, Anne

2015-06-30

Response to stress is dysregulated in psychosis (PSY). fMRI studies showed hyperactivity in hypothalamus (HYPO), hippocampus (HIPP), amygdala (AMYG), anterior cingulate (ACC), orbital and medial prefrontal (OFC; mPFC) cortices, with some studies reporting sex differences. We predicted abnormal steroid hormone levels in PSY would be associated with sex differences in hyperactivity in HYPO, AMYG, and HIPP, and hypoactivity in PFC and ACC, with more severe deficits in men. We studied 32 PSY cases (50.0% women) and 39 controls (43.6% women) using a novel visual stress challenge while collecting blood. PSY males showed BOLD hyperactivity across all hypothesized regions, including HYPO and ACC by FWE-correction. Females showed hyperactivity in HIPP and AMYG and hypoactivity in OFC and mPFC, the latter FWE-corrected. Interaction of group by sex was significant in mPFC (F = 7.00, p = 0.01), with PSY females exhibiting the lowest activity. Male hyperactivity in HYPO and ACC was significantly associated with hypercortisolemia post-stress challenge, and mPFC with low androgens. Steroid hormones and neural activity were dissociated in PSY women. Findings suggest disruptions in neural circuitry-hormone associations in response to stress are sex-dependent in psychosis, particularly in prefrontal cortex. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

Medullary thyroid carcinoma: Application of Thyroid Imaging Reporting and Data System (TI-RADS) Classification.

Science.gov (United States)

Yun, Gabin; Kim, Yeo Koon; Choi, Sang Il; Kim, Ji-Hoon

2018-04-21

To evaluate the applicability of ultrasound (US)-based Thyroid Imaging Reporting and Data System (TI-RADS) for evaluating medullary thyroid carcinoma (MTC). US images and medical records of patients with cytopathology-confirmed MTC between June 2003 and November 2016 were retrospectively reviewed. Four independent reviewers (two experienced and two inexperienced radiologists) evaluated 57 pre-operative US images of patients with MTC for shape, composition, echogenicity, margin, calcification of the MTC nodules, and categorized the nodules using TI-RADS classification. Weighted Kappa statistics was used to determine the inter-observer agreement of TI-RADS. Univariate and multivariate analyses were performed to assess US findings associated with lymph node metastasis. Ninety-five percent of nodules were classified as either high suspicion (68%) or intermediate suspicion (26%). The overall inter-rater agreement was good (Kappa 0.84, agreement 91.52%), and inexperienced reviewers also showed good agreements with the most experienced reviewer (weighted Kappa 0.73 and 0.81). According to the univariate analysis, TI-RADS category 5, shape, microcalcification, and extrathyroid extension were significantly associated with lymph node metastasis in MTC patients (p = 0.003, 0.008, 0.001, and 0.021, respectively). As per the multivariate analysis, the presence of microcalcification and the irregular shape of the nodule were significantly associated with metastatic lymph nodes in MTC patients (odds ratio, 26.6; 95% CI, 2.7-263.7, p = 0.005, odds ratio, 14.7; 95% CI, 1.3-170, p = 0.031, respectively). TI-RADS is applicable for the evaluation of MTC nodules with good inter-observer agreement.

Vandetanib (100 mg) in patients with locally advanced or metastatic hereditary medullary thyroid cancer.

Science.gov (United States)

Robinson, Bruce G; Paz-Ares, Luis; Krebs, Annetta; Vasselli, James; Haddad, Robert

2010-06-01

Vandetanib is a once-daily oral inhibitor of vascular endothelial growth factor receptor-2 and epidermal growth factor receptor tyrosine kinases that also inhibits rearranged during transfection kinase activity. Vandetanib (300 mg/d) has previously demonstrated antitumor activity in patients with advanced hereditary medullary thyroid cancer (MTC). This study investigated the efficacy and safety of 100 mg/d vandetanib in patients with advanced hereditary MTC. Eligible patients with unresectable, measurable, locally advanced, or metastatic hereditary MTC received 100 mg/d vandetanib. Upon disease progression, eligible patients could enter postprogression treatment with 300 mg/d vandetanib until a withdrawal criterion was met. The primary objective was to assess the objective response rate by response evaluation criteria in solid tumors. The study comprised 19 patients (13 males, six females; mean age 45 yr). Confirmed objective partial responses were observed in three patients, yielding an objective response rate of 16% (95% confidence interval 3.4-39.6). Stable disease lasting 24 wk or longer was reported in a further 10 patients (53%); the disease control rate was therefore 68% (95% confidence interval 43.4-87.4). Serum levels of calcitonin and carcinoembryonic antigen showed a sustained 50% or greater decrease from baseline in 16% (three of 19) and 5% (one of 19) of patients, respectively. Adverse events were predominantly grade 1 or 2 and consistent with previous vandetanib monotherapy studies. Vandetanib at a once-daily dose of 100 mg has clinically relevant antitumor activity in patients with locally advanced or metastatic hereditary MTC and an overall acceptable safety profile.

Limbic-thalamo-cortical projections and reward-related circuitry integrity affects eating behavior: A longitudinal DTI study in adolescents with restrictive eating disorders.

Directory of Open Access Journals (Sweden)

Gaia Olivo

Full Text Available Few studies have used diffusion tensor imaging (DTI to investigate the micro-structural alterations of WM in patients with restrictive eating disorders (rED, and longitudinal data are lacking. Twelve patients with rED were scanned at diagnosis and after one year of family-based treatment, and compared to twenty-four healthy controls (HCs through DTI analysis. A tract-based spatial statistics procedure was used to investigate diffusivity parameters: fractional anisotropy (FA and mean, radial and axial diffusivities (MD, RD and AD, respectively. Reduced FA and increased RD were found in patients at baseline in the corpus callosum, corona radiata and posterior thalamic radiation compared with controls. However, no differences were found between follow-up patients and controls, suggesting a partial normalization of the diffusivity parameters. In patients, trends for a negative correlation were found between the baseline FA of the right anterior corona radiata and the Eating Disorder Examination Questionnaire total score, while a positive trend was found between the baseline FA in the splenium of corpus callosum and the weight loss occurred between maximal documented weight and time of admission. A positive trend for correlation was also found between baseline FA in the right anterior corona radiata and the decrease in the Obsessive-Compulsive Inventory Revised total score over time. Our results suggest that the integrity of the limbic-thalamo-cortical projections and the reward-related circuitry are important for cognitive control processes and reward responsiveness in regulating eating behavior.

Cutaneous Metastasis of Medullary Carcinoma Thyroid Masquerading as Subcutaneous Nodules Anterior Chest and Mandibular Region

Directory of Open Access Journals (Sweden)

Rahul Mannan

2014-01-01

Full Text Available Cutaneous metastasis of underlying primary malignancies can present to dermatologist with chief complaints of cutaneous lesions. The underlying malignancy is generally diagnosed much later after a complete assessment of the concerned case. Medullary carcinoma thyroid (MCT is a relatively uncommon primary neoplasia of the thyroid. Very few cases presenting as cutaneous metastases of MCT have been reported in the literature. Most of the cases which have been reported are of the papillary and the follicular types. We here report a case of a patient who presented in the dermatology clinic with the primary complaint of multiple subcutaneous nodules in anterior chest wall and left side of body of mandible. By systematic application of clinical and diagnostic skills these nodules were diagnosed as cutaneous metastasis of MCT bringing to the forefront a history of previously operated thyroid neoplasm. So clinically, the investigation of a flesh coloured subcutaneous nodule, presenting with a short duration, particularly in scalp, jaw, or anterior chest wall should include possibility of metastastic deposits. A dermatologist should keep a possibility of an internal organ malignancy in patients while investigating a case of flesh coloured subcutaneous nodules, presenting with short duration. A systematic application of clinical and diagnostic skills will eventually lead to such a diagnosis even when not suspected clinically at its primary presentation. A prompt and an emphatic diagnosis and treatment will have its bearing on the eventual outcome in all these patients.

Hypothalamic–pituitary–adrenal and hypothalamic–pituitary–gonadal axes: sex differences in regulation of stress responsivity

Science.gov (United States)

Oyola, Mario G.; Handa, Robert J.

2018-01-01

Gonadal hormones play a key role in the establishment, activation, and regulation of the hypothalamic–pituitary–adrenal (HPA) axis. By influencing the response and sensitivity to releasing factors, neurotransmitters, and hormones, gonadal steroids help orchestrate the gain of the HPA axis to fine-tune the levels of stress hormones in the general circulation. From early life to adulthood, gonadal steroids can differentially affect the HPA axis, resulting in sex differences in the responsivity of this axis. The HPA axis influences many physiological functions making an organism’s response to changes in the environment appropriate for its reproductive status. Although the acute HPA response to stressors is a beneficial response, constant activation of this circuitry by chronic or traumatic stressful episodes may lead to a dysregulation of the HPA axis and cause pathology. Compared to males, female mice and rats show a more robust HPA axis response, as a result of circulating estradiol levels which elevate stress hormone levels during non-threatening situations, and during and after stressors. Fluctuating levels of gonadal steroids in females across the estrous cycle are a major factor contributing to sex differences in the robustness of HPA activity in females compared to males. Moreover, gonadal steroids may also contribute to epigenetic and organizational influences on the HPA axis even before puberty. Correspondingly, crosstalk between the hypothalamic–pituitary–gonadal (HPG) and HPA axes could lead to abnormalities of stress responses. In humans, a dysregulated stress response is one of the most common symptoms seen across many neuropsychiatric disorders, and as a result, such interactions may exacerbate peripheral pathologies. In this review, we discuss the HPA and HPG axes and review how gonadal steroids interact with the HPA axis to regulate the stress circuitry during all stages in life. PMID:28859530

Hypothalamic-pituitary-adrenal and hypothalamic-pituitary-gonadal axes: sex differences in regulation of stress responsivity.

Science.gov (United States)

Oyola, Mario G; Handa, Robert J

2017-09-01

Gonadal hormones play a key role in the establishment, activation, and regulation of the hypothalamic-pituitary-adrenal (HPA) axis. By influencing the response and sensitivity to releasing factors, neurotransmitters, and hormones, gonadal steroids help orchestrate the gain of the HPA axis to fine-tune the levels of stress hormones in the general circulation. From early life to adulthood, gonadal steroids can differentially affect the HPA axis, resulting in sex differences in the responsivity of this axis. The HPA axis influences many physiological functions making an organism's response to changes in the environment appropriate for its reproductive status. Although the acute HPA response to stressors is a beneficial response, constant activation of this circuitry by chronic or traumatic stressful episodes may lead to a dysregulation of the HPA axis and cause pathology. Compared to males, female mice and rats show a more robust HPA axis response, as a result of circulating estradiol levels which elevate stress hormone levels during non-threatening situations, and during and after stressors. Fluctuating levels of gonadal steroids in females across the estrous cycle are a major factor contributing to sex differences in the robustness of HPA activity in females compared to males. Moreover, gonadal steroids may also contribute to epigenetic and organizational influences on the HPA axis even before puberty. Correspondingly, crosstalk between the hypothalamic-pituitary-gonadal (HPG) and HPA axes could lead to abnormalities of stress responses. In humans, a dysregulated stress response is one of the most common symptoms seen across many neuropsychiatric disorders, and as a result, such interactions may exacerbate peripheral pathologies. In this review, we discuss the HPA and HPG axes and review how gonadal steroids interact with the HPA axis to regulate the stress circuitry during all stages in life.

Regulation of bacterial virulence by Csr (Rsm) systems.

Science.gov (United States)

Vakulskas, Christopher A; Potts, Anastasia H; Babitzke, Paul; Ahmer, Brian M M; Romeo, Tony

2015-06-01

Most bacterial pathogens have the remarkable ability to flourish in the external environment and in specialized host niches. This ability requires their metabolism, physiology, and virulence factors to be responsive to changes in their surroundings. It is no surprise that the underlying genetic circuitry that supports this adaptability is multilayered and exceedingly complex. Studies over the past 2 decades have established that the CsrA/RsmA proteins, global regulators of posttranscriptional gene expression, play important roles in the expression of virulence factors of numerous proteobacterial pathogens. To accomplish these tasks, CsrA binds to the 5' untranslated and/or early coding regions of mRNAs and alters translation, mRNA turnover, and/or transcript elongation. CsrA activity is regulated by noncoding small RNAs (sRNAs) that contain multiple CsrA binding sites, which permit them to sequester multiple CsrA homodimers away from mRNA targets. Environmental cues sensed by two-component signal transduction systems and other regulatory factors govern the expression of the CsrA-binding sRNAs and, ultimately, the effects of CsrA on secretion systems, surface molecules and biofilm formation, quorum sensing, motility, pigmentation, siderophore production, and phagocytic avoidance. This review presents the workings of the Csr system, the paradigm shift that it generated for understanding posttranscriptional regulation, and its roles in virulence networks of animal and plant pathogens. Copyright © 2015, American Society for Microbiology. All Rights Reserved.

FOXN1: a master regulator gene of thymic epithelial development programme

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Rosa eRomano

2013-07-01

Full Text Available T cell ontogeny is a sophisticated process, which takes place within the thymus through a series of well-defined discrete stages. The process requires a proper lympho-stromal interaction. In particular, cortical and medullary thymic epithelial cells (cTECs, mTECs drive T cell differentiation, education and selection processes, while the thymocyte-dependent signals allow TECs to maturate and provide an appropriate thymic microenvironment. Alterations in genes implicated in thymus organogenesis, including Tbx1, Pax1, Pax3, Pax9, Hoxa3, Eya1 and Six1, affect this well-orchestrated process, leading to disruption of thymic architecture. Of note, in both human and mice, the primordial TECs are yet unable to fully support T cell development and only after the transcriptional activation of the Forkhead-box n1 (FOXN1 gene in the thymic epithelium this essential function is acquired. FOXN1 is a master regulator in the TEC lineage specification in that it down-stream promotes transcription of genes, which, in turn, regulate TECs differentiation. In particular, FOXN1 mainly regulates TEC patterning in the fetal stage and TEC homeostasis in the postnatal thymus. An inborn null mutation in FOXN1 leads to Nude/SCID phenotype in mouse, rat and humans. In Foxn1-/- nude animals, initial formation of the primordial organ is arrested and the primordium is not colonized by hematopoietic precursors, causing a severe primary T cell immunodeficiency. In humans, the Nude/SCID phenotype is characterized by congenital alopecia of the scalp, eyebrows, and eyelashes, nail dystrophy and a severe T cell immunodeficiency, inherited as an autosomal recessive disorder. Aim of this review is to summarize all the scientific information so far available to better characterize the pivotal role of the master regulator FOXN1 transcription factor in the TEC lineage specifications and functionality.

Generation of a tenascin-C-CreER2 knockin mouse line for conditional DNA recombination in renal medullary interstitial cells.

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Wenjuan He

Full Text Available Renal medullary interstitial cells (RMIC are specialized fibroblast-like cells that exert important functions in maintaining body fluid homeostasis and systemic blood pressure. Here, we generated a RMIC specific tenascin-C promoter driven inducible CreER2 knockin mouse line with an EGFP reporter. Similar as endogenous tenascin-C expression, the reporter EGFP expression in the tenascin-C-CreER2(+/- mice was observed in the inner medulla of the kidney, and co-localized with COX2 but not with AQP2 or AQP1, suggesting selective expression in RMICs. After recombination (tenascin-C-CreER2(+/-/ROSA26-lacZ(+/- mice + tamoxifen, β-gal activity was restricted to the cells in the inner medulla of the kidney, and didn't co-localize with AQP2, consistent with selective Cre recombinase activity in RMICs. Cre activity was not obvious in other major organs or without tamoxifen treatment. This inducible RMIC specific Cre mouse line should therefore provide a novel tool to manipulate genes of interest in RMICs.

Intensity of anxiety is modified via complex integrative stress circuitries.

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Smith, Justin P; Prince, Melissa A; Achua, Justin K; Robertson, James M; Anderson, Raymond T; Ronan, Patrick J; Summers, Cliff H

2016-01-01

Escalation of anxious behavior while environmentally and socially relevant contextual events amplify the intensity of emotional response produces a testable gradient of anxiety shaped by integrative circuitries. Apprehension of the Stress-Alternatives Model apparatus (SAM) oval open field (OF) is measured by the active latency to escape, and is delayed by unfamiliarity with the passageway. Familiar OF escape is the least anxious behavior along the continuum, which can be reduced by anxiolytics such as icv neuropeptide S (NPS). Social aggression increases anxiousness in the SAM, reducing the number of mice willing to escape by 50%. The apprehension accompanying escape during social aggression is diminished by anxiolytics, such as exercise and corticotropin releasing-factor receptor 1 (CRF1) antagonism, but exacerbated by anxiogenic treatment, like antagonism of α2-adrenoreceptors. What is more, the anxiolytic CRF1 and anxiogenic α2-adrenoreceptor antagonists also modify behavioral phenotypes, with CRF1 antagonism allowing escape by previously submissive animals, and α2-adrenoreceptor antagonism hindering escape in mice that previously engaged in it. Gene expression of NPS and brain-derived neurotrophic factor (BDNF) in the central amygdala (CeA), as well as corticosterone secretion, increased concomitantly with the escalating anxious content of the mouse-specific anxiety continuum. The general trend of CeA NPS and BDNF expression suggested that NPS production was promoted by increasing anxiousness, and that BDNF synthesis was associated with learning about ever-more anxious conditions. The intensity gradient for anxious behavior resulting from varying contextual conditions may yield an improved conceptualization of the complexity of mechanisms producing the natural continuum of human anxious conditions, and potential therapies that arise therefrom. Copyright © 2015 Elsevier Ltd. All rights reserved.

GABA regulates synaptic integration of newly generated neurons in the adult brain

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Ge, Shaoyu; Goh, Eyleen L. K.; Sailor, Kurt A.; Kitabatake, Yasuji; Ming, Guo-Li; Song, Hongjun

2006-02-01

Adult neurogenesis, the birth and integration of new neurons from adult neural stem cells, is a striking form of structural plasticity and highlights the regenerative capacity of the adult mammalian brain. Accumulating evidence suggests that neuronal activity regulates adult neurogenesis and that new neurons contribute to specific brain functions. The mechanism that regulates the integration of newly generated neurons into the pre-existing functional circuitry in the adult brain is unknown. Here we show that newborn granule cells in the dentate gyrus of the adult hippocampus are tonically activated by ambient GABA (γ-aminobutyric acid) before being sequentially innervated by GABA- and glutamate-mediated synaptic inputs. GABA, the major inhibitory neurotransmitter in the adult brain, initially exerts an excitatory action on newborn neurons owing to their high cytoplasmic chloride ion content. Conversion of GABA-induced depolarization (excitation) into hyperpolarization (inhibition) in newborn neurons leads to marked defects in their synapse formation and dendritic development in vivo. Our study identifies an essential role for GABA in the synaptic integration of newly generated neurons in the adult brain, and suggests an unexpected mechanism for activity-dependent regulation of adult neurogenesis, in which newborn neurons may sense neuronal network activity through tonic and phasic GABA activation.

Disturbance in the neural circuitry underlying positive emotional processing in post-traumatic stress disorder (PTSD). An fMRI study.

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Jatzko, Alexander; Schmitt, Andrea; Demirakca, Traute; Weimer, Erik; Braus, Dieter F

2006-03-01

This study was designed to investigate the circuitry underlying movie-induced positive emotional processing in subjects with chronic PTSD. Ten male subjects with chronic PTSD and ten matched controls were studied. In an fMRI-paradigm a sequence of a wellknown Walt Disney cartoon with positive emotional valence was shown. PTSD subjects showed an increased activation in the right posterior temporal, precentral and superior frontal cortex. Controls recruited more emotion-related regions bilateral in the temporal pole and areas of the left fusiform and parahippocampal gyrus. This pilot study is the first to reveal alterations in the processing of positive emotions in PTSD possibly reflecting a neuronal correlate of the symptom of emotional numbness in PTSD.

Role of the medulla oblongata in normal and high arterial blood pressure regulation: the contribution of Escola Paulista de Medicina - UNIFESP.

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Cravo, Sergio L; Campos, Ruy R; Colombari, Eduardo; Sato, Mônica A; Bergamaschi, Cássia M; Pedrino, Gustavo R; Ferreira-Neto, Marcos L; Lopes, Oswaldo U

2009-09-01

Several forms of experimental evidence gathered in the last 37 years have unequivocally established that the medulla oblongata harbors the main neural circuits responsible for generating the vasomotor tone and regulating arterial blood pressure. Our current understanding of this circuitry derives mainly from the studies of Pedro Guertzenstein, a former student who became Professor of Physiology at UNIFESP later, and his colleagues. In this review, we have summarized the main findings as well as our collaboration to a further understanding of the ventrolateral medulla and the control of arterial blood pressure under normal and pathological conditions.

The role of BDNF in depression on the basis of its location in the neural circuitry

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Hui YU; Zhe-yu CHEN

2011-01-01

Depression is one of the most prevalent and life-threatening forms of mental illnesses and the neural circuitry underlying depression remains incompletely understood. Most attention in the field has focused on hippocampal and frontal cortical regions for their roles in depression and antidepressant action. While these regions no doubt play important roles in the mental illness, there is compelling evi-dence that other brain regions are also involved. Brain-derived neurotrophic factor (BDNF) is broadly expressed in the developing and adult mammalian brain and has been implicated in development, neural regeneration, synaptic transmission, synaptic plasticity and neurogenesis. Recently BDNF has been shown to play an important role in the pathophysiology of depression, however there are con-troversial reports about the effects of BDNF on depression. Here, we present an overview of the current knowledge concerning BDNF actions and associated intracellular signaling in hippocampus, prefrontal cortex, nucleus accumbens (NAc) and amygdala as their rela-tion to depression.

Bilateral primary motor cortex circuitry is modulated due to theta burst stimulation to left dorsal premotor cortex and bimanual training.

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Neva, Jason L; Vesia, Michael; Singh, Amaya M; Staines, W Richard

2015-08-27

Motor preparatory and execution activity is enhanced after a single session of bimanual visuomotor training (BMT). Recently, we have shown that increased primary motor cortex (M1) excitability occurs when BMT involves simultaneous activation of homologous muscles and these effects are enhanced when BMT is preceded by intermittent theta burst stimulation (iTBS) to the left dorsal premotor cortex (lPMd). The neural mechanisms underlying these modulations are unclear, but may include interhemispheric interactions between homologous M1s and connectivity with premotor regions. The purpose of this study was to investigate the possible intracortical and interhemispheric modulations of the extensor carpi radials (ECR) representation in M1 bilaterally due to: (1) BMT, (2) iTBS to lPMd, and (3) iTBS to lPMd followed by BMT. This study tests three related hypotheses: (1) BMT will enhance excitability within and between M1 bilaterally, (2) iTBS to lPMd will primarily enhance left M1 (lM1) excitability, and (3) the combination of these interventions will cause a greater enhancement of bilateral M1 excitability. We used single and paired-pulse transcranial magnetic stimulation (TMS) to quantify M1 circuitry bilaterally. The results demonstrate the neural mechanisms underlying the early markers of rapid functional plasticity associated with BMT and iTBS to lPMd primarily relate to modulations of long-interval inhibitory (i.e. GABAB-mediated) circuitry within and between M1s. This work provides novel insight into the underlying neural mechanisms involved in M1 excitability changes associated with BMT and iTBS to lPMd. Critically, this work may inform rehabilitation training and stimulation techniques that modulate cortical plasticity after brain injury. Copyright © 2015. Published by Elsevier B.V.

Food motivation circuitry hypoactivation related to hedonic and nonhedonic aspects of hunger and satiety in women with active anorexia nervosa and weight-restored women with anorexia nervosa.

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Holsen, Laura M; Lawson, Elizabeth A; Blum, Justine; Ko, Eunice; Makris, Nikos; Fazeli, Pouneh K; Klibanski, Anne; Goldstein, Jill M

2012-09-01

Previous studies have provided evidence of food motivation circuitry dysfunction in individuals with anorexia nervosa. However, methodological limitations present challenges to the development of a cohesive neurobiological model of anorexia nervosa. Our goal was to investigate the neural circuitry of appetite dysregulation across states of hunger and satiety in active and weight-restored phases of anorexia nervosa using robust methodology to advance our understanding of potential neural circuitry abnormalities related to hedonic and nonhedonic state and trait. We scanned women with active anorexia nervosa, weight-restored women with anorexia nervosa and healthy-weight controls on a 3-T Siemens magnetic resonance scanner while they viewed images of high- and low-calorie foods and objects before (premeal) and after (postmeal) eating a 400 kcal meal. We enrolled 12 women with active disease, 10 weight-restored women with anorexia nervosa and 11 controls in our study. Compared with controls, both weight-restored women and those with active disease demonstrated hypoactivity premeal in the hypothalamus, amygdala and anterior insula in response to high-calorie foods (v. objects). Postmeal, hypoactivation in the anterior insula persisted in women with active disease. Percent signal change in the anterior insula was positively correlated with food stimuli ratings and hedonic and nonhedonic appetite ratings in controls, but not women with active disease. Our findings are limited by a relatively small sample size, which prevented the use of an analysis of variance model and exploration of interaction effects, although our substantial effect sizes of between-group differences suggest adequate power for our statistical analysis approach. Participants taking psychotropic medications were included. Our data provide evidence of potential state and trait hypoactivations in food motivation regions involved in the assessment of food's reward value and integration of these with

Adrenal Gland Microenvironment and Its Involvement in the Regulation of Stress-induced Hormone Secretion during Sepsis.

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Waldemar Kanczkowski

2016-12-01

Full Text Available Survival of all living organisms depends on maintenance of a steady state of homeostasis, which process relies on its ability to react and adapt to various physical and emotional threats. The defense against stress is executed by the hypothalamic-pituitary-adrenal axis and the sympathetic-adrenal medullary system. Adrenal gland is a major effector organ of stress system. During stress adrenal gland rapidly respond with increased secretion of glucocorticoids and catecholamines into circulation, which hormones, in turn, affect metabolism, to provide acutely energy, vasculature to increase blood pressure and the immune system to prevent it from extensive activation. Sepsis resulting from microbial infections is a sustained and extreme example of stress situation. In many critical ill patients levels of both corticotropin-releasing hormone and adrenocorticotropin, two major regulators of adrenal hormone production, are suppressed. Levels of glucocorticoids however, remain normal or are elevated in these patients, suggesting a shift from central to local intraadrenal regulation of adrenal stress response. Among many mechanisms potentially involved in this process, reduced glucocorticoid metabolism and local intraadrenal activation of hormone production mediated by adrenocortical and chromaffin cell interactions, the adrenal vascular system and the immune-adrenal crosstalk play a key role. Consequently, any impairment in function of these systems, can ultimately affect adrenal stress response. The purpose of this mini review is to present and discuss recent advances in our understanding of the adrenal gland microenvironment, and its role in regulation of stress-induced hormone secretion.

Diverse Genetic Regulon of the Virulence-Associated Transcriptional Regulator MucR in Brucella abortus 2308

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Caswell, Clayton C.; Elhassanny, Ahmed E. M.; Planchin, Emilie E.; Roux, Christelle M.; Weeks-Gorospe, Jenni N.; Ficht, Thomas A.; Dunman, Paul M.

2013-01-01

The Ros-type regulator MucR is one of the few transcriptional regulators that have been linked to virulence in Brucella. Here, we show that a Brucella abortus in-frame mucR deletion strain exhibits a pronounced growth defect during in vitro cultivation and, more importantly, that the mucR mutant is attenuated in cultured macrophages and in mice. The genetic basis for the attenuation of Brucella mucR mutants has not been defined previously, but in the present study the genes regulated by MucR in B. abortus have been elucidated using microarray analysis and real-time reverse transcription-PCR (RT-PCR). In B. abortus 2308, MucR regulates a wide variety of genes whose products may function in establishing and maintaining cell envelope integrity, polysaccharide biosynthesis, iron homeostasis, genome plasticity, and transcriptional regulation. Particularly notable among the MucR-regulated genes identified is arsR6 (nolR), which encodes a transcriptional regulator previously linked to virulence in Brucella melitensis 16 M. Importantly, electrophoretic mobility shift assays (EMSAs) determined that a recombinant MucR protein binds directly to the promoter regions of several genes repressed by MucR (including arsR6 [nolR]), and in Brucella, as in other alphaproteobacteria, MucR binds to its own promoter to repress expression of the gene that encodes it. Overall, these studies have uncovered the diverse genetic regulon of MucR in Brucella, and in doing so this work has begun to define the MucR-controlled genetic circuitry whose misregulation contributes to the virulence defect of Brucella mucR mutants. PMID:23319565

Level of conus medullaris termination in adult population analyzed by kinetic magnetic resonance imaging.

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Liu, An; Yang, Kaixiang; Wang, Daling; Li, Changqing; Ren, Zhiwei; Yan, Shigui; Buser, Zorica; Wang, Jeffrey C

2017-07-01

To investigate the change of conus medullaris termination (CMT) level in neutral, flexion and extension positions and to analyze the effects of age and gender on the CMT level. The midline sagittal T2-weighted kinetic magnetic resonance imaging (kMRI) study of 585 patients was retrospectively reviewed to identify the level of CMT. All patients were in an upright position. A straight line perpendicular to the long axis of the cord was drawn from the tip of the cord and then subtended to the adjacent vertebra or disk space. The CMT level was labeled in relation to the upper, middle and lower segments of adjacent vertebra or disk space and assigned values from 0 to 12 [0 = upper third of T12 (T12U), and 12 = upper third of L3 (L3U)]. All parameters were collected for neutral, flexion and extension positions. The level of CMT had the highest incidence (17.61%) at L1 lower (L1L) in neutral position, 17.44% at L1 upper (L1U) in flexion, and 16.92% at L1 middle (L1M) in extension with no significant differences among three positions (p > 0.05) in weight-bearing status. Moreover, the level of CMT was not correlated with age (p > 0.05). In terms of gender, the level of CMT was lower in women than in men in neutral position, flexion, and extension (p level of CMT in the neutral position was in accordance with previous cadaveric and supine-position MRI studies, and it did not change with flexion and extension. Women had lower CMT level than men, especially in the older population. This information can be very valuable when performing spinal anesthesia and spinal punctures.

Selective Mitochondrial Uptake of MKT-077 Can Suppress Medullary Thyroid Carcinoma Cell Survival and

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Dmytro Starenki

2015-12-01

Full Text Available BackgroundMedullary thyroid carcinoma (MTC is a neuroendocrine tumor mainly caused by mutations in the rearranged during transfection (RET proto-oncogene. Not all patients with progressive MTC respond to current therapy inhibiting RET, demanding additional therapeutic strategies. We recently demonstrated that disrupting mitochondrial metabolism using a mitochondria-targeted agent or by depleting a mitochondrial chaperone effectively suppressed human MTC cells in culture and in mouse xenografts by inducing apoptosis and RET downregulation. These observations led us to hypothesize that mitochondria are potential therapeutic targets for MTC. This study further tests this hypothesis using1-ethyl-2-[[3-ethyl-5-(3-methylbenzothiazolin-2-yliden]-4-oxothiazolidin-2-ylidenemethyl] pyridinium chloride (MKT-077, a water-soluble rhodocyanine dye analogue, which can selectively accumulate in mitochondria.MethodsThe effects of MKT-077 on cell proliferation, survival, expression of RET and tumor protein 53 (TP53, and mitochondrial activity were determined in the human MTC lines in culture and in mouse xenografts.ResultsMKT-077 induced cell cycle arrest in TT and MZ-CRC-1. Intriguingly, MKT-077 also induced RET downregulation and strong cell death responses in TT cells, but not in MZ-CRC-1 cells. This discrepancy was mainly due to the difference between the capacities of these cell lines to retain MKT-077 in mitochondria. The cytotoxicity of MKT-077 in TT cells was mainly attributed to oxidative stress while being independent of TP53. MKT-077 also effectively suppressed tumor growth of TT xenografts.ConclusionMKT-077 can suppress cell survival of certain MTC subtypes by accumulating in mitochondria and interfering with mitochondrial activity although it can also suppress cell proliferation via other mechanisms. These results consistently support the hypothesis that mitochondrial targeting has therapeutic potential for MTC.

DNA breaks and chromatin structural changes enhance the transcription of autoimmune regulator target genes.

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Guha, Mithu; Saare, Mario; Maslovskaja, Julia; Kisand, Kai; Liiv, Ingrid; Haljasorg, Uku; Tasa, Tõnis; Metspalu, Andres; Milani, Lili; Peterson, Pärt

2017-04-21

The autoimmune regulator (AIRE) protein is the key factor in thymic negative selection of autoreactive T cells by promoting the ectopic expression of tissue-specific genes in the thymic medullary epithelium. Mutations in AIRE cause a monogenic autoimmune disease called autoimmune polyendocrinopathy-candidiasis-ectodermal dystrophy. AIRE has been shown to promote DNA breaks via its interaction with topoisomerase 2 (TOP2). In this study, we investigated topoisomerase-induced DNA breaks and chromatin structural alterations in conjunction with AIRE-dependent gene expression. Using RNA sequencing, we found that inhibition of TOP2 religation activity by etoposide in AIRE-expressing cells had a synergistic effect on genes with low expression levels. AIRE-mediated transcription was not only enhanced by TOP2 inhibition but also by the TOP1 inhibitor camptothecin. The transcriptional activation was associated with structural rearrangements in chromatin, notably the accumulation of γH2AX and the exchange of histone H1 with HMGB1 at AIRE target gene promoters. In addition, we found the transcriptional up-regulation to co-occur with the chromatin structural changes within the genomic cluster of carcinoembryonic antigen-like cellular adhesion molecule genes. Overall, our results suggest that the presence of AIRE can trigger molecular events leading to an altered chromatin landscape and the enhanced transcription of low-expressed genes. © 2017 by The American Society for Biochemistry and Molecular Biology, Inc.

On Certain New Methodology for Reducing Sensor and Readout Electronics Circuitry Noise in Digital Domain

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Kizhner, Semion; Miko, Joseph; Bradley, Damon; Heinzen, Katherine

2008-01-01

NASA Hubble Space Telescope (HST) and upcoming cosmology science missions carry instruments with multiple focal planes populated with many large sensor detector arrays. These sensors are passively cooled to low temperatures for low-level light (L3) and near-infrared (NIR) signal detection, and the sensor readout electronics circuitry must perform at extremely low noise levels to enable new required science measurements. Because we are at the technological edge of enhanced performance for sensors and readout electronics circuitry, as determined by thermal noise level at given temperature in analog domain, we must find new ways of further compensating for the noise in the signal digital domain. To facilitate this new approach, state-of-the-art sensors are augmented at their array hardware boundaries by non-illuminated reference pixels, which can be used to reduce noise attributed to sensors. There are a few proposed methodologies of processing in the digital domain the information carried by reference pixels, as employed by the Hubble Space Telescope and the James Webb Space Telescope Projects. These methods involve using spatial and temporal statistical parameters derived from boundary reference pixel information to enhance the active (non-reference) pixel signals. To make a step beyond this heritage methodology, we apply the NASA-developed technology known as the Hilbert- Huang Transform Data Processing System (HHT-DPS) for reference pixel information processing and its utilization in reconfigurable hardware on-board a spaceflight instrument or post-processing on the ground. The methodology examines signal processing for a 2-D domain, in which high-variance components of the thermal noise are carried by both active and reference pixels, similar to that in processing of low-voltage differential signals and subtraction of a single analog reference pixel from all active pixels on the sensor. Heritage methods using the aforementioned statistical parameters in the

A coordinated interdependent protein circuitry stabilizes the kinetochore ensemble to protect CENP-A in the human pathogenic yeast Candida albicans.

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Jitendra Thakur

Full Text Available Unlike most eukaryotes, a kinetochore is fully assembled early in the cell cycle in budding yeasts Saccharomyces cerevisiae and Candida albicans. These kinetochores are clustered together throughout the cell cycle. Kinetochore assembly on point centromeres of S. cerevisiae is considered to be a step-wise process that initiates with binding of inner kinetochore proteins on specific centromere DNA sequence motifs. In contrast, kinetochore formation in C. albicans, that carries regional centromeres of 3-5 kb long, has been shown to be a sequence independent but an epigenetically regulated event. In this study, we investigated the process of kinetochore assembly/disassembly in C. albicans. Localization dependence of various kinetochore proteins studied by confocal microscopy and chromatin immunoprecipitation (ChIP assays revealed that assembly of a kinetochore is a highly coordinated and interdependent event. Partial depletion of an essential kinetochore protein affects integrity of the kinetochore cluster. Further protein depletion results in complete collapse of the kinetochore architecture. In addition, GFP-tagged kinetochore proteins confirmed similar time-dependent disintegration upon gradual depletion of an outer kinetochore protein (Dam1. The loss of integrity of a kinetochore formed on centromeric chromatin was demonstrated by reduced binding of CENP-A and CENP-C at the centromeres. Most strikingly, Western blot analysis revealed that gradual depletion of any of these essential kinetochore proteins results in concomitant reduction in cellular protein levels of CENP-A. We further demonstrated that centromere bound CENP-A is protected from the proteosomal mediated degradation. Based on these results, we propose that a coordinated interdependent circuitry of several evolutionarily conserved essential kinetochore proteins ensures integrity of a kinetochore formed on the foundation of CENP-A containing centromeric chromatin.

Immunohistological Analysis of the Jun Family and the Signal Transducers and Activators of Transcription in Thymus

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Alexandra Papoudou-Bai

2015-01-01

Full Text Available The Jun family and the signal transducers and activators of transcription (STAT are involved in proliferation and apoptosis. Moreover, c-Jun and STAT3 cooperate to regulate apoptosis. Therefore, we used double immunostaining to investigate the immunotopographical distribution of phospho-c-Jun (p-c-Jun, JunB, JunD, p-STAT3, p-STAT5, and p-STAT6 in human thymus. JunD was frequently expressed by thymocytes with higher expression in medullary compared to cortical thymocytes. p-c-Jun was frequently expressed by cortical and medullary thymic epithelial cells (TEC and Hassall bodies (HB. p-STAT3 was frequently expressed by TEC with higher expression in cortical compared to medullary TEC and HB. p-c-Jun, JunB, p-STAT3, p-STAT5, and p-STAT6 were rarely expressed by thymocytes. JunB and JunD were expressed by rare cortical TEC with higher expression in medullary TEC. p-STAT5 and p-STAT6 were expressed by rare cortical and medullary TEC. Double immunostaining revealed p-c-Jun and JunD expression in rare CD11c positive dendritic cells. Our findings suggest a notable implication of JunD in the physiology of thymocytes and p-c-Jun and p-STAT3 in the physiology of TEC. The diversity of the immunotopographical distribution and the expression levels of p-c-Jun, JunB, JunD, p-STAT3, p-STAT5, and p-STAT6 indicates that they are differentially involved in the differentiation of TEC, thymocytes, and dendritic cells.

Normal distribution and medullary-to-cortical shift of Nestin-expressing cells in acute renal ischemia.

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Patschan, D; Michurina, T; Shi, H K; Dolff, S; Brodsky, S V; Vasilieva, T; Cohen-Gould, L; Winaver, J; Chander, P N; Enikolopov, G; Goligorsky, M S

2007-04-01

Nestin, a marker of multi-lineage stem and progenitor cells, is a member of intermediate filament family, which is expressed in neuroepithelial stem cells, several embryonic cell types, including mesonephric mesenchyme, endothelial cells of developing blood vessels, and in the adult kidney. We used Nestin-green fluorescent protein (GFP) transgenic mice to characterize its expression in normal and post-ischemic kidneys. Nestin-GFP-expressing cells were detected in large clusters within the papilla, along the vasa rectae, and, less prominently, in the glomeruli and juxta-glomerular arterioles. In mice subjected to 30 min bilateral renal ischemia, glomerular, endothelial, and perivascular cells showed increased Nestin expression. In the post-ischemic period, there was an increase in fluorescence intensity with no significant changes in the total number of Nestin-GFP-expressing cells. Time-lapse fluorescence microscopy performed before and after ischemia ruled out the possibility of engraftment by the circulating Nestin-expressing cells, at least within the first 3 h post-ischemia. Incubation of non-perfused kidney sections resulted in a medullary-to-cortical migration of Nestin-GFP-positive cells with the rate of expansion of their front averaging 40 microm/30 min during the first 3 h and was detectable already after 30 min of incubation. Explant matrigel cultures of the kidney and aorta exhibited sprouting angiogenesis with cells co-expressing Nestin and endothelial marker, Tie-2. In conclusion, several lines of circumstantial evidence identify a sub-population of Nestin-expressing cells with the mural cells, which are recruited in the post-ischemic period to migrate from the medulla toward the renal cortex. These migrating Nestin-positive cells may be involved in the process of post-ischemic tissue regeneration.

Identification of Driving ALK Fusion Genes and Genomic Landscape of Medullary Thyroid Cancer.

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Jun Ho Ji

2015-08-01

Full Text Available The genetic landscape of medullary thyroid cancer (MTC is not yet fully understood, although some oncogenic mutations have been identified. To explore genetic profiles of MTCs, formalin-fixed, paraffin-embedded tumor tissues from MTC patients were assayed on the Ion AmpliSeq Cancer Panel v2. Eighty-four sporadic MTC samples and 36 paired normal thyroid tissues were successfully sequenced. We discovered 101 hotspot mutations in 18 genes in the 84 MTC tissue samples. The most common mutation was in the ret proto-oncogene, which occurred in 47 cases followed by mutations in genes encoding Harvey rat sarcoma viral oncogene homolog (N = 14, serine/threonine kinase 11 (N = 11, v-kit Hardy-Zuckerman 4 feline sarcoma viral oncogene homolog (N = 6, mutL homolog 1 (N = 4, Kiesten rat sarcoma viral oncogene homolog (N = 3 and MET proto-oncogene (N = 3. We also evaluated anaplastic lymphoma kinase (ALK rearrangement by immunohistochemistry and break-apart fluorescence in situ hybridization (FISH. Two of 98 screened cases were positive for ALK FISH. To identify the genomic breakpoint and 5' fusion partner of ALK, customized targeted cancer panel sequencing was performed using DNA from tumor samples of the two patients. Glutamine:fructose-6-phosphate transaminase 1 (GFPT1-ALK and echinoderm microtubule-associated protein-like 4 (EML4-ALK fusions were identified. Additional PCR analysis, followed by Sanger sequencing, confirmed the GFPT1-ALK fusion, indicating that the fusion is a result of intra-chromosomal translocation or deletion. Notably, a metastatic MTC case harboring the EML4-ALK fusion showed a dramatic response to an ALK inhibitor, crizotinib. In conclusion, we found several genetic mutations in MTC and are the first to identify ALK fusions in MTC. Our results suggest that the EML4-ALK fusion in MTC may be a potential driver mutation and a valid target of ALK inhibitors. Furthermore, the GFPT1-ALK fusion may be a potential candidate for molecular

Hyperleptinemia in Neonatally Overfed Female Rats Does Not Dysregulate Feeding Circuitry

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Ilvana Ziko

2017-10-01

Full Text Available Neonatal overfeeding during the first weeks of life in male rats is associated with a disruption in the peripheral and central leptin systems. Neonatally overfed male rats have increased circulating leptin in the first 2 weeks of life, which corresponds to an increase in body weight compared to normally fed counterparts. These effects are associated with a short-term disruption in the connectivity of neuropeptide Y (NPY, agouti-related peptide (AgRP, and pro-opiomelanocortin (POMC neurons within the regions of the hypothalamus responsible for control of energy balance and food intake. Female rats that are overfed during the first weeks of their life experience similar changes in circulating leptin levels as well as in their body weight. However, it has not yet been studied whether these metabolic changes are associated with the same central effects as observed in males. Here, we hypothesized that hyperleptinemia associated with neonatal overfeeding would lead to changes in central feeding circuitry in females as it does in males. We assessed hypothalamic NPY, AgRP, and POMC gene expression and immunoreactivity at 7, 12, or 14 days of age, as well as neuronal activation in response to exogenous leptin in neonatally overfed and control female rats. Neonatally overfed female rats were hyperleptinemic and were heavier than controls. However, these metabolic changes were not mirrored centrally by changes in hypothalamic NPY, AGRP, and POMC fiber density. These findings are suggestive of sex differences in the effects of neonatal overfeeding and of differences in the ability of the female and male central systems to respond to changes in the early life nutritional environment.

Deficiency of autoimmune regulator impairs the immune tolerance effect of bone marrow-derived dendritic cells in mice.

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Huo, Feifei; Li, Dongbei; Zhao, Bo; Luo, Yadong; Zhao, Bingjie; Zou, Xueyang; Li, Yi; Yang, Wei

2018-02-01

As a transcription factor, autoimmune regulator (Aire) participates in thymic negative selection and maintains immune tolerance mainly by regulating the ectopic expression of tissue-restricted antigens (TRAs) in medullary thymic epithelial cells (mTECs). Aire is also expressed in dendritic cells (DCs). DCs are professional antigen-presenting cells (APCs) that affect the differentiation of T cells toward distinct subpopulations and participate in the immune response and tolerance, thereby playing an important role in maintaining homeostasis. To determine the role of Aire in maintaining immune tolerance by bone marrow-derived dendritic cells (BMDCs), in the present study we utilized Aire-knockout mice to examine the changes of maturation status and TRAs expression on BMDCs, additionally investigate the differentiation of CD4 + T cells. The results showed that expression of costimulatory molecule and major histocompatibility complex class II (MHC-II) molecule was increased and expression of various TRAs was decreased in BMDCs from Aire-knockout mice. Aire deficiency reduced the differentiation of naïve CD4 + T cells into type 2T helper (Th2) cells and regulatory T cells (Tregs) but enhanced the differentiation of naïve CD4 + T cells into Th1 cells, Th17 cells, and follicular helper T (Tfh) cells. The results demonstrate that Aire expressed by BMDCs plays an important role in the maintenance of homeostasis by regulating TRA expression and the differentiation of T cell subsets.

GATA-1 directly regulates Nanog in mouse embryonic stem cells

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Li, Wen-Zhong; Ai, Zhi-Ying [College of Life Sciences, Northwest A& F University, Yangling 712100 (China); Key Laboratory of Animal Biotechnology, Ministry of Agriculture, Northwest A& F University, Yangling 712100 (China); Wang, Zhi-Wei [School of Life Sciences and Medical Center, University of Science and Technology of China, Hefei, Anhui 230027 (China); Chen, Lin-Lin [College of Life Sciences, Northwest A& F University, Yangling 712100 (China); Key Laboratory of Animal Biotechnology, Ministry of Agriculture, Northwest A& F University, Yangling 712100 (China); Guo, Ze-Kun, E-mail: gzknwaf@126.com [College of Veterinary Medicine, Northwest A& F University, Yangling 712100 (China); Key Laboratory of Animal Biotechnology, Ministry of Agriculture, Northwest A& F University, Yangling 712100 (China); Zhang, Yong, E-mail: zylabnwaf@126.com [College of Veterinary Medicine, Northwest A& F University, Yangling 712100 (China); Key Laboratory of Animal Biotechnology, Ministry of Agriculture, Northwest A& F University, Yangling 712100 (China)

2015-09-25

Nanog safeguards pluripotency in mouse embryonic stem cells (mESCs). Insight into the regulation of Nanog is important for a better understanding of the molecular mechanisms that control pluripotency of mESCs. In a silico analysis, we identify four GATA-1 putative binding sites in Nanog proximal promoter. The Nanog promoter activity can be significantly repressed by ectopic expression of GATA-1 evidenced by a promoter reporter assay. Mutation studies reveal that one of the four putative binding sites counts for GATA-1 repressing Nanog promoter activity. Direct binding of GATA-1 on Nanog proximal promoter is confirmed by electrophoretic mobility shift assay and chromatin immunoprecipitation. Our data provide new insights into the expanded regulatory circuitry that coordinates Nanog expression. - Highlights: • The Nanog proximal promoter conceives functional element for GATA-1. • GATA-1 occupies the Nanog proximal promoter in vitro and in vivo. • GATA-1 transcriptionally suppresses Nanog.

A gene expression system offering multiple levels of regulation: the Dual Drug Control (DDC) system.

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Sudomoina, Marina; Latypova, Ekaterina; Favorova, Olga O; Golemis, Erica A; Serebriiskii, Ilya G

2004-04-29

Whether for cell culture studies of protein function, construction of mouse models to enable in vivo analysis of disease epidemiology, or ultimately gene therapy of human diseases, a critical enabling step is the ability to achieve finely controlled regulation of gene expression. Previous efforts to achieve this goal have explored inducible drug regulation of gene expression, and construction of synthetic promoters based on two-hybrid paradigms, among others. In this report, we describe the combination of dimerizer-regulated two-hybrid and tetracycline regulatory elements in an ordered cascade, placing expression of endpoint reporters under the control of two distinct drugs. In this Dual Drug Control (DDC) system, a first plasmid expresses fusion proteins to DBD and AD, which interact only in the presence of a small molecule dimerizer; a second plasmid encodes a cassette transcriptionally responsive to the first DBD, directing expression of the Tet-OFF protein; and a third plasmid encodes a reporter gene transcriptionally responsive to binding by Tet-OFF. We evaluate the dynamic range and specificity of this system in comparison to other available systems. This study demonstrates the feasibility of combining two discrete drug-regulated expression systems in a temporally sequential cascade, without loss of dynamic range of signal induction. The efficient layering of control levels allowed by this combination of elements provides the potential for the generation of complex control circuitry that may advance ability to regulate gene expression in vivo.

A gene expression system offering multiple levels of regulation: the Dual Drug Control (DDC system

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Golemis Erica A

2004-04-01

Full Text Available Abstract Background Whether for cell culture studies of protein function, construction of mouse models to enable in vivo analysis of disease epidemiology, or ultimately gene therapy of human diseases, a critical enabling step is the ability to achieve finely controlled regulation of gene expression. Previous efforts to achieve this goal have explored inducible drug regulation of gene expression, and construction of synthetic promoters based on two-hybrid paradigms, among others. Results In this report, we describe the combination of dimerizer-regulated two-hybrid and tetracycline regulatory elements in an ordered cascade, placing expression of endpoint reporters under the control of two distinct drugs. In this Dual Drug Control (DDC system, a first plasmid expresses fusion proteins to DBD and AD, which interact only in the presence of a small molecule dimerizer; a second plasmid encodes a cassette transcriptionally responsive to the first DBD, directing expression of the Tet-OFF protein; and a third plasmid encodes a reporter gene transcriptionally responsive to binding by Tet-OFF. We evaluate the dynamic range and specificity of this system in comparison to other available systems. Conclusion This study demonstrates the feasibility of combining two discrete drug-regulated expression systems in a temporally sequential cascade, without loss of dynamic range of signal induction. The efficient layering of control levels allowed by this combination of elements provides the potential for the generation of complex control circuitry that may advance ability to regulate gene expression in vivo.

Dynamic neural network models of the premotoneuronal circuitry controlling wrist movements in primates.

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Maier, M A; Shupe, L E; Fetz, E E

2005-10-01

Dynamic recurrent neural networks were derived to simulate neuronal populations generating bidirectional wrist movements in the monkey. The models incorporate anatomical connections of cortical and rubral neurons, muscle afferents, segmental interneurons and motoneurons; they also incorporate the response profiles of four populations of neurons observed in behaving monkeys. The networks were derived by gradient descent algorithms to generate the eight characteristic patterns of motor unit activations observed during alternating flexion-extension wrist movements. The resulting model generated the appropriate input-output transforms and developed connection strengths resembling those in physiological pathways. We found that this network could be further trained to simulate additional tasks, such as experimentally observed reflex responses to limb perturbations that stretched or shortened the active muscles, and scaling of response amplitudes in proportion to inputs. In the final comprehensive network, motor units are driven by the combined activity of cortical, rubral, spinal and afferent units during step tracking and perturbations. The model displayed many emergent properties corresponding to physiological characteristics. The resulting neural network provides a working model of premotoneuronal circuitry and elucidates the neural mechanisms controlling motoneuron activity. It also predicts several features to be experimentally tested, for example the consequences of eliminating inhibitory connections in cortex and red nucleus. It also reveals that co-contraction can be achieved by simultaneous activation of the flexor and extensor circuits without invoking features specific to co-contraction.

Análise comparativa da avaliação funcional realizada na lesão medular em animais Comparative analysis of functional evaluation performed in medullary injury in animals

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Alessandra Iague Molina

2004-03-01

Full Text Available A avaliação comportamental após, a contusão da medula espinhal, enfocou por um tempo a locomoção em campo aberto usando uma escala de classificação desenvolvida por Tarlov et al.(18. Tarlov(17 realizou estudos experimentais em cães, produzindo compressão medular com atribuição de zero a cinco para graduação dos movimentos do animal. Contudo, esta escala tem sido modificada por pesquisadores e suas alterações feitas por vários grupos tornaram as comparações das medidas do resultado locomotor difíceis. Um aspecto crítico da pesquisa utilizando lesão medular em animais é a padronização da avaliação da recuperação locomotora. A escala desenvolvida por Tator(19 é simples e de fácil utilização, porém pode não analisar todos os aspectos necessários . Basso, Beattie e Bresnahan(2,3 apresentaram uma escala de classificação com índice de recuperação locomotora em ratos que sofreram lesão medular produzida em laboratório. Os dados indicam que a escala BBB é uma medida válida para a recuperação locomotora capaz de distinguir os resultados comportamentais em função de ferimentos diferentes e para prever alterações anatômicas no centro da lesão. O propósito deste estudo foi analisar e comparar escalas de classificação locomotora sem ambigüidade, eficientes e expandida para se padronizar as medidas resultantes nos laboratórios.The behavior evaluation after a spinal medulla injury focused the locomotion in field during a certain time, using a classification scale developed by Tarlov et al.(18. Tarlov(17 performed experimental studies in dogs, producing medullary compression and assigning a graduation from zero to five to the animal movements. However, this scale has been changed by researchers and its changes, made by several groups, became difficult the comparisons of the measures of the locomotor result. One critical aspect of the research with medullary injury in animals is the standardization of the

Relationship of the Lumbar Lordosis Angle to the Level of Termination of the Conus Medullaris and Thecal Sac

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C. D. Moussallem

2014-01-01

Full Text Available The level of termination of the conus medullaris (CM and thecal sac (TS is subject to variations. We try to correlate in this study these variations with the lumbar lordosis angle (LLA using MRI scans. A retrospective study was conducted using available MRI scans of the lumbar spine. The CM level of termination (CMLT and the TS level of termination (TSLT were identified according to a vertebral level after dividing it into 3 parts. The LLA was also identified for each individual. Linear regression models were fitted to the data available on 141 individuals. Of these 70 were males and 71 were females. The most common site of CMLT was at the upper third of L1 (32.6% and that of the TSLT was at the middle third of S2 (29.8%. The mean LLA was 46° (20°–81°. The most proximal CMLT was at the upper third of T12, whereas the most distal one was at the upper third of L2. The most proximal TSLT was at the upper third of S1, whereas the most distal one was at S3-S4 disc space. The CMLT showed a positive correlation with the LLA. In conclusion the CMLT and TSLT may be related to variations of the LLA.

[Study on effects of Corydalis yanhusuo and L-THP on dopamine of reward circuitry in conditioned place preference rats and comparison].

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Yu, Shou-Yang; Yang, Pei-Run; Qian, Gang; Wu, Ming-Song; Bai, Wei-Feng; Tu, Ping; Luo, Su-Yuan

2013-11-01

To study and compare the effect of Corydalis yanhusuo and L-THP on dopamine neurotransmitter and D2 receptor of reward circuitry in various cerebral areas of conditioned place preference model rats and the comparison of their effects. The CPP model was established by injecting morphine in rats with increasing doses for 10 days. The initial dose of 10 mg x kg(-1), and the final dose of 100 mg x kg(-1), with 10 mg x kg(-1) increased each day. At 48 h after the final training, CPP was adopted to detect the successful establishment of the model. On the same day (12 d), they were orally administered with 2, 1, 0.5 g x kg(-1) C. yanhusuo (containing 0.153, 0.077 and 0.038 mg L-THP) and L-THP (3.76, 1.88, 0.94 mg x kg(-1)) for six days. On 18 d, CPP test was performed again. Next day, HPLC was adopted to determine the content of dopamine neurotransmitters of reward circuitry in VTA-NAc-PFC; Immunohistochemistry and Western blotting were adopted to detect the expression of D2 receptors. Compared with the physiological saline treatment group, C. yanhusuo (2, 1 g x kg(-1)) and L-THP (3.76, 1.88 mg x kg(-1)) groups showed that rats stayed in a notably shorter period in white boxes (morphine-accompanied boxes) (P THP in accelerating the recession of morphine's CPP effect Regarding the inhibition of morphine's CPP effect and the effect on dopamine system, the effect of C. yanhusuo traditional Chinese medicine containing one-fold L-THP monomer is equal to that of the independent application of around 24-fold L-THP monomer.

Bidirectional regulation of bakuchiol, an estrogenic-like compound, on catecholamine secretion

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Mao, Haoping; Wang, Hong; Ma, Shangwei; Xu, Yantong; Zhang, Han; Wang, Yuefei [Tianjin State Key Laboratory of Modern Chinese Medicine, Key Laboratory of Pharmacology of Traditional Chinese Medicine Formulae (China); Institute of Traditional Chinese Medicine, Tianjin University of Traditional Chinese Medicine, Tianjin (China); Niu, Zichang [First Teaching Hospital of Tianjin University of Traditional Chinese Medicine, Tianjin (China); Fan, Guanwei; Zhu, Yan [Tianjin State Key Laboratory of Modern Chinese Medicine, Key Laboratory of Pharmacology of Traditional Chinese Medicine Formulae (China); Institute of Traditional Chinese Medicine, Tianjin University of Traditional Chinese Medicine, Tianjin (China); Gao, Xiu Mei, E-mail: gaoxiumei@tjutcm.edu.cn [Tianjin State Key Laboratory of Modern Chinese Medicine, Key Laboratory of Pharmacology of Traditional Chinese Medicine Formulae (China); Institute of Traditional Chinese Medicine, Tianjin University of Traditional Chinese Medicine, Tianjin (China)

2014-01-01

Excess or deficiency of catecholamine (CA) secretion was related with several diseases. Recently, estrogen and phytoestrogens were reported to regulate the activity of CA system. Bakuchiol is a phytoestrogen isolated from the seeds of Psoralea corylifolia L. (Leguminosae) which has been used in Traditional Chinese medicine as a tonic or aphrodisiac. In the present study, bovine adrenal medullary cells were employed to investigate the effects and mechanisms of bakuchiol on the regulation of CA secretion. Further, its anti-depressant like and anti-stress effects were evaluated by using behavioral despair and chronic immobilization stress models. Our results indicated that bakuchiol showed bidirectional regulation on CA secretion. It stimulated basal CA secretion in a concentration dependent manner (p < 0.01), while it reduced 300 μM acetylcholine (ACh) (p < 0.01), 100 μM veratridine (Ver) (p < 0.01) and 56 mM K{sup +} (p < 0.05) induced CA secretion, respectively. We also found that the stimulation of basal CA secretion by bakuchiol may act through estrogen-like effect and the JNK pathway in an extra-cellular calcium independent manner. Further, bakuchiol elevated tyrosine hydroxylase Ser40 and Ser31 phosphorylation (p < 0.01) through the PKA and ERK1/2 pathways, respectively. Bakuchiol inhibited ACh, Ver and 56 mM K{sup +} induced CA secretion was related with reduction of intracellular calcium rise. In vivo experiments, we found that bakuchiol significantly reduced immobilization time in behavioral despair mouse (p < 0.05 or 0.01), and plasma epinephrine (E) and norepinephrine (NE) levels in chronic immobilization stress (p < 0.05). Overall, these results present a bidirectional regulation of bakuchiol on CA secretion which indicated that bakuchiol may exert anti-stress and the potential anti-depressant-like effects. - Highlights: • Bakuchiol stimulated basal catecholamine secretion. • Bakuchiol inhibited various secretagogues induced catecholamine secretion

Interactions between entorhinal axons and target hippocampal neurons: a role for glutamate in the development of hippocampal circuitry.

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Mattson, M P; Lee, R E; Adams, M E; Guthrie, P B; Kater, S B

1988-11-01

A coculture system consisting of input axons from entorhinal cortex explants and target hippocampal pyramidal neurons was used to demonstrate that glutamate, released spontaneously from afferent axons, can influence both dendritic geometry of target neurons and formation of presumptive synaptic sites. Dendritic outgrowth was reduced in hippocampal neurons growing on entorhinal axons when compared with neurons growing off the axons. Presumptive presynaptic sites were observed in association with hippocampal neuron dendrites and somas. HPLC analysis showed that glutamate was released from the explants in an activity- and Ca2(+)-dependent manner. The general glutamate receptor antagonist D-glutamylglycine significantly increased dendritic outgrowth in pyramidal neurons associated with entorhinal axons and reduced presumptive presynaptic sites. Tetrodotoxin and reduction of extracellular Ca2+ also promoted dendritic outgrowth and reduced the formation of presumptive synaptic sites. The results suggest that the neurotransmitter glutamate may play important roles in the development of hippocampal circuitry.

DFsn collaborates with Highwire to down-regulate the Wallenda/DLK kinase and restrain synaptic terminal growth

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DiAntonio Aaron

2007-08-01

Full Text Available Abstract Background The growth of new synapses shapes the initial formation and subsequent rearrangement of neural circuitry. Genetic studies have demonstrated that the ubiquitin ligase Highwire restrains synaptic terminal growth by down-regulating the MAP kinase kinase kinase Wallenda/dual leucine zipper kinase (DLK. To investigate the mechanism of Highwire action, we have identified DFsn as a binding partner of Highwire and characterized the roles of DFsn in synapse development, synaptic transmission, and the regulation of Wallenda/DLK kinase abundance. Results We identified DFsn as an F-box protein that binds to the RING-domain ubiquitin ligase Highwire and that can localize to the Drosophila neuromuscular junction. Loss-of-function mutants for DFsn have a phenotype that is very similar to highwire mutants – there is a dramatic overgrowth of synaptic termini, with a large increase in the number of synaptic boutons and branches. In addition, synaptic transmission is impaired in DFsn mutants. Genetic interactions between DFsn and highwire mutants indicate that DFsn and Highwire collaborate to restrain synaptic terminal growth. Finally, DFsn regulates the levels of the Wallenda/DLK kinase, and wallenda is necessary for DFsn-dependent synaptic terminal overgrowth. Conclusion The F-box protein DFsn binds the ubiquitin ligase Highwire and is required to down-regulate the levels of the Wallenda/DLK kinase and restrain synaptic terminal growth. We propose that DFsn and Highwire participate in an evolutionarily conserved ubiquitin ligase complex whose substrates regulate the structure and function of synapses.

Radiation-Hardened Circuitry Using Mask-Programmable Analog Arrays. Report 3

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Britton, Jr, Charles L. [Oak Ridge National Lab. (ORNL), Oak Ridge, TN (United States); Shelton, Jacob H. [Oak Ridge National Lab. (ORNL), Oak Ridge, TN (United States); Ericson, Milton Nance [Oak Ridge National Lab. (ORNL), Oak Ridge, TN (United States); Blalock, Benjamin [Univ. of Tennessee, Knoxville, TN (United States)

2015-03-01

As the recent accident at Fukushima Daiichi so vividly demonstrated, telerobotic technologies capable of withstanding high radiation environments need to be readily available to enable operations, repair, and recovery under severe accident scenarios when human entry is extremely dangerous or not possible. Telerobotic technologies that enable remote operation in high dose rate environments have undergone revolutionary improvement over the past few decades. However, much of this technology cannot be employed in nuclear power environments because of the radiation sensitivity of the electronics and the organic insulator materials currently in use. This is a report of the activities involving Task 3 of the Nuclear Energy Enabling Technologies (NEET) 2 project Radiation Hardened Circuitry Using Mask-Programmable Analog Arrays [1]. Evaluation of the performance of the system for both pre- and post-irradiation as well as operation at elevated temperature will be performed. Detailed performance of the system will be documented to ensure the design meets requirements prior to any extended evaluation. A suite of tests will be developed which will allow evaluation before and after irradiation and during temperature. Selection of the radiation exposure facilities will be determined in the early phase of the project. Radiation exposure will consist of total integrated dose (TID) up to 200 kRad or above with several intermediate doses during test. Dose rates will be in various ranges determined by the facility that will be used with a target of 30 kRad/hr. Many samples of the pre-commercial devices to be used will have been tested in previous projects to doses of at least 300 kRad and temperatures up to 125C. The complete systems will therefore be tested for performance at intermediate doses. Extended temperature testing will be performed up to the limit of the commercial sensors. The test suite performed at each test point will consist of operational testing of the three basic

The Neural Circuitry of Expertise: Perceptual Learning and Social Cognition

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Michael eHarre

2013-12-01

Full Text Available Amongst the most significant questions we are confronted with today include the integration of the brain's micro-circuitry, our ability to build the complex social networks that underpin society and how our society impacts on our ecological environment. In trying to unravel these issues one place to begin is at the level of the individual: to consider how we accumulate information about our environment, how this information leads to decisions and how our individual decisions in turn create our social environment. While this is an enormous task, we may already have at hand many of the tools we need. This article is intended to review some of the recent results in neuro-cognitive research and show how they can be extended to two very specific types of expertise: perceptual expertise and social cognition. These two cognitive skills span a vast range of our genetic heritage. Perceptual expertise developed very early in our evolutionary history and is likely a highly developed part of all mammals' cognitive ability. On the other hand social cognition is most highly developed in humans in that we are able to maintain larger and more stable long term social connections with more behaviourally diverse individuals than any other species. To illustrate these ideas I will discuss board games as a toy model of social interactions as they include many of the relevant concepts: perceptual learning, decision-making, long term planning and understanding the mental states of other people. Using techniques that have been developed in mathematical psychology, I show that we can represent some of the key features of expertise using stochastic differential equations. Such models demonstrate how an expert's long exposure to a particular context influences the information they accumulate in order to make a decision.These processes are not confined to board games, we are all experts in our daily lives through long exposure to the many regularities of daily tasks and

NMR studies of renal phosphate metabolites in vivo: Effects of hydration and dehydration

International Nuclear Information System (INIS)

Wolff, S.D.; Eng, C.; Balaban, R.S.

1988-01-01

The present study characterizes the 31 P-nuclear magnetic resonance (NMR) spectrum of rabbit kidneys in vivo and evaluates the effect of hydration on phosphorous metabolites including the organic solute glycerophosphorylcholine (GPC). Cortical phosphorylethanolamine is the predominant component of the phosphomonoester region of the 31 P spectrum. The contribution of blood to the spectrum is mainly from 2,3 diphosphoglycerate, which comprises ∼30% of the inorganic phosphate region. Acute infusion of 0.9% saline decreases the sodium content of the inner medulla by >50% in 15 min as shown by 23 Na imaging. Despite this medullary Na dilution, no change in renal GPC content was observed for >1 h even with the addition of furosemide or furosemide and antidiuretic hormone. However, 20 h of chronic dehydration with 0.45% saline did result in a 30% decrease in renal GPC content when compared with dehydrated animals. These findings are consistent with GPC not playing a role in the short-term regulation of the medullary intracellular milieu in response to acute reductions in medullary Na content

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

International Nuclear Information System (INIS)

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

2016-01-01

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

Vandetanib for the treatment of patients with locally advanced or metastatic hereditary medullary thyroid cancer.

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Wells, Samuel A; Gosnell, Jessica E; Gagel, Robert F; Moley, Jeffrey; Pfister, David; Sosa, Julie A; Skinner, Michael; Krebs, Annetta; Vasselli, James; Schlumberger, Martin

2010-02-10

PURPOSE There is no effective therapy for patients with distant metastasis of medullary thyroid carcinoma (MTC). Activating mutations in the RET proto-oncogene cause hereditary MTC, which provides a strong therapeutic rationale for targeting RET kinase activity. This open-label, phase II study assessed the efficacy of vandetanib, a selective oral inhibitor of RET, vascular endothelial growth factor receptor, and epidermal growth factor receptor signaling, in patients with advanced hereditary MTC. METHODS Patients with unresectable locally advanced or metastatic hereditary MTC received initial treatment with once-daily oral vandetanib 300 mg. The dose was adjusted additionally in some patients on the basis of observed toxicity until disease progression or any other withdrawal criterion was met. The primary assessment was objective tumor response (by RECIST [Response Evaluation Criteria in Solid Tumors]). Results Thirty patients received initial treatment with vandetanib 300 mg/d. On the basis of investigator assessments, 20% of patients (ie, six of 30 patients) experienced a confirmed partial response (median duration of response at data cutoff, 10.2 months). An additional 53% of patients (ie, 16 of 30 patients) experienced stable disease at >/= 24 weeks, which yielded a disease control rate of 73% (ie, 22 of 30 patients). In 24 patients, serum calcitonin levels showed a 50% or greater decrease from baseline that was maintained for at least 4 weeks; 16 patients showed a similar reduction in serum carcinoembryonic antigen levels. The most common adverse events were diarrhea (70%), rash (67%), fatigue (63%), and nausea (63%). CONCLUSION In this study, vandetanib demonstrated durable objective partial responses and disease control with a manageable adverse event profile. These results demonstrate that vandetanib may provide an effective therapeutic option in patients with advanced hereditary MTC, a rare disease for which there has been no effective therapy.

Regulation of the mesolimbic dopamine circuit by feeding peptides.

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Liu, S; Borgland, S L

2015-03-19

Polypeptides produced in the gastrointestinal tract, stomach, adipocytes, pancreas and brain that influence food intake are referred to as 'feeding-related' peptides. Most peptides that influence feeding exert an inhibitory effect (anorexigenic peptides). In contrast, only a few exert a stimulating effect (orexigenic peptides), such as ghrelin. Homeostatic feeding refers to when food consumed matches energy deficits. However, in western society where access to palatable energy-dense food is nearly unlimited, food is mostly consumed for non-homeostatic reasons. Emerging evidence implicates the mesocorticolimbic circuitry, including dopamine neurons of the ventral tegmental area (VTA), as a key substrate for non-homeostatic feeding. VTA dopamine neurons encode cues that predict rewards and phasic release of dopamine in the ventral striatum motivates animals to forage for food. To elucidate how feeding-related peptides regulate reward pathways is of importance to reveal the mechanisms underlying non-homeostatic or hedonic feeding. Here, we review the current knowledge of how anorexigenic peptides and orexigenic peptides act within the VTA. Copyright © 2015 IBRO. Published by Elsevier Ltd. All rights reserved.

Dialectical behavior therapy alters emotion regulation and amygdala activity in patients with borderline personality disorder.

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Goodman, Marianne; Carpenter, David; Tang, Cheuk Y; Goldstein, Kim E; Avedon, Jennifer; Fernandez, Nicolas; Mascitelli, Kathryn A; Blair, Nicholas J; New, Antonia S; Triebwasser, Joseph; Siever, Larry J; Hazlett, Erin A

2014-10-01

Siever and Davis' (1991) psychobiological framework of borderline personality disorder (BPD) identifies affective instability (AI) as a core dimension characterized by prolonged and intense emotional reactivity. Recently, deficient amygdala habituation, defined as a change in response to repeated relative to novel unpleasant pictures within a session, has emerged as a biological correlate of AI in BPD. Dialectical behavior therapy (DBT), an evidence-based treatment, targets AI by teaching emotion-regulation skills. This study tested the hypothesis that BPD patients would exhibit decreased amygdala activation and improved habituation, as well as improved emotion regulation with standard 12-month DBT. Event-related fMRI was obtained pre- and post-12-months of standard-DBT in unmedicated BPD patients. Healthy controls (HCs) were studied as a benchmark for normal amygdala activity and change over time (n = 11 per diagnostic-group). During each scan, participants viewed an intermixed series of unpleasant, neutral and pleasant pictures presented twice (novel, repeat). Change in emotion regulation was measured with the Difficulty in Emotion Regulation (DERS) scale. fMRI results showed the predicted Group × Time interaction: compared with HCs, BPD patients exhibited decreased amygdala activation with treatment. This post-treatment amygdala reduction in BPD was observed for all three pictures types, but particularly marked in the left hemisphere and during repeated-emotional pictures. Emotion regulation measured with the DERS significantly improved with DBT in BPD patients. Improved amygdala habituation to repeated-unpleasant pictures in patients was associated with improved overall emotional regulation measured by the DERS (total score and emotion regulation strategy use subscale). These findings have promising treatment implications and support the notion that DBT targets amygdala hyperactivity-part of the disturbed neural circuitry underlying emotional dysregulation

A Positive Regulatory Loop between a Wnt-Regulated Non-coding RNA and ASCL2 Controls Intestinal Stem Cell Fate.

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Giakountis, Antonis; Moulos, Panagiotis; Zarkou, Vasiliki; Oikonomou, Christina; Harokopos, Vaggelis; Hatzigeorgiou, Artemis G; Reczko, Martin; Hatzis, Pantelis

2016-06-21

The canonical Wnt pathway plays a central role in stem cell maintenance, differentiation, and proliferation in the intestinal epithelium. Constitutive, aberrant activity of the TCF4/β-catenin transcriptional complex is the primary transforming factor in colorectal cancer. We identify a nuclear long non-coding RNA, termed WiNTRLINC1, as a direct target of TCF4/β-catenin in colorectal cancer cells. WiNTRLINC1 positively regulates the expression of its genomic neighbor ASCL2, a transcription factor that controls intestinal stem cell fate. WiNTRLINC1 interacts with TCF4/β-catenin to mediate the juxtaposition of its promoter with the regulatory regions of ASCL2. ASCL2, in turn, regulates WiNTRLINC1 transcriptionally, closing a feedforward regulatory loop that controls stem cell-related gene expression. This regulatory circuitry is highly amplified in colorectal cancer and correlates with increased metastatic potential and decreased patient survival. Our results uncover the interplay between non-coding RNA-mediated regulation and Wnt signaling and point to the diagnostic and therapeutic potential of WiNTRLINC1. Copyright © 2016 The Author(s). Published by Elsevier Inc. All rights reserved.

Results of early thyroidectomy for medullary thyroid carcinoma in children with multiple endocrine neoplasia type 2.

Science.gov (United States)

Telander, R L; Zimmerman, D; van Heerden, J A; Sizemore, G W

1986-12-01

Children with multiple endocrine neoplasia type 2 (MEN2) often develop medullary carcinoma of the thyroid (MCT) or its precursor, C-cell hyperplasia. Survival results are improved if malignancy is diagnosed early from the results of plasma immunoreactive calcitonin (iCT) measurement. The effect of early detection and thyroidectomy in children with MEN2 syndrome was determined by reviewing the experience between 1975 and 1985. Seventeen children with MEN2 who were 12 years old or younger underwent a total thyroidectomy for MCT or C-cell hyperplasia. iCT was measured in all patients preoperatively and postoperatively. Of the 17 children, 14 (82%) had MEN2a and 3 (18%) had MEN2b. There were 14 (82%) female and three (18%) male patients; their mean age was 6.97 years (range 1.5 to 12 years). In all patients, the diagnosis of MCT was made from initial elevated levels of iCT after stimulation with pentagastrin. Three patients had clinical evidence of disease preoperatively. All patients underwent a total thyroidectomy and lymph nodes were removed from the central zone; a neck dissection was performed in the three with clinically obvious disease. MCT with C-cell hyperplasia was found in 11 children and C-cell hyperplasia alone in six. Of the 11 with carcinoma, eight had bilateral disease and three unilateral. Six children had bilateral C-cell hyperplasia. All 17 children were alive and feeling well at the time of this report; however, three had evidence of metastatic disease according to iCT measurements. None of the children had recurrent nerve injuries; one had evidence of hypoparathyroidism.(ABSTRACT TRUNCATED AT 250 WORDS)

Imprinted ZnO nanostructure-based electrochemical sensing of calcitonin: A clinical marker for medullary thyroid carcinoma

International Nuclear Information System (INIS)

Patra, Santanu; Roy, Ekta; Madhuri, Rashmi; Sharma, Prashant K.

2015-01-01

Highlights: • Molecular imprinting-based sensor for medullary thyroid carcinoma marker was developed. • ZnO nanostructure was used as a platform for synthesis of imprinted polymer. • Imprinted polymer was prepared by ARGET–ATRP method. • A novel and biocompatible tyrosine amino acid derivative was used as monomer. • Linear working range is found from 9.99 ng L −1 to 7.919 mg L −1 with LOD 3.09 ng L −1 . - Abstract: The present work describes an exciting method for the selective and sensitive determination of calcitonin in human blood serum samples. Adopting the surface molecular imprinting technique, a calcitonin-imprinted polymer was prepared on the surface of the zinc oxide nanostructure. Firstly, a biocompatible tyrosine derivative as a monomer was grafted onto the surface of zinc oxide nanostructure followed by their polymerization on vinyl functionalized electrode surface by activator regenerated by electron transfer–atom transfer radical polymerization (ARGET–ATRP) technique. Such sensor can predict the small change in the concentration of calcitonin in the human body and it may also consider to be as cost-effective, renewable, disposable, and reliable for clinical studies having no such cross-reactivity and matrix effect from real samples. The morphologies and properties of the proposed sensor were characterized by scanning electron microscopy, cyclic voltammetry, difference pulse voltammetry and chronocoulometry. The linear working range was found to be 9.99 ng L −1 to 7.919 mg L −1 and the detection limit as low as 3.09 ± 0.01 ng L −1 (standard deviation for three replicate measurements) (S/N = 3)

Mitochondria-Targeted Nitroxide, Mito-CP, Suppresses Medullary Thyroid Carcinoma Cell Survival In Vitro and In Vivo

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Starenki, Dmytro

2013-01-01

Context: Medullary thyroid carcinoma (MTC) is a neuroendocrine tumor mainly caused by mutations in the RET proto-oncogene. For MTC therapy, the U.S. Food and Drug Administration recently approved vandetanib and cabozantinib, multikinase inhibitors targeting RET and other tyrosine kinase receptors of vascular endothelial growth factor, epidermal growth factor, or hepatocyte growth factor. Nevertheless, not all patients with the progressive MTC respond to these drugs, requiring the development of additional therapeutic modalities that have distinct activity. Objective: We aimed to evaluate mitochondria-targeted carboxy-proxyl (Mito-CP), a mitochondria-targeted redox-sensitive agent, for its tumor-suppressive efficacy against MTC. Design: In vitro cultures of 2 human MTC cell lines, TT and MZ-CRC-1, and TT xenografts in mice were treated with Mito-CP in comparison with vandetanib. The effects on cell survival/death, RET expression, mitochondrial integrity, and oxidative stress were determined. Results: Contrary to vandetanib, Mito-CP induced RET downregulation and strong cytotoxic effects in both cell lines in vitro, including caspase-dependent apoptosis. These effects were accompanied by mitochondrial membrane depolarization, decreased oxygen consumption, and increased oxidative stress in cells. Intriguingly, Mito-CP–induced cell death, but not RET downregulation, was partially inhibited by the reactive oxygen species scavenger, N-acetyl-cysteine, indicating that Mito-CP mediates tumor-suppressive effects via redox-dependent as well as redox-independent mechanisms. Orally administered Mito-CP effectively suppressed TT xenografts in mice, with an efficacy comparable to vandetanib and relatively low toxicity to animals. Conclusion: Our results suggest that Mito-CP can effectively suppress MTC cell growth/survival via a mechanism distinct from vandetanib effects. Mitochondrial targeting may be a potential strategy for MTC therapy. PMID:23509102

Wfs1- deficient rats develop primary symptoms of Wolfram syndrome: insulin-dependent diabetes, optic nerve atrophy and medullary degeneration.

Science.gov (United States)

Plaas, Mario; Seppa, Kadri; Reimets, Riin; Jagomäe, Toomas; Toots, Maarja; Koppel, Tuuliki; Vallisoo, Tuuli; Nigul, Mait; Heinla, Indrek; Meier, Riho; Kaasik, Allen; Piirsoo, Andres; Hickey, Miriam A; Terasmaa, Anton; Vasar, Eero

2017-08-31

Wolfram syndrome (WS) is a rare autosomal-recessive disorder that is caused by mutations in the WFS1 gene and is characterized by juvenile-onset diabetes, optic atrophy, hearing loss and a number of other complications. Here, we describe the creation and phenotype of Wfs1 mutant rats, in which exon 5 of the Wfs1 gene is deleted, resulting in a loss of 27 amino acids from the WFS1 protein sequence. These Wfs1-ex5-KO232 rats show progressive glucose intolerance, which culminates in the development of diabetes mellitus, glycosuria, hyperglycaemia and severe body weight loss by 12 months of age. Beta cell mass is reduced in older mutant rats, which is accompanied by decreased glucose-stimulated insulin secretion from 3 months of age. Medullary volume is decreased in older Wfs1-ex5-KO232 rats, with the largest decreases at the level of the inferior olive. Finally, older Wfs1-ex5-KO232 rats show retinal gliosis and optic nerve atrophy at 15 months of age. Electron microscopy revealed axonal degeneration and disorganization of the myelin in the optic nerves of older Wfs1-ex5-KO232 rats. The phenotype of Wfs1-ex5-KO232 rats indicates that they have the core symptoms of WS. Therefore, we present a novel rat model of WS.

In search of the next memory inside the circuitry from the oldest to the emerging non-volatile memories

CERN Document Server

Campardo, Giovanni

2017-01-01

This book provides students and practicing chip designers with an easy-to-follow yet thorough, introductory treatment of the most promising emerging memories under development in the industry. Focusing on the chip designer rather than the end user, this book offers expanded, up-to-date coverage of emerging memories circuit design. After an introduction on the old solid-state memories and the fundamental limitations soon to be encountered, the working principle and main technology issues of each of the considered technologies (PCRAM, MRAM, FeRAM, ReRAM) are reviewed and a range of topics related to design is explored: the array organization, sensing and writing circuitry, programming algorithms and error correction techniques are reviewed comparing the approach followed and the constraints for each of the technologies considered. Finally the issue of radiation effects on memory devices has been briefly treated. Additionally some considerations are entertained about how emerging memories can find a place in the...

Cellular and Circuitry Bases of Autism: Lessons Learned from the Temporospatial Manipulation of Autism Genes in the Brain

Institute of Scientific and Technical Information of China (English)

Samuel W.Hulbert; Yong-hui Jiang

2017-01-01

Transgenic mice carrying mutations that cause Autism Spectrum Disorders (ASDs) continue to be valuable for determining the molecular underpinnings of the disorders.Recently,researchers have taken advantage of such models combined with Cre-loxP and similar systems to manipulate gene expression over space and time.Thus,a clearer picture is starting to emerge of the cell types,circuits,brain regions,and developmental time periods underlying ASDs.ASD-causing mutations have been restricted to or rescued specifically in excitatory or inhibitory neurons,different neurotransmitter systems,and cells specific to the forebrain or cerebellum.In addition,mutations have been induced or corrected in adult mice,providing some evidence for the plasticity and reversibility of core ASD symptoms.The limited availability of Cre lines that are highly specific to certain cell types or time periods provides a challenge to determining the cellular and circuitry bases of autism,but other technological advances may eventually overcome this obstacle.

High prevalence of exon 8 G533C mutation in apparently sporadic medullary thyroid carcinoma in Greece.

Science.gov (United States)

Sarika, H L; Papathoma, A; Garofalaki, M; Vasileiou, V; Vlassopoulou, B; Anastasiou, E; Alevizaki, M

2012-12-01

Genetic screening for ret mutation has become routine practice in the evaluation of medullary thyroid carcinoma (MTC). Approximately 25% of these tumours are familial, and they occur as components of the multiple endocrine neoplasia type 2 syndromes (MEN 2A and 2B) or familial MTC. In familial cases, the majority of mutations are found in exons 10, 11, 13, 14 or 15 of the ret gene. A rare mutation involving exon 8 (G533C) has recently been reported in familial cases of MTC in Brazil and Greece; some of these cases were originally thought to be sporadic. The aim of this study was to re-evaluate a series of sporadic cases of MTC, with negative family history, and screen them for germline mutations in exon 8. Genomic DNA was extracted from peripheral lymphocytes in 129 unrelated individuals who had previously been characterized as 'sporadic' based on the negative family history and negative screening for ret gene mutations. Samples were analysed in Applied Biosystems 7500 real-time PCR and confirmed by sequencing. The G533C exon 8 mutation was identified in 10 of 129 patients with sporadic MTC. Asymptomatic gene carriers were subsequently identified in other family members. In our study, we found that 7·75% patients with apparently sporadic MTC do carry G533C mutation involving exon 8 of ret. We feel that there is now a need to include exon 8 mutation screening in all patients diagnosed as sporadic MTC, in Greece. © 2012 Blackwell Publishing Ltd.

Ventilatory response to hypercapnia and hypoxia after extensive lesion of medullary serotonergic neurons in newborn conscious piglets.

Science.gov (United States)

Penatti, E M; Berniker, A V; Kereshi, B; Cafaro, C; Kelly, M L; Niblock, M M; Gao, H G; Kinney, H C; Li, A; Nattie, E E

2006-10-01

Acute inhibition of serotonergic (5-HT) neurons in the medullary raphé (MR) using a 5-HT(1A) receptor agonist had an age-dependent impact on the "CO(2) response" of piglets (33). Our present study explored the effect of chronic 5-HT neuron lesions in the MR and extra-raphé on the ventilatory response to hypercapnia and hypoxia in piglets, with possible implications on the role of 5-HT in the sudden infant death syndrome. We established four experimental groups. Group 1 (n = 11) did not undergo any treatment. Groups 2, 3, and 4 were injected with either vehicle or the neurotoxin 5,7-dihydroxytryptamine in the cisterna magna during the first week of life (group 2, n = 9; group 4, n = 11) or second week of life (group 3, n = 10). Ventilation was recorded in response to 5% CO(2) (all groups) and 12% O(2) (group 2) during wakefulness and sleep up to postnatal day 25. Surprisingly, the piglets did not reveal changes in their CO(2) sensitivity during early postnatal development. Overall, considerable lesions of 5-HT neurons (up to 65% decrease) in the MR and extra-raphé had no impact on the CO(2) response, regardless of injection time. Postlesion raphé plasticity could explain why we observed no effect. 5,7-Dihydroxytryptamine-treated males, however, did present a lower CO(2) response during sleep. Hypoxia significantly altered the frequency during sleep in lesioned piglets. Further studies are necessary to elucidate the role of plasticity, sex, and 5-HT abnormalities in sudden infant death syndrome.

Micronutrient status (calcium, zinc, vitamins D and E) in patients with medullary thyroid carcinoma: A cross-sectional study.

Science.gov (United States)

Emami, Ali; Nazem, Mohammad Reza; Shekarriz, Reza; Hedayati, Mehdi

2017-09-01

The aim of this study was to evaluate the micronutrient status of Iranian patients with medullary thyroid carcinoma (MTC) and to analyze potential relationships with respect to MTC risk. This was a cross-sectional study (Tehran Thyroid Cancer Survey 2015-2016). We measured and compared preoperative serum calcium, zinc, and vitamins D and E in patients with MTC and healthy controls. Forty cases with MTC and 40 (age-, sex-, and body mass index-matched) healthy controls voluntarily participated in the project. Serum calcium, zinc, and vitamin D and E concentrations were lower in the patients with cancer (P Ca calcium remarkably associated with enhanced risk for thyroid cancer (odds ratio [OR], 6.5; P = 0.001). Likewise, serum vitamin E was linked to the risk for cancer (OR, 1.31; P = 0.056). Moreover, serum zinc was correlated with vitamin E and calcium (r = +0.23; P = 0.04 and r = +0.25, P = 0.03; respectively). We also observed a correlation between calcium and vitamin E (r = +0.27; P = 0.02). A multiple-micronutrient decrease was confirmed in patients with MTC. A low serum calcium level was a potent risk factor for MTC. Findings from the present study suggest that dietary intake and/or supplementation of micronutrients, especially calcium and vitamin E, may be beneficial in reducing the risk for thyroid cancer. Copyright © 2017 Elsevier Inc. All rights reserved.

Nuclear deterrents: Intrinsic regulators of IL-1β-induced effects on hippocampal neurogenesis.

Science.gov (United States)

O'Léime, Ciarán S; Cryan, John F; Nolan, Yvonne M

2017-11-01

Hippocampal neurogenesis, the process by which new neurons are born and develop into the host circuitry, begins during embryonic development and persists throughout adulthood. Over the last decade considerable insights have been made into the role of hippocampal neurogenesis in cognitive function and the cellular mechanisms behind this process. Additionally, an increasing amount of evidence exists on the impact of environmental factors, such as stress and neuroinflammation on hippocampal neurogenesis and subsequent impairments in cognition. Elevated expression of the pro-inflammatory cytokine interleukin-1β (IL-1β) in the hippocampus is established as a significant contributor to the neuronal demise evident in many neurological and psychiatric disorders and is now known to negatively regulate hippocampal neurogenesis. In order to prevent the deleterious effects of IL-1β on neurogenesis it is necessary to identify signalling pathways and regulators of neurogenesis within neural progenitor cells that can interact with IL-1β. Nuclear receptors are ligand regulated transcription factors that are involved in modulating a large number of cellular processes including neurogenesis. In this review we focus on the signalling mechanisms of specific nuclear receptors involved in regulating neurogenesis (glucocorticoid receptors, peroxisome proliferator activated receptors, estrogen receptors, and nuclear receptor subfamily 2 group E member 1 (NR2E1 or TLX)). We propose that these nuclear receptors could be targeted to inhibit neuroinflammatory signalling pathways associated with IL-1β. We discuss their potential to be therapeutic targets for neuroinflammatory disorders affecting hippocampal neurogenesis and associated cognitive function. Copyright © 2017 Elsevier Inc. All rights reserved.

Effects of direct social experience on trust decisions and neural reward circuitry

Directory of Open Access Journals (Sweden)

Dominic S. Fareri

2012-10-01

Full Text Available The human striatum is integral for reward-processing and supports learning by linking experienced outcomes with prior expectations. Recent endeavors implicate the striatum in processing outcomes of social interactions, such as social approval/rejection, as well as in learning reputations of others. Interestingly, social impressions often influence our behavior with others during interactions. Information about an interaction partner’s moral character acquired from biographical information hinders updating of expectations after interactions via top down modulation of reward circuitry. An outstanding question is whether initial impressions formed through experience similarly modulate the ability to update social impressions at the behavioral and neural level. We investigated the role of experienced social information on trust behavior and reward-related BOLD activity. Participants played a computerized ball tossing game with three fictional partners manipulated to be perceived as good, bad or neutral. Participants then played an iterated trust game as investors with these same partners while undergoing fMRI. Unbeknownst to participants, partner behavior in the trust game was random and unrelated to their ball-tossing behavior. Participants’ trust decisions were influenced by their prior experience in the ball tossing game, investing less often with the bad partner compared to the good and neutral. Reinforcement learning models revealed that participants were more sensitive to updating their beliefs about good and bad partners when experiencing outcomes consistent with initial experience. Increased striatal and anterior cingulate BOLD activity for positive versus negative trust game outcomes emerged, which further correlated with model-derived prediction-error (PE learning signals. These results suggest that initial impressions formed from direct social experience can be continually shaped by consistent information through reward learning

Effects of Direct Social Experience on Trust Decisions and Neural Reward Circuitry

Science.gov (United States)

Fareri, Dominic S.; Chang, Luke J.; Delgado, Mauricio R.

2012-01-01

The human striatum is integral for reward-processing and supports learning by linking experienced outcomes with prior expectations. Recent endeavors implicate the striatum in processing outcomes of social interactions, such as social approval/rejection, as well as in learning reputations of others. Interestingly, social impressions often influence our behavior with others during interactions. Information about an interaction partner’s moral character acquired from biographical information hinders updating of expectations after interactions via top down modulation of reward circuitry. An outstanding question is whether initial impressions formed through experience similarly modulate the ability to update social impressions at the behavioral and neural level. We investigated the role of experienced social information on trust behavior and reward-related BOLD activity. Participants played a computerized ball-tossing game with three fictional partners manipulated to be perceived as good, bad, or neutral. Participants then played an iterated trust game as investors with these same partners while undergoing fMRI. Unbeknownst to participants, partner behavior in the trust game was random and unrelated to their ball-tossing behavior. Participants’ trust decisions were influenced by their prior experience in the ball-tossing game, investing less often with the bad partner compared to the good and neutral. Reinforcement learning models revealed that participants were more sensitive to updating their beliefs about good and bad partners when experiencing outcomes consistent with initial experience. Increased striatal and anterior cingulate BOLD activity for positive versus negative trust game outcomes emerged, which further correlated with model-derived prediction error learning signals. These results suggest that initial impressions formed from direct social experience can be continually shaped by consistent information through reward learning mechanisms. PMID:23087604

Modification of medullary respiratory-related discharge patterns by behaviors and states of arousal.

Science.gov (United States)

Chang, F C

1992-02-07

The modulatory influences of behaviors and states of arousal on bulbar respiratory-related unit (RRU) discharge patterns were studied in an unanesthetized, freely behaving guinea pig respiratory model system. When fully instrumented, this model system permits concurrent monitoring and recording of (i) single units from either Bötzinger complex or nucleus para-ambiguus; (ii) electrocorticogram; and, (iii) diaphragmatic EMG. In addition to being used in surveys of RRU discharge patterns in freely behaving states, the model system also offered a unique opportunity in investigating the effects of pentobarbital on RRU discharge patterns before, throughout the course of, and during recovery from anesthesia. In anesthetized preparations, a particular RRU discharge pattern (such as tonic, incrementing or decrementing) typically displayed little, if any notable variation. The most striking development following pentobarbital was a state of progressive bradypnea attributable to a significantly augmented RRU cycle duration, burst duration and an increase in the RRU spike frequencies during anesthesia. In freely behaving states, medullary RRU activities rarely adhered to a fixed, immutable discharge pattern. More specifically, the temporal organization (such as burst duration, cycle duration, and the extent of modulation of within-burst spike frequencies) of RRU discharge patterns regularly showed complex and striking variations, not only with states of arousal (sleep/wakefulness, anesthesia) but also with discrete alterations in electrocorticogram (ECoG) activities and a multitude of on-going behavioral repertoires such as volitional movement, postural modification, phonation, mastication, deglutition, sniffing/exploratory behavior, alerting/startle reflexes. Only during sleep, and on occasions when the animal assumed a motionless, resting posture, could burst patterns of relatively invariable periodicity and uniform temporal attributes be observed. RRU activities during

Electric field induced needle-pulsed arc discharge carbon nanotube production apparatus: Circuitry and mechanical design

Energy Technology Data Exchange (ETDEWEB)

Kia, Kaveh Kazemi [Department of Electrical and Computer Engineering, Islamic Azad University of Bonab, Bonab (Iran, Islamic Republic of); Bonabi, Fahimeh [Department of Engineering, Islamic Azad University of Bonab, Bonab (Iran, Islamic Republic of)

2012-12-15

A simple and low cost apparatus is reported to produce multiwall carbon nanotubes and carbon nano-onions by a low power short pulsed arc discharge reactor. The electric circuitry and the mechanical design details and a micro-filtering assembly are described. The pulsed-plasma is generated and applied between two graphite electrodes. The pulse width is 0.3 {mu}s. A strong dc electric field is established along side the electrodes. The repetitive discharges occur in less than 1 mm distance between a sharp tip graphite rod as anode, and a tubular graphite as cathode. A hydrocarbon vapor, as carbon source, is introduced through the graphite nozzle in the cathode assembly. The pressure of the chamber is controlled by a vacuum pump. A magnetic field, perpendicular to the plasma path, is provided. The results show that the synergetic use of a pulsed-current and a dc power supply enables us to synthesize carbon nanoparticles with short pulsed plasma. The simplicity and inexpensiveness of this plan is noticeable. Pulsed nature of plasma provides some extra degrees of freedom that make the production more controllable. Effects of some design parameters such as electric field, pulse frequency, and cathode shape are discussed. The products are examined using scanning probe microscopy techniques.

Electric field induced needle-pulsed arc discharge carbon nanotube production apparatus: circuitry and mechanical design.

Science.gov (United States)

Kia, Kaveh Kazemi; Bonabi, Fahimeh

2012-12-01

A simple and low cost apparatus is reported to produce multiwall carbon nanotubes and carbon nano-onions by a low power short pulsed arc discharge reactor. The electric circuitry and the mechanical design details and a micro-filtering assembly are described. The pulsed-plasma is generated and applied between two graphite electrodes. The pulse width is 0.3 μs. A strong dc electric field is established along side the electrodes. The repetitive discharges occur in less than 1 mm distance between a sharp tip graphite rod as anode, and a tubular graphite as cathode. A hydrocarbon vapor, as carbon source, is introduced through the graphite nozzle in the cathode assembly. The pressure of the chamber is controlled by a vacuum pump. A magnetic field, perpendicular to the plasma path, is provided. The results show that the synergetic use of a pulsed-current and a dc power supply enables us to synthesize carbon nanoparticles with short pulsed plasma. The simplicity and inexpensiveness of this plan is noticeable. Pulsed nature of plasma provides some extra degrees of freedom that make the production more controllable. Effects of some design parameters such as electric field, pulse frequency, and cathode shape are discussed. The products are examined using scanning probe microscopy techniques.

Intranasal insulin modulates intrinsic reward and prefrontal circuitry of the human brain in lean women.

Science.gov (United States)

Kullmann, Stephanie; Frank, Sabine; Heni, Martin; Ketterer, Caroline; Veit, Ralf; Häring, Hans-Ulrich; Fritsche, Andreas; Preissl, Hubert

2013-01-01

There is accumulating evidence that food consumption is controlled by a wide range of brain circuits outside of the homeostatic system. Activation in these brain circuits may override the homeostatic system and also contribute to the enormous increase of obesity. However, little is known about the influence of hormonal signals on the brain's non-homeostatic system. Thus, selective insulin action in the brain was investigated by using intranasal application. We performed 'resting-state' functional magnetic resonance imaging in 17 healthy lean female subjects to assess intrinsic brain activity by fractional amplitude of low-frequency fluctuations (fALFF) before, 30 and 90 min after application of intranasal insulin. Here, we showed that insulin modulates intrinsic brain activity in the hypothalamus and orbitofrontal cortex. Furthermore, we could show that the prefrontal and anterior cingulate cortex response to insulin is associated with body mass index. This demonstrates that hormonal signals as insulin may reduce food intake by modifying the reward and prefrontal circuitry of the human brain, thereby potentially decreasing the rewarding properties of food. Due to the alarming increase in obesity worldwide, it is of great importance to identify neural mechanisms of interaction between the homeostatic and non-homeostatic system to generate new targets for obesity therapy. Copyright © 2012 S. Karger AG, Basel.

Chloroplasts as source and target of cellular redox regulation: a discussion on chloroplast redox signals in the context of plant physiology.

Science.gov (United States)

Baier, Margarete; Dietz, Karl-Josef

2005-06-01

During the evolution of plants, chloroplasts have lost the exclusive genetic control over redox regulation and antioxidant gene expression. Together with many other genes, all genes encoding antioxidant enzymes and enzymes involved in the biosynthesis of low molecular weight antioxidants were transferred to the nucleus. On the other hand, photosynthesis bears a high risk for photo-oxidative damage. Concomitantly, an intricate network for mutual regulation by anthero- and retrograde signals has emerged to co-ordinate the activities of the different genetic and metabolic compartments. A major focus of recent research in chloroplast regulation addressed the mechanisms of redox sensing and signal transmission, the identification of regulatory targets, and the understanding of adaptation mechanisms. In addition to redox signals communicated through signalling cascades also used in pathogen and wounding responses, specific chloroplast signals control nuclear gene expression. Signalling pathways are triggered by the redox state of the plastoquinone pool, the thioredoxin system, and the acceptor availability at photosystem I, in addition to control by oxolipins, tetrapyrroles, carbohydrates, and abscisic acid. The signalling function is discussed in the context of regulatory circuitries that control the expression of antioxidant enzymes and redox modulators, demonstrating the principal role of chloroplasts as the source and target of redox regulation.

Flexible thin film circuitry enabling ubiquitous electronics via post-fabrication customization (Presentation Recording)

Science.gov (United States)

Cobb, Brian

2015-09-01

For decades, the electronics industry has been accurately described by Moore's Law, where the march towards increasing density and smaller feature sizes has enabled continuous cost reductions and performance improvements. With flexible electronics, this perpetual scaling is not foreseen to occur. Instead, the industry will be dominated by Wright's Law, first proposed in 1936, where increasing demand for high volumes of product will drive costs down. We have demonstrated thin film based circuitry compatible with flexible substrates with high levels of functionality designed for such a high volume industry. This includes a generic 8-bit microprocessor totaling more than 3.5k TFTs operating at 2.1 kHz. We have also developed a post fabrication programming technique via inkjet printing of conductive spots to form a one-time programmable instruction generator, allowing customization of the processor for a specific task. The combination demonstrates the possibility to achieve the high volume production of identical products necessary to reap the benefits promised by Wright's Law, while still retaining the individualization necessary for application differentiation. This is of particular importance in the area of item level identification via RFID, where low cost and individualized identification are necessary. Remotely powered RFID tags have been fabricated using an oxide semiconductor based TFT process. This process is compatible with the post-fabrication printing process to detail individual identification codes, with the goal of producing low cost, high volume flexible tags. The goal is to produce tags compatible with existing NFC communication protocols in order to communicate with readers that are already ubiquitous in the market.

Somatostatin receptor scintigraphy using 99mTc-EDDA/HYNIC-TOC in patients with medullary thyroid carcinoma.

Science.gov (United States)

Czepczyński, Rafał; Parisella, Maria Gemma; Kosowicz, Jerzy; Mikołajczak, Renata; Ziemnicka, Katarzyna; Gryczyńska, Maria; Sowiński, Jerzy; Signore, Alberto

2007-10-01

Several new somatostatin analogues have been developed for the diagnosis and therapy of different tumours. Since somatostatin receptors are often over-expressed in medullary thyroid carcinoma (MTC), the aim of our study was to evaluate the utility of scintigraphy with the somatostatin analogue (99m)Tc-EDDA/HYNIC-TOC in MTC in comparison with other diagnostic techniques. Forty-five patients with MTC, aged 14-83 years, were investigated. Scintigraphy using (99m)Tc-EDDA/HYNIC-TOC (Tektrotyd) was performed 2 and 4 h post injection of 740 MBq (20 mCi) of the tracer. Other imaging techniques were also applied and analysed in individual cases (ultrasonography, computed tomography, (99m)Tc(V)-DMSA, (131)I-MIBG, (99m)Tc-MDP, (111)In-DTPA-octreotide and (18)F-FDG-PET) and compared with (99m)Tc-EDDA/HYNIC-TOC. In group 1 (eight patients before thyroidectomy), uptake of the tracer was found in the primary tumours. In group 2 (six patients with remission), a false positive result was found in one patient; in the remaining five patients, no pathological foci were visualised. In group 3 (31 patients with post-surgical hypercalcitoninaemia), scintigraphy was true positive in 23 patients (74.2%): uptake in the thyroid bed was found in five patients, in the lymph nodes in 18 and in bone metastases in four. Using (99m)Tc-EDDA/HYNIC-TOC scintigraphy, the overall sensitivity was 79.5%, specificity 83.3%, accuracy 80.0%, positive predictive value 96.9% and negative predictive value 38.5%. (99m)Tc-EDDA/HYNIC-TOC is clinically useful for scintigraphy in the follow-up of patients with MTC. It can be used in clinical practice for preoperative evaluation, for localisation of local recurrence or distant metastases and particularly for therapy decision making.

Somatostatin receptor scintigraphy using 99mTc-EDDA/HYNIC-TOC in patients with medullary thyroid carcinoma

International Nuclear Information System (INIS)

Czepczynski, Rafal; Kosowicz, Jerzy; Ziemnicka, Katarzyna; Gryczynska, Maria; Sowinski, Jerzy; Parisella, Maria G.; Mikolajczak, Renata; Signore, Alberto

2007-01-01

Several new somatostatin analogues have been developed for the diagnosis and therapy of different tumours. Since somatostatin receptors are often over-expressed in medullary thyroid carcinoma (MTC), the aim of our study was to evaluate the utility of scintigraphy with the somatostatin analogue 99m Tc-EDDA/HYNIC-TOC in MTC in comparison with other diagnostic techniques. Forty-five patients with MTC, aged 14-83 years, were investigated. Scintigraphy using 99m Tc-EDDA/HYNIC-TOC (Tektrotyd) was performed 2 and 4 h post injection of 740 MBq (20 mCi) of the tracer. Other imaging techniques were also applied and analysed in individual cases (ultrasonography, computed tomography, 99m Tc(V)-DMSA, 131 I-MIBG, 99m Tc-MDP, 111 In-DTPA-octreotide and 18 F-FDG-PET) and compared with 99m Tc-EDDA/HYNIC-TOC. In group 1 (eight patients before thyroidectomy), uptake of the tracer was found in the primary tumours. In group 2 (six patients with remission), a false positive result was found in one patient; in the remaining five patients, no pathological foci were visualised. In group 3 (31 patients with post-surgical hypercalcitoninaemia), scintigraphy was true positive in 23 patients (74.2%): uptake in the thyroid bed was found in five patients, in the lymph nodes in 18 and in bone metastases in four. Using 99m Tc-EDDA/HYNIC-TOC scintigraphy, the overall sensitivity was 79.5%, specificity 83.3%, accuracy 80.0%, positive predictive value 96.9% and negative predictive value 38.5%. 99m Tc-EDDA/HYNIC-TOC is clinically useful for scintigraphy in the follow-up of patients with MTC. It can be used in clinical practice for preoperative evaluation, for localisation of local recurrence or distant metastases and particularly for therapy decision making. (orig.)

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

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

2016-06-15

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

Cushing syndrome secondary to a medullary thyroid carcinoma: report of a case and review of the literature = Síndrome de Cushing secundario a carcinoma medular de tiroides: descripción de un caso y revisión de la literatura

Directory of Open Access Journals (Sweden)

Gutiérrez Restrepo, Johnayro

2014-08-01

Full Text Available We report the case of a 29-year old female who was evaluated because of a thyroid tumor. The initial pathological classification was an insular thyroid carcinoma. There was strong involvement in the neck, mediastinum and lungs. Three years after receiving specific therapy for her thyroid neoplasia, she developed a Cushing syndrome and liver lesions suggestive of metastases from the primary tumor. A review of the previous pathological material revealed a medullary thyroid carcinoma producing ACTH, instead of the insular carcinoma. Based on this case a review of the literature is presented.

Differential regulation of microtubule severing by APC underlies distinct patterns of projection neuron and interneuron migration

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Eom, Tae-Yeon; Stanco, Amelia; Guo, Jiami; Wilkins, Gary; Deslauriers, Danielle; Yan, Jessica; Monckton, Chase; Blair, Josh; Oon, Eesim; Perez, Abby; Salas, Eduardo; Oh, Adrianna; Ghukasyan, Vladimir; Snider, William D.; Rubenstein, John L. R.; Anton, E. S.

2014-01-01

Coordinated migration of distinct classes of neurons to appropriate positions leads to the formation of functional neuronal circuitry in the cerebral cortex. Two major classes of cortical neurons, interneurons and projection neurons, utilize distinctly different modes (radial vs. tangential) and routes of migration to arrive at their final positions in the cerebral cortex. Here, we show that adenomatous polyposis coli (APC) modulates microtubule (MT) severing in interneurons to facilitate tangential mode of interneuron migration, but not the glial-guided, radial migration of projection neurons. APC regulates the stability and activity of the MT severing protein p60-katanin in interneurons to promote the rapid remodeling of neuronal processes necessary for interneuron migration. These findings reveal how severing and restructuring of MTs facilitate distinct modes of neuronal migration necessary for laminar organization of neurons in the developing cerebral cortex. PMID:25535916

Hybrid nanowire ion-to-electron transducers for integrated bioelectronic circuitry (Conference Presentation)

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Carrad, Damon J.; Mostert, Bernard; Meredith, Paul; Micolich, Adam P.

2016-09-01

A key task in bioelectronics is the transduction between ionic/protonic signals and electronic signals at high fidelity. This is a considerable challenge since the two carrier types exhibit intrinsically different physics. We present our work on a new class of organic-inorganic transducing interface utilising semiconducting InAs and GaAs nanowires directly gated with a proton transporting hygroscopic polymer consisting of undoped polyethylene oxide (PEO) patterned to nanoscale dimensions by a newly developed electron-beam lithography process [1]. Remarkably, we find our undoped PEO polymer electrolyte gate dielectric [2] gives equivalent electrical performance to the more traditionally used LiClO4-doped PEO [3], with an ionic conductivity three orders of magnitude higher than previously reported for undoped PEO [4]. The observed behaviour is consistent with proton conduction in PEO. We attribute our undoped PEO-based devices' performance to the small external surface and high surface-to-volume ratio of both the nanowire conducting channel and patterned PEO dielectric in our devices, as well as the enhanced hydration afforded by device processing and atmospheric conditions. In addition to studying the basic transducing mechanisms, we also demonstrate high-fidelity ionic to electronic conversion of a.c. signals at frequencies up to 50 Hz. Moreover, by combining complementary n- and p-type transducers we demonstrate functional hybrid ionic-electronic circuits can achieve logic (NOT operation), and with some further engineering of the nanowire contacts, potentially also amplification. Our device structures have significant potential to be scaled towards realising integrated bioelectronic circuitry. [1] D.J. Carrad et al., Nano Letters 14, 94 (2014). [2] D.J. Carrad et al., Manuscript in preparation (2016). [3] S.H. Kim et al., Advanced Materials 25, 1822 (2013). [4] S.K. Fullerton-Shirey et al., Macromolecules 42, 2142 (2009).

Skeletal dosimetry for external exposures to photons based on {mu}CT images of spongiosa: Consideration of voxel resolution, cluster size, and medullary bone surfaces

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Kramer, R.; Khoury, H. J.; Vieira, J. W.; Brown, K. A. Robson [Departamento de Energia Nuclear, Universidade Federal de Pernambuco, Avenida Professor Luiz Freire 1000, Cidade Universitaria, CEP 50740-540, Recife, Pernambuco (Brazil); Centro Federal de Educacao Tecnologica de Pernambuco, Avenida Professor Luiz Freire 500, CEP 50740-540, Recife, Pernambuco, Brazil and Escola Politecnica, UPE, Rua Benfica 455, CEP 50751-460, Recife, Pernambuco (Brazil); Imaging Laboratory, Department of Archaeology and Anthropology, University of Bristol, 43 Woodland Road, Bristol BS8 1UU (United Kingdom)

2009-11-15

Skeletal dosimetry based on {mu}CT images of trabecular bone has recently been introduced to calculate the red bone marrow (RBM) and the bone surface cell (BSC) equivalent doses in human phantoms for external exposure to photons. In order to use the {mu}CT images for skeletal dosimetry, spongiosa voxels in the skeletons were replaced at run time by so-called micromatrices, which have exactly the size of a spongiosa voxel and contain segmented trabecular bone and marrow microvoxels. A cluster (=parallelepiped) of 2x2x2=8 micromatrices was used systematically and periodically throughout the spongiosa volume during the radiation transport calculation. Systematic means that when a particle leaves a spongiosa voxel to enter into a neighboring spongiosa voxel, then the next micromatrix in the cluster will be used. Periodical means that if the particle travels through more than two spongiosa voxels in a row, then the cluster will be repeated. Based on the bone samples available at the time, clusters of up to 3x3x3=27 micromatrices were studied. While for a given trabecular bone volume fraction the whole-body RBM equivalent dose showed converging results for cluster sizes between 8 and 27 micromatrices, this was not the case for the BSC equivalent dose. The BSC equivalent dose seemed to be very sensitive to the number, form, and thickness of the trabeculae. In addition, the cluster size and/or the microvoxel resolution were considered to be possible causes for the differences observed. In order to resolve this problem, this study used a bone sample large enough to extract clusters containing up to 8x8x8=512 micromatrices and which was scanned with two different voxel resolutions. Taking into account a recent proposal, this investigation also calculated the BSC equivalent dose on medullary surfaces of cortical bone in the arm and leg bones. The results showed (1) that different voxel resolutions have no effect on the RBM equivalent dose but do influence the BSC equivalent

Medullary aplasia secondary to an irradiation accident: Treatment options and evolution of the concepts; L'aplasie medullaire secondaire a un accident d'irradiation : options therapeutiques et evolution des concepts

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De Revel, T. [Service d' Hematologie, HIA Percy, et Service de Neurovirologie, Commissariat a l' Energie Atomique, Fontenay-aux-Roses (France); Fagot, T.; Souleau, B. [Service d' Hematologie, HIA Percy, Clamart (France); Dormont, D. [Service de Neurovirologie, Commissariat a l' Energie Atomique, Fontenay-aux-Roses (France); Nedellec, G. [Service d' Hematologie, HIA Percy, Clamart (France)

2002-07-01

Bone marrow grafting following accidental irradiation exposure should be viewed in the perspective of a severe myeloablative syndrome linked to high medullary damage for a dose range higher than 6-8 Gy, resulting in very late or no recovery. Prognosis will depend on the presence or absence of radio-combined injuries, the toxicity of the transplant procedure, and the risk of rejection induced by insufficient percritical immunosuppression. It is in this context that new cell therapy modalities, which combine enhanced peripheral hematopoietic cell engraftment and high immunosuppressive conditioning regimen with low extrahematological toxicity, inducing early and stable mixed lymphomyeloid chimerism with minimal morbidity, can be considered. Such an approach is being evaluated in the treatment of patients with hematological malignancies at high risk of transplant-related mortality using conventional bone marrow methods. (author)

Pressor response to L-cysteine injected into the cisterna magna of conscious rats involves recruitment of hypothalamic vasopressinergic neurons.

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Takemoto, Yumi

2013-03-01

The sulfur-containing non-essential amino acid L-cysteine injected into the cisterna magna of adult conscious rats produces an increase in blood pressure. The present study examined if the pressor response to L-cysteine is stereospecific and involves recruitment of hypothalamic vasopressinergic neurons and medullary noradrenergic A1 neurons. Intracisternally injected D-cysteine produced no cardiovascular changes, while L-cysteine produced hypertension and tachycardia in freely moving rats, indicating the stereospecific hemodynamic actions of L-cysteine via the brain. The double labeling immunohistochemistry combined with c-Fos detection as a marker of neuronal activation revealed significantly higher numbers of c-Fos-positive vasopressinergic neurons both in the supraoptic and paraventricular nuclei and tyrosine hydroxylase containing medullary A1 neurons, of L-cysteine-injected rats than those injected with D-cysteine as iso-osmotic control. The results indicate that the cardiovascular responses to intracisternal injection of L-cysteine in the conscious rat are stereospecific and include recruitment of hypothalamic vasopressinergic neurons both in the supraoptic and paraventricular nuclei, as well as of medullary A1 neurons. The findings may suggest a potential function of L-cysteine as an extracellular signal such as neuromodulators in central regulation of blood pressure.

Pituitary Adenylate-Cyclase Activating Polypeptide Regulates Hunger- and Palatability-Induced Binge Eating

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Matthew M. Hurley

2016-08-01

Full Text Available While pituitary adenylate cyclase activating polypeptide (PACAP signaling in the hypothalamic ventromedial nuclei (VMN has been shown to regulate feeding, a challenge in unmasking a role for this peptide in obesity is that excess feeding can involve numerous mechanisms including homeostatic (hunger and hedonic-related (palatability drives. In these studies, we first isolated distinct feeding drives by developing a novel model of binge behavior in which homeostatic-driven feeding was temporally separated from feeding driven by food palatability. We found that stimulation of the VMN, achieved by local microinjections of AMPA, decreased standard chow consumption in food-restricted rats (e.g., homeostatic feeding; surprisingly, this manipulation failed to alter palatable food consumption in satiated rats (e.g., hedonic feeding. In contrast, inhibition of the nucleus accumbens (NAc, through local microinjections of GABA receptor agonists baclofen and muscimol, decreased hedonic feeding without altering homeostatic feeding. PACAP microinjections produced the site-specific changes in synaptic transmission needed to decrease feeding via VMN or NAc circuitry. PACAP into the NAc mimicked the actions of GABA agonists by reducing hedonic feeding without altering homeostatic feeding. In contrast, PACAP into the VMN mimicked the actions of AMPA by decreasing homeostatic feeding without affecting hedonic feeding. Slice electrophysiology recordings verified PACAP excitation of VMN neurons and inhibition of NAc neurons. These data suggest that the VMN and NAc regulate distinct circuits giving rise to unique feeding drives, but that both can be regulated by the neuropeptide PACAP to potentially curb excessive eating stemming from either drive.

Cognitive regulation during decision making shifts behavioral control between ventromedial and dorsolateral prefrontal value systems.

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Hutcherson, Cendri A; Plassmann, Hilke; Gross, James J; Rangel, Antonio

2012-09-26

Cognitive regulation is often used to influence behavioral outcomes. However, the computational and neurobiological mechanisms by which it affects behavior remain unknown. We studied this issue using an fMRI task in which human participants used cognitive regulation to upregulate and downregulate their cravings for foods at the time of choice. We found that activity in both ventromedial prefrontal cortex (vmPFC) and dorsolateral prefrontal cortex (dlPFC) correlated with value. We also found evidence that two distinct regulatory mechanisms were at work: value modulation, which operates by changing the values assigned to foods in vmPFC and dlPFC at the time of choice, and behavioral control modulation, which operates by changing the relative influence of the vmPFC and dlPFC value signals on the action selection process used to make choices. In particular, during downregulation, activation decreased in the value-sensitive region of dlPFC (indicating value modulation) but not in vmPFC, and the relative contribution of the two value signals to behavior shifted toward the dlPFC (indicating behavioral control modulation). The opposite pattern was observed during upregulation: activation increased in vmPFC but not dlPFC, and the relative contribution to behavior shifted toward the vmPFC. Finally, ventrolateral PFC and posterior parietal cortex were more active during both upregulation and downregulation, and were functionally connected with vmPFC and dlPFC during cognitive regulation, which suggests that they help to implement the changes to the decision-making circuitry generated by cognitive regulation.

Divergent circuitry underlying food reward and intake effects of ghrelin: dopaminergic VTA-accumbens projection mediates ghrelin's effect on food reward but not food intake.

Science.gov (United States)

Skibicka, Karolina P; Shirazi, Rozita H; Rabasa-Papio, Cristina; Alvarez-Crespo, Mayte; Neuber, Corinna; Vogel, Heike; Dickson, Suzanne L

2013-10-01

Obesity has reached global epidemic proportions and creating an urgent need to understand mechanisms underlying excessive and uncontrolled food intake. Ghrelin, the only known circulating orexigenic hormone, potently increases food reward behavior. The neurochemical circuitry that links ghrelin to the mesolimbic reward system and to the increased food reward behavior remains unclear. Here we examine whether VTA-NAc dopaminergic signaling is required for the effects of ghrelin on food reward and intake. In addition, we examine the possibility of endogenous ghrelin acting on the VTA-NAc dopamine neurons. A D1-like or a D2 receptor antagonist was injected into the NAc in combination with ghrelin microinjection into the VTA to investigate whether this blockade attenuates ghrelin-induced food reward behavior. VTA injections of ghrelin produced a significant increase in food motivation/reward behavior, as measured by sucrose-induced progressive ratio operant conditioning, and chow intake. Pretreatment with either a D1-like or D2 receptor antagonist into the NAc, completely blocked the reward effect of ghrelin, leaving chow intake intact. We also found that this circuit is potentially relevant for the effects of endogenously released ghrelin as both antagonists reduced fasting (a state of high circulating levels of ghrelin) elevated sucrose-motivated behavior but not chow hyperphagia. Taken together our data identify the VTA to NAc dopaminergic projections, along with D1-like and D2 receptors in the NAc, as essential elements of the ghrelin responsive circuits controlling food reward behavior. Interestingly results also suggest that food reward behavior and simple intake of chow are controlled by divergent circuitry, where NAc dopamine plays an important role in food reward but not in food intake. Copyright © 2013 The Authors. Published by Elsevier Ltd.. All rights reserved.

Examination of the somatostatin receptor status in non-medullary thyroid cancer; Untersuchungen zum Somatostatinrezeptor-Status bei nicht-medullaeren Schilddruesenkarzinomen

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Goerges, R.; Brandt-Mainz, K.; Bockisch, A. [Essen Univ. (Gesamthochschule) (Germany). Klinik und Poliklinik fuer Nuklearmedizin; Kahaly, G. [Mainz Univ. (Germany). Klinik und Poliklinik fuer Medizin - Endokrinologie und Stoffwechselerkrankungen; Mueller-Brand, J.; Maecke, H. [Kantonsspital Basel (Switzerland). Inst. fuer Nuklearmedizin; Walgenbach, S. [Mainz Univ. (Germany). Klinik und Poliklinik fuer Allgemein- und Abdominalchirurgie; Bruns, C. [Praeklinische Forschung Novartis, Basel (Switzerland); Andreas, J. [Universitaetsklinik Mainz (Germany). Klinik und Poliklinik fuer Nuklearmedizin

1999-06-01

Aim: Recent in-vitro and in-vivo studies demonstrated a somatostatin receptor expression in some non-medullary thyroid carcinomas. In this study we investigated the somatostatin receptor status for this particular tumor entity in a larger patient group. Subject and methods: We compared 131-iodine with 111-In-pentetreotide scans in 24 patients with metastasizing, non-medullary thyroid cancer. The findings were correlated with other imaging modalities. Additionally, we performed receptor autoradiography in one patient, octreotide therapy in another patient and administration of 90-Y- and 111-In-DOTATOC in 2 consecutive patients. Results: In the 15 patients with papillary or follicular carcinoma, 111-In-pentetreotide was inferior to 131-I in 8/15, equal in 1/15, and superior in 6/15 patients. In 8/9 of the patients with Huerthle cell cacinoma, metastases showed a 111-In-pentetreotide accumulation of various intensity, while 131-iodine scans were negative except for one patient. 111-In-pentetreotide was equal or superior compared to 201-Tl or 99m-Tc-sestamibi, but for the most part inferior in comparison with 18-F-FDG-PET. The findings of 111-In-pentetreotide scintigraphy correlated well with the receptor autoradiography and the accumulation of DOTATOC, but not with the therapeutic effect of `cold` octreotide on the thyroid cancer metastases. Conclusions: Several metastases of papillary and follicular carcinoma, and the majority of Huerthle cell cancer metastases can express somatostatin receptors. 111-In-pentetreotide scintigraphy is a promising tool for localization of metastases especially in Huerthle cell cancer or if PET is not available, and may be useful for selection of possible candidates, if therapeutic effective {beta}-emitting somatostatin analogues will be available for routine application. (orig.) [Deutsch] Ziel: in aktuellen In-vitro und In-vivo-Untersuchungen wurde eine Somatostatinrezeptor-Expression bei einigen nicht

Human brain evolution and the "Neuroevolutionary Time-depth Principle:" Implications for the Reclassification of fear-circuitry-related traits in DSM-V and for studying resilience to warzone-related posttraumatic stress disorder.

Science.gov (United States)

Bracha, H Stefan

2006-07-01

The DSM-III, DSM-IV, DSM-IV-TR and ICD-10 have judiciously minimized discussion of etiologies to distance clinical psychiatry from Freudian psychoanalysis. With this goal mostly achieved, discussion of etiological factors should be reintroduced into the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-V). A research agenda for the DSM-V advocated the "development of a pathophysiologically based classification system". The author critically reviews the neuroevolutionary literature on stress-induced and fear circuitry disorders and related amygdala-driven, species-atypical fear behaviors of clinical severity in adult humans. Over 30 empirically testable/falsifiable predictions are presented. It is noted that in DSM-IV-TR and ICD-10, the classification of stress and fear circuitry disorders is neither mode-of-acquisition-based nor brain-evolution-based. For example, snake phobia (innate) and dog phobia (overconsolidational) are clustered together. Similarly, research on blood-injection-injury-type-specific phobia clusters two fears different in their innateness: 1) an arguably ontogenetic memory-trace-overconsolidation-based fear (hospital phobia) and 2) a hardwired (innate) fear of the sight of one's blood or a sharp object penetrating one's skin. Genetic architecture-charting of fear-circuitry-related traits has been challenging. Various, non-phenotype-based architectures can serve as targets for research. In this article, the author will propose one such alternative genetic architecture. This article was inspired by the following: A) Nesse's "Smoke-Detector Principle", B) the increasing suspicion that the "smooth" rather than "lumpy" distribution of complex psychiatric phenotypes (including fear-circuitry disorders) may in some cases be accounted for by oligogenic (and not necessarily polygenic) transmission, and C) insights from the initial sequence of the chimpanzee genome and comparison with the human genome by the Chimpanzee Sequencing

Lightweight Battery Charge Regulator Used to Track Solar Array Peak Power

Science.gov (United States)

Soeder, James F.; Button, Robert M.

1999-01-01

A battery charge regulator based on the series-connected boost regulator (SCBR) technology has been developed for high-voltage spacecraft applications. The SCBR regulates the solar array power during insolation to prevent battery overcharge or undercharge conditions. It can also be used to provide regulated battery output voltage to spacecraft loads if necessary. This technology uses industry-standard dc-dc converters and a unique interconnection to provide size, weight, efficiency, fault tolerance, and modularity benefits over existing systems. The high-voltage SCBR shown in the photograph has demonstrated power densities of over 1000 watts per kilogram (W/kg). Using four 150-W dc-dc converter modules, it can process 2500 W of power at 120 Vdc with a minimum input voltage of 90 Vdc. Efficiency of the SCBR was 94 to 98 percent over the entire operational range. Internally, the unit is made of two separate SCBR s, each with its own analog control circuitry, to demonstrate the modularity of the technology. The analog controllers regulate the output current and incorporate the output voltage limit with active current sharing between the two units. They also include voltage and current telemetry, on/off control, and baseplate temperature sensors. For peak power tracking, the SCBR was connected to a LabView-based data acquisition system for telemetry and control. A digital control algorithm for tracking the peak power point of a solar array was developed using the principle of matching the source impedance with the load impedance for maximum energy transfer. The algorithm was successfully demonstrated in a simulated spacecraft electrical system at the Boeing PhantomWorks High Voltage Test Facility in Seattle, Washington. The system consists of a 42-string, high-voltage solar array simulator, a 77-cell, 80-ampere-hour (A-hr) nickel-hydrogen battery, and a constant power-load module. The SCBR and the LabView control algorithm successfully tracked the solar array peak

A Developmental Neuroscience of Borderline Pathology: Emotion Dysregulation and Social Baseline Theory

Science.gov (United States)

Hughes, Amy E.; Crowell, Sheila E.; Uyeji, Lauren; Coan, James A.

2012-01-01

Theoretical and empirical research has linked poor emotion regulation abilities with dysfunctional frontolimbic circuitry. Consistent with this, research on borderline personality disorder (BPD) finds that frontolimbic dysfunction is a predominant neural substrate underlying the disorder. Emotion regulation is profoundly compromised in BPD.…

Thermionic integrated circuit technology for high power space applications

International Nuclear Information System (INIS)

Yadavalli, S.R.

1984-01-01

Thermionic triode and integrated circuit technology is in its infancy and it is emerging. The Thermionic triode can operate at relatively high voltages (up to 2000V) and at least tens of amperes. These devices, including their use in integrated circuitry, operate at high temperatures (800 0 C) and are very tolerant to nuclear and other radiations. These properties can be very useful in large space power applications such as that represented by the SP-100 system which uses a nuclear reactor. This paper presents an assessment of the application of thermionic integrated circuitry with space nuclear power system technology. A comparison is made with conventional semiconductor circuitry considering a dissipative shunt regulator for SP-100 type nuclear power system rated at 100 kW. The particular advantages of thermionic circuitry are significant reductions in size and mass of heat dissipation and radiation shield subsystems

Regulation of alternative splicing of Slo K+ channels in adrenal and pituitary during the stress-hyporesponsive period of rat development.

Science.gov (United States)

Lai, Guey-Jen; McCobb, David P

2006-08-01

Stress triggers release of ACTH from the pituitary, glucocorticoids from the adrenal cortex, and epinephrine from the adrenal medulla. Although functions differ, these hormone systems interact in many ways. Previous evidence indicates that pituitary and steroid hormones regulate alternative splicing of the Slo gene at the stress axis-regulated exon (STREX), with functional implications for the calcium-activated K+ channels prominent in adrenal medullary and pituitary cells. Here we examine the role of corticosterone in Slo splicing regulation in pituitary and adrenal tissues during the stress-hyporesponsive period of early rat postnatal life. The sharp drop in plasma corticosterone (CORT) that defines this period offers a unique opportunity to test CORT's role in Slo splicing. We report that in both adrenal and pituitary tissues, the percentage of Slo transcripts having STREX declines and recovers in parallel with CORT. Moreover, addition of 500 nm CORT to cultures of anterior pituitary cells from 13-, 21-, and 30-d postnatal animals increased the percentage of Slo transcripts with STREX, whereas 20 microm CORT reduced STREX representation. Applied to adrenal chromaffin cells, 20 microm CORT decreased STREX inclusion, whereas neither 500 nm nor 2 microm had any effect. The mineralocorticoid receptor antagonist RU28318 abolished the effect of 500 nm CORT on splicing in pituitary cells, whereas the glucocorticoid receptor antagonist RU38486 blocked the effect of 20 microm CORT on adrenal chromaffin cells. These results support the hypothesis that the abrupt, transient drop in CORT during the stress-hyporesponsive period drives the transient decline in STREX splice variant representation in pituitary, but not adrenal.

Impaired neural structure and function contributing to autonomic symptoms in congenital central hypoventilation syndrome.

Science.gov (United States)

Harper, Ronald M; Kumar, Rajesh; Macey, Paul M; Harper, Rebecca K; Ogren, Jennifer A

2015-01-01

Congenital central hypoventilation syndrome (CCHS) patients show major autonomic alterations in addition to their better-known breathing deficiencies. The processes underlying CCHS, mutations in the PHOX2B gene, target autonomic neuronal development, with frame shift extent contributing to symptom severity. Many autonomic characteristics, such as impaired pupillary constriction and poor temperature regulation, reflect parasympathetic alterations, and can include disturbed alimentary processes, with malabsorption and intestinal motility dyscontrol. The sympathetic nervous system changes can exert life-threatening outcomes, with dysregulation of sympathetic outflow leading to high blood pressure, time-altered and dampened heart rate and breathing responses to challenges, cardiac arrhythmia, profuse sweating, and poor fluid regulation. The central mechanisms contributing to failed autonomic processes are readily apparent from structural and functional magnetic resonance imaging studies, which reveal substantial cortical thinning, tissue injury, and disrupted functional responses in hypothalamic, hippocampal, posterior thalamic, and basal ganglia sites and their descending projections, as well as insular, cingulate, and medial frontal cortices, which influence subcortical autonomic structures. Midbrain structures are also compromised, including the raphe system and its projections to cerebellar and medullary sites, the locus coeruleus, and medullary reflex integrating sites, including the dorsal and ventrolateral medullary nuclei. The damage to rostral autonomic sites overlaps metabolic, affective and cognitive regulatory regions, leading to hormonal disruption, anxiety, depression, behavioral control, and sudden death concerns. The injuries suggest that interventions for mitigating hypoxic exposure and nutrient loss may provide cellular protection, in the same fashion as interventions in other conditions with similar malabsorption, fluid turnover, or hypoxic exposure.

Impaired Neural Structure and Function Contributing to Autonomic Symptoms in Congenital Central Hypoventilation Syndrome

Directory of Open Access Journals (Sweden)

Ronald M Harper

2015-10-01

Full Text Available Congenital central hypoventilation syndrome (CCHS patients show major autonomic alterations in addition to their better-known breathing deficiencies. The processes underlying CCHS, mutations in the PHOX2B gene, target autonomic neuronal development, with frame shift extent contributing to symptom severity. Many autonomic characteristics, such as impaired pupillary constriction and poor temperature regulation, reflect parasympathetic alterations, and can include disturbed alimentary processes, with malabsorption and intestinal motility dyscontrol. The sympathetic nervous system changes can exert life-threatening outcomes, with dysregulation of sympathetic outflow leading to high blood pressure, time-altered and dampened heart rate and breathing responses to challenges, cardiac arrhythmia, profuse sweating, and poor fluid regulation. The central mechanisms contributing to failed autonomic processes are readily apparent from structural and functional magnetic resonance imaging studies, which reveal substantial cortical thinning, tissue injury, and disrupted functional responses in hypothalamic, hippocampal, posterior thalamic, and basal ganglia sites and their descending projections, as well as insular, cingulate, and medial frontal cortices, which influence subcortical autonomic structures. Midbrain structures are also compromised, including the raphe system and its projections to cerebellar and medullary sites, the locus coeruleus, and medullary reflex integrating sites, including the dorsal and ventrolateral medullary nuclei. The damage to rostral autonomic sites overlaps metabolic, affective and cognitive regulatory regions, leading to hormonal disruption, anxiety, depression, behavioral control, and sudden death concerns. The injuries suggest that interventions for mitigating hypoxic exposure and nutrient loss may provide cellular protection, in the same fashion as interventions in other conditions with similar malabsorption, fluid turnover

Neural circuitry of abdominal pain-related fear learning and reinstatement in irritable bowel syndrome.

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Icenhour, A; Langhorst, J; Benson, S; Schlamann, M; Hampel, S; Engler, H; Forsting, M; Elsenbruch, S

2015-01-01

Altered pain anticipation likely contributes to disturbed central pain processing in chronic pain conditions like irritable bowel syndrome (IBS), but the learning processes shaping the expectation of pain remain poorly understood. We assessed the neural circuitry mediating the formation, extinction, and reactivation of abdominal pain-related memories in IBS patients compared to healthy controls (HC) in a differential fear conditioning paradigm. During fear acquisition, predictive visual cues (CS(+)) were paired with rectal distensions (US), while control cues (CS(-)) were presented unpaired. During extinction, only CSs were presented. Subsequently, memory reactivation was assessed with a reinstatement procedure involving unexpected USs. Using functional magnetic resonance imaging, group differences in neural activation to CS(+) vs CS(-) were analyzed, along with skin conductance responses (SCR), CS valence, CS-US contingency, state anxiety, salivary cortisol, and alpha-amylase activity. The contribution of anxiety symptoms was addressed in covariance analyses. Fear acquisition was altered in IBS, as indicated by more accurate contingency awareness, greater CS-related valence change, and enhanced CS(+)-induced differential activation of prefrontal cortex and amygdala. IBS patients further revealed enhanced differential cingulate activation during extinction and greater differential hippocampal activation during reinstatement. Anxiety affected neural responses during memory formation and reinstatement. Abdominal pain-related fear learning and memory processes are altered in IBS, mediated by amygdala, cingulate cortex, prefrontal areas, and hippocampus. Enhanced reinstatement may contribute to hypervigilance and central pain amplification, especially in anxious patients. Preventing a 'relapse' of learned fear utilizing extinction-based interventions may be a promising treatment goal in IBS. © 2014 John Wiley & Sons Ltd.

The banana code – Natural blend processing in the olfactory circuitry of Drosophila melanogaster

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Marco eSchubert

2014-02-01

Full Text Available Odor information is predominantly perceived as complex odor blends. For Drosophila melanogaster one of the most attractive blends is emitted by an over-ripe banana. To analyze how the fly’s olfactory system processes natural blends we combined the experimental advantages of gas chromatography and functional imaging (GC-I. In this way, natural banana compounds were presented successively to the fly antenna in close to natural occurring concentrations. This technique allowed us to identify the active odor components, use these compounds as stimuli and measure odor-induced Ca2+ signals in input and output neurons of the Drosophila antennal lobe (AL, the first olfactory neuropil. We demonstrate that mixture interactions of a natural blend are very rare and occur only at the AL output level resulting in a surprisingly linear blend representation. However, the information regarding single components is strongly modulated by the olfactory circuitry within the AL leading to a higher similarity between the representation of individual components and the banana blend. This observed modulation might tune the olfactory system in a way to distinctively categorize odor components and improve the detection of suitable food sources. Functional GC-I thus enables analysis of virtually any unknown natural odorant blend and its components in their relative occurring concentrations and allows characterization of neuronal responses of complete neural assemblies. This technique can be seen as a valuable complementary method to classical GC/electrophysiology techniques, and will be a highly useful tool in future investigations of insect-insect and insect-plant chemical interactions.

MicroRNAs as Regulators of Adipogenic Differentiation of Mesenchymal Stem Cells

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Hamam, Dana; Ali, Dalia; Kassem, Moustapha

2015-01-01

MicroRNAs (miRNAs) constitute complex regulatory network, fine tuning the expression of a myriad of genes involved in different biological and physiological processes, including stem cell differentiation. Mesenchymal stem cells (MSCs) are multipotent stem cells present in the bone marrow stroma......, and the stroma of many other tissues, and can give rise to a number of mesoderm-type cells including adipocytes and osteoblasts, which form medullary fat and bone tissues, respectively. The role of bone marrow fat in bone mass homeostasis is an area of intensive investigation with the aim of developing novel...

Sensory integration regulating male courtship behavior in Drosophila.

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Dimitrije Krstic

Full Text Available The courtship behavior of Drosophila melanogaster serves as an excellent model system to study how complex innate behaviors are controlled by the nervous system. To understand how the underlying neural network controls this behavior, it is not sufficient to unravel its architecture, but also crucial to decipher its logic. By systematic analysis of how variations in sensory inputs alter the courtship behavior of a naïve male in the single-choice courtship paradigm, we derive a model describing the logic of the network that integrates the various sensory stimuli and elicits this complex innate behavior. This approach and the model derived from it distinguish (i between initiation and maintenance of courtship, (ii between courtship in daylight and in the dark, where the male uses a scanning strategy to retrieve the decamping female, and (iii between courtship towards receptive virgin females and mature males. The last distinction demonstrates that sexual orientation of the courting male, in the absence of discriminatory visual cues, depends on the integration of gustatory and behavioral feedback inputs, but not on olfactory signals from the courted animal. The model will complement studies on the connectivity and intrinsic properties of the neurons forming the circuitry that regulates male courtship behavior.

X-ray tube current control

International Nuclear Information System (INIS)

Dupuis, W.A.; Resnick, T.A.

1982-01-01

A closed loop feedback system for controlling the current output of an x-ray tube. The system has circuitry for improving the transient response and stability of the x-ray tube current over a substantial nonlinear portion of the tube current production characteristic. The system includes a reference generator for applying adjustable step function reference signals representing desired tube currents. The system also includes means for instantaneous sensing of actual tube current. An error detector compares the value of actual and reference tube current and produces an error signal as a function of their difference. The system feedback loop includes amplification circuitry for controlling x-ray tube filament dc voltage to regulate tube current as a function of the error signal value. The system also includes compensation circuitry, between the reference generator and the amplification circuitry, to vary the loop gain of the feedback control system as a function of the reference magnitude

A systematic review of the neural bases of psychotherapy for anxiety and related disorders.

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Brooks, Samantha J; Stein, Dan J

2015-09-01

Brain imaging studies over two decades have delineated the neural circuitry of anxiety and related disorders, particularly regions involved in fear processing and in obsessive-compulsive symptoms. The neural circuitry of fear processing involves the amygdala, anterior cingulate, and insular cortex, while cortico-striatal-thalamic circuitry plays a key role in obsessive-compulsive disorder. More recently, neuroimaging studies have examined how psychotherapy for anxiety and related disorders impacts on these neural circuits. Here we conduct a systematic review of the findings of such work, which yielded 19 functional magnetic resonance imaging studies examining the neural bases of cognitive-behavioral therapy (CBT) in 509 patients with anxiety and related disorders. We conclude that, although each of these related disorders is mediated by somewhat different neural circuitry, CBT may act in a similar way to increase prefrontal control of subcortical structures. These findings are consistent with an emphasis in cognitive-affective neuroscience on the potential therapeutic value of enhancing emotional regulation in various psychiatric conditions.

Taste Reward Circuitry Related Brain Structures Characterize Ill and Recovered Anorexia Nervosa and Bulimia Nervosa

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Frank, Guido K.; Shott, Megan E.; Hagman, Jennifer O.; Mittal, Vijay A.

2013-01-01

Objective The pathophysiology of the eating disorder anorexia nervosa remains obscure, but structural brain alterations could be functionally important biomarkers. Here we assessed taste pleasantness and reward sensitivity in relation to brain structure, which might be related to food avoidance commonly seen in eating disorders. Method We used structural magnetic resonance brain imaging to study gray and white matter volumes in individuals with restricting type currently ill (n = 19) or recovered-anorexia nervosa (n = 24), bulimia nervosa (n= 19) and healthy control women (n=24). Results All eating disorder groups showed increased gray matter volume of the medial orbitofrontal cortex (gyrus rectus). Manually tracing confirmed larger gyrus rectus volume, and predicted taste pleasantness across all groups. The analyses also indicated other morphological differences between diagnostic categories: Ill and recovered-anorexia nervosa had increased right, while bulimia nervosa had increased left antero-ventral insula gray matter volumes compared to controls. Furthermore, dorsal striatum volumes were reduced in recovered-anorexia and bulimia nervosa, and predicted sensitivity to reward in the eating disorder groups. The eating disorder groups also showed reduced white matter in right temporal and parietal areas when compared to healthy controls. Notably, the results held when controlling for a range of covariates (e.g., age, depression, anxiety, medications). Conclusion Brain structure in medial orbitofrontal cortex, insula and striatum is altered in eating disorders and suggests altered brain circuitry that has been associated with taste pleasantness and reward value. PMID:23680873

Intramedullary tuberculoma: A case report

International Nuclear Information System (INIS)

Maamar, M.; El Quessar, A.; El Fatemi, N.; El Hassani, My R.; Chakir, N.; Jiddane, M.

2007-01-01

Study design: We report a case of intra-medullary tuberculoma in a 22 year-old man with progressive paraparesis and sphincter dysfunction. Objectives: To present a case of intra-medullary tuberculosis and to describe the MRI's contribution to the diagnosis. Summary of background data: Intra-medullary spinal tuberculoma is a rare form of central nervous system tuberculosis. The subject and diagnosis methods: The patient, a 22 year-old man, presented with an intra-medullary tuberculoma of the dorsal spinal cord diagnosed after 6 month history of progressive paraparesis and sphincter dysfunction. MRI visualized ring enhancement of the intra-medullary dorsal lesion. Results: Total resection of the intra-medullary mass was performed through a posterior myelotomy. Histological examination revealed a granulomatous necrosis with caseum. The patient was treated with four anti-tuberculosis drugs in association with corticotherapy. The paraparesis and sphincter dysfunction improved. Conclusions: Intra-medullary spinal tuberculoma is rare, but must be considered in the differential diagnosis of spinal cord compression

Neurocircuitry of drug reward

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Ikemoto, Satoshi; Bonci, Antonello

2013-01-01

In recent years, neuroscientists have produced profound conceptual and mechanistic advances on the neurocircuitry of reward and substance use disorders. Here, we will provide a brief review of intracranial drug self-administration and optogenetic self-stimulation studies that identified brain regions and neurotransmitter systems involved in drug- and reward-related behaviors. Also discussed is a theoretical framework that helps to understand the functional properties of the circuitry involved in these behaviors. The circuitry appears to be homeostatically regulated and mediate anticipatory processes that regulate behavioral interaction with the environment in response to salient stimuli. That is, abused drugs or, at least, some may act on basic motivation and mood processes, regulating behavior-environment interaction. Optogenetics and related technologies have begun to uncover detailed circuit mechanisms linking key brain regions in which abused drugs act for rewarding effects. PMID:23664810

Optogenetic deconstruction of sleep-wake circuitry in the brain

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Antoine Adamantidis

2010-01-01

Full Text Available How does the brain regulate the sleep-wake cycle? What are the temporal codes of sleep- and wake-promoting neural circuits? How do these circuits interact with each other across the light/dark cycle? Over the past few decades, many studies from a variety of disciplines have made substantial progress in answering these fundamental questions. For example, neurobiologists have identified multiple, redundant wake-promoting circuits in the brainstem, hypothalamus, and basal forebrain. Sleep-promoting circuits have been found in the preoptic area and hypothalamus. One of the greatest challenges in recent years has been to selectively record and manipulate these sleep-wake centers in vivo with high spatial and temporal resolution. Recent developments in microbial opsin-based neuromodulation tools, collectively referred to as “optogenetics,” have provided a novel method to demonstrate causal links between neural activity and specific behaviors. Here, we propose to use optogenetics as a fundamental tool to probe the necessity, sufficiency, and connectivity of defined neural circuits in the regulation of sleep and wakefulness.

Early Forming a Hummingbird-like Hovering Neural Network Circuitry Pattern with Reentrant Spatiotemporal Energy-Sensory Orientation Privileged to Avoid “Epilepsy” Based on a Biomimetic Acetylcholinesterase Memcapacitor Prosthesis

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Ellen T. Chen

2015-08-01

Full Text Available The hummingbird’s significant asymmetry hovering flight with energy conservation pattern is remarkable among all vertebrates. However, little is known to human’s neuronal network circuitry current flow pattern for whether or not has this privilege during slow wave sleeping (SWS. What is the advantage in order to avoid diseases if we have this network pattern ? A memory device was developed with nanostructured biomimetic acetylcholinesterase (ACHE gorge membrane on gold chips as memcapacitor 1, served as a normal brain network prosthesis, compared with a mutated ACHE prosthesis as device 2, for evaluation of neuronal network circuitry integrity in the presence of Amyloid- beta (Ab under the conditions of free from tracers and antibodies in spiked NIST SRM 965A human serum. Three categories of Reentrant Energy-Sensory images are presented based on infused brain pulse energies in a matrix of “Sensory Biomarkers” having frequencies over 0.25-333 Hz at free and fixed Ab levels, respectively. Early non-symptomatic epilepsy was indentified and predicted by device 2 due to Pathological High Frequency Oscillation (pHFO and large areas of 38 µM Ab re-depositions. Device 1 sensitively “feels” Ab damage because of its Frequency Oscillation (HFO enhanced the hummingbird- like hovering pattern with higher reentrant energy sensitivity of 0.12 pj/bit/s/µm3 without Ab compared with Ab, 13 aj/bit/s/µm3/nM over 3.8-471 nM range over 0.003-4s. Device 1 reliably detected early CR dysfunction privileged to avoid epilepsy.

Renal water molecular diffusion characteristics in healthy native kidneys: assessment with diffusion tensor MR imaging.

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Zhenfeng Zheng

Full Text Available BACKGROUND: To explore the characteristics of diffusion tensor imaging (DTI and magnetic resonance (MR imaging in healthy native kidneys. METHODS: Seventy-three patients without chronic kidney disease underwent DTI-MRI with spin echo-echo planar (SE-EPI sequences accompanied by an array spatial sensitivity encoding technique (ASSET. Cortical and medullary mean, axial and radial diffusivity (MD, AD and RD, fractional anisotropy (FA and primary, secondary and tertiary eigenvalues (λ1, λ2, λ3 were analysed in both kidneys and in different genders. RESULTS: Cortical MD, λ2, λ3, and RD values were higher than corresponding medullary values. The cortical FA value was lower than the medullary FA value. Medullary λ1 and RD values in the left kidney were lower than in the right kidney. Medullary λ2, and λ3 values in women were higher than those in men. Medullary FA values in women were lower than those in men. Medullary FA (r = 0.351, P = 0.002 and λ1 (r = 0.277, P = 0.018 positively correlated with eGFR. Medullary FA (r = -0.25, P = 0.033 negatively correlated with age. CONCLUSIONS: Renal water molecular diffusion differences exist in human kidneys and genders. Age and eGFR correlate with medullary FA and primary eigenvalue.

Axitinib treatment in advanced RAI-resistant differentiated thyroid cancer (DTC) and refractory medullary thyroid cancer (MTC).

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Capdevila, Jaume; Trigo, José Manuel; Aller, Javier; Manzano, José Luís; Adrián, Silvia García; Llopis, Carles Zafón; Reig, Òscar; Bohn, Uriel; Cajal, Teresa Ramón Y; Duran-Poveda, Manuel; Astorga, Beatriz González; López-Alfonso, Ana; Martínez, Javier Medina; Porras, Ignacio; Reina, Juan Jose; Palacios, Nuria; Grande, Enrique; Cillán, Elena; Matos, Ignacio; Grau, Juan Jose

2017-10-01

Axitinib, an antiangiogenic multikinase inhibitor (MKI), was evaluated in the compassionate use programme (CUP) in Spain (October 2012-November 2014). 47 patients with advanced radioactive iodine (RAI)-refractory differentiated thyroid cancer (DTC, n  = 34) or medullary thyroid cancer (MTC, n  = 13) with documented disease progression were treated with axitinib 5 mg b.i.d. The primary efficacy endpoint was objective response rate (ORR) by Response Evaluation Criteria In Solid Tumors (RECIST) v1.1. Progression-free survival (PFS) and adverse events (AEs) were secondary objectives. Regulatory authorities validated the CUP, and all patients signed informed consent form. Axitinib was administered as first-line therapy in 17 patients (36.2%), as second-line in 18 patients (38.3%) and as third/fourth-line in 12 patients (25.5%). With a median follow-up of 11.5 months (0-24.3), ORR was 27.7% (DTC: 29.4% and MTC: 23.1%) and median PFS was 8.1 months (95% CI: 4.1-12.2) (DTC: 7.4 months (95% CI: 3.1-11.8) and MTC: 9.4 months (95% CI: 4.8-13.9)). Better outcomes were reported with first-line axitinib, with an ORR of 53% and a median PFS of 13.6 months compared with 16.7% and 10.6 months as second-line treatment. Twelve (25.5%) patients required dose reduction to 3 mg b.i.d. All-grade AEs included asthenia (53.2%), diarrhoea (36.2%), hypertension (31.9%) and mucositis (29.8%); grade 3/4 AEs included anorexia (6.4%), diarrhoea (4.3%) and cardiac toxicity (4.3%). Axitinib had a tolerable safety profile and clinically meaningful activity in refractory and progressive thyroid cancer regardless of histology as first-line therapy. To our knowledge, this is the first time that cross-resistance between MKIs is suggested in thyroid cancer, highlighting the importance of prospective sequential clinical studies. © 2017 European Society of Endocrinology.

Phosphodiesterase 9A regulates central cGMP and modulates responses to cholinergic and monoaminergic perturbation in vivo.

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Kleiman, Robin J; Chapin, Douglas S; Christoffersen, Curt; Freeman, Jody; Fonseca, Kari R; Geoghegan, Kieran F; Grimwood, Sarah; Guanowsky, Victor; Hajós, Mihály; Harms, John F; Helal, Christopher J; Hoffmann, William E; Kocan, Geralyn P; Majchrzak, Mark J; McGinnis, Dina; McLean, Stafford; Menniti, Frank S; Nelson, Fredrick; Roof, Robin; Schmidt, Anne W; Seymour, Patricia A; Stephenson, Diane T; Tingley, Francis David; Vanase-Frawley, Michelle; Verhoest, Patrick R; Schmidt, Christopher J

2012-05-01

Cyclic nucleotides are critical regulators of synaptic plasticity and participate in requisite signaling cascades implicated across multiple neurotransmitter systems. Phosphodiesterase 9A (PDE9A) is a high-affinity, cGMP-specific enzyme widely expressed in the rodent central nervous system. In the current study, we observed neuronal staining with antibodies raised against PDE9A protein in human cortex, cerebellum, and subiculum. We have also developed several potent, selective, and brain-penetrant PDE9A inhibitors and used them to probe the function of PDE9A in vivo. Administration of these compounds to animals led to dose-dependent accumulation of cGMP in brain tissue and cerebrospinal fluid, producing a range of biological effects that implied functional significance for PDE9A-regulated cGMP in dopaminergic, cholinergic, and serotonergic neurotransmission and were consistent with the widespread distribution of PDE9A. In vivo effects of PDE9A inhibition included reversal of the respective disruptions of working memory by ketamine, episodic and spatial memory by scopolamine, and auditory gating by amphetamine, as well as potentiation of risperidone-induced improvements in sensorimotor gating and reversal of the stereotypic scratching response to the hallucinogenic 5-hydroxytryptamine 2A agonist mescaline. The results suggested a role for PDE9A in the regulation of monoaminergic circuitry associated with sensory processing and memory. Thus, PDE9A activity regulates neuronal cGMP signaling downstream of multiple neurotransmitter systems, and inhibition of PDE9A may provide therapeutic benefits in psychiatric and neurodegenerative diseases promoted by the dysfunction of these diverse neurotransmitter systems.

Bilingualism yields language-specific plasticity in left hemisphere's circuitry for learning to read in young children.

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Jasińska, K K; Berens, M S; Kovelman, I; Petitto, L A

2017-04-01

How does bilingual exposure impact children's neural circuitry for learning to read? Theories of bilingualism suggests that exposure to two languages may yield a functional and neuroanatomical adaptation to support the learning of two languages (Klein et al., 2014). To test the hypothesis that this neural adaptation may vary as a function of structural and orthographic characteristics of bilinguals' two languages, we compared Spanish-English and French-English bilingual children, and English monolingual children, using functional Near Infrared Spectroscopy neuroimaging (fNIRS, ages 6-10, N =26). Spanish offers consistent sound-to-print correspondences ("phonologically transparent" or "shallow"); such correspondences are more opaque in French and even more opaque in English (which has both transparent and "phonologically opaque" or "deep" correspondences). Consistent with our hypothesis, both French- and Spanish-English bilinguals showed hyperactivation in left posterior temporal regions associated with direct sound-to-print phonological analyses and hypoactivation in left frontal regions associated with assembled phonology analyses. Spanish, but not French, bilinguals showed a similar effect when reading Irregular words. The findings inform theories of bilingual and cross-linguistic literacy acquisition by suggesting that structural characteristics of bilinguals' two languages and their orthographies have a significant impact on children's neuro-cognitive architecture for learning to read. Copyright © 2016 The Authors. Published by Elsevier Ltd.. All rights reserved.

PV Interneurons: Critical Regulators of E/I Balance for Prefrontal Cortex-Dependent Behavior and Psychiatric Disorders

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Brielle R. Ferguson

2018-05-01

Full Text Available Elucidating the prefrontal cortical microcircuit has been challenging, given its role in multiple complex behaviors, including working memory, cognitive flexibility, attention, social interaction and emotional regulation. Additionally, previous methodological limitations made it difficult to parse out the contribution of certain neuronal subpopulations in refining cortical representations. However, growing evidence supports a fundamental role of fast-spiking parvalbumin (PV GABAergic interneurons in regulating pyramidal neuron activity to drive appropriate behavioral responses. Further, their function is heavily diminished in the prefrontal cortex (PFC in numerous psychiatric diseases, including schizophrenia and autism. Previous research has demonstrated the importance of the optimal balance of excitation and inhibition (E/I in cortical circuits in maintaining the efficiency of cortical information processing. Although we are still unraveling the mechanisms of information representation in the PFC, the E/I balance seems to be crucial, as pharmacological, chemogenetic and optogenetic approaches for disrupting E/I balance induce impairments in a range of PFC-dependent behaviors. In this review, we will explore two key hypotheses. First, PV interneurons are powerful regulators of E/I balance in the PFC, and help optimize the representation and processing of supramodal information in PFC. Second, diminishing the function of PV interneurons is sufficient to generate an elaborate symptom sequelae corresponding to those observed in a range of psychiatric diseases. Then, using this framework, we will speculate on whether this circuitry could represent a platform for the development of therapeutic interventions in disorders of PFC function.

Angiotensin II and Renal Tubular Ion Transport

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Patricia Valles

2005-01-01

Evidence for the regulation of H+-ATPase activity in vivo and in vitro by trafficking/exocytosis has been provided. An additional level of H+-ATPase regulation via protein synthesis may be important as well. Recently, we have shown that both aldosterone and angiotensin II provide such a mechanism of regulation in vivo at the level of the medullary collecting tubule. Interestingly, in this part of the nephron, the effects of aldosterone and angiotensin II are not sodium dependent, whereas in the cortical collecting duct, both aldosterone and angiotensin II, by contrast, affect H+ secretion by sodium-dependent mechanisms.

Associação entre o ângulo de Norberg, o percentual de cobertura da cabeça femoral, o índice cortical e o ângulo de inclinação em cães com displasia coxofemoral Associations among Norberg angle, percentage of femoral head coverage, cortico-medullary index, and femoral inclination angle in dogs with hip dysplasia

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G.L.T. Vieira

2010-10-01

Full Text Available Foram avaliadas 386 radiografias da articulação coxofemoral, sendo 220 de cães da raça Pastor Alemão, 112 machos e 108 fêmeas, e 166 da raça Labrador Retriever, 69 machos e 97 fêmeas. As radiografias foram classificadas segundo o grau de displasia coxofemoral (DCF, e foram mensurados o ângulo de inclinação, o ângulo de Norberg, o índice cortical e o percentual de cobertura da cabeça femoral de ambos os lados. As variáveis foram associadas mediante análise estatística multivariada de componentes principais. As variáveis índice cortical e ângulo de inclinação foram inversamente associadas. A raça Pastor Alemão apresentou valores de índice cortical e graus de DCF mais baixos em relação à raça Labrador Retriever. Maior ângulo de inclinação foi associado a menor ângulo de Norberg e menor percentual de cobertura. Animais mais velhos apresentaram menor ângulo de Norberg, menor porcentagem de cobertura e maior grau de DCF. Nas fêmeas, foram observados menor porcentagem de cobertura, menor ângulo de Norberg e maior grau de DCF. Pode-se concluir que o ângulo de inclinação e o índice cortical não demonstraram associação com a DCF.A total of 386 radiographs of the pelvis were evaluated, being 220 of German Shepherd dogs (112 males and 108 females and 166 of Labrador Retrievers (69 males and 97 females. The radiographs were degree classified regarding the of hip dysplasia (DHD. The Norberg and inclination angles, the cortico-medullary index, and the percentage coverage of the femoral head were measured and associated using multivariate statistical technique (principal component analysis. The cortico-medullary index and the inclination angle were inversely associated. The results indicated that German Shepherd Dogs showed lower cortico-medullary index and DHD compared with Labrador Retrievers. The higher the inclination angle, the lower the Norberg angle and percentage coverage of the femoral head. It was observed

Neurocognitive and electrophysiological evidence of altered face processing in parents of children with autism: implications for a model of abnormal development of social brain circuitry in autism.

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Dawson, Geraldine; Webb, Sara Jane; Wijsman, Ellen; Schellenberg, Gerard; Estes, Annette; Munson, Jeffrey; Faja, Susan

2005-01-01

Neuroimaging and behavioral studies have shown that children and adults with autism have impaired face recognition. Individuals with autism also exhibit atypical event-related brain potentials to faces, characterized by a failure to show a negative component (N170) latency advantage to face compared to nonface stimuli and a bilateral, rather than right lateralized, pattern of N170 distribution. In this report, performance by 143 parents of children with autism on standardized verbal, visual-spatial, and face recognition tasks was examined. It was found that parents of children with autism exhibited a significant decrement in face recognition ability relative to their verbal and visual spatial abilities. Event-related brain potentials to face and nonface stimuli were examined in 21 parents of children with autism and 21 control adults. Parents of children with autism showed an atypical event-related potential response to faces, which mirrored the pattern shown by children and adults with autism. These results raise the possibility that face processing might be a functional trait marker of genetic susceptibility to autism. Discussion focuses on hypotheses regarding the neurodevelopmental and genetic basis of altered face processing in autism. A general model of the normal emergence of social brain circuitry in the first year of life is proposed, followed by a discussion of how the trajectory of normal development of social brain circuitry, including cortical specialization for face processing, is altered in individuals with autism. The hypothesis that genetic-mediated dysfunction of the dopamine reward system, especially its functioning in social contexts, might account for altered face processing in individuals with autism and their relatives is discussed.

Determining the control circuitry of redox metabolism at the genome-scale.

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Stephen Federowicz

2014-04-01

Full Text Available Determining how facultative anaerobic organisms sense and direct cellular responses to electron acceptor availability has been a subject of intense study. However, even in the model organism Escherichia coli, established mechanisms only explain a small fraction of the hundreds of genes that are regulated during electron acceptor shifts. Here we propose a qualitative model that accounts for the full breadth of regulated genes by detailing how two global transcription factors (TFs, ArcA and Fnr of E. coli, sense key metabolic redox ratios and act on a genome-wide basis to regulate anabolic, catabolic, and energy generation pathways. We first fill gaps in our knowledge of this transcriptional regulatory network by carrying out ChIP-chip and gene expression experiments to identify 463 regulatory events. We then interfaced this reconstructed regulatory network with a highly curated genome-scale metabolic model to show that ArcA and Fnr regulate >80% of total metabolic flux and 96% of differential gene expression across fermentative and nitrate respiratory conditions. Based on the data, we propose a feedforward with feedback trim regulatory scheme, given the extensive repression of catabolic genes by ArcA and extensive activation of chemiosmotic genes by Fnr. We further corroborated this regulatory scheme by showing a 0.71 r(2 (p<1e-6 correlation between changes in metabolic flux and changes in regulatory activity across fermentative and nitrate respiratory conditions. Finally, we are able to relate the proposed model to a wealth of previously generated data by contextualizing the existing transcriptional regulatory network.

From Belly to Brain: Targeting the Ghrelin Receptor in Appetite and Food Intake Regulation

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Ken Howick

2017-01-01

Full Text Available Ghrelin is the only known peripherally-derived orexigenic hormone, increasing appetite and subsequent food intake. The ghrelinergic system has therefore received considerable attention as a therapeutic target to reduce appetite in obesity as well as to stimulate food intake in conditions of anorexia, malnutrition and cachexia. As the therapeutic potential of targeting this hormone becomes clearer, it is apparent that its pleiotropic actions span both the central nervous system and peripheral organs. Despite a wealth of research, a therapeutic compound specifically targeting the ghrelin system for appetite modulation remains elusive although some promising effects on metabolic function are emerging. This is due to many factors, ranging from the complexity of the ghrelin receptor (Growth Hormone Secretagogue Receptor, GHSR-1a internalisation and heterodimerization, to biased ligand interactions and compensatory neuroendocrine outputs. Not least is the ubiquitous expression of the GHSR-1a, which makes it impossible to modulate centrallymediated appetite regulation without encroaching on the various peripheral functions attributable to ghrelin. It is becoming clear that ghrelin’s central signalling is critical for its effects on appetite, body weight regulation and incentive salience of food. Improving the ability of ghrelin ligands to penetrate the blood brain barrier would enhance central delivery to GHSR-1a expressing brain regions, particularly within the mesolimbic reward circuitry.

The correlation between dysphagia and involvement of the ambiguous nucleus on MRI in acute-phase lateral medullary syndrome

International Nuclear Information System (INIS)

Kurono, Hiroko; Uesaka, Yoshikazu; Kunimoto, Masanari; Imafuku, Ichirou

2006-01-01

In this study, the clinical features and MRI findings of 21 patients admitted for acute lateral medullary syndrome, including 10 patients with dysphagia, were examined. According to Cytoarchitecture of the Human Brain Stem (Olszewski, J and Baxter, D), MRI-identified lesions were classified into four groups based on their location (upper, middle-upper, middle-lower, and lower parts of the medulla oblongata). We also examined whether each lesion involved the ambiguous nucleus (AN). We then studied the correlation between dysphagia and involvement of the AN. Ten patients had dysphagia, which improved very quickly in all but one. In the horizontal plane, lesions of all patients with dysphagia exhibited AN involvement, suggesting that dysphagia is strongly correlated with AN involvement. Among the 8 patients with lesions in the upper part of the medulla oblongata, the lesions of 7 patients included the AN, and 6 of those 7 patients had dysphagia. Among the 5 patients with lesions in the middle-upper part of the medulla oblongata, the lesions of two contained the AN, and one of those two patients had dysphagia. Among the 6 patients with lesions in the middle-lower part of the medulla oblongata, all lesions contained the AN, but only 3 of the patients exhibited dysphagia. In both patients who had lesions in the lower part of the medulla oblongata, the lesions did not include the AN and neither patient had dysphagia. Patients who had lesions involving the AN in the rostral part of the medulla oblongata were more likely to have dysphagia than the other patients. On the other hand, half of the patients with lesions involving the AN in the middle-lower part of the medulla oblongata did not have dysphagia. This might suggest that the caudal part of the AN has little involvement in the mechanisms of dysphagia. (author)

Vandetanib in patients with locally advanced or metastatic medullary thyroid cancer: a randomized, double-blind phase III trial.

Science.gov (United States)

Wells, Samuel A; Robinson, Bruce G; Gagel, Robert F; Dralle, Henning; Fagin, James A; Santoro, Massimo; Baudin, Eric; Elisei, Rossella; Jarzab, Barbara; Vasselli, James R; Read, Jessica; Langmuir, Peter; Ryan, Anderson J; Schlumberger, Martin J

2012-01-10

There is no effective therapy for patients with advanced medullary thyroid carcinoma (MTC). Vandetanib, a once-daily oral inhibitor of RET kinase, vascular endothelial growth factor receptor, and epidermal growth factor receptor signaling, has previously shown antitumor activity in a phase II study of patients with advanced hereditary MTC. Patients with advanced MTC were randomly assigned in a 2:1 ratio to receive vandetanib 300 mg/d or placebo. On objective disease progression, patients could elect to receive open-label vandetanib. The primary end point was progression-free survival (PFS), determined by independent central Response Evaluation Criteria in Solid Tumors (RECIST) assessments. Between December 2006 and November 2007, 331 patients (mean age, 52 years; 90% sporadic; 95% metastatic) were randomly assigned to receive vandetanib (231) or placebo (100). At data cutoff (July 2009; median follow-up, 24 months), 37% of patients had progressed and 15% had died. The study met its primary objective of PFS prolongation with vandetanib versus placebo (hazard ratio [HR], 0.46; 95% CI, 0.31 to 0.69; P < .001). Statistically significant advantages for vandetanib were also seen for objective response rate (P < .001), disease control rate (P = .001), and biochemical response (P < .001). Overall survival data were immature at data cutoff (HR, 0.89; 95% CI, 0.48 to 1.65). A final survival analysis will take place when 50% of the patients have died. Common adverse events (any grade) occurred more frequently with vandetanib compared with placebo, including diarrhea (56% v 26%), rash (45% v 11%), nausea (33% v 16%), hypertension (32% v 5%), and headache (26% v 9%). Vandetanib demonstrated therapeutic efficacy in a phase III trial of patients with advanced MTC (ClinicalTrials.gov NCT00410761).

Glycogen synthase kinase 3α regulates urine concentrating mechanism in mice

DEFF Research Database (Denmark)

Nørregaard, Rikke; Tao, Shixin; Nilsson, Line

2015-01-01

vasopressin. When water deprived, they failed to concentrate their urine to the same level as WT littermates. The addition of 1-desamino-8-d-arginine vasopressin to isolated inner medullary collecting ducts increased the cAMP response in WT mice, but this response was reduced in GSK3αKO mice, suggesting......KO mice, the polyuric response was markedly reduced. This study demonstrates, for the first time, that GSK3α could play a crucial role in renal urine concentration and suggest that GSK3α might be one of the initial targets of Li(+) in LiCl-induced nephrogenic diabetes insipidus....

Autologous Adrenal Medullary, Fetal Mesencephalic, and Fetal Adrenal Brain Transplantation in Parkinson's Disease: A Long-Term Postoperative Follow-Up

Science.gov (United States)

Madrazo, Ignacio; Franco-Bourland, Rebecca; Aguilera, Maricarmen; Ostrosky-Solis, Feggy; Madrazo, Mario; Cuevas, Carlos; Catrejon, Hugo; Guizar-Zahagun, Gabriel; Magallon, Eduardo

1991-01-01

We report on the clinical status of 5 patients with Parkinson's disease (PD) 3 years after autologous adrenal medullary (AM)-to-caudate nucleus (CN) implanfion, and of 2 PD patients, 2 years after fetal ventral mesencephalon (VM)- and fetal adrenal (A)-to-CN homotransplantation. Current clinical evaluation of 4 of the AM grafted patients revealed sustained bilateral amelioration of their PD signs, most notably of rgidity, postural imbalance and gait disturbances, resulting in a substantial improvement in their quality of life. the disease-related dystonia of one of them disappeared only 2 years after surgery. The levodopa requirements of 2 of these patients and the anticholinergic therapy of another have been reduced. In agreement with the satisfactory clinical evaluation of these 4 patients, their neuropsychological and electrophysiological improvements, initially registered 3 months after surgery, have been maintained for 3 years. After 1 year of significant recovery, the 5th patient of this group has almost returned to her preoperative state. The 2 homotransplanted patients also showed sustained bilateral improvement of their PD signs. Two years after surgery, the most improved signs of the fetal VM case were rigidity, bradykinesia, postural imbalance, gait disturbances and facial expression. The fetal A case has only shown amelioration of rigidity and bradykinesia. Neither of them has shown significant neuropsychological changes. Their current levodopa requirements are less than before surgery. The improvements shown here by PD patients after brain tissue grafts go beyond those obtained using any other therapeutic approach, when levodopa fails. Although more studies and the development of these procedures are obviously required, these initial human trials appear to be resisting the test of time. PMID:1782251

Neural Mechanisms of Circadian Regulation of Natural and Drug Reward

Directory of Open Access Journals (Sweden)

Lauren M. DePoy

2017-01-01

Full Text Available Circadian rhythms are endogenously generated near 24-hour variations of physiological and behavioral functions. In humans, disruptions to the circadian system are associated with negative health outcomes, including metabolic, immune, and psychiatric diseases, such as addiction. Animal models suggest bidirectional relationships between the circadian system and drugs of abuse, whereby desynchrony, misalignment, or disruption may promote vulnerability to drug use and the transition to addiction, while exposure to drugs of abuse may entrain, disrupt, or perturb the circadian timing system. Recent evidence suggests natural (i.e., food and drug rewards may influence overlapping neural circuitry, and the circadian system may modulate the physiological and behavioral responses to these stimuli. Environmental disruptions, such as shifting schedules or shorter/longer days, influence food and drug intake, and certain mutations of circadian genes that control cellular rhythms are associated with altered behavioral reward. We highlight the more recent findings associating circadian rhythms to reward function, linking environmental and genetic evidence to natural and drug reward and related neural circuitry.

Conservatism and the neural circuitry of threat: economic conservatism predicts greater amygdala–BNST connectivity during periods of threat vs safety

Science.gov (United States)

Muftuler, L Tugan; Larson, Christine L

2018-01-01

Abstract Political conservatism is associated with an increased negativity bias, including increased attention and reactivity toward negative and threatening stimuli. Although the human amygdala has been implicated in the response to threatening stimuli, no studies to date have investigated whether conservatism is associated with altered amygdala function toward threat. Furthermore, although an influential theory posits that connectivity between the amygdala and bed nucleus of the stria terminalis (BNST) is important in initiating the response to sustained or uncertain threat, whether individual differences in conservatism modulate this connectivity is unknown. To test whether conservatism is associated with increased reactivity in neural threat circuitry, we measured participants’ self-reported social and economic conservatism and asked them to complete high-resolution fMRI scans while under threat of an unpredictable shock and while safe. We found that economic conservatism predicted greater connectivity between the BNST and a cluster of voxels in the left amygdala during threat vs safety. These results suggest that increased amygdala–BNST connectivity during threat may be a key neural correlate of the enhanced negativity bias found in conservatism. PMID:29126127

Brain-to-brain synchrony in parent-child dyads and the relationship with emotion regulation revealed by fNIRS-based hyperscanning.

Science.gov (United States)

Reindl, Vanessa; Gerloff, Christian; Scharke, Wolfgang; Konrad, Kerstin

2018-05-25

Parent-child synchrony, the coupling of behavioral and biological signals during social contact, may fine-tune the child's brain circuitries associated with emotional bond formation and the child's development of emotion regulation. Here, we examined the neurobiological underpinnings of these processes by measuring parent's and child's prefrontal neural activity concurrently with functional near-infrared spectroscopy hyperscanning. Each child played both a cooperative and a competitive game with the parent, mostly the mother, as well as an adult stranger. During cooperation, parent's and child's brain activities synchronized in the dorsolateral prefrontal and frontopolar cortex (FPC), which was predictive for their cooperative performance in subsequent trials. No significant brain-to-brain synchrony was observed in the conditions parent-child competition, stranger-child cooperation and stranger-child competition. Furthermore, parent-child compared to stranger-child brain-to-brain synchrony during cooperation in the FPC mediated the association between the parent's and the child's emotion regulation, as assessed by questionnaires. Thus, we conclude that brain-to-brain synchrony may represent an underlying neural mechanism of the emotional connection between parent and child, which is linked to the child's development of adaptive emotion regulation. Future studies may uncover whether brain-to-brain synchrony can serve as a neurobiological marker of the dyad's socio-emotional interaction, which is sensitive to risk conditions, and can be modified by interventions. Copyright © 2018. Published by Elsevier Inc.

Wired for behavior: from development to function of innate limbic system circuitry

Directory of Open Access Journals (Sweden)

Katie eSokolowski

2012-04-01

Full Text Available The limbic system of the brain regulates a number of behaviors that are essential for the survival of all vertebrate species including humans. The limbic system predominantly controls appropriate responses to stimuli with social, emotional or motivational salience, which includes innate behaviors such as mating, aggression and defense. Activation of circuits regulating these innate behaviors begins in the periphery with sensory stimulation (primarily via the olfactory system in rodents, and is then processed in the brain by a set of delineated structures that primarily includes the amygdala and hypothalamus. While the basic neuroanatomy of these connections is well established, much remains unknown about how information is processed within innate circuits and how genetic hierarchies regulate development and function of these circuits. Utilizing innovative technologies including channel rhodopsin-based circuit manipulation and genetic manipulation in rodents, recent studies have begun to answer these central questions. In this article we review the current understanding of how limbic circuits regulate sexually dimorphism and how these circuits are established and shaped during pre- and post-natal development. We also discuss how understanding developmental processes of innate circuit formation may inform behavioral alterations observed in neurodevelopmental disorders, such as autism spectrum disorders, which are characterized by limbic system dysfunction.

Oxytocin in the medial prefrontal cortex regulates maternal care, maternal aggression and anxiety during the postpartum period

Science.gov (United States)

Sabihi, Sara; Dong, Shirley M.; Durosko, Nicole E.; Leuner, Benedetta

2014-01-01

The neuropeptide oxytocin (OT) acts on a widespread network of brain regions to regulate numerous behavioral adaptations during the postpartum period including maternal care, maternal aggression, and anxiety. In the present study, we examined whether this network also includes the medial prefrontal cortex (mPFC). We found that bilateral infusion of a highly specific oxytocin receptor antagonist (OTR-A) into the prelimbic (PL) region of the mPFC increased anxiety-like behavior in postpartum, but not virgin, females. In addition, OTR blockade in the postpartum mPFC impaired maternal care behaviors and enhanced maternal aggression. Overall, these results suggest that OT in the mPFC modulates maternal care and aggression, as well as anxiety-like behavior, during the postpartum period. Although the relationship among these behaviors is complicated and further investigation is required to refine our understanding of OT actions in the maternal mPFC, these data nonetheless provide new insights into neural circuitry of OT-mediated postpartum behaviors. PMID:25147513

Neurogenetic Impairments of Brain Reward Circuitry Links to Reward Deficiency Syndrome (RDS): Potential Nutrigenomic Induced Dopaminergic Activation

Science.gov (United States)

Blum, K; Oscar-Berman, M; Giordano, J; Downs, BW; Simpatico, T; Han, D; Femino, John

2012-01-01

Work from our laboratory in both in-patient and outpatient facilities utilizing the Comprehensive Analysis of Reported Drugs (CARD)™ found a significant lack of compliance to prescribed treatment medications and a lack of abstinence from drugs of abuse during active recovery. This unpublished, ongoing research provides an impetus to develop accurate genetic diagnosis and holistic approaches that will safely activate brain reward circuitry in the mesolimbic dopamine system. This editorial focuses on the neurogenetics of brain reward systems with particular reference to genes related to dopaminergic function. The terminology “Reward Deficiency Syndrome” (RDS), used to describe behaviors found to have an association with gene-based hypodopaminergic function, is a useful concept to help expand our understanding of Substance Use Disorder (SUD), process addictions, and other obsessive, compulsive and impulsive behaviors. This editorial covers the neurological basis of pleasure and the role of natural and unnatural reward in motivating and reinforcing behaviors. Additionally, it briefly describes the concept of natural dopamine D2 receptor agonist therapy coupled with genetic testing of a panel of reward genes, the Genetic Addiction Risk Score (GARS). It serves as a spring-board for this combination of novel approaches to the prevention and treatment of RDS that was developed from fundamental genomic research. We encourage further required studies. PMID:23264886

Germline mutation of RET proto-oncogene’s exons 17 and 18 in Iranian medullary thyroid carcinoma patients

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Marjan Zarif Yeganeh

2017-03-01

Full Text Available Background: Thyroid carcinoma is the most common endocrine malignancy. Medullary thyroid carcinoma (MTC approximately accounts for 5-10% of all thyroid carcinoma. Nowadays, it is obviously, the mutations in REarranged during transfection (RET proto-oncogene, especially, mutations in exons 10, 11 and 16 are associated with MTC pathogenesis and occurrence. Thus, early diagnosis of MTC by mutation detection in RET proto-oncogene allows to identify patients who do not have any developed symptoms. The aim of this study was to screening of germline mutations in RET proto-oncogene exons 17 and 18 in MTC patients and their first degree relatives in Iranian population. Methods: In this cross-sectional study, three hundred eleven participates (190 patients, 121 their relatives were referred to endocrine research center, Shahid Beheshti University of Medical Science during September 2013 until September 2015. The inclusion criteria were pathological and clinical diagnosis. After whole blood sampling, genomic DNA was extracted from peripheral blood leucocytes using the standard Salting Out/Proteinase K method. Nucleotide change detection in exons 17 and 18 was performed using PCR and direct DNA sequencing methods. Results: In this study, twenty missense mutations [CGC>TGC, c.2944C>T, p.Arg982Cys (rs17158558] which included 16 heterozygote and 4 homozygote mutations were found in codon 982 (exon 18. In the present study, 154 G>A (rs2742236 and 4 C>T (rs370072408 nucleotide changes were detected in exons 18 and intron 17 respectively. There was no mutation in exon 17. Conclusion: It seems that because of arginine to cysteine substitutions in RET tyrosine kinase protein structure and its polyphen score (0.955 and SIFT score (0.01 the mutation in codon 982 (exon 18 could be have pathogenic effects. On the other hands, the mentioned mutation frequency was 6.4% among MTC patients, so this mutation of exon 18 could be checked in genetic screening tests of RET

Altered structural and effective connectivity in anorexia and bulimia nervosa in circuits that regulate energy and reward homeostasis.

Science.gov (United States)

Frank, G K W; Shott, M E; Riederer, J; Pryor, T L

2016-11-01

Anorexia and bulimia nervosa are severe eating disorders that share many behaviors. Structural and functional brain circuits could provide biological links that those disorders have in common. We recruited 77 young adult women, 26 healthy controls, 26 women with anorexia and 25 women with bulimia nervosa. Probabilistic tractography was used to map white matter connectivity strength across taste and food intake regulating brain circuits. An independent multisample greedy equivalence search algorithm tested effective connectivity between those regions during sucrose tasting. Anorexia and bulimia nervosa had greater structural connectivity in pathways between insula, orbitofrontal cortex and ventral striatum, but lower connectivity from orbitofrontal cortex and amygdala to the hypothalamus (Pbulimia nervosa effective connectivity was directed from anterior cingulate via ventral striatum to the hypothalamus. Across all groups, sweetness perception was predicted by connectivity strength in pathways connecting to the middle orbitofrontal cortex. This study provides evidence that white matter structural as well as effective connectivity within the energy-homeostasis and food reward-regulating circuitry is fundamentally different in anorexia and bulimia nervosa compared with that in controls. In eating disorders, anterior cingulate cognitive-emotional top down control could affect food reward and eating drive, override hypothalamic inputs to the ventral striatum and enable prolonged food restriction.

Role of 188Re(V)DMSA in the diagnosis and therapy of medullary thyroid carcinoma: a pilot study in an animal model

International Nuclear Information System (INIS)

Learoyd, D.L.; Roach, P.J.; Snowdon, G.M.; Dadachova, K.; Moreau, A.M.; Robinson, B.G.

1999-01-01

Full text: 99 Tc m (V)DMSA has been reported to be highly sensitive in the diagnosis of medullary thyroid cancer (MTC). Rhenium-188, a beta emitter, has potential for therapy of MTC. However, initial studies with 188 Re indicate high renal uptake which may interfere with potential therapeutic applications of this radiopharmaceutical. A modified radiolabelling method has been shown to reduced the renal uptake of 188 Re(V)DMSA in control animals. The aims of this study were to determine whether there is uptake of modified 188 Re(V)DMSA in nude mice injected with an MTC cell line and whether there is potential for MTC therapy. Two groups of mice were injected in the left flank (SC) with TT cell line, and in mice showing tumour growth a low-dose (400 kBq) of 188 Re(V)DMSA was injected via a tail vein 8 weeks later. Biodistribution was performed on several mice and several others were given 'therapy' injections (8 MBq) to determine whether tumour shrinkage could be objectively observed. Tracer uptake was highest in bone and kidneys but tumour uptake was relatively low. However, no new tumour growth was seen in any of the mice subsequent to therapy injections and 1 mouse showed complete remission within 5 weeks of injection. Further animal and human studies will need to be performed to determine the potential role of this modified 118 Re(V)DMSA in patients with MTC

Letak Conus Medularis terhadap Vertebra Menggunakan Hasil Pencitraan Magnetic Resonance Imaging di Rumah Sakit Dr. Hasan Sadikin Bandung untuk Anestesi Spinal

Directory of Open Access Journals (Sweden)

Nurfitriani

2014-12-01

Full Text Available The position of conus medullaris is important to be identified by anesthesiologists during spinal anesthesia to avoid serious spinal cord trauma risk. Conus medullaris can be accurately identified through magnetic resonance imaging (MRI images. The aim of this study was to determine the distribution of conus medullaris in Indonesians through a descriptive observation using magnetic resonance imaging (MRI images of lumbosacral. The locations of conus medullaris were observed retrospectively on 135 MRI images scanned, aged 18–65 years, during the period of January 2013 to March 2014 at the Departement of Radiology, Dr. Hasan Sadikin General Hospital Bandung. From this study, it was revealed that the conus medullaris are mostly located at the middle third of L1, ranging from the middle third of T12 to the lower third of L2. With gender as a parameter, it was shown that the distribution of conus medullaris in women tends to be more caudal than in men

Effects of Repeated Stress on Age-Dependent GABAergic Regulation of the Lateral Nucleus of the Amygdala.

Science.gov (United States)

Zhang, Wei; Rosenkranz, J Amiel

2016-08-01

The adolescent age is associated with lability of mood and emotion. The onset of depression and anxiety disorders peaks during adolescence and there are differences in symptomology during adolescence. This points to differences in the adolescent neural circuitry that underlies mood and emotion, such as the amygdala. The human adolescent amygdala is more responsive to evocative stimuli, hinting to less local inhibitory regulation of the amygdala, but this has not been explored in adolescents. The amygdala, including the lateral nucleus (LAT) of the basolateral amygdala complex, is sensitive to stress. The amygdala undergoes maturational processes during adolescence, and therefore may be more vulnerable to harmful effects of stress during this time period. However, little is known about the effects of stress on the LAT during adolescence. GABAergic inhibition is a key regulator of LAT activity. Therefore, the purpose of this study was to test whether there are differences in the local GABAergic regulation of the rat adolescent LAT, and differences in its sensitivity to repeated stress. We found that LAT projection neurons are subjected to weaker GABAergic inhibition during adolescence. Repeated stress reduced in vivo endogenous and exogenous GABAergic inhibition of LAT projection neurons in adolescent rats. Furthermore, repeated stress decreased measures of presynaptic GABA function and interneuron activity in adolescent rats. In contrast, repeated stress enhanced glutamatergic drive of LAT projection neurons in adult rats. These results demonstrate age differences in GABAergic regulation of the LAT, and age differences in the mechanism for the effects of repeated stress on LAT neuron activity. These findings provide a substrate for increased mood lability in adolescents, and provide a substrate by which adolescent repeated stress can induce distinct behavioral outcomes and psychiatric symptoms.

Marijuana and cannabinoid regulation of brain reward circuits

OpenAIRE

Lupica, Carl R; Riegel, Arthur C; Hoffman, Alexander F

2004-01-01

The reward circuitry of the brain consists of neurons that synaptically connect a wide variety of nuclei. Of these brain regions, the ventral tegmental area (VTA) and the nucleus accumbens (NAc) play central roles in the processing of rewarding environmental stimuli and in drug addiction. The psychoactive properties of marijuana are mediated by the active constituent, Δ9-THC, interacting primarily with CB1 cannabinoid receptors in a large number of brain areas. However, it is the activation o...

Sleep and metabolism: role of hypothalamic neuronal circuitry.

Science.gov (United States)

Rolls, Asya; Schaich Borg, Jana; de Lecea, Luis

2010-10-01

Sleep and metabolism are intertwined physiologically and behaviorally, but the neural systems underlying their coordination are still poorly understood. The hypothalamus is likely to play a major role in the regulation sleep, metabolism, and their interaction. And increasing evidence suggests that hypocretin cells in the lateral hypothalamus may provide particularly important contributions. Here we review: 1) direct interactions between biological arousal and metabolic systems in the hypothalamus, and 2) indirect interactions between these two systems mediated by stress or reward, emphasizing the role of hypocretins. An increased understanding of the mechanisms underlying these interactions may provide novel approaches for the treatment of patients with sleep disorders and obesity, as well as suggest new therapeutic strategies for symptoms of aging, stress, or addiction. Copyright © 2010. Published by Elsevier Ltd.

Conservatism and the neural circuitry of threat: economic conservatism predicts greater amygdala-BNST connectivity during periods of threat vs safety.

Science.gov (United States)

Pedersen, Walker S; Muftuler, L Tugan; Larson, Christine L

2018-01-01

Political conservatism is associated with an increased negativity bias, including increased attention and reactivity toward negative and threatening stimuli. Although the human amygdala has been implicated in the response to threatening stimuli, no studies to date have investigated whether conservatism is associated with altered amygdala function toward threat. Furthermore, although an influential theory posits that connectivity between the amygdala and bed nucleus of the stria terminalis (BNST) is important in initiating the response to sustained or uncertain threat, whether individual differences in conservatism modulate this connectivity is unknown. To test whether conservatism is associated with increased reactivity in neural threat circuitry, we measured participants' self-reported social and economic conservatism and asked them to complete high-resolution fMRI scans while under threat of an unpredictable shock and while safe. We found that economic conservatism predicted greater connectivity between the BNST and a cluster of voxels in the left amygdala during threat vs safety. These results suggest that increased amygdala-BNST connectivity during threat may be a key neural correlate of the enhanced negativity bias found in conservatism. © The Author (2017). Published by Oxford University Press.

Scientific works of research workers of the army health service

International Nuclear Information System (INIS)

1995-01-01

Ten articles about the effects of gamma radiation on human or animal cells are studied here. Regulation of cytokines, effect of interleukin 6, expression of the C-fos protein, interest of the study of a biological check up after an accidental irradiation, interaction and transport of cysteamine( radioprotector), approach of a treatment of radioinduced medullary aplasia, expression of TNF alpha and gelatinase B, are the subjects related here. (N.C.)

Scientific works of research workers of the army health service; Travaux scientifiques des chercheurs du service de sante des armees

Energy Technology Data Exchange (ETDEWEB)

NONE

1996-12-31

Ten articles about the effects of gamma radiation on human or animal cells are studied here. Regulation of cytokines, effect of interleukin 6, expression of the C-fos protein, interest of the study of a biological check up after an accidental irradiation, interaction and transport of cysteamine( radioprotector), approach of a treatment of radioinduced medullary aplasia, expression of TNF alpha and gelatinase B, are the subjects related here. (N.C.).

Scientific works of research workers of the army health service; Travaux scientifiques des chercheurs du service de sante des armees

Energy Technology Data Exchange (ETDEWEB)

NONE

1995-12-31

Ten articles about the effects of gamma radiation on human or animal cells are studied here. Regulation of cytokines, effect of interleukin 6, expression of the C-fos protein, interest of the study of a biological check up after an accidental irradiation, interaction and transport of cysteamine( radioprotector), approach of a treatment of radioinduced medullary aplasia, expression of TNF alpha and gelatinase B, are the subjects related here. (N.C.).

Enhanced bilateral somatostatin receptor expression in mediastinal lymph nodes (''chimney sign'') in occult metastatic medullary thyroid cancer: a typical site of tumour manifestation?

International Nuclear Information System (INIS)

Behr, T.M.; Gratz, S.; Markus, P.M.; Dunn, R.M.; Huefner, M.; Becker, H.; Becker, W.

1997-01-01

In medullary thyroid cancer (MTC), post-surgically elevated plasma calcitonin and/or carcinoembryonic antigen levels frequently indicate persisting metastatic disease, although conventional diagnostic procedures fail to localize the responsible lesions (occult disease). Somatostatin analogues have been used successfully in disease localization, but recently concerns have been raised that increased thoracic uptake of indium-111 pentetreotide in patients with previous external beam irradiation may represent a false-positive finding, caused by post-irradiation pulmonary fibrosis. We recently examined seven patients with metastatic MTC by somatostatin receptor scintigraphy (six with occult and one with established disease). In four patients, all of whom had stable or slowly rising tumour marker levels over several years, a chimney-like bilateral mediastinal uptake of indium-111 pentetreotide was found. In two patients with persisting hypercalcitonaemia immediately after primary surgery, supraclavicular lymph node metastases were identified as the responsible lesions. None of these seven patients had prior external beam radiation therapy. In two cases, histological confirmation was obtained. In one patient, disease progression could be shown during follow-up. These data suggest that bilateral mediastinal lymph node involvement is a typical site of disease in slowly progressing occult metastatic MTC; the ''chimney sign'' may represent a typical finding with somatostatin analogues in such cases. Therefore, we believe that even in the case of prior external beam irradiation, mediastinal uptake of octreotide might represent metastatic MTC rather than radiation fibrosis. (orig.). With 2 figs., 1 tab