Modules in the brain stem and spinal cord underlying motor behaviors

PubMed Central

Cheung, Vincent C. K.; Bizzi, Emilio

2011-01-01

Previous studies using intact and spinalized animals have suggested that coordinated movements can be generated by appropriate combinations of muscle synergies controlled by the central nervous system (CNS). However, which CNS regions are responsible for expressing muscle synergies remains an open question. We address whether the brain stem and spinal cord are involved in expressing muscle synergies used for executing a range of natural movements. We analyzed the electromyographic (EMG) data recorded from frog leg muscles before and after transection at different levels of the neuraxis—rostral midbrain (brain stem preparations), rostral medulla (medullary preparations), and the spinal-medullary junction (spinal preparations). Brain stem frogs could jump, swim, kick, and step, while medullary frogs could perform only a partial repertoire of movements. In spinal frogs, cutaneous reflexes could be elicited. Systematic EMG analysis found two different synergy types: 1) synergies shared between pre- and posttransection states and 2) synergies specific to individual states. Almost all synergies found in natural movements persisted after transection at rostral midbrain or medulla but not at the spinal-medullary junction for swim and step. Some pretransection- and posttransection-specific synergies for a certain behavior appeared as shared synergies for other motor behaviors of the same animal. These results suggest that the medulla and spinal cord are sufficient for the expression of most muscle synergies in frog behaviors. Overall, this study provides further evidence supporting the idea that motor behaviors may be constructed by muscle synergies organized within the brain stem and spinal cord and activated by descending commands from supraspinal areas. PMID:21653716

Blockade of Opioid Receptors in the Medullary Reticularis Nucleus Dorsalis, but not the Rostral Ventromedial Medulla, Prevents Analgesia Produced by Diffuse Noxious Inhibitory Control in Rats With Muscle Inflammation

PubMed Central

de Resende, Marcos A.; Silva, Luis Felipe S.; Sato, Karina; Arendt-Nielsen, Lars; Sluka, Kathleen A.

2014-01-01

Diffuse Noxious Inhibitory Controls (DNIC) involves application of a noxious stimulus outside the testing site to produce analgesia. In human subjects with a variety of chronic pain conditions, DNIC is less effective; however, in animal studies, DNIC is more effective after tissue injury. While opioids are involved in DNIC analgesia, the pathways involved in this opioid-induced analgesia are not clear. The aim of the present study was to test the effectiveness of DNIC in inflammatory muscle pain, and to study which brainstem sites mediate DNIC- analgesia. Rats were injected with 3% carrageenan into their gastrocnemius muscle and responses to cutaneous and muscle stimuli were assessed before and after inflammation, and before and after DNIC induced by noxious heat applied to the tail (45°C and 47°C). Naloxone was administered systemically, into rostral ventromedial medulla (RVM), or bilaterally into the medullary reticularis nucleus dorsalis (MdD) prior to the DNIC-conditioning stimuli. DNIC produced a similar analgesic effect in both acute and the chronic phases of inflammation reducing both cutaneous and muscle sensitivity in a dose-dependent manner. Naloxone systemically or microinjected into the MdD prevented DNIC-analgesia, while naloxone into the RVM had no effect on DNIC analgesia. Thus, DNIC analgesia involves activation of opioid receptors in the MdD. PMID:21330219

Fiber Tracts of the Medial and Inferior Surfaces of the Cerebrum.

PubMed

Baydin, Serhat; Gungor, Abuzer; Tanriover, Necmettin; Baran, Oguz; Middlebrooks, Erik H; Rhoton, Albert L

2017-02-01

Fiber dissection studies of the cerebrum have focused on the lateral surface. No comparable detailed studies have been done on the medial and inferior surfaces. The object of this study was to examine the fiber tracts, cortical, and subcortical structures of the medial and inferior aspects of the brain important in planning operative approaches along the interhemispheric fissure, parafalcine area, and basal surfaces of the cerebrum. Twenty formalin-fixed human hemispheres (10 brains) were examined by fiber dissection technique under ×6-×40 magnifications. The superior longitudinal fasciculus I, cingulum, inferior longitudinal fasciculus, uncinate fasciculus, optic radiations, tapetum, and callosal fibers were dissected step by step from medial to lateral, exposing the nucleus accumbens, subthalamic nucleus, red nucleus, and central midline structures (fornix, stria medullaris, and stria terminalis). Finally, the central core structures were dissected from medial to lateral. Understanding the fiber network underlying the medial and inferior aspects of the brain is important in surgical planning for approaches along the interhemispheric fissure, parafalcine area, and basal surfaces of the cerebrum. Copyright © 2016. Published by Elsevier Inc.

Organization of diencephalic projections from the medullary subnucleus reticularis dorsalis and the adjacent cuneate nucleus: a retrograde and anterograde tracer study in the rat.

PubMed

Villanueva, L; Desbois, C; Le Bars, D; Bernard, J F

1998-01-05

The distribution and organization of diencephalic projections from the subnucleus reticularis dorsalis (SRD) and the neighbouring cuneate nucleus (Cu) were studied in the rat by using microinjections of Phaseolus vulgaris leucoagglutinin in SRD and Cu and wheat germ agglutinin-apo horseradish peroxidase-gold in some selected thalamic areas. As previously reported, the efferent projections from the Cu were essentially contralateral and terminated mainly in the ventroposterolateral thalamic nucleus. Less dense terminals from the Cu were also observed in the posterior thalamic group, the ventral aspect of the zona incerta and the caudal and dorsal portion of the reuniens area. Retrograde tracer injections in the medial ventroposterolateral thalamic nucleus labeled numerous cells in the contralateral Cu, with a smaller number in the gracile nucleus. From the SRD, terminals were observed in the lateral aspect of the ventromedial thalamic nucleus, the lateral parafascicular area and, to a lesser extent, in the ventral aspect of the zona incerta and the core of the reuniens area. Retrograde tracer injections in the lateral part of the ventromedial thalamic nucleus labeled cells in the caudal medulla, many of which were located in the dorsal-most aspect of the SRD throughout its caudo-rostral extent. The existence of SRD-thalamic connections reinforces the idea that the caudal reticular formation is an important nociceptive relay to the thalamus. Our data shed new light on old hypotheses suggesting that, in addition to spino-thalamic pathways, spino-reticulo-thalamic pathways may play an important role in distributing pain signals to the forebrain.

Brainstem mechanisms underlying the cough reflex and its regulation.

PubMed

Mutolo, Donatella

2017-09-01

Cough is a very important airway protective reflex. Cough-related inputs are conveyed to the caudal nucleus tractus solitarii (cNTS) that projects to the brainstem respiratory network. The latter is reconfigured to generate the cough motor pattern. A high degree of modulation is exerted on second-order neurons and the brainstem respiratory network by sensory inputs and higher brain areas. Two medullary structures proved to have key functions in cough production and to be strategic sites of action for centrally active drugs: the cNTS and the caudal ventral respiratory group (cVRG). Drugs microinjected into these medullary structures caused downregulation or upregulation of the cough reflex. The results suggest that inhibition and disinhibition are prominent regulatory mechanisms of this reflex and that both the cNTS and the cVRG are essential in the generation of the entire cough motor pattern. Studies on the basic neural mechanisms subserving the cough reflex may provide hints for novel therapeutic approaches. Different proposals for further investigations are advanced. Copyright © 2017 Elsevier B.V. All rights reserved.

Expression of Sex Steroid Hormone Receptors in Vagal Motor Neurons Innervating the Trachea and Esophagus in Mouse

PubMed Central

Mukudai, Shigeyuki; Ichi Matsuda, Ken; Bando, Hideki; Takanami, Keiko; Nishio, Takeshi; Sugiyama, Yoichiro; Hisa, Yasuo; Kawata, Mitsuhiro

2016-01-01

The medullary vagal motor nuclei, the nucleus ambiguus (NA) and dorsal motor nucleus of the vagus (DMV), innervate the respiratory and gastrointestinal tracts. We conducted immunohistochemical analysis of expression of the androgen receptor (AR) and estrogen receptor α (ERα), in relation to innervation of the trachea and esophagus via vagal motor nuclei in mice. AR and ERα were expressed in the rostral NA and in part of the DMV. Tracing experiments using cholera toxin B subunit demonstrated that neurons of vagal motor nuclei that innervate the trachea and esophagus express AR and ERα. There was no difference in expression of sex steroid hormone receptors between trachea- and esophagus-innervating neurons. These results suggest that sex steroid hormones may act on vagal motor nuclei via their receptors, thereby regulating functions of the trachea and esophagus. PMID:27006520

Involvement of the avian song system in reproductive behaviour

PubMed Central

Wild, J. Martin; Botelho, João F.

2015-01-01

The song system of songbirds consists of an interconnected set of forebrain nuclei that has traditionally been regarded as dedicated to the learning and production of song. Here, however, we suggest that the song system could also influence muscles used in reproductive behaviour, such as the cloacal sphincter muscle. We show that the same medullary nucleus, retroambigualis (RAm), that projects upon spinal motoneurons innervating expiratory muscles (which provide the pressure head for vocalization) and upon vocal motoneurons for respiratory–vocal coordination also projects upon cloacal motoneurons. Furthermore, RAm neurons projecting to sacral spinal levels were shown to receive direct projections from nucleus robustus arcopallialis (RA) of the forebrain song system. Thus, by indicating a possible disynaptic relationship between RA and motoneurons innervating the reproductive organ, in both males and females, these results potentially extend the role of the song system to include consummatory as well as appetitive aspects of reproductive behaviour. PMID:26631245

Nociceptive Afferents to the Premotor Neurons That Send Axons Simultaneously to the Facial and Hypoglossal Motoneurons by Means of Axon Collaterals

PubMed Central

Dong, Yulin; Li, Jinlian; Zhang, Fuxing; Li, Yunqing

2011-01-01

It is well known that the brainstem premotor neurons of the facial nucleus and hypoglossal nucleus coordinate orofacial nociceptive reflex (ONR) responses. However, whether the brainstem PNs receive the nociceptive projection directly from the caudal spinal trigeminal nucleus is still kept unclear. Our present study focuses on the distribution of premotor neurons in the ONR pathways of rats and the collateral projection of the premotor neurons which are involved in the brainstem local pathways of the orofacial nociceptive reflexes of rat. Retrograde tracer Fluoro-gold (FG) or FG/tetramethylrhodamine-dextran amine (TMR-DA) were injected into the VII or/and XII, and anterograde tracer biotinylated dextran amine (BDA) was injected into the caudal spinal trigeminal nucleus (Vc). The tracing studies indicated that FG-labeled neurons receiving BDA-labeled fibers from the Vc were mainly distributed bilaterally in the parvicellular reticular formation (PCRt), dorsal and ventral medullary reticular formation (MdD, MdV), supratrigeminal nucleus (Vsup) and parabrachial nucleus (PBN) with an ipsilateral dominance. Some FG/TMR-DA double-labeled premotor neurons, which were observed bilaterally in the PCRt, MdD, dorsal part of the MdV, peri-motor nucleus regions, contacted with BDA-labeled axonal terminals and expressed c-fos protein-like immunoreactivity which induced by subcutaneous injection of formalin into the lip. After retrograde tracer wheat germ agglutinated horseradish peroxidase (WGA-HRP) was injected into VII or XII and BDA into Vc, electron microscopic study revealed that some BDA-labeled axonal terminals made mainly asymmetric synapses on the dendritic and somatic profiles of WGA-HRP-labeled premotor neurons. These data indicate that some premotor neurons could integrate the orofacial nociceptive input from the Vc and transfer these signals simultaneously to different brainstem motonuclei by axonal collaterals. PMID:21980505

Development of tectal connectivity across metamorphosis in the bullfrog (Rana catesbeiana).

PubMed

Horowitz, Seth S; Simmons, Andrea Megela

2010-01-01

In the bullfrog (Rana catesbeiana), the process of metamorphosis culminates in the appearance of new visual and visuomotor behaviors reflective of the emergence of binocular vision and visually-guided prey capture behaviors as the animal transitions to life on land. Using several different neuroanatomical tracers, we examined the substrates that may underlie these behavioral changes by tracing the afferent and efferent connectivity of the midbrain optic tectum across metamorphic development. Intratectal, tectotoral, tectotegmental, tectobulbar, and tecto-thalamic tracts exhibit similar trajectories of neurobiotin fiber label across the developmental span from early larval tadpoles to adults. Developmental variability was apparent primarily in intensity and distribution of cell and puncta label in target nuclei. Combined injections of cholera toxin subunit β and Phaseolus vulgaris leucoagglutinin consistently label cell bodies, puncta, or fiber segments bilaterally in midbrain targets including the pretectal gray, laminar nucleus of the torus semicircularis, and the nucleus of the medial longitudinal fasciculus. Developmentally stable label was observed bilaterally in medullary targets including the medial vestibular nucleus, lateral vestibular nucleus, and reticular gray, and in forebrain targets including the posterior and ventromedial nuclei of the thalamus. The nucleus isthmi, cerebellum, lateral line nuclei, medial septum, ventral striatum, and medial pallium show more developmentally variable patterns of connectivity. Our results suggest that even during larval development, the optic tectum contains substrates for integration of visual with auditory, vestibular, and somatosensory cues, as well as for guidance of motivated behaviors. Copyright © 2011 S. Karger AG, Basel.

Intraspinal microstimulation and diaphragm activation after cervical spinal cord injury

PubMed Central

Mercier, L. M.; Gonzalez-Rothi, E. J.; Streeter, K. A.; Posgai, S. S.; Poirier, A. S.; Fuller, D. D.; Reier, P. J.

2016-01-01

Intraspinal microstimulation (ISMS) using implanted electrodes can evoke locomotor movements after spinal cord injury (SCI) but has not been explored in the context of respiratory motor output. An advantage over epidural and direct muscle stimulation is the potential of ISMS to selectively stimulate components of the spinal respiratory network. The present study tested the hypothesis that medullary respiratory activity could be used to trigger midcervical ISMS and diaphragm motor unit activation in rats with cervical SCI. Studies were conducted after acute (hours) and subacute (5–21 days) C2 hemisection (C2Hx) injury in adult rats. Inspiratory bursting in the genioglossus (tongue) muscle was used to trigger a 250-ms train stimulus (100 Hz, 100–200 μA) to the ventral C4 spinal cord, targeting the phrenic motor nucleus. After both acute and subacute injury, genioglossus EMG activity effectively triggered ISMS and activated diaphragm motor units during the inspiratory phase. The ISMS paradigm also evoked short-term potentiation of spontaneous inspiratory activity in the previously paralyzed hemidiaphragm (i.e., bursting persisting beyond the stimulus period) in ∼70% of the C2Hx animals. We conclude that medullary inspiratory output can be used to trigger cervical ISMS and diaphragm activity after SCI. Further refinement of this method may enable “closed-loop-like” ISMS approaches to sustain ventilation after severe SCI. NEW & NOTEWORTHY We examined the feasibility of using intraspinal microstimulation (ISMS) of the cervical spinal cord to evoke diaphragm activity ipsilateral to acute and subacute hemisection of the upper cervical spinal cord of the rat. This proof-of-concept study demonstrated the efficacy of diaphragm activation, using an upper airway respiratory EMG signal to trigger ISMS at the level of the ipsilesional phrenic nucleus during acute and advanced postinjury intervals. PMID:27881723

Glycemic state regulates melanocortin, but not nesfatin-1, responsiveness of glucose-sensing neurons in the nucleus of the solitary tract.

PubMed

Mimee, Andrea; Ferguson, Alastair V

2015-04-15

The nucleus of the solitary tract (NTS) is a medullary integrative center with critical roles in the coordinated control of energy homeostasis. Here, we used whole cell current-clamp recordings on rat NTS neurons in slice preparation to identify the presence of physiologically relevant glucose-sensing neurons. The majority of NTS neurons (n = 81) were found to be glucose-responsive, with 35% exhibiting a glucose-excited (GE) phenotype (mean absolute change in membrane potential: 9.5 ± 1.1 mV), and 21% exhibiting a glucose-inhibited (GI) response (mean: 6.3 ± 0.7 mV). Furthermore, we found glucose-responsive cells are preferentially influenced by the anorexigenic peptide α-melanocyte-stimulating hormone (α-MSH), but not nesfatin-1. Accordingly, alterations in glycemic state have profound effects on the responsiveness of NTS neurons to α-MSH, but not to nesfatin-1. Indeed, NTS neurons showed increasing responsiveness to α-MSH as extracellular glucose concentrations were decreased, and in hypoglycemic conditions, all NTS neurons were depolarized by α-MSH (mean 10.6 ± 3.2 mV; n = 8). Finally, decreasing levels of extracellular glucose correlated with a significant hyperpolarization of the baseline membrane potential of NTS neurons, highlighting the modulatory effect of glucose on the baseline excitability of cells in this region. Our findings reveal individual NTS cells are capable of integrating multiple sources of metabolically relevant inputs, highlight the rapid capacity for plasticity in medullary melanocortin circuits, and emphasize the critical importance of physiological recording conditions for electrophysiological studies pertaining to the central control of energy homeostasis. Copyright © 2015 the American Physiological Society.

Glycemic state regulates melanocortin, but not nesfatin-1, responsiveness of glucose-sensing neurons in the nucleus of the solitary tract

PubMed Central

Mimee, Andrea

2015-01-01

The nucleus of the solitary tract (NTS) is a medullary integrative center with critical roles in the coordinated control of energy homeostasis. Here, we used whole cell current-clamp recordings on rat NTS neurons in slice preparation to identify the presence of physiologically relevant glucose-sensing neurons. The majority of NTS neurons (n = 81) were found to be glucose-responsive, with 35% exhibiting a glucose-excited (GE) phenotype (mean absolute change in membrane potential: 9.5 ± 1.1 mV), and 21% exhibiting a glucose-inhibited (GI) response (mean: 6.3 ± 0.7 mV). Furthermore, we found glucose-responsive cells are preferentially influenced by the anorexigenic peptide α-melanocyte-stimulating hormone (α-MSH), but not nesfatin-1. Accordingly, alterations in glycemic state have profound effects on the responsiveness of NTS neurons to α-MSH, but not to nesfatin-1. Indeed, NTS neurons showed increasing responsiveness to α-MSH as extracellular glucose concentrations were decreased, and in hypoglycemic conditions, all NTS neurons were depolarized by α-MSH (mean 10.6 ± 3.2 mV; n = 8). Finally, decreasing levels of extracellular glucose correlated with a significant hyperpolarization of the baseline membrane potential of NTS neurons, highlighting the modulatory effect of glucose on the baseline excitability of cells in this region. Our findings reveal individual NTS cells are capable of integrating multiple sources of metabolically relevant inputs, highlight the rapid capacity for plasticity in medullary melanocortin circuits, and emphasize the critical importance of physiological recording conditions for electrophysiological studies pertaining to the central control of energy homeostasis. PMID:25695291

Blockade of opioid receptors in the medullary reticularis nucleus dorsalis, but not the rostral ventromedial medulla, prevents analgesia produced by diffuse noxious inhibitory control in rats with muscle inflammation.

PubMed

de Resende, Marcos A; Silva, Luis Felipe S; Sato, Karina; Arendt-Nielsen, Lars; Sluka, Kathleen A

2011-06-01

Diffuse Noxious Inhibitory Controls (DNIC) involves application of a noxious stimulus outside the testing site to produce analgesia. In human subjects with a variety of chronic pain conditions, DNIC is less effective; however, in animal studies, DNIC is more effective after tissue injury. While opioids are involved in DNIC analgesia, the pathways involved in this opioid-induced analgesia are not clear. The aim of the present study was to test the effectiveness of DNIC in inflammatory muscle pain, and to study which brainstem sites mediate DNIC- analgesia. Rats were injected with 3% carrageenan into their gastrocnemius muscle and responses to cutaneous and muscle stimuli were assessed before and after inflammation, and before and after DNIC induced by noxious heat applied to the tail (45 °C and 47 °C). Naloxone was administered systemically, into rostral ventromedial medulla (RVM), or bilaterally into the medullary reticularis nucleus dorsalis (MdD) prior to the DNIC-conditioning stimuli. DNIC produced a similar analgesic effect in both acute and the chronic phases of inflammation reducing both cutaneous and muscle sensitivity in a dose-dependent manner. Naloxone systemically or microinjected into the MdD prevented DNIC-analgesia, while naloxone into the RVM had no effect on DNIC analgesia. Thus, DNIC analgesia involves activation of opioid receptors in the MdD. The current study shows that DNIC activates opioid receptors in the MdD, but not the RVM, to produce analgesia. These data are important for understanding clinical studies on DNIC as well as for potential treatment of chronic pain patients. Copyright © 2011 American Pain Society. Published by Elsevier Inc. All rights reserved.

Glycinergic Pathways of the Central Auditory System and Adjacent Reticular Formation of the Rat.

NASA Astrophysics Data System (ADS)

Hunter, Chyren

The development of techniques to visualize and identify specific transmitters of neuronal circuits has stimulated work on the characterization of pathways in the rat central nervous system that utilize the inhibitory amino acid glycine as its neurotransmitter. Glycine is a major inhibitory transmitter in the spinal cord and brainstem of vertebrates where it satisfies the major criteria for neurotransmitter action. Some of these characteristics are: uneven distribution in brain, high affinity reuptake mechanisms, inhibitory neurophysiological actions on certain neuronal populations, uneven receptor distribution and the specific antagonism of its actions by the convulsant alkaloid strychnine. Behaviorally, antagonism of glycinergic neurotransmission in the medullary reticular formation is linked to the development of myoclonus and seizures which may be initiated by auditory as well as other stimuli. In the present study, decreases in the concentration of glycine as well as the density of glycine receptors in the medulla with aging were found and may be responsible for the lowered threshold for strychnine seizures observed in older rats. Neuroanatomical pathways in the central auditory system and medullary and pontine reticular formation (RF) were investigated using retrograde transport of tritiated glycine to identify glycinergic pathways; immunohistochemical techniques were used to corroborate the location of glycine neurons. Within the central auditory system, retrograde transport studies using tritiated glycine demonstrated an ipsilateral glycinergic pathway linking nuclei of the ascending auditory system. This pathway has its cell bodies in the medial nucleus of the trapezoid body (MNTB) and projects to the ventrocaudal division of the ventral nucleus of the lateral lemniscus (VLL). Collaterals of this glycinergic projection terminate in the ipsilateral lateral superior olive (LSO). Other glycinergic pathways found were afferent to the VLL and have their origin in the ventral and lateral nuclei of the trapezoid body (MVPO and LVPO). Bilateral projections from the nucleus reticularis pontis oralis (RPOo), to the VLL were also identified as glycinergic. This projection may link motor output systems to ascending auditory input, generating the auditory behavioral responses seen with glycine antagonism in animal models of myoclonus and seizure.

Receptor-Selective Agonists Induce Emesis and Fos Expression in the Brain and Enteric Nervous System of the Least Shrew (Cryptotis parva)

PubMed Central

Ray, Andrew P.; Chebolu, Seetha; Darmani, Nissar A.

2009-01-01

Research on the mechanisms of emesis has implicated multiple neurotransmitters via both central (dorsal vagal complex) and peripheral (enteric neurons and enterochromaffin cells) anatomical substrates. Taking advantage of advances in receptor-specific agonists, and utilizing Fos expression as a functional activity marker, this study demonstrates a strong, but incomplete, overlap in anatomical substrates for a variety of emetogens. We used cisplatin and specific agonists to 5-HT3 serotonergic, D2/D3 dopaminergic, and NK1 tachykininergic receptors to induce vomiting in the least shrew (Cryptotis parva), and quantified the resulting Fos expression. The least shrew is a small mammal whose responses to emetic challenges are very similar to its human counterparts. In all cases, the enteric nervous system, nucleus of the solitary tract, and dorsal motor nucleus of the vagus demonstrated significantly increased Fos immunoreactivity (Fos-IR). However, Fos-IR induction was notably absent from the area postrema following the dopaminergic and NK1 receptor-specific agents. Two brain nuclei not usually discussed regarding emesis, the dorsal raphe nucleus and paraventricular thalamic nucleus, also demonstrated increased emesis-related Fos-IR. Taken together, these data suggest the dorsal vagal complex is part of a common pathway for a variety of distinct emetogens, but there are central emetic substrates, both medullary and diencephalic, that can be accessed without directly stimulating the area postrema. PMID:19699757

Genetically Expressed Transneuronal Tracer Reveals Direct and Indirect Serotonergic Descending Control Circuits

PubMed Central

BRAZ, JOÃO MANUEL; BASBAUM, ALLAN I.

2016-01-01

Despite the evidence for a significant contribution of brainstem serotonergic (5HT) systems to the control of spinal cord “pain” transmission neurons, attention has turned recently to the influence of nonserotonergic neurons, including the facilitatory and inhibitory controls that originate from so-called “on” and “off” cells of the rostroventral medulla (RVM). Unclear, however, is the extent to which these latter circuits interact with or are influenced by the serotonergic cell groups. To address this question we selectively targeted expression of a transneuronal tracer, wheat germ agglutinin (WGA), in the 5HT neurons so as to study the interplay between the 5HT and non-5HT systems. In addition to confirming the direct medullary 5HT projection to the spinal cord we also observed large numbers of non-5HT neurons, in the medullary nucleus reticularis gigantocellularis and magnocellularis, that were WGA-immunoreactive, i.e., were transneuronally labeled from 5HT neurons. Fluoro-Gold injections into the spinal cord established that these reticular neurons are not only postsynaptic to the 5HT neurons of the medulla, but that most are also at the origin of descending, bulbospinal pathways. By contrast, we found no evidence that neurons of the midbrain periaqueductal gray that project to the RVM are postsynaptic to midbrain or medullary 5HT neurons. Finally, we found very few examples of WGA-immunoreactive noradrenergic neurons, which suggests that there is considerable independence of the monoaminergic bulbospinal pathways. Our results indicate that 5HT neurons influence “pain” processing at the spinal cord level both directly and indirectly via feedforward connections with multiple non-5HT descending control pathways. PMID:18273889

Responses of opioid and serotonin containing medullary raphe neurons to electroacupuncture

PubMed Central

Guo, Zhi-Ling; Moazzami, Ali R.; Tjen-A-Looi, Stephanie; Longhurst, John C.

2008-01-01

The midline medulla oblongata, which includes the nucleus raphe obscurus, raphe magnus and raphe pallidus (NRP), is involved in regulation of cardiovascular responses. Opioids and serotonin (5-HT) are thought to function as important neurotransmitters in this region. We previously have demonstrated that electroacupuncture (EA) at the Neiguan-Jianshi acupoints (P5-P6, overlying the median nerves) attenuates sympathoexcitatory blood pressure reflexes through its influence on several brain regions. However, the role of these three raphe nuclei in the acupuncture responses is unknown. In baroreceptor denervated and vagotomized cats, the present study evaluated c-Fos activation in the raphe nuclei induced by EA and examined its relationship to enkephalin and 5-HT. To enhance detection of perikarya containing enkephalin, colchicine (90–100 μg/kg) was administered into the subarachnoid space in anesthetized cats 28–30 hours before the placement of acupuncture needles at P5-P6 acupoints with or without electrical stimulation for 30 min. Perikarya containing the opioid and 5-HT were found in the raphe nuclei of all animals following application of colchicine. Compared to controls without electrical stimulation (n=5), c-Fos immunoreactivity and neurons double-labeled with c-Fos and either enkephalin or 5-HT were found more frequently in all three midline medullary nuclei, especially in NRP (n=6, all P<0.05) of EA-treated cats. Moreover, neurons triple-labeled with c-Fos, enkephalin and 5-HT were noted frequently in the NRP following EA stimulation. These results suggest that the medullary raphe nuclei, particularly the NRP, process somatic signals during EA and participate in EA-related modulation of cardiovascular function through an opioid or serotonergic mechanism. PMID:18656464

Abnormalities in substance P neurokinin-1 receptor binding in key brainstem nuclei in sudden infant death syndrome related to prematurity and sex.

PubMed

Bright, Fiona M; Vink, Robert; Byard, Roger W; Duncan, Jhodie R; Krous, Henry F; Paterson, David S

2017-01-01

Sudden infant death syndrome (SIDS) involves failure of arousal to potentially life threatening events, including hypoxia, during sleep. While neuronal dysfunction and abnormalities in neurotransmitter systems within the medulla oblongata have been implicated, the specific pathways associated with autonomic and cardiorespiratory failure are unknown. The neuropeptide substance P (SP) and its tachykinin neurokinin-1 receptor (NK1R) have been shown to play an integral role in the modulation of homeostatic function in the medulla, including regulation of respiratory rhythm generation, integration of cardiovascular control, and modulation of the baroreceptor reflex and mediation of the chemoreceptor reflex in response to hypoxia. Abnormalities in SP neurotransmission may therefore result in autonomic dysfunction during sleep and contribute to SIDS deaths. [125I] Bolton Hunter SP autoradiography was used to map the distribution and density of the SP, NK1R to 13 specific nuclei intimately related to cardiorespiratory function and autonomic control in the human infant medulla of 55 SIDS and 21 control (non-SIDS) infants. Compared to controls, SIDS cases exhibited a differential, abnormal developmental profile of the SP/NK1R system in the medulla. Furthermore the study revealed significantly decreased NK1R binding within key medullary nuclei in SIDS cases, principally in the nucleus tractus solitarii (NTS) and all three subdivisions of the inferior portion of the olivo-cerebellar complex; the principal inferior olivary complex (PIO), medial accessory olive (MAO) and dorsal accessory olive (DAO). Altered NK1R binding was significantly influenced by prematurity and male sex, which may explain the increased risk of SIDS in premature and male infants. Abnormal NK1R binding in these medullary nuclei may contribute to the defective interaction of critical medullary mechanisms with cerebellar sites, resulting in an inability of a SIDS infant to illicit appropriate respiratory and motor responses to life threatening challenges during sleep. These observations support the concept that abnormalities in a multi-neurotransmitter network within key nuclei of the medullary homeostatic system may underlie the pathogenesis of a subset of SIDS cases.

Abnormalities in substance P neurokinin-1 receptor binding in key brainstem nuclei in sudden infant death syndrome related to prematurity and sex

PubMed Central

Vink, Robert; Byard, Roger W.; Duncan, Jhodie R.; Krous, Henry F.; Paterson, David S.

2017-01-01

Sudden infant death syndrome (SIDS) involves failure of arousal to potentially life threatening events, including hypoxia, during sleep. While neuronal dysfunction and abnormalities in neurotransmitter systems within the medulla oblongata have been implicated, the specific pathways associated with autonomic and cardiorespiratory failure are unknown. The neuropeptide substance P (SP) and its tachykinin neurokinin-1 receptor (NK1R) have been shown to play an integral role in the modulation of homeostatic function in the medulla, including regulation of respiratory rhythm generation, integration of cardiovascular control, and modulation of the baroreceptor reflex and mediation of the chemoreceptor reflex in response to hypoxia. Abnormalities in SP neurotransmission may therefore result in autonomic dysfunction during sleep and contribute to SIDS deaths. [125I] Bolton Hunter SP autoradiography was used to map the distribution and density of the SP, NK1R to 13 specific nuclei intimately related to cardiorespiratory function and autonomic control in the human infant medulla of 55 SIDS and 21 control (non-SIDS) infants. Compared to controls, SIDS cases exhibited a differential, abnormal developmental profile of the SP/NK1R system in the medulla. Furthermore the study revealed significantly decreased NK1R binding within key medullary nuclei in SIDS cases, principally in the nucleus tractus solitarii (NTS) and all three subdivisions of the inferior portion of the olivo-cerebellar complex; the principal inferior olivary complex (PIO), medial accessory olive (MAO) and dorsal accessory olive (DAO). Altered NK1R binding was significantly influenced by prematurity and male sex, which may explain the increased risk of SIDS in premature and male infants. Abnormal NK1R binding in these medullary nuclei may contribute to the defective interaction of critical medullary mechanisms with cerebellar sites, resulting in an inability of a SIDS infant to illicit appropriate respiratory and motor responses to life threatening challenges during sleep. These observations support the concept that abnormalities in a multi-neurotransmitter network within key nuclei of the medullary homeostatic system may underlie the pathogenesis of a subset of SIDS cases. PMID:28931039

The serotonergic anatomy of the developing human medulla oblongata: implications for pediatric disorders of homeostasis.

PubMed

Kinney, Hannah C; Broadbelt, Kevin G; Haynes, Robin L; Rognum, Ingvar J; Paterson, David S

2011-07-01

The caudal serotonergic (5-HT) system is a critical component of a medullary "homeostatic network" that regulates protective responses to metabolic stressors such as hypoxia, hypercapnia, and hyperthermia. We define anatomically the caudal 5-HT system in the human medulla as 5-HT neuronal cell bodies located in the raphé (raphé obscurus, raphé magnus, and raphé pallidus), extra-raphé (gigantocellularis, paragigantocellularis lateralis, intermediate reticular zone, lateral reticular nucleus, and nucleus subtrigeminalis), and ventral surface (arcuate nucleus). These 5-HT neurons are adjacent to all of the respiratory- and autonomic-related nuclei in the medulla where they are positioned to modulate directly the responses of these effector nuclei. In the following review, we highlight the topography and development of the caudal 5-HT system in the human fetus and infant, and its inter-relationships with nicotinic, GABAergic, and cytokine receptors. We also summarize pediatric disorders in early life which we term "developmental serotonopathies" of the caudal (as well as rostral) 5-HT domain and which are associated with homeostatic imbalances. The delineation of the development and organization of the human caudal 5-HT system provides the critical foundation for the neuropathologic elucidation of its disorders directly in the human brain. Copyright © 2011 Elsevier B.V. All rights reserved.

The Serotonergic Anatomy of the Developing Human Medulla Oblongata: Implications for Pediatric Disorders of Homeostasis

PubMed Central

Kinney, Hannah C.; Broadbelt, Kevin G.; Haynes, Robin L.; Rognum, Ingvar J.; Paterson, David S.

2011-01-01

The caudal serotonergic (5-HT) system is a critical component of a medullary “homeostatic network” that regulates protective responses to metabolic stressors such as hypoxia, hypercapnia, and hyperthermia. We define anatomically the caudal 5-HT system in the human medulla as 5-HT neuronal cell bodies located in the raphé (raphé obscurus, raphé magnus, and raphé pallidus), extra-raphé (gigantocellularis, paragigantocellularis lateralis, intermediate reticular zone, lateral reticular nucleus, and nucleus subtrigeminalis), and ventral surface (arcuate nucleus). These 5-HT neurons are adjacent to all of the respiratory- and autonomic-related nuclei in the medulla where they are positioned to modulate directly the responses of these effector nuclei. In the following review, we highlight the topography and development of the caudal 5-HT system in the human fetus and infant, and its inter-relationships with nicotinic, GABAergic, and cytokine receptors. We also summarize pediatric disorders in early life which we term “developmental serotonopathies” of the caudal (as well as rostral) 5-HT domain and which are associated with homeostatic imbalances. The delineation of the development and organization of the human caudal 5-HT system provides the critical foundation for the neuropathologic elucidation of its disorders directly in the human brain. PMID:21640183

The role of lateral habenula-dorsal raphe nucleus circuits in higher brain functions and psychiatric illness.

PubMed

Zhao, Hua; Zhang, Bei-Lin; Yang, Shao-Jun; Rusak, Benjamin

2015-01-15

Serotonergic neurons in the dorsal raphe nucleus (DRN) play an important role in regulation of many physiological functions. The lateral nucleus of the habenular complex (LHb) is closely connected to the DRN both morphologically and functionally. The LHb is a key regulator of the activity of DRN serotonergic neurons, and it also receives reciprocal input from the DRN. The LHb is also a major way-station that receives limbic system input via the stria medullaris and provides output to the DRN and thereby indirectly connects a number of other brain regions to the DRN. The complex interactions of the LHb and DRN contribute to the regulation of numerous important behavioral and physiological mechanisms, including those regulating cognition, reward, pain sensitivity and patterns of sleep and waking. Disruption of these functions is characteristic of major psychiatric illnesses, so there has been a great deal of interest in how disturbed LHb-DRN interactions may contribute to the symptoms of these illnesses. This review summarizes recent research related to the roles of the LHb-DRN system in regulation of higher brain functions and the possible role of disturbed LHb-DRN function in the pathogenesis of psychiatric disorders, especially depression. Copyright © 2014 Elsevier B.V. All rights reserved.

Particle motion is broadly represented in the vestibular medulla of the bullfrog across larval development.

PubMed

Simmons, Andrea Megela; Flores, Victoria

2012-04-01

In their shallow-water habitats, bullfrog (Rana catesbeiana) tadpoles are exposed to both underwater and airborne sources of acoustic stimulation. We probed the representation of underwater particle motion throughout the tadpole's dorsal medulla to determine its spatial extent over larval life. Using neurobiotin-filled micropipettes, we recorded neural activity to z-axis particle motion (frequencies of 40-200 Hz) in the medial vestibular nucleus, lateral vestibular nucleus, dorsal medullary nucleus (DMN), and along the dorsal arcuate pathway. Sensitivity was comparable in the medial and lateral vestibular nuclei, with estimated thresholds between 0.016 and 12.5 μm displacement. Neither best responding frequency nor estimated threshold varied significantly over larval stage. Transport of neurobiotin from active recording sites was also stable over development. The DMN responded poorly to z-axis particle motion, but did respond to low-frequency pressure stimulation. These data suggest that particle motion is represented widely and stably in the tadpole's vestibular medulla. This is in marked contrast to the representation of pressure stimulation in the auditory midbrain, where a transient "deaf period" of non-responsiveness and decreased connectivity occurs immediately prior to metamorphic climax. We suggest that, in bullfrogs, sensitivity to particle motion and to pressure follows different developmental trajectories.

Particle motion is broadly represented in the vestibular medulla of the bullfrog across larval development

PubMed Central

Flores, Victoria

2012-01-01

In their shallow-water habitats, bullfrog (Rana catesbeiana) tadpoles are exposed to both underwater and airborne sources of acoustic stimulation. We probed the representation of underwater particle motion throughout the tadpole’s dorsal medulla to determine its spatial extent over larval life. Using neurobiotin-filled micropipettes, we recorded neural activity to z-axis particle motion (frequencies of 40–200 Hz) in the medial vestibular nucleus, lateral vestibular nucleus, dorsal medullary nucleus (DMN), and along the dorsal arcuate pathway. Sensitivity was comparable in the medial and lateral vestibular nuclei, with estimated thresholds between 0.016 and 12.5 μm displacement. Neither best responding frequency nor estimated threshold varied significantly over larval stage. Transport of neurobiotin from active recording sites was also stable over development. The DMN responded poorly to z-axis particle motion, but did respond to low-frequency pressure stimulation. These data suggest that particle motion is represented widely and stably in the tadpole’s vestibular medulla. This is in marked contrast to the representation of pressure stimulation in the auditory midbrain, where a transient “deaf period” of non-responsiveness and decreased connectivity occurs immediately prior to metamorphic climax. We suggest that, in bullfrogs, sensitivity to particle motion and to pressure follows different developmental trajectories. PMID:22198742

GSFC Systems Test and Operation Language (STOL) functional requirements and language description

NASA Technical Reports Server (NTRS)

Desjardins, R.; Hall, G.; Mcguire, J.; Merwarth, P.; Mocarsky, W.; Truszkowski, W.; Villasenor, A.; Brosi, F.; Burch, P.; Carey, D.

1978-01-01

The Systems Tests and Operation Language (STOL) provides the means for user communication with payloads, applications programs, and other ground system elements. It is a systems operation language that enables an operator or user to communicate a command to a computer system. The system interprets each high level language directive from the user and performs the indicated action, such as executing a program, printing out a snapshot, or sending a payload command. This document presents the following: (1) required language features and implementation considerations; (2) basic capabilities; (3) telemetry, command, and input/output directives; (4) procedure definition and control; (5) listing, extension, and STOL nucleus capabilities.

Chronic prenatal exposure to carbon monoxide results in a reduction in tyrosine hydroxylase-immunoreactivity and an increase in choline acetyltransferase-immunoreactivity in the fetal medulla: implications for Sudden Infant Death Syndrome.

PubMed

Tolcos, M; McGregor, H; Walker, D; Rees, S

2000-03-01

Maternal cigarette smoking during pregnancy is associated with a significantly increased risk of Sudden Infant Death Syndrome (SIDS). This study investigated the effects of prenatal exposure to carbon monoxide (CO), a major component of cigarette smoke, on the neuroglial and neurochemical development of the medulla in the fetal guinea pig. Pregnant guinea pigs were exposed to 200 p.p.m CO for 10 h per day from day 23-25 of gestation (term = 68 days) until day 61-63, at which time fetuses were removed and brains collected for analysis. Using immunohistochemistry and quantitative image analysis, examination of the medulla of CO-exposed fetuses revealed a significant decrease in tyrosine hydroxylase-immunoreactivity (TH-IR) in the nucleus tractus solitarius, dorsal motor nucleus of the vagus (DMV), area postrema, intermediate reticular nucleus, and the ventrolateral medulla (VLM), and a significant increase in choline acetyltransferase-immunoreactivity (ChAT-IR) in the DMV and hypoglossal nucleus compared with controls. There was no difference between groups in immunoreactivity for the m2 muscarinic acetylcholine receptor, substance P- or met-enkephalin in any of the medullary nuclei examined, nor was there evidence of reactive astrogliosis. The results show that prenatal exposure to CO affects cholinergic and catecholaminergic pathways in the medulla of the guinea pig fetus, particularly in cardiorespiratory centers, regions thought to be compromised in SIDS.

Thyroid cancer - medullary carcinoma

MedlinePlus

Thyroid - medullary carcinoma; Cancer - thyroid (medullary carcinoma); MTC; Thyroid nodule - medullary ... in children and adults. Unlike other types of thyroid cancer, MTC is less likely to be caused by ...

Characterization and localization of /sup 3/H-arginine8-vasopressin binding to rat kidney and brain tissue

DOE Office of Scientific and Technical Information (OSTI.GOV)

Dorsa, D.M.; Majumdar, L.A.; Petracca, F.M.

Anatomic, behavioral and pharmacologic evidence suggests that arginine8-vasopressin (AVP) serves as a CNS neurotransmitter or neuromodulator. AVP binding to membrane and tissue slice preparations from brain and kidney was characterized, and the anatomical distribution of these binding sites was examined. Conditions for the binding assay were optimized using kidney medullary tissue. Binding of /sup 3/H-AVP (S.A. . 30-51 Ci/mmol, NEN) to brain and kidney membranes and tissue slices was saturable, temperature dependent, linearly related to protein concentration (or number of tissue slices), reversible, and specific since the ability of cold AVP to displace /sup 3/H-AVP from binding was greater thanmore » oxytocin and other related peptide fragments. Autoradiographic localization of /sup 3/H-AVP binding was restricted to kidney medullary tissue. In brain tissue, /sup 3/H-AVP binding was found to occur in concentrated foci. Brainstem areas such as the nucleus tractus solitarius (NTS) showed a high density of AVP binding sites. Since local injections of AVP into the NTS have been shown to influence blood pressure, the present study presents the first anatomical evidence for the presence of AVP specific binding sites which might mediate this effect.« less

Local vasotocin modulation of the pacemaker nucleus resembles distinct electric behaviors in two species of weakly electric fish.

PubMed

Perrone, Rossana; Migliaro, Adriana; Comas, Virginia; Quintana, Laura; Borde, Michel; Silva, Ana

2014-01-01

The neural bases of social behavior diversity in vertebrates have evolved in close association with hypothalamic neuropeptides. In particular, arginine-vasotocin (AVT) is a key integrator underlying differences in behavior across vertebrate taxa. Behavioral displays in weakly electric fish are channeled through specific patterns in their electric organ discharges (EODs), whose rate is ultimately controlled by a medullary pacemaker nucleus (PN). We first explored interspecific differences in the role of AVT as modulator of electric behavior in terms of EOD rate between the solitary Gymnotus omarorum and the gregarious Brachyhypopomus gauderio. In both species, AVT IP injection (10μg/gbw) caused a progressive increase of EOD rate of about 30%, which was persistent in B. gauderio, and attenuated after 30min in G. omarorum. Secondly, we demonstrated by in vitro electrophysiological experiments that these behavioral differences can be accounted by dissimilar effects of AVT upon the PN in itself. AVT administration (1μM) to the perfusion bath of brainstem slices containing the PN produced a small and transient increase of PN activity rate in G. omarorum vs the larger and persistent increase previously reported in B. gauderio. We also identified AVT neurons, for the first time in electric fish, using immunohistochemistry techniques and confirmed the presence of hindbrain AVT projections close to the PN that might constitute the anatomical substrate for AVT influences on PN activity. Taken together, our data reinforce the view of the PN as an extremely plastic medullary central pattern generator that not only responds to higher influences to adapt its function to diverse contexts, but also is able to intrinsically shape its response to neuropeptide actions, thus adding a hindbrain target level to the complexity of the global integration of central neuromodulation of electric behavior. Copyright © 2014 Elsevier Ltd. All rights reserved.

Ascending caudal medullary catecholamine pathways drive sickness-induced deficits in exploratory behavior: brain substrates for fatigue?

PubMed

Gaykema, Ronald P A; Goehler, Lisa E

2011-03-01

Immune challenges can lead to marked behavioral changes, including fatigue, reduced social interest, anorexia, and somnolence, but the precise neuronal mechanisms that underlie sickness behavior remain elusive. Part of the neurocircuitry influencing behavior associated with illness likely includes viscerosensory nuclei located in the caudal brainstem, based on findings that inactivation of the dorsal vagal complex (DVC) can prevent social withdrawal. These brainstem nuclei contribute multiple neuronal projections that target different components of autonomic and stress-related neurocircuitry. In particular, catecholaminergic neurons in the ventrolateral medulla (VLM) and DVC target the hypothalamus and drive neuroendocrine responses to immune challenge, but their particular role in sickness behavior is not known. To test whether this catecholamine pathway also mediates sickness behavior, we compared effects of DVC inactivation with targeted lesion of the catecholamine pathway on exploratory behavior, which provides an index of motivation and fatigue, and associated patterns of brain activation assessed by immunohistochemical detection of c-Fos protein. LPS treatment dramatically reduced exploratory behavior, and produced a pattern of increased c-Fos expression in brain regions associated with stress and autonomic adjustments paraventricular hypothalamus (PVN), bed nucleus of the stria terminalis (BST), central amygdala (CEA), whereas activation was reduced in regions involved in exploratory behavior (hippocampus, dorsal striatum, ventral tuberomammillary nucleus, and ventral tegmental area). Both DVC inactivation and catecholamine lesion prevented reductions in exploratory behavior and completely blocked the inhibitory LPS effects on c-Fos expression in the behavior-associated regions. In contrast, LPS-induced activation in the CEA and BST was inhibited by DVC inactivation but not by catecholamine lesion. The findings support the idea that parallel pathways from immune-sensory caudal brainstem sources target distinct populations of forebrain neurons that likely mediate different aspects of sickness. The caudal medullary catecholaminergic projections to the hypothalamus may significantly contribute to brain mechanisms that induce behavioral "fatigue" in the context of physiological stressors. Copyright © 2010 Elsevier Inc. All rights reserved.

Ascending caudal medullary catecholamine pathways drive sickness-induced deficits in exploratory behavior: brain substrates for fatigue?

PubMed Central

Gaykema, Ronald P.A.; Goehler, Lisa E.

2010-01-01

Immune challenges can lead to marked behavioral changes, including fatigue, reduced social interest, anorexia, and somnolence, but the precise neuronal mechanisms that underlie sickness behavior remain elusive. Part of the neurocircuitry influencing behavior associated with illness likely includes viscerosensory nuclei located in the caudal brainstem, based on findings that inactivation of the dorsal vagal complex (DVC) can prevent social withdrawal. These brainstem nuclei contribute multiple neuronal projections that target different components of autonomic and stress-related neurocircuitry. In particular, catecholaminergic neurons in the ventrolateral medulla (VLM) and DVC target the hypothalamus and drive neuroendocrine responses to immune challenge, but their particular role in sickness behavior is not known. To test whether this catecholamine pathway also mediates sickness behavior, we compared effects of DVC inactivation with targeted lesion of the catecholamine pathway on exploratory behavior, which provides an index of motivation and fatigue, and associated patterns of brain activation assessed by immunohistochemical detection of c-Fos protein. LPS treatment dramatically reduced exploratory behavior, and produced a pattern of increased c-Fos expression in brain regions associated with stress and autonomic adjustments paraventricular hypothalamus (PVN), bed nucleus of the stria terminalis (BST), central amygdala (CEA), whereas activation was reduced in regions involved in exploratory behavior (hippocampus, dorsal striatum, ventral tuberomammillary nucleus, and ventral tegmental area). Both DVC inactivation and catecholamine lesion prevented reductions in exploratory behavior and completely blocked the inhibitory LPS effects on c-Fos expression in the behavior-associated regions. In contrast, LPS-induced activation in the CEA and BST was inhibited by DVC inactivation but not by catecholamine lesion. The findings support the idea that parallel pathways from immune-sensory caudal brainstem sources target distinct populations of forebrain neurons that likely mediate different aspects of sickness. The caudal medullary catecholaminergic projections to the hypothalamus may significantly contribute to brain mechanisms that induce behavioral “fatigue” in the context of physiological stressors. PMID:21075199

Dysphagia in a patient with bilateral medial medullary infarcts.

PubMed

Paliwal, Vimal K; Kalita, Jayanti; Misra, Usha K

2009-09-01

Bilateral medial medullary infarct is a rare stroke syndrome and only a handful of cases have been described. Dysphagia as a manifestation of medullary infarcts is well recognized but often associated with lateral medullary infarct. Bilateral medial medullary infarcts are commonly associated with severe dysphagia in addition to a number of other signs and symptoms. We describe a patient who had bilateral medial medullary infarct with severe dysphagia in addition to quadriplegia and respiratory difficulty, and analyze infarct topography with respect to dysphagia, risk factors, vascular territories involved, and prognosis in view of previously reported cases.

Selective Ablation of Tumor Suppressors in Parafollicular C Cells Elicits Medullary Thyroid Carcinoma.

PubMed

Song, Hai; Lin, Chuwen; Yao, Erica; Zhang, Kuan; Li, Xiaoling; Wu, Qingzhe; Chuang, Pao-Tien

2017-03-03

Among the four different types of thyroid cancer, treatment of medullary thyroid carcinoma poses a major challenge because of its propensity of early metastasis. To further investigate the molecular mechanisms of medullary thyroid carcinoma and discover candidates for targeted therapies, we developed a new mouse model of medullary thyroid carcinoma based on our CGRP CreER mouse line. This system enables gene manipulation in parafollicular C cells in the thyroid, the purported cells of origin of medullary thyroid carcinoma. Selective inactivation of tumor suppressors, such as p53 , Rb , and Pten , in mature parafollicular C cells via an inducible Cre recombinase from CGRP CreER led to development of murine medullary thyroid carcinoma. Loss of Pten accelerated p53 / Rb -induced medullary thyroid carcinoma, indicating interactions between pathways controlled by tumor suppressors. Moreover, labeling differentiated parafollicular C cells by CGRP CreER allows us to follow their fate during malignant transformation to medullary thyroid tumor. Our findings support a model in which mutational events in differentiated parafollicular C cells result in medullary thyroid carcinoma. Through expression analysis including RNA-Seq, we uncovered major signaling pathways and networks that are perturbed following the removal of tumor suppressors. Taken together, these studies not only increase our molecular understanding of medullary thyroid carcinoma but also offer new candidates for designing targeted therapies or other treatment modalities. © 2017 by The American Society for Biochemistry and Molecular Biology, Inc.

[A Case of Hereditary Medullary Thyroid Cancer (MEN2A/FMTC) Diagnosed at the Time of Recurrence].

PubMed

Enomoto, Keisuke; Shimizu, Kotaro; Hirose, Masayuki; Miyabe, Haruka; Morizane, Natsue; Takenaka, Yukinori; Shimazu, Kohki; Fushimi, Hiroaki; Uno, Atsuhiko

2015-03-01

We report a 42-year-old man with hereditary medullary thyroid cancer (multiple endocrine neoplasia, MEN2A/familial medullary thyroid carcinoma, FMTC), which was diagnosed at the time of tumor recurrence. He had a past history of a left thyroidectomy with neck dissection 7 years previously. A RET gene analysis revealed a point mutation (codon 618), and we diagnosed him as having hereditary medullary thyroid cancer. We resected the recurrent tumor in the right thyroid lobe together with performing a right lateral and central neck dissection. A RET gene analysis should be performed for patients with medullary thyroid cancer. When a RET gene mutation is present, a total thyroidectomy must be performed for the medullary thyroid cancer.

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

PubMed

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.

A review of 17 cases of carcinoma of the thyroid and phaeochromocytoma

PubMed Central

Williams, E. D.

1965-01-01

The salient features of 15 cases of carcinoma of the thyroid and phaeochromocytoma taken from the literature and two personal cases are reviewed. The significant points noted are the frequency with which the adrenal tumours were bilateral, the frequency with which a family history of phaeochromocytoma (six cases) and thyroid carcinoma (four cases) was present, and the frequency with which the type of thyroid tumour was medullary carcinoma. In four of the 15 published cases the thyroid tumour was described as being medullary. Two personal cases both had medullary carcinoma of the thyroid, and this was also the type of thyroid carcinoma present in five of the published cases in which the thyroid histology was personally reviewed, making a total of 11 medullary carcinomas out of 17 cases. At least one other tumour was probably medullary, judging by the histological description. It is suggested that the association between phaeochromocytoma and thyroid carcinoma is specifically with medullary carcinoma of the thyroid. Both personal cases showed multiple neural tumours; and because of this and the association with phaeochromocytoma the possible neural origin of medullary carcinoma of the thyroid is briefly discussed. The occurrence in a few cases of parathyroid tumours has raised the possibility that these cases are related to the multiple endocrine adenoma syndrome. The dissimilarity between the cases with medullary carcinoma of the thyroid and phaeochromocytoma and those cases with ademonas involving pituitary, parathyroid, adrenal cortex and pancreatic islets is stressed. The term `medullary tumour syndrome' is suggested as a convenient non-committal name for this association of medullary carcinoma of the thyroid with tumours of the adrenal medulla. Images PMID:14304238

Renal Medullary and Urinary Oxygen Tension during Cardiopulmonary Bypass in the Rat

PubMed Central

Sgouralis, Ioannis; Evans, Roger G.; Layton, Anita T.

2017-01-01

Renal hypoxia could result from a mismatch in renal oxygen supply and demand, particularly in the renal medulla. Medullary hypoxic damage is believed to give rise to acute kidney injury, which is a prevalent complication of cardiac surgery performed on cardiopulmonary bypass (CPB). To determine the mechanisms that could lead to medullary hypoxia during CPB in the rat kidney, we developed a mathematical model which incorporates (i) autoregulation of renal blood flow and glomerular filtration rate, (ii) detailed oxygen transport and utilization in the renal medulla, and (iii) oxygen transport along the ureter. Within the outer medulla, the lowest interstitial tissue PO2, which is an indicator of renal hypoxia, is predicted near the thick ascending limbs. Interstitial tissue PO2 exhibits a general decrease along the inner medullary axis, but urine PO2 increases significantly along the ureter. Thus, bladder urinary PO2 is predicted to be substantially higher than medullary PO2. The model is used to identify the phase of cardiac surgery performed on CPB that is associated with the highest risk for hypoxic kidney injury. Simulation results indicate that the outer medulla’s vulnerability to hypoxic injury depends, in part, on the extent to which medullary blood flow is autoregulated. With imperfect medullary blood flow autoregulation, the model predicts that the rewarming phase of CPB, in which medullary blood flow is low but medullary oxygen consumption remains high, is the phase in which the kidney is most likely to suffer hypoxic injury. PMID:27281792

Amygdala connections with jaw, tongue and laryngo-pharyngeal premotor neurons.

PubMed

Van Daele, D J; Fazan, V P S; Agassandian, K; Cassell, M D

2011-03-17

As the central nucleus (CE) is the only amygdaloid nucleus to send axons to the pons and medulla, it is thought to be involved in the expression of conditioned responses by accessing hindbrain circuitry generating stereotypic responses to aversive stimuli. Responses to aversive oral stimuli include gaping and tongue protrusion generated by central pattern generators and other premotor neurons in the ponto-medullary reticular formation. We investigated central nucleus connections with the reticular formation by identifying premotor reticular formation neurons through the retrograde trans-synaptic transport of pseudorabies virus (PRV) inoculated into masseter, genioglossus, thyroarytenoid or inferior constrictor muscles in combination with anterograde labeling of CE axons with biotinylated dextran amine. Three dimensional mapping of PRV infected premotor neurons revealed specific clusters of these neurons associated with different oro-laryngo-pharyngeal muscles, particularly in the parvicellular reticular formation. CE axon terminals were concentrated in certain parvicellular clusters but overall putative contacts were identified with premotor neurons associated with all four oro-laryngo-pharyngeal muscles investigated. We also mapped the retrograde trans-synaptic spread of PRV through the various nuclei of the amygdaloid complex. Medial CE was the first amygdala structure infected (4 days post-inoculation) with trans-synaptic spread to the lateral CE and the caudomedial parvicellular basolateral nucleus by day 5 post-inoculation. Infected neurons were only very rarely found in the lateral capsular CE and the lateral nucleus and then at only the latest time points. The data demonstrate that the CE is directly connected with clusters of reticular premotor neurons that may represent complex pattern generators and/or switching elements for the generation of stereotypic oral and laryngo-pharyngeal movements during aversive oral stimulation. Serial connections through the amygdaloid complex linked with the oro-laryngo-pharyngeal musculature appear quite distinct from those believed to sub-serve fear responses, suggesting there are distinct "channels" for the acquisition and expression of particular conditioned behaviors. Copyright © 2011 IBRO. Published by Elsevier Ltd. All rights reserved.

Sunitinib in Treating Patients With Thyroid Cancer That Did Not Respond to Iodine I 131 and Cannot Be Removed by Surgery

ClinicalTrials.gov

2017-08-18

Recurrent Thyroid Gland Carcinoma; Stage III Thyroid Gland Follicular Carcinoma; Stage III Thyroid Gland Medullary Carcinoma; Stage IV Thyroid Gland Follicular Carcinoma; Stage IV Thyroid Gland Medullary Carcinoma; Stage IV Thyroid Gland Papillary Carcinoma; Stage IVA Thyroid Gland Follicular Carcinoma; Stage IVA Thyroid Gland Medullary Carcinoma; Stage IVA Thyroid Gland Papillary Carcinoma; Stage IVB Thyroid Gland Follicular Carcinoma; Stage IVB Thyroid Gland Medullary Carcinoma; Stage IVB Thyroid Gland Papillary Carcinoma; Stage IVC Thyroid Gland Follicular Carcinoma; Stage IVC Thyroid Gland Medullary Carcinoma; Stage IVC Thyroid Gland Papillary Carcinoma; Thyroid Gland Oncocytic Follicular Carcinoma

Immunohistochemical Localization of AT1a, AT1b, and AT2 Angiotensin II Receptor Subtypes in the Rat Adrenal, Pituitary, and Brain with a Perspective Commentary

PubMed Central

Premer, Courtney; Lamondin, Courtney; Mitzey, Ann; Speth, Robert C.; Brownfield, Mark S.

2013-01-01

Angiotensin II increases blood pressure and stimulates thirst and sodium appetite in the brain. It also stimulates secretion of aldosterone from the adrenal zona glomerulosa and epinephrine from the adrenal medulla. The rat has 3 subtypes of angiotensin II receptors: AT1a, AT1b, and AT2. mRNAs for all three subtypes occur in the adrenal and brain. To immunohistochemically differentiate these receptor subtypes, rabbits were immunized with C-terminal fragments of these subtypes to generate receptor subtype-specific antibodies. Immunofluorescence revealed AT1a and AT2 receptors in adrenal zona glomerulosa and medulla. AT1b immunofluorescence was present in the zona glomerulosa, but not the medulla. Ultrastructural immunogold labeling for the AT1a receptor in glomerulosa and medullary cells localized it to plasma membrane, endocytic vesicles, multivesicular bodies, and the nucleus. AT1b and AT2, but not AT1a, immunofluorescence was observed in the anterior pituitary. Stellate cells were AT1b positive while ovoid cells were AT2 positive. In the brain, neurons were AT1a, AT1b, and AT2 positive, but glia was only AT1b positive. Highest levels of AT1a, AT1b, and AT2 receptor immunofluorescence were in the subfornical organ, median eminence, area postrema, paraventricular nucleus, and solitary tract nucleus. These studies complement those employing different techniques to characterize Ang II receptors. PMID:23573410

Medullary Thyroid Carcinoma Program | Center for Cancer Research

Cancer.gov

Medullary Thyroid Carcinoma Program Multiple endocrine neoplasia (MEN) types 2A and 2B are rare genetic diseases, which lead to the development of medullary thyroid cancer, usually in childhood. Surgery is the only standard treatment.

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

PubMed

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.

Increased Dietary Sodium Induces COX2 Expression by activating NFκB in Renal Medullary Interstitial Cells

PubMed Central

Zhao, Min; Davis, Linda S.; Blackwell, Timothy S.; Yull, Fiona; Breyer, Matthew D.; Hao, Chuan-Ming

2013-01-01

High salt diet induces renal medullary COX2 expression. Selective blockade of renal medullary COX2 activity in rats causes salt sensitive hypertension, suggesting a role for renal medullary COX2 in maintaining systemic sodium balance. The present study characterized the cellular location of COX2 induction in the kidney of mice following high salt diet and examined the role of NFκB in mediating this COX2 induction in response to increased dietary salt. High salt diet (8% NaCl) for 3 days markedly increased renal medullary COX2 expression in C57Bl/6J mice. Co-immunofluorescence using a COX2 antibody and antibodies against AQP2, ClC-K, AQP1 and CD31 showed that high salt diet-induced COX2 was selectively expressed in renal medullary interstitial cells. By using NFκB reporter transgenic mice, we observed a 7 fold increase of luciferase activity in the renal medulla of the NFκB-luciferase reporter mice following high salt diet, and a robust induction of EGFP expression mainly in renal medullary interstitial cells of the NFκB-EGFP reporter mice following high salt diet. Treating high salt diet fed C57Bl/6J mice with selective IκB kinase inhibitor IMD-0354 (8mg/kg bw) substantially suppressed COX2 induction in renal medulla, and also significantly reduced urinary PGE2. These data therefore suggest that renal medullary interstitial cell NFκB plays an important role in mediating renal medullary COX2 expression and promoting renal PGE2 synthesis in response to increased dietary sodium. PMID:23900806

The three subtypes of atrial natriuretic peptide (ANP) receptors are expressed in the rat adrenal gland.

PubMed

Grandclément, B; Ronsin, B; Morel, G

1997-03-01

Atrial natriuretic peptide (ANP) actions are mediated by highly selective and specific receptors. Three subtypes have been characterized and cloned: ANP receptor-A (or GC-A), -B (or GC-B) and -C (the so-called clearance receptor). In rat adrenal gland, the mRNA for each subtype was detected using 35S-dUTP or digoxigenin-11-dUTP specific labeled probes, and in situ hybridization at light and electron microscopic levels respectively. The three subtypes were expressed the most abundantly in the zona glomerulosa. The amount of GC-A mRNA expression, quantified using macro-autoradiography and densitometry, was higher than the amounts of GC-B mRNA and ANPR-C mRNA both in zona glomerulosa and medullary of adrenal gland. At electron microscopic level, the three subtypes of ANPR were revealed in glomerulosa cells. A noticeable signal was also present in the medullary area, especially for GC-A mRNA, in adrenaline-containing chromaffin cells. No signal was detected in noradrenaline-containing chromaffin cells. The subcellular localization of the three mRNAs is similar: in the cytoplasmic matrix and in the euchromatin of the nucleus in each cell of glomerulosa, and in the same compartments of the adrenaline-containing chromaffin cells. These data indicate that the adrenal gland is an important target tissue for ANP action both in glomerulosa cells and adrenaline-containing chromaffin cells. The mRNA expression levels were different for each ANPR subtype.

Intrinsic Membrane Properties of Pre-oromotor Neurons in the Intermediate Zone of the Medullary Reticular Formation

PubMed Central

Venugopal, Sharmila; Boulant, Jack A.; Chen, Zhixiong; Travers, Joseph B.

2010-01-01

Neurons in the lower brainstem that control consummatory behavior are widely distributed in the reticular formation (RF) of the pons and medulla. The intrinsic membrane properties of neurons within this distributed system shape complex excitatory and inhibitory inputs from both orosensory and central structures implicated in homeostatic control to produce coordinated oromotor patterns. The current study explored the intrinsic membrane properties of neurons in the intermediate subdivision of the medullary reticular formation (IRt). Neurons in the IRt receive input from the overlying (gustatory) nucleus of the solitary tract and project to the oromotor nuclei. Recent behavioral pharmacology studies as well as computational modeling suggest that inhibition in the IRt plays an important role in the transition from a taste-initiated oromotor pattern of ingestion to one of rejection. The present study explored the impact of hyperpolarization on membrane properties. In response to depolarization, neurons responded with either a tonic discharge, an irregular/burst pattern or were spike-adaptive. A hyperpolarizing pre-pulse modulated the excitability of most (82%) IRt neurons to subsequent depolarization. Instances of both increased (30%) and decreased (52%) excitability were observed. Currents induced by the hyperpolarization included an outward 4-AP sensitive K+ current that suppressed excitability and an inward cation current that increased excitability. These currents are also present in other subpopulations of RF neurons that influence the oromotor nuclei and we discuss how these currents could alter ring characteristics to impact pattern generation. PMID:20338224

Increased dietary sodium induces COX2 expression by activating NFκB in renal medullary interstitial cells.

PubMed

He, Wenjuan; Zhang, Min; Zhao, Min; Davis, Linda S; Blackwell, Timothy S; Yull, Fiona; Breyer, Matthew D; Hao, Chuan-Ming

2014-02-01

High salt diet induces renal medullary cyclooxygenase 2 (COX2) expression. Selective blockade of renal medullary COX2 activity in rats causes salt-sensitive hypertension, suggesting a role for renal medullary COX2 in maintaining systemic sodium balance. The present study characterized the cellular location of COX2 induction in the kidney of mice following high salt diet and examined the role of NFκB in mediating this COX2 induction in response to increased dietary salt. High salt diet (8 % NaCl) for 3 days markedly increased renal medullary COX2 expression in C57Bl/6 J mice. Co-immunofluorescence using a COX2 antibody and antibodies against aquaporin-2, ClC-K, aquaporin-1, and CD31 showed that high salt diet-induced COX2 was selectively expressed in renal medullary interstitial cells. By using NFκB reporter transgenic mice, we observed a sevenfold increase of luciferase activity in the renal medulla of the NFκB-luciferase reporter mice following high salt diet, and a robust induction of enhanced green fluorescent protein (EGFP) expression mainly in renal medullary interstitial cells of the NFκB-EGFP reporter mice following high salt diet. Treating high salt diet-fed C57Bl/6 J mice with selective IκB kinase inhibitor IMD-0354 (8 mg/kg bw) substantially suppressed COX2 induction in renal medulla, and also significantly reduced urinary prostaglandin E2 (PGE2). These data therefore suggest that renal medullary interstitial cell NFκB plays an important role in mediating renal medullary COX2 expression and promoting renal PGE2 synthesis in response to increased dietary sodium.

Cellular transport of l-arginine determines renal medullary blood flow in control rats, but not in diabetic rats despite enhanced cellular uptake capacity.

PubMed

Persson, Patrik; Fasching, Angelica; Teerlink, Tom; Hansell, Peter; Palm, Fredrik

2017-02-01

Diabetes mellitus is associated with decreased nitric oxide bioavailability thereby affecting renal blood flow regulation. Previous reports have demonstrated that cellular uptake of l-arginine is rate limiting for nitric oxide production and that plasma l-arginine concentration is decreased in diabetes. We therefore investigated whether regional renal blood flow regulation is affected by cellular l-arginine uptake in streptozotocin-induced diabetic rats. Rats were anesthetized with thiobutabarbital, and the left kidney was exposed. Total, cortical, and medullary renal blood flow was investigated before and after renal artery infusion of increasing doses of either l-homoarginine to inhibit cellular uptake of l-arginine or N ω -nitro- l-arginine methyl ester (l-NAME) to inhibit nitric oxide synthase. l-Homoarginine infusion did not affect total or cortical blood flow in any of the groups, but caused a dose-dependent reduction in medullary blood flow. l-NAME decreased total, cortical and medullary blood flow in both groups. However, the reductions in medullary blood flow in response to both l-homoarginine and l-NAME were more pronounced in the control groups compared with the diabetic groups. Isolated cortical tubular cells displayed similar l-arginine uptake capacity whereas medullary tubular cells isolated from diabetic rats had increased l-arginine uptake capacity. Diabetics had reduced l-arginine concentrations in plasma and medullary tissue but increased l-arginine concentration in cortical tissue. In conclusion, the reduced l-arginine availability in plasma and medullary tissue in diabetes results in reduced nitric oxide-mediated regulation of renal medullary hemodynamics. Cortical blood flow regulation displays less dependency on extracellular l-arginine and the upregulated cortical tissue l-arginine may protect cortical hemodynamics in diabetes. Copyright © 2017 the American Physiological Society.

MR Anatomy of Deep Brain Nuclei with Special Reference to Specific Diseases and Deep Brain Stimulation Localization

PubMed Central

Telford, Ryan; Vattoth, Surjith

2014-01-01

Summary Diseases affecting the basal ganglia and deep brain structures vary widely in etiology and include metabolic, infectious, ischemic, and neurodegenerative conditions. Some neurologic diseases, such as Wernicke encephalopathy or pseudohypoparathyroidism, require specific treatments, which if unrecognized could lead to further complications. Other pathologies, such as hypertrophic olivary degeneration, if not properly diagnosed may be mistaken for a primary medullary neoplasm and create unnecessary concern. The deep brain structures are complex and can be difficult to distinguish on routine imaging. It is imperative that radiologists first understand the intrinsic anatomic relationships between the different basal ganglia nuclei and deep brain structures with magnetic resonance (MR) imaging. It is important to understand the "normal" MR signal characteristics, locations, and appearances of these structures. This is essential to recognizing diseases affecting the basal ganglia and deep brain structures, especially since most of these diseases result in symmetrical, and therefore less noticeable, abnormalities. It is also crucial that neurosurgeons correctly identify the deep brain nuclei presurgically for positioning deep brain stimulator leads, the most important being the subthalamic nucleus for Parkinson syndromes and the thalamic ventral intermediate nucleus for essential tremor. Radiologists will be able to better assist clinicians in diagnosis and treatment once they are able to accurately localize specific deep brain structures. PMID:24571832

Animal models of medullary thyroid cancer: state of the art and view to the future.

PubMed

Vitale, Giovanni; Gaudenzi, Germano; Circelli, Luisa; Manzoni, Marco F; Bassi, Andrea; Fioritti, Niccolò; Faggiano, Antongiulio; Colao, Annamaria

2017-01-01

Medullary thyroid carcinoma is a neuroendocrine tumour originating from parafollicular C cells accounting for 5-10% of thyroid cancers. Increased understanding of disease-specific molecular targets of therapy has led to the regulatory approval of two drugs (vandetanib and cabozantinib) for the treatment of medullary thyroid carcinoma. These drugs increase progression-free survival; however, they are often poorly tolerated and most treatment responses are transient. Animal models are indispensable tools for investigating the pathogenesis, mechanisms for tumour invasion and metastasis and new therapeutic approaches for cancer. Unfortunately, only few models are available for medullary thyroid carcinoma. This review provides an overview of the state of the art of animal models in medullary thyroid carcinoma and highlights future developments in this field, with the aim of addressing salient features and clinical relevance. © 2017 Society for Endocrinology.

Adrenal medullary hyperplasia. Hyperplasia-pheochromocytoma sequence.

PubMed

Kurihara, K; Mizuseki, K; Kondo, T; Ohoka, H; Mannami, M; Kawai, K

1990-09-01

We present a case of unilateral adrenal medullary hyperplasia in a 63-year-old woman with clinical signs and symptoms of pheochromocytoma unassociated with multiple endocrine neoplasia. The surgically removed adrenal gland revealed diffuse medullary hyperplasia with multiple micronodules measuring up to 2 mm. The micronodules were composed of enlarged chromaffin cells with atypia, histologically similar to those of pheochromocytoma, forming small solid alveolar patterns separated by a fibrovascular stroma. Removal of the hyperplastic adrenal gland resulted in disappearance of paroxysmal nocturnal hypertension and palpitation. These results suggest that diffuse and nodular medullary hyperplasia is the precursor of pheochromocytoma.

Bone sialoprotein keratan sulfate proteoglycan (BSP-KSPG) and FGF-23 are important physiological components of medullary bone.

PubMed

Hadley, Jill A; Horvat-Gordon, Maria; Kim, Woo-Kyun; Praul, Craig A; Burns, Dennis; Leach, Roland M

2016-04-01

Medullary bone is a specialized bone found in the marrow cavity of laying birds. It provides a significant contribution to the calcium supply for egg shell formation. Medullary bone is distinguished from cortical bone by the presence of large amounts of a keratan sulfate proteoglycan (KSPG). The aims of the present experiment are to confirm the identity of the core protein of KSPG, identify a marker of medullary bone metabolism, and determine whether changes in keratan sulfate (KS) concentration in blood are associated with the egg-laying cycle. Using two different isolation techniques- one specific for bone and another for blood- we have identified bone sialoprotein (BSP) to be the core protein of this KSPG. We also determined that the amount of keratan sulfate (KS) in laying hen blood fluctuates in synchrony with the egg-laying cycle, and thus can serve as a specific marker for medullary bone metabolism. During the course of this investigation, we also found FGF-23 (phosphatonin) to be expressed in medullary bone, in synchrony with the egg-laying cycle. Western blotting was used to demonstrate the presence of this peptide in both laying hen blood and medullary bone extracts. The importance of FGF-23 (phosphatonin) and parathyroid hormone in normalizing the dramatic changes in plasma calcium and phosphorus during the 24h egg-laying cycle is discussed. Copyright © 2016 Elsevier Inc. All rights reserved.

Diagnosing colorectal medullary carcinoma: interobserver variability and clinicopathological implications.

PubMed

Lee, Lik Hang; Yantiss, Rhonda K; Sadot, Eran; Ren, Bing; Calvacanti, Marcela Santos; Hechtman, Jaclyn F; Ivelja, Sinisa; Huynh, Be; Xue, Yue; Shitilbans, Tatiana; Guend, Hamza; Stadler, Zsofia K; Weiser, Martin R; Vakiani, Efsevia; Gönen, Mithat; Klimstra, David S; Shia, Jinru

2017-04-01

Colorectal medullary carcinoma, recognized by the World Health Organization as a distinct histologic subtype, is commonly regarded as a specific entity with an improved prognosis and unique molecular pathogenesis. A fundamental but as yet unaddressed question, however, is whether it can be diagnosed reproducibly. In this study, by analyzing 80 colorectal adenocarcinomas whose dominant growth pattern was solid (thus encompassing medullary carcinoma and its mimics), we provided a detailed description of the morphological spectrum from "classic medullary histology" to nonmedullary poorly differentiated histologies and demonstrated significant overlapping between categories. By assessing a selected subset (n=30) that represented the spectrum of histologies, we showed that the interobserver agreement for diagnosing medullary carcinoma by using 2010 World Health Organization criteria was poor; the κ value among 5 gastrointestinal pathologists was only 0.157 (95% confidence interval, 0.127-0.263; P=.001). When we arbitrarily classified the entire cohort into "classic" and "indeterminate" medullary tumors (group 1, n=19; group 2, n=26, respectively) and nonmedullary poorly differentiated tumors (group 3, n=35), groups 1 and 2 were more likely to exhibit mismatch repair protein deficiency than group 3 (P<.001); however, improved survival could not be detected in either group compared with group 3. Our findings suggest that the diagnosis of medullary carcinoma, as currently applied, may only serve as a morphological descriptor indicating an increased likelihood of mismatch-repair deficiency. Additional evidence including a more objective classification system is needed before medullary carcinoma can be regarded as a distinct entity with prognostic relevance. Until such evidence becomes available, caution should be exercised when making this diagnosis, as well as when comparing results across different studies. Copyright © 2016 Elsevier Inc. All rights reserved.

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

PubMed Central

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

Sneeze related area in the medulla: localisation of the human sneezing centre?

PubMed

Seijo-Martínez, M; Varela-Freijanes, A; Grandes, J; Vázquez, F

2006-04-01

Sneezing is a rarely explored symptom in neurological practice. In the cat, a sneeze evoking centre is located in the medulla. The existence of a sneezing centre has not been confirmed in humans. A case with abnormal sneezing secondary to a strategic infarct in the right latero-medullary region is presented. A 66 year old man suddenly presented paroxysmal sneezing followed by ataxia, right sided motor and sensory symptoms, and hoarseness. The application of stimuli to the right nasal fossa did not evoke sneezing nor the wish to sneeze. The same stimuli to the contralateral nasal fossa evoked normal sneezing. The preservation of the superficial sensitivity of the nasal fossa indicates that the lesion was localised in the hypothetical human sneezing centre, very close to the spinal trigeminal tract and nucleus. This centre appears to be bilateral and functionally independent on both sides.

Sneeze related area in the medulla: localisation of the human sneezing centre?

PubMed Central

Seijo‐Martínez, M; Varela‐Freijanes, A; Grandes, J; Vázquez, F

2006-01-01

Sneezing is a rarely explored symptom in neurological practice. In the cat, a sneeze evoking centre is located in the medulla. The existence of a sneezing centre has not been confirmed in humans. A case with abnormal sneezing secondary to a strategic infarct in the right latero‐medullary region is presented. A 66 year old man suddenly presented paroxysmal sneezing followed by ataxia, right sided motor and sensory symptoms, and hoarseness. The application of stimuli to the right nasal fossa did not evoke sneezing nor the wish to sneeze. The same stimuli to the contralateral nasal fossa evoked normal sneezing. The preservation of the superficial sensitivity of the nasal fossa indicates that the lesion was localised in the hypothetical human sneezing centre, very close to the spinal trigeminal tract and nucleus. This centre appears to be bilateral and functionally independent on both sides. PMID:16354739

Emergence of the pre-Bötzinger respiratory rhythm generator in the mouse embryo.

PubMed

Thoby-Brisson, Muriel; Trinh, Jean-Baptiste; Champagnat, Jean; Fortin, Gilles

2005-04-27

To obtain insights into the emergence of rhythmogenic circuits supporting respiration, we monitored spontaneous activities in isolated brainstem and medullary transverse slice preparations of mouse embryos, combining electrophysiological and calcium imaging techniques. At embryonic day 15 (E15), in a restricted region ventral to the nucleus ambiguus, we observed the onset of a sustained high-frequency (HF) respiratory-like activity in addition to a preexisting low-frequency activity having a distinct initiation site, spatial extension, and susceptibility to gap junction blockers. At the time of its onset, the HF generator starts to express the neurokinin 1 receptor, is connected bilaterally, requires active AMPA/kainate glutamatergic synapses, and is modulated by substance P and the mu-opioid agonist D-Ala2-N-Me-Phe4-Glycol5-enkephalin. We conclude that a rhythm generator sharing the properties of the neonatal pre-Bötzinger complex becomes active during E15 in mice.

Intrinsic membrane properties of pre-oromotor neurons in the intermediate zone of the medullary reticular formation.

PubMed

Venugopal, S; Boulant, J A; Chen, Z; Travers, J B

2010-06-16

Neurons in the lower brainstem that control consummatory behavior are widely distributed in the reticular formation (RF) of the pons and medulla. The intrinsic membrane properties of neurons within this distributed system shape complex excitatory and inhibitory inputs from both orosensory and central structures implicated in homeostatic control to produce coordinated oromotor patterns. The current study explored the intrinsic membrane properties of neurons in the intermediate subdivision of the medullary reticular formation (IRt). Neurons in the IRt receive input from the overlying (gustatory) nucleus of the solitary tract and project to the oromotor nuclei. Recent behavioral pharmacology studies as well as computational modeling suggest that inhibition in the IRt plays an important role in the transition from a taste-initiated oromotor pattern of ingestion to one of rejection. The present study explored the impact of hyperpolarization on membrane properties. In response to depolarization, neurons responded with either a tonic discharge, an irregular/burst pattern or were spike-adaptive. A hyperpolarizing pre-pulse modulated the excitability of most (82%) IRt neurons to subsequent depolarization. Instances of both increased (30%) and decreased (52%) excitability were observed. Currents induced by the hyperpolarization included an outward 4-aminopyridine (4-AP) sensitive K+ current that suppressed excitability and an inward cation current that increased excitability. These currents are also present in other subpopulations of RF neurons that influence the oromotor nuclei and we discuss how these currents could alter firing characteristics to impact pattern generation. 2010 IBRO. Published by Elsevier Ltd. All rights reserved.

Suppression of third ventricular NPY-elicited feeding following medullary reticular formation infusions of muscimol.

PubMed

Travers, Joseph B; Herman, Kenneth; Travers, Susan P

2010-04-01

The appetitive component of feeding is controlled by forebrain substrates, but the consummatory behaviors of licking, mastication, and swallowing are organized in the brainstem. The target of forebrain appetitive signals is unclear but likely includes regions of the medullary reticular formation (RF). This study was undertaken to determine the necessity of different RF regions for mastication induced by a descending appetitive signal. We measured solid food intake in response to third ventricular (3V) infusions of the orexigenic peptide neuropeptide Y 3-36 in awake, freely moving rats and determined whether focal RF infusions of the GABAA agonist muscimol suppressed eating. RF infusions were centered in either the lateral tegmental field, comprising the intermediate (IRt) and parvocellular (PCRt) RF, or in the nucleus gigantocellularis (Gi). Infusions of NPY 3-36 (5 microg/5 microl) into 3V significantly increased feeding of solid food over a 90-min period compared with the noninfused condition (4.3 g +/- 0.56 vs. 0.57 g +/- 0.57, p < .001). NPY 3-36-induced food intake was suppressed (1.7 g +/- 0.48) by simultaneous infusions of muscimol (0.6 mM/100 nl) into the IRt/PCRt (p < .01). Coincident with the decrease in feeding was a decrease in the amplitude of anterior digastric muscle contractions in response to intraoral sucrose infusions. In contrast, infusions of muscimol into Gi had no discernible effect on food intake or EMG amplitude. These data suggest that the IRt/PCRt is essential for forebrain-initiated mastication, but that the Gi is not a necessary link in this pathway.

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

PubMed

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.

Bilateral medial medullary infarction due to bilateral vertebral artery dissection.

PubMed

Fukuda, Masafumi; Aiba, Toyotaka; Takahashi, Sho

2004-03-01

We describe a 52-year-old woman who experienced transient motor weakness and numbness of the left extremities and presented 2 days later with severe hemiparesis and sensory impairment of the right extremities and right lingual palsy. Magnetic resonance imaging (MRI) revealed bilateral upper medial medullary infarction, primarily in the left ventral portion. The findings of both three-dimensional (3D) computed tomographic and conventional angiography suggested dissection of both intracranial vertebral arteries (VAs). Medial medullary infarction is generally caused by atherosclerosis within a VA or anterior spinal artery. This is the first report of bilateral medial medullary infarction due to dissection of both intracranial VAs.

Role of medullary progenitor cells in epithelial cell migration and proliferation

PubMed Central

Chen, Dong; Chen, Zhiyong; Zhang, Yuning; Park, Chanyoung; Al-Omari, Ahmed

2014-01-01

This study is aimed at characterizing medullary interstitial progenitor cells and to examine their capacity to induce tubular epithelial cell migration and proliferation. We have isolated a progenitor cell side population from a primary medullary interstitial cell line. We show that the medullary progenitor cells (MPCs) express CD24, CD44, CXCR7, CXCR4, nestin, and PAX7. MPCs are CD34 negative, which indicates that they are not bone marrow-derived stem cells. MPCs survive >50 passages, and when grown in epithelial differentiation medium develop phenotypic characteristics of epithelial cells. Inner medulla collecting duct (IMCD3) cells treated with conditioned medium from MPCs show significantly accelerated cell proliferation and migration. Conditioned medium from PGE2-treated MPCs induce tubule formation in IMCD3 cells grown in 3D Matrigel. Moreover, most of the MPCs express the pericyte marker PDGFR-b. Our study shows that the medullary interstitium harbors a side population of progenitor cells that can differentiate to epithelial cells and can stimulate tubular epithelial cell migration and proliferation. The findings of this study suggest that medullary pericyte/progenitor cells may play a critical role in collecting duct cell injury repair. PMID:24808539

Non-chemosensitive parafacial neurons simultaneously regulate active expiration and airway patency under hypercapnia in rats.

PubMed

de Britto, Alan A; Moraes, Davi J A

2017-03-15

Hypercapnia or parafacial respiratory group (pFRG) disinhibition at normocapnia evokes active expiration in rats by recruitment of pFRG late-expiratory (late-E) neurons. We show that hypercapnia simultaneously evoked active expiration and exaggerated glottal dilatation by late-E synaptic excitation of abdominal, hypoglossal and laryngeal motoneurons. Simultaneous rhythmic expiratory activity in previously silent pFRG late-E neurons, which did not express the marker of ventral medullary CO 2 -sensitive neurons (transcription factor Phox2b), was also evoked by hypercapnia. Hypercapnia-evoked active expiration, neural and neuronal late-E activities were eliminated by pFRG inhibition, but not after blockade of synaptic excitation. Hypercapnia produces disinhibition of non-chemosensitive pFRG late-E neurons to evoke active expiration and concomitant cranial motor respiratory responses controlling the oropharyngeal and upper airway patency. Hypercapnia produces active expiration in rats and the recruitment of late-expiratory (late-E) neurons located in the parafacial respiratory group (pFRG) of the ventral medullary brainstem. We tested the hypothesis that hypercapnia produces active expiration and concomitant cranial respiratory motor responses controlling the oropharyngeal and upper airway patency by disinhibition of pFRG late-E neurons, but not via synaptic excitation. Phrenic nerve, abdominal nerve (AbN), cranial respiratory motor nerves, subglottal pressure, and medullary and spinal neurons/motoneurons were recorded in in situ preparations of juvenile rats. Hypercapnia evoked AbN active expiration, exaggerated late-E discharges in cranial respiratory motor outflows, and glottal dilatation via late-E synaptic excitation of abdominal, hypoglossal and laryngeal motoneurons. Simultaneous rhythmic late-E activity in previously silent pFRG neurons, which did not express the marker of ventral medullary CO 2 -sensitive neurons (transcription factor Phox2b), was also evoked by hypercapnia. In addition, hypercapnia-evoked AbN active expiration, neural and neuronal late-E activities were eliminated by pFRG inhibition, but not after blockade of synaptic excitation. On the other hand, pFRG inhibition did not affect either hypercapnia-induced inspiratory increases in respiratory motor outflows or CO 2 sensitivity of the more medial Phox2b-positive neurons in the retrotrapezoid nucleus (RTN). Our data suggest that neither RTN Phox2b-positive nor other CO 2 -sensitive brainstem neurons activate Phox2b-negative pFRG late-E neurons under hypercapnia to produce AbN active expiration and concomitant cranial motor respiratory responses controlling the oropharyngeal and upper airway patency. Hypercapnia produces disinhibition of non-chemosensitive pFRG late-E neurons in in situ preparations of juvenile rats to activate abdominal, hypoglossal and laryngeal motoneurons. © 2016 The Authors. The Journal of Physiology © 2016 The Physiological Society.

Physical and radiological findings specific for medullary carcinoma of the thyroid gland.

PubMed

Fujimoto, Y; Oka, A; Fukumitsu, M; Obara, T; Akisada, M

1975-06-01

Preoperative physical and radiological findings, if specific to a certain extent, are important for detecting patients with sporadic form of medullary thyroid carcinoma and especially for the first patient in the family having a hereditary form of medullary thyroid carcinoma and pheochromocytoma syndrome. To delineate clinical features of medullary thyroid carcinoma, a total of 9 patients with this tumor were reviewed retrospectively. In most patients, the thyroid lesions were located in the upper two thirds of the lobe, which was determined by careful palpation or 131I scintiscanning of the thyroid. The primary lesion in the thyroid could be felt more or less as a round, sharply demarcated nodule with fairly good mobility. These findings suggested rather a benign thyroid nodule when there was no lymph node involvement. However, it could be considered a sign suggesting medullary thyroid carcinoma when accompanied by marked lymph node metastasis. In our recent 2 cases, the diagnosis of medullary thyroid carcinoma was strongly suspected on these clinical bases, one of the cases being presented in detail. In 4 patients, lymph node metastasis in the central neck extended to either submandibular or upper mediastinal regions or both. In about one third of the patients, calcified deposits were shown in the cervical roentgenograms. With the use of soft tissue roentgenography, grossly punctate calcific deposits associated with psammoma-like shadows were recognized and the pattern was a criterion for definitive diagnosis of medullary thyroid carcinoma.

Pazopanib Hydrochloride in Treating Patients With Advanced Thyroid Cancer

ClinicalTrials.gov

2018-05-08

Recurrent Thyroid Gland Carcinoma; Stage III Differentiated Thyroid Gland Carcinoma AJCC v7; Stage III Thyroid Gland Medullary Carcinoma AJCC v7; Stage IVA Differentiated Thyroid Gland Carcinoma AJCC v7; Stage IVA Thyroid Gland Medullary Carcinoma AJCC v7; Stage IVA Thyroid Gland Undifferentiated (Anaplastic) Carcinoma AJCC v7; Stage IVB Differentiated Thyroid Gland Carcinoma AJCC v7; Stage IVB Thyroid Gland Medullary Carcinoma AJCC v7; Stage IVB Thyroid Gland Undifferentiated (Anaplastic) Carcinoma AJCC v7; Stage IVC Differentiated Thyroid Gland Carcinoma AJCC v7; Stage IVC Thyroid Gland Medullary Carcinoma AJCC v7; Stage IVC Thyroid Gland Undifferentiated (Anaplastic) Carcinoma AJCC v7; Thyroglobulin Antibody Negative; Thyroid Gland Undifferentiated (Anaplastic) Carcinoma

Effect of medullary cavity in cancellous bone on two-wave phenomenon

NASA Astrophysics Data System (ADS)

Hachiken, Takuma; Nakanishi, Shoko; Matsukawa, Mami

2016-07-01

Osteoporotic patients have a larger medullary cavity in their cancellous bone than healthy people. In this study, the effect of the medullary cavity on the two-wave phenomenon was experimentally investigated using a cancellous bone model and a radius bone model. In the cancellous bone model, with the increase in hole (medullary cavity) diameter, the amplitudes of the fast waves became smaller, whereas the amplitudes of the slow waves became larger. In the radius bone model, the fast wave overlapped with the circumferential wave. The slow wave became larger with increasing hole diameter. The analysis of the slow wave thus seems to be useful for the in vivo diagnosis of the degree of osteoporosis.

Spontaneous nystagmus in dorsolateral medullary infarction indicates vestibular semicircular canal imbalance.

PubMed

Rambold, H; Helmchen, C

2005-01-01

Spontaneous nystagmus caused by dorsolateral medullary infarction may be of vestibular origin. To test if imbalance of the central pathways of the semicircular canals contributes to spontaneous nystagmus in dorsolateral medullary syndrome. We examined four patients with dorsolateral medullary syndrome and recorded spontaneous nystagmus binocularly at gaze straight ahead with the three-dimensional search coil technique. The median slow phase velocity of the nystagmus was analysed in the light and in the dark, and the normalised velocity axes were compared with the rotation axes as predicted from anatomical data of the semicircular canal. The slow phase rotation axes of all patients aligned best with the rotation axes resulting from stimulation of the contralesional posterior and horizontal semicircular canals. This alignment cannot be explained by pure otolith imbalance. We propose that vestibular imbalance caused by an ipsilesional lesion of the central semicircular canal pathways of the horizontal and anterior semicircular canals largely accounts for spontaneous nystagmus in dorsolateral medullary syndrome.

Acetazolamide on the ventral medulla of the cat increases phrenic output and delays the ventilatory response to CO2.

PubMed Central

Coates, E L; Li, A H; Nattie, E E

1991-01-01

1. Acetazolamide (0.1 mM) applied to the surface of the rostral ventrolateral medulla or microinjected beneath the medullary surface in chloralose-urethane-anaesthetized, vagotomized, carotid-denervated, paralysed, servo-ventilated cats produced a long-lasting increase in integrated phrenic nerve activity. 2. Extracellular pH measured beneath the rostral ventrolateral medulla exhibited a long-lasting decrease after surface acetazolamide but was not a good predictor, in each individual animal, of changes in phrenic activity. 3. Medullary carbonic anhydrase inhibition reduced the slope and the half-time of the phrenic response to rapid step CO2 increases. Conversely, acetazolamide did not affect the phrenic response to steady-state CO2 increases. 4. These data indicate that localized inhibition of medullary carbonic anhydrase causes a centrally mediated increase in ventilation that we attribute to medullary tissue hypercapnia and acidosis. In addition, these data indicate that medullary carbonic anhydrase may play a role in central CO2 chemotransduction. Images Fig. 8 PMID:1816381

Do egg-laying crocodilian (Alligator mississippiensis) archosaurs form medullary bone?

PubMed

Schweitzer, M H; Elsey, R M; Dacke, C G; Horner, J R; Lamm, E-T

2007-04-01

It is beyond question that Mesozoic dinosaurs, like Aves and Crocodylia, are archosaurs. However, within the archosaurian clade, the origin and distribution of some major features are less clear, particularly with respect to reproductive physiology. Medullary bone, a highly mineralized, bony reproductive tissue present in the endosteal cavities of all extant egg-laying birds thus far examined, has recently been reported in Tyrannosaurus rex. Its presence or absence in extant crocodilians, therefore, may shed light on the timing of its evolutionary appearance. If medullary bone is present in all three taxa, it arose before the three lineages diverged. However, if medullary bone arose after this divergence, it may be present in both extinct dinosaurs and birds, or in birds only. If present in extinct dinosaurs and birds, but not crocodilians, it would indicate that it arose in the common ancestor of this clade, thus adding support to the closer phylogenetic relationship of dinosaurs and birds relative to crocodilians. Thus, the question of whether the crocodilian Alligator mississippiensis forms medullary bone during the production of eggs has important evolutionary significance. Our examination of long bones from several alligators (two alligators with eggs in the oviducts, one that had produced eggs in the past but was not currently in reproductive phase, an immature female and an adult male) shows no differences on the endosteal surfaces of the long bones, and no evidence of medullary bone, supporting the hypothesis that medullary bone first evolved in the dinosaur-bird line, after the divergence of crocodilians from this lineage.

Characteristics of microRNAs enriched in specific cell types and primary tissue types in solid organs.

PubMed

Kriegel, Alison J; Liu, Yong; Liu, Pengyuan; Baker, Maria Angeles; Hodges, Matthew R; Hua, Xing; Liang, Mingyu

2013-12-01

Knowledge of miRNA expression and function in specific cell types in solid organs is limited because of difficulty in obtaining appropriate specimens. We used laser capture microdissection to obtain nine tissue regions from rats, including the nucleus of the solitary tract, hypoglossal motor nucleus, ventral respiratory column/pre-Bötzinger complex, and midline raphe nucleus from the brain stem, myocardium and coronary artery from the heart, and glomerulus, proximal convoluted tubule, and medullary thick ascending limb from the kidney. Each tissue region consists of or is enriched for a specific cell type. Differential patterns of miRNA expression obtained by deep sequencing of minute amounts of laser-captured cells were highly consistent with data obtained from real-time PCR analysis. miRNA expression patterns correctly clustered the specimens by tissue regions and then by primary tissue types (neural, muscular, or epithelial). The aggregate difference in miRNA profiles between tissue regions that contained the same primary tissue type was as large as one-half of the aggregate difference between primary tissue types. miRNAs differentially expressed between primary tissue types are more likely to be abundant miRNAs, while miRNAs differentially expressed between tissue regions containing the same primary tissue type were distributed evenly across the abundance spectrum. The tissue type-enriched miRNAs were more likely to target genes enriched for specific functional categories compared with either cell type-enriched miRNAs or randomly selected miRNAs. These data indicate that the role of miRNAs in determining characteristics of primary tissue types may be different than their role in regulating cell type-specific functions in solid organs.

Nucleus of the solitary tract in the C57BL/6J mouse: Subnuclear parcellation, chorda tympani nerve projections, and brainstem connections.

PubMed

Ganchrow, Donald; Ganchrow, Judith R; Cicchini, Vanessa; Bartel, Dianna L; Kaufman, Daniel; Girard, David; Whitehead, Mark C

2014-05-01

The nucleus of the solitary tract (NST) processes gustatory and related somatosensory information rostrally and general viscerosensory information caudally. To compare its connections with those of other rodents, this study in the C57BL/6J mouse provides a subnuclear cytoarchitectonic parcellation (Nissl stain) of the NST into rostral, intermediate, and caudal divisions. Subnuclei are further characterized by NADPH staining and P2X2 immunoreactivity (IR). Cholera toxin subunit B (CTb) labeling revealed those NST subnuclei receiving chorda tympani nerve (CT) afferents, those connecting with the parabrachial nucleus (PBN) and reticular formation (RF), and those interconnecting NST subnuclei. CT terminals are densest in the rostral central (RC) and medial (M) subnuclei; less dense in the rostral lateral (RL) subnucleus; and sparse in the ventral (V), ventral lateral (VL), and central lateral (CL) subnuclei. CTb injection into the PBN retrogradely labels cells in the aforementioned subnuclei; RC and M providing the largest source of PBN projection neurons. Pontine efferent axons terminate mainly in V and rostral medial (RM) subnuclei. CTb injection into the medullary RF labels cells and axonal endings predominantly in V at rostral and intermediate NST levels. Small CTb injections within the NST label extensive projections from the rostral division to caudal subnuclei. Projections from the caudal division primarily interconnect subnuclei confined to the caudal division of the NST; they also connect with the area postrema. P2X2 -IR identifies probable vagal nerve terminals in the central (Ce) subnucleus in the intermediate/caudal NST. Ce also shows intense NADPH staining and does not project to the PBN. Copyright © 2013 Wiley Periodicals, Inc.

Nucleus of the solitary tract in the C57BL/6J mouse: Subnuclear parcellation, chorda tympani nerve projections, and brainstem connections

PubMed Central

Ganchrow, Donald; Ganchrow, Judith R; Cicchini, Vanessa; Bartel, Dianna L; Kaufman, Daniel; Girard, David; Whitehead, Mark C

2013-01-01

The nucleus of the solitary tract (NST) processes gustatory and related somatosensory information rostrally and general viscerosensory information caudally. To compare its connections with those of other rodents, this study in the C57BL/6J mouse provides a subnuclear cytoarchitectonic parcellation (Nissl stain) of the NST into rostral, intermediate, and caudal divisions. Subnuclei are further characterized by NADPH staining and P2X2 immunoreactivity (IR). Cholera toxin subunit B (CTb) labeling revealed those NST subnuclei receiving chorda tympani nerve (CT) afferents, those connecting with the parabrachial nucleus (PBN) and reticular formation (RF), and those interconnecting NST subnuclei. CT terminals are densest in the rostral central (RC) and medial (M) subnuclei; less dense in the rostral lateral (RL) subnucleus; and sparse in the ventral (V), ventral lateral (VL), and central lateral (CL) subnuclei. CTb injection into the PBN retrogradely labels cells in the aforementioned subnuclei; RC and M providing the largest source of PBN projection neurons. Pontine efferent axons terminate mainly in V and rostral medial (RM) subnuclei. CTb injection into the medullary RF labels cells and axonal endings predominantly in V at rostral and intermediate NST levels. Small CTb injections within the NST label extensive projections from the rostral division to caudal subnuclei. Projections from the caudal division primarily interconnect subnuclei confined to the caudal division of the NST; they also connect with the area postrema. P2X2-IR identifies probable vagal nerve terminals in the central (Ce) subnucleus in the intermediate/caudal NST. Ce also shows intense NADPH staining and does not project to the PBN. J. Comp. Neurol. 522:1565–1596, 2014. PMID:24151133

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.

PubMed

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.

Isolated medial medullary infarction due to vertebral artery dissection.

PubMed

Wakita, M; Matsuoka, H; Hamada, R; Kasuya, J; Osame, M

2003-12-01

A 54-year-old man developed left hemiparesis and tactile and deep sensory disturbance following onset of rightside cervical pain. These symptoms resulted from an isolated infarct in the right medial area of the upper medulla oblongata and intracranial vertebral artery (VA) dissection. Atherosclerotic disease of the VA is the most common cause of medial medullary infarction. In past reports of isolated medial medullary infarction, only a few cases involved VA dissection.

Plasticity of Intact Rubral Projections Mediates Spontaneous Recovery of Function after Corticospinal Tract Injury

PubMed Central

Siegel, Chad S.; Fink, Kathren L.; Strittmatter, Stephen M.

2015-01-01

Axons in the adult CNS fail to regenerate after injury, and therefore recovery from spinal cord injury (SCI) is limited. Although full recovery is rare, a modest degree of spontaneous recovery is observed consistently in a broad range of clinical and nonclinical situations. To define the mechanisms mediating spontaneous recovery of function after incomplete SCI, we created bilaterally complete medullary corticospinal tract lesions in adult mice, eliminating a crucial pathway for voluntary skilled movement. Anatomic and pharmacogenetic tools were used to identify the pathways driving spontaneous functional recovery in wild-type and plasticity-sensitized mice lacking Nogo receptor 1. We found that plasticity-sensitized mice recovered 50% of normal skilled locomotor function within 5 weeks of lesion. This significant, yet incomplete, spontaneous recovery was accompanied by extensive sprouting of intact rubrofugal and rubrospinal projections with the emergence of a de novo circuit between the red nucleus and the nucleus raphe magnus. Transient silencing of this rubro–raphe circuit in vivo via activation of the inhibitory DREADD (designer receptor exclusively activated by designer drugs) receptor hM4di abrogated spontaneous functional recovery. These data highlight the pivotal role of uninjured motor circuit plasticity in supporting functional recovery after trauma, and support a focus of experimental strategies on enhancing intact circuit rearrangement to promote functional recovery after SCI. PMID:25632122

Role of glutamate receptors in the dorsal reticular nucleus in formalin-induced secondary allodynia.

PubMed

Ambriz-Tututi, Mónica; Palomero-Rivero, Marcela; Ramirez-López, Fernanda; Millán-Aldaco, Diana; Drucker-Colín, And René

2013-10-01

The role of glutamate receptors present in the medullary dorsal reticular nucleus (DRt) in the formalin test and formalin-induced secondary nociception was studied in rats. Secondary mechanical allodynia was assessed with von Frey filaments applied to the rat's hindpaw, and secondary thermal hyperalgesia was evaluated with the tail-immersion test. The selective glutamate receptor antagonists MK801 (N-methyl-D-aspartate receptor antagonist), 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX) (AMPA/KA receptor antagonist) and A841720 (metabotropic glutamate 1 receptor antagonist) were injected into the DRt before or 6 days after formalin injection in the rat. In the formalin test, the three antagonists significantly reduced the number of flinches in both phases of the test. DRt microinjection of MK801 or A841720, but not of CNQX, reduced both secondary nociceptive behaviors. Moreover, pre-treatment with the three antagonists injected into the DRt prevented the development of secondary mechanical allodynia and secondary thermal hyperalgesia. Similarly, in these rats, the number of c-Fos-like immunoreactive neurons were markedly reduced in both the superficial and deep lamina of the dorsal horn. Our findings support the role of DRt as a pain facilitator in acute and chronic pain states, and suggest a key role of glutamate receptors during the development and maintenance of formalin-induced secondary allodynia. © 2013 Federation of European Neuroscience Societies and John Wiley & Sons Ltd.

Eliminating medullary 5-HT neurons delays arousal and decreases the respiratory response to repeated episodes of hypoxia in neonatal rat pups

PubMed Central

Schneider, Robert W.; Tobia, Christine M.; Commons, Kathryn G.

2015-01-01

Arousal from sleep is a critical defense mechanism when infants are exposed to hypoxia, and an arousal deficit has been postulated as contributing to the etiology of the sudden infant death syndrome (SIDS). The brainstems of SIDS infants are deficient in serotonin (5-HT) and tryptophan hydroxylase (TPH) and have decreased binding to 5-HT receptors. This study explores a possible connection between medullary 5-HT neuronal activity and arousal from sleep in response to hypoxia. Medullary raphe 5-HT neurons were eliminated from neonatal rat pups with intracisterna magna (CM) injections of 5,7-dihydroxytryptamine (DHT) at P2-P3. Each pup was then exposed to four episodes of hypoxia during sleep at three developmental ages (P5, P15, and P25) to produce an arousal response. Arousal, heart rate, and respiratory rate responses of DHT-injected pups were compared with pups that received CM artificial cerebrospinal fluid (aCSF) and those that received DHT but did not have a significant reduction in medullary 5-HT neurons. During each hypoxia exposure, the time to arousal from the onset of hypoxia (latency) was measured together with continuous measurements of heart and respiratory rates, oxyhemoglobin saturation, and chamber oxygen concentration. DHT-injected pups with significant losses of medullary 5-HT neurons exhibited significantly longer arousal latencies and decreased respiratory rate responses to hypoxia compared with controls. These results support the hypothesis that in newborn and young rat pups, 5-HT neurons located in the medullary raphe contribute to the arousal response to hypoxia. Thus alterations medullary 5-HT mechanisms might contribute to an arousal deficit and contribute to death in SIDS infants. PMID:26702023

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

PubMed

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.

Characteristics of stroke mechanisms in patients with medullary infarction.

PubMed

Lee, M J; Park, Y G; Kim, S J; Lee, J J; Bang, O Y; Kim, J S

2012-11-01

Few studies have focused on the mechanisms underlying medullary infarctions. Our aim in this study was to investigate stroke mechanisms in patients with medullary infarctions and to determine the clinical, radiological and laboratory characteristics of these patients with different underlying stroke etiologies. Consecutive patients with medullary infarction were analysed. Stroke mechanisms were classified as large artery disease (LAD), cardiogenic embolism (CE), small vessel disease (SVD), arterial dissection or undetermined etiology. Clinical, radiological and laboratory factors were analysed according to the location of the lesion and stroke mechanisms. A total of 77 patients were enrolled in this study. Amongst them, 53 (68.8%) patients had lateral medullary infarction (LMI), 22 (28.6%) had medial medullary infarction (MMI), and the remaining 2 (2.6%) had hemimedullary infarction. In both LMI and MMI patients, LAD was the most frequently encountered stroke mechanism. Arterial dissection was the second most common cause followed by SVD and CE in patients with LMI, whereas SVD was more frequently observed (P < 0.001) and dissection and CE were less prevalent (P < 0.001 and P = 0.024, respectively) in MMI than in LMI. Regarding differences amongst stroke etiologies, patients with dissection were younger and had a significantly lower incidence of metabolic syndrome (P = 0.002 and P = 0.009, respectively) than patients with LAD and SVD. Patients in the LAD (19/34, 60%) and dissection groups (12/14, 75%) had abnormal perfusion-weighted MRI (PWI) findings, whereas all patients with SVD (9/9) had normal PWI findings (P < 0.001). Stroke mechanisms in medullary infarction differ between LMI and MMI. Clinical and radiological characteristics, especially PWI features, are helpful in discriminating the etiologies of stroke in these patients. © 2012 The Author(s) European Journal of Neurology © 2012 EFNS.

Dorsal and ventral aspects of the most caudal medullary reticular formation have differential roles in modulation and formation of the respiratory motor pattern in rat.

PubMed

Jones, Sarah E; Stanić, Davor; Dutschmann, Mathias

2016-12-01

The respiratory pattern generator of mammals is anatomically organized in lateral respiratory columns (LRCs) within the brainstem. LRC compartments serve specific functions in respiratory pattern and rhythm generation. While the caudal medullary reticular formation (cMRF) has respiratory functions reportedly related to the mediation of expulsive respiratory reflexes, it remains unclear whether neurons of the cMRF functionally belong to the LRC. In the present study we specifically investigated the respiratory functions of the cMRF. Tract tracing shows that the cMRF has substantial connectivity with key compartments of the LRC, particularly the parafacial respiratory group and the Kölliker-Fuse nuclei. These neurons have a loose topography and are located in the ventral and dorsal cMRF. Systematic mapping of the cMRF with glutamate stimulation revealed potent respiratory modulation of the respiratory motor pattern from both dorsal and ventral injection sites. Pharmacological inhibition of the cMRF with the GABA-receptor agonist isoguvacine produced significant and robust changes to the baseline respiratory motor pattern (decreased laryngeal post-inspiratory and abdominal expiratory motor activity, delayed inspiratory off-switch and increased respiratory frequency) after dorsal cMRF injection, while ventral injections had no effect. The present data indicate that the ventral cMRF is not an integral part of the respiratory pattern generator and merely serves as a relay for sensory and/or higher command-related modulation of respiration. On the contrary, the dorsal aspect of the cMRF clearly has a functional role in respiratory pattern formation. These findings revive the largely abandoned concept of a dorsal respiratory group that contributes to the generation of the respiratory motor pattern.

Electrical stimulation of rhesus monkey nucleus reticularis gigantocellularis. II. Effects on metrics and kinematics of ongoing gaze shifts to visual targets.

PubMed

Freedman, Edward G; Quessy, Stephan

2004-06-01

Saccade kinematics are altered by ongoing head movements. The hypothesis that a head movement command signal, proportional to head velocity, transiently reduces the gain of the saccadic burst generator (Freedman 2001, Biol Cybern 84:453-462) can account for this observation. Using electrical stimulation of the rhesus monkey nucleus reticularis gigantocellularis (NRG) to alter the head contribution to ongoing gaze shifts, two critical predictions of this gaze control hypothesis were tested. First, this hypothesis predicts that activation of the head command pathway will cause a transient reduction in the gain of the saccadic burst generator. This should alter saccade kinematics by initially reducing velocity without altering saccade amplitude. Second, because this hypothesis does not assume that gaze amplitude is controlled via feedback, the added head contribution (produced by NRG stimulation on the side ipsilateral to the direction of an ongoing gaze shift) should lead to hypermetric gaze shifts. At every stimulation site tested, saccade kinematics were systematically altered in a way that was consistent with transient reduction of the gain of the saccadic burst generator. In addition, gaze shifts produced during NRG stimulation were hypermetric compared with control movements. For example, when targets were briefly flashed 30 degrees from an initial fixation location, gaze shifts during NRG stimulation were on average 140% larger than control movements. These data are consistent with the predictions of the tested hypothesis, and may be problematic for gaze control models that rely on feedback control of gaze amplitude, as well as for models that do not posit an interaction between head commands and the saccade burst generator.

UNMYELINATED FIBERS OF THE ANTERIOR ETHMOIDAL NERVE IN THE RAT CO-LOCALIZE WITH NEURONS IN THE MEDULLARY DORSAL HORN AND VENTROLATERAL MEDULLA ACTIVATED BY NASAL STIMULATION

PubMed Central

Hollandsworth, Michael P.; DiNovo, Karyn M.; McCulloch, Paul F.

2009-01-01

The anterior ethmoidal nerve (AEN) innervates the nasal passages and external nares, and serves as the afferent limb of the nasopharyngeal and diving responses. However, although 65% of the AEN is composed of unmyelinated fibers, it has not been determined whether this afferent signal is carried by unmyelinated or myelinated fibers. We used the transganglionic tracers WGA-HRP, IB4-HRP, and CTB-HRP to trace the central projections of the AEN of the rat. Interpretation of the labeling patterns suggests that AEN unmyelinated fibers project primarily to the ventral tip of the ipsilateral medullary dorsal horn (MDH) at the level of the area postrema. Other unmyelinated projections were to the ventral paratrigeminal nucleus and ventrolateral medulla, specifically the Bötzinger and RVLM/C1 regions. Myelinated AEN fibers projected to the ventral paratrigeminal and mesencephalic trigeminal nuclei. Stimulating the nasal passages of urethane-anesthetized rats with ammonia vapors produced the nasopharyngeal response that included apnea, bradycardia and an increase in arterial blood pressure. Central projections of the AEN co-localized with neurons within both MDH and RVLM/C1 that were activated by nasal stimulation. Within the ventral MDH the density of AEN terminal projections positively correlated with the rostral-caudal location of activated neurons, especially at and just caudal to the obex. We conclude that unmyelinated AEN terminal projections are involved in the activation of neurons in the MDH and ventrolateral medulla that participate in the nasopharyngeal response in the rat. We also found that IB4-HRP was a much less robust tracer than WGA-HRP. PMID:19732757

Autologous Adrenal Medullary, Fetal Mesencephalic, and Fetal Adrenal Brain Transplantation in Parkinson's Disease: A Long-Term Postoperative Follow-Up

PubMed Central

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

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

PubMed

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.

Veliparib, Capecitabine, and Temozolomide in Patients With Advanced, Metastatic, and Recurrent Neuroendocrine Tumor

ClinicalTrials.gov

2017-09-26

Functional Pancreatic Neuroendocrine Tumor; Malignant Somatostatinoma; Merkel Cell Carcinoma; Metastatic Adrenal Gland Pheochromocytoma; Metastatic Carcinoid Tumor; Multiple Endocrine Neoplasia Type 1; Multiple Endocrine Neoplasia Type 2A; Multiple Endocrine Neoplasia Type 2B; Neuroendocrine Neoplasm; Non-Functional Pancreatic Neuroendocrine Tumor; Pancreatic Glucagonoma; Pancreatic Insulinoma; Recurrent Adrenal Cortex Carcinoma; Recurrent Adrenal Gland Pheochromocytoma; Recurrent Merkel Cell Carcinoma; Somatostatin-Producing Neuroendocrine Tumor; Stage III Adrenal Cortex Carcinoma; Stage III Thyroid Gland Medullary Carcinoma; Stage IIIA Merkel Cell Carcinoma; Stage IIIB Merkel Cell Carcinoma; Stage IV Adrenal Cortex Carcinoma; Stage IV Merkel Cell Carcinoma; Stage IVA Thyroid Gland Medullary Carcinoma; Stage IVB Thyroid Gland Medullary Carcinoma; Stage IVC Thyroid Gland Medullary Carcinoma; Thymic Carcinoid Tumor; VIP-Producing Neuroendocrine Tumor; Well Differentiated Adrenal Cortex Carcinoma; Zollinger Ellison Syndrome

Evaluation of Renal Oxygenation Level Changes after Water Loading Using Susceptibility-Weighted Imaging and T2* Mapping.

PubMed

Ding, Jiule; Xing, Wei; Wu, Dongmei; Chen, Jie; Pan, Liang; Sun, Jun; Xing, Shijun; Dai, Yongming

2015-01-01

To assess the feasibility of susceptibility-weighted imaging (SWI) while monitoring changes in renal oxygenation level after water loading. Thirty-two volunteers (age, 28.0 ± 2.2 years) were enrolled in this study. SWI and multi-echo gradient echo sequence-based T2(*) mapping were used to cover the kidney before and after water loading. Cortical and medullary parameters were measured using small regions of interest, and their relative changes due to water loading were calculated based on baseline and post-water loading data. An intraclass correlation coefficient analysis was used to assess inter-observer reliability of each parameter. A receiver operating characteristic curve analysis was conducted to compare the performance of the two methods for detecting renal oxygenation changes due to water loading. Both medullary phase and medullary T2(*) values increased after water loading (p < 0.001), although poor correlations were found between the phase changes and the T2(*) changes (p > 0.05). Interobserver reliability was excellent for the T2(*) values, good for SWI cortical phase values, and moderate for the SWI medullary phase values. The area under receiver operating characteristic curve of the SWI medullary phase values was 0.85 and was not different from the medullary T2(*) value (0.84). Susceptibility-weighted imaging enabled monitoring changes in the oxygenation level in the medulla after water loading, and may allow comparable feasibility to detect renal oxygenation level changes due to water loading compared with that of T2(*) mapping.

Abnormalities in hemispheric specialization of caudate nucleus connectivity in schizophrenia

PubMed Central

Mueller, Sophia; Wang, Danhong; Pan, Ruiqi; Holt, Daphne J.; Liu, Hesheng

2015-01-01

Importance Hemispheric specialization of the human brain is a marker of successful neurodevelopment. Altered brain asymmetry that has been repeatedly reported in schizophrenia may represent consequences of disrupted neurodevelopment in the disorder. However, a complete picture of functional specialization in the schizophrenic brain and its connectional substrates are yet to be unveiled. Objective We aimed to quantify intrinsic hemispheric specialization at a cortical and subcortical level and to reveal potential disease effects in schizophrenia. Design/Participants Resting-state functional connectivity MRI has been previously used to quantitatively measure hemispheric specialization in healthy subjects, in a reliable manner. Here we quantified the intrinsic hemispheric specialization at the whole brain level in 31 patients with schizophrenia and 37 demographically matched healthy control subjects using resting-state functional connectivity MRI. Results The caudate nucleus, and cortical regions with connections to the caudate nucleus, showed markedly abnormal hemispheric specialization in schizophrenia. Compared to healthy controls, patients exhibited weaker specialization in the left, but the opposite pattern in the right, caudate nucleus. Schizophrenia patients also displayed a disruption of the inter-hemispheric coordination among the cortical regions with connections to the caudate nucleus. A linear classifier based on the specialization of the caudate nucleus distinguished patients from controls with a classification accuracy of 74%. Conclusions and Relevance These data suggested that hemispheric specialization could serve as a potential imaging biomarker of schizophrenia that, compared to task-based fMRI measures, is less prone to the confounding effects of variation in task compliance, cognitive ability, and command of language. PMID:25830688

Abnormalities in hemispheric specialization of caudate nucleus connectivity in schizophrenia.

PubMed

Mueller, Sophia; Wang, Danhong; Pan, Ruiqi; Holt, Daphne J; Liu, Hesheng

2015-06-01

Hemispheric specialization of the human brain is a marker of successful neurodevelopment. Altered brain asymmetry that has been repeatedly reported in schizophrenia may represent consequences of disrupted neurodevelopment in the disorder. However, a complete picture of functional specialization in the schizophrenic brain and its connectional substrates is yet to be unveiled. To quantify intrinsic hemispheric specialization at cortical and subcortical levels and to reveal potential disease effects in schizophrenia. Resting-state functional connectivity magnetic resonance imaging has been previously used to quantitatively measure hemispheric specialization in healthy individuals in a reliable manner. We quantified the intrinsic hemispheric specialization at the whole brain level in 31 patients with schizophrenia and 37 demographically matched healthy controls from November 28, 2007, through June 29, 2010, using resting-state functional magnetic resonance imaging. The caudate nucleus and cortical regions with connections to the caudate nucleus had markedly abnormal hemispheric specialization in schizophrenia. Compared with healthy controls, patients exhibited weaker specialization in the left, but the opposite pattern in the right, caudate nucleus (P < .001). Patients with schizophrenia also had a disruption of the interhemispheric coordination among the cortical regions with connections to the caudate nucleus. A linear classifier based on the specialization of the caudate nucleus distinguished patients from controls with a classification accuracy of 74% (with a sensitivity of 68% and a specificity of 78%). These data suggest that hemispheric specialization could serve as a potential imaging biomarker of schizophrenia that, compared with task-based functional magnetic resonance imaging measures, is less prone to the confounding effects of variation in task compliance, cognitive ability, and command of language.

Ventral medullary neurones excited from the hypothalamic and mid-brain defence areas.

PubMed

Hilton, S M; Smith, P R

1984-07-01

In cats anaesthetised with chloralose, the ventral medulla was explored in and around the strip previously identified as the location of the efferent pathway from the hypothalamic and mid-brain defence areas to the spinal cord, in a search for neurones excited by electrical stimulation of the defence areas. Such units were found mostly in the caudal part of this strip, at a depth of not more than 500 microns from the surface. Nearly all were located in the ventral part of nucleus paragigantocellularis lateralis (PGL) at the level of the rostral pole of the inferior olive. There was evidence of temporal and spatial facilitation, indicating a convergent excitatory input from the defence areas onto neurones in PGL. This is consistent with earlier evidence of a synaptic relay in the efferent pathway at this site. When the pathway is blocked at this site, arterial blood pressure falls profoundly, so activity in these neurones may be essential for the normal level of sympathetic nerve activity.

Recovery of Dysphagia in Lateral Medullary Stroke

PubMed Central

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

Recovery of Dysphagia in lateral medullary stroke.

PubMed

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.

Birth-related expression of c-fos, c-jun and substance P mRNAs in the rat brainstem and pia mater: possible relationship to changes in central chemosensitivity.

PubMed

Wickström, H R; Holgert, H; Hökfelt, T; Lagercrantz, H

1999-02-05

In situ hybridization was used to characterize respiration-related areas of the brainstem activated around the time of birth as well as their postnatal sensitivity to CO2. Levels of mRNA corresponding to the immediate early genes (IEG), c-fos and c-jun, and of substance P precursor, ppt-A, were determined in rat fetuses (E21) and neonatal pups (1 h, 1 day and 6 days after normal birth) and after exposure to hypercapnia (12% CO2 for 1 h). Transient increases in c-fos mRNA were observed in the central chemoreceptor area of the ventral medullary surface (VMS), in the lateral reticular nucleus (LRN), in the nucleus of the solitary tract (NTS), and in the nucleus raphé pallidus (RPA) 1 h after birth. Increased expression of c-fos mRNA in the VMS could also be evoked by hypercapnia and this response was particularly pronounced 1 day after birth. On the other hand, c-jun mRNA could be detected already at E21 in the hypoglossal nucleus (XII) and LRN and these levels were not significantly altered at 1 h after birth. There was, however, an increase in the expression of c-jun mRNA in the pia mater surrounding the brainstem after birth. At 1 day after birth, c-jun mRNA levels had decreased in the LRN and pia mater, and later on (6 days after birth) in XII. Furthermore, the ppt-A mRNA level in NTS increased immediately after birth and remained high 1 and 6 days later. These results suggest that (a) the central chemoreceptor area of the VMS, as well as the NTS, LRN, RPA and pia mater are activated following birth; (b) the VMS, but not the other structures examined, can be activated immediately after birth by hypercapnia; and (c) increased expression of ppt-A mRNA may be related to the transition of respiratory control at birth. Copyright 1998 Elsevier Science B.V.

Blockade of renal medullary bradykinin B2 receptors increases tubular sodium reabsorption in rats fed a normal-salt diet

PubMed Central

Sivritas, Sema-Hayriye; Ploth, David W.; Fitzgibbon, Wayne R.

2008-01-01

The present study was performed to test the hypothesis that under normal physiological conditions and/or during augmentation of kinin levels, intrarenal kinins act on medullary bradykinin B2 (BKB2) receptors to acutely increase papillary blood flow (PBF) and therefore Na+ excretion. We determined the effect of acute inner medullary interstitial (IMI) BKB2 receptor blockade on renal hemodynamics and excretory function in rats fed either a normal (0.23%)- or a low (0.08%)-NaCl diet. For each NaCl diet, two groups of rats were studied. Baseline renal hemodynamic and excretory function were determined during IMI infusion of 0.9% NaCl into the left kidney. The infusion was then either changed to HOE-140 (100 μg·kg−1·h−1, treated group) or maintained with 0.9% NaCl (time control group), and the parameters were again determined. In rats fed a normal-salt diet, HOE-140 infusion decreased left kidney Na+ excretion (urinary Na+ extraction rate) and fractional Na+ excretion by 40 ± 5% and 40 ± 4%, respectively (P < 0.01), but did not alter glomerular filtration rate, inner medullary blood flow (PBF), or cortical blood flow. In rats fed a low-salt diet, HOE-140 infusion did not alter renal regional hemodynamics or excretory function. We conclude that in rats fed a normal-salt diet, kinins act tonically via medullary BKB2 receptors to increase Na+ excretion independent of changes in inner medullary blood flow. PMID:18632797

Notch3 as a novel therapeutic target in metastatic medullary thyroid cancer.

PubMed

Lou, Irene; Odorico, Scott; Yu, Xiao-Min; Harrison, April; Jaskula-Sztul, Renata; Chen, Herbert

2018-01-01

Medullary thyroid cancer portends poor survival once liver metastasis occurs. We hypothesize that Notch3 overexpression in medullary thyroid cancer liver metastasis will decrease proliferation and growth of the tumor. TT cells were modified genetically to overexpress Notch3 in the presence of doxycycline, creating the TT-Notch3 cell line. Mice were injected intrasplenically with either TT-Notch3 or control vector TT-TRE cells. Each cell line had 3 treatment groups: control with 12 weeks of standard chow, early DOX with doxycycline chow at day 0 and for 70 days thereafter, and late DOX with doxycycline chow at 8 weeks. Each animal underwent micro-computed tomography to evaluate for tumor formation and tumor quantification was performed. Animals were killed at 12 weeks, and the harvested liver was stained with Ki-67, hematoxylin and eosin, and Notch3. Induction of Notch3 did not prevent formation of medullary thyroid cancer liver metastases as all mice in the early DOX group developed tumors. However, induction of Notch after medullary thyroid cancer liver tumor formation decreased tumor size, as seen on micro-computed tomography scans (late DOX group). This translated to a 37-fold decrease in tumor volume (P = .001). Notch3 overexpression also resulted in decreased Ki-67 index (P = .038). Moreover, Notch3 induction led to increased areas of neutrophil infiltration and necrosis on hematoxylin and eosin staining of the tumors CONCLUSION: Notch3 overexpression demonstrates an antiproliferative effect on established metastatic medullary thyroid cancer liver tumors and is a potential therapeutic target in treatment. Copyright © 2017 Elsevier Inc. All rights reserved.

Acute reductions in blood flow restricted to the dorsomedial medulla induce a pressor response in rats.

PubMed

Waki, Hidefumi; Bhuiyan, Mohammad E R; Gouraud, Sabine S; Takagishi, Miwa; Hatada, Atsutoshi; Kohsaka, Akira; Paton, Julian F R; Maeda, Masanobu

2011-08-01

The brainstem nucleus of the solitary tract (nucleus tractus solitarii, NTS) is a pivotal region for regulating the set-point of arterial pressure, the mechanisms of which are not fully understood. Based on evidence that the NTS exhibits O2-sensing mechanisms, we examined whether a localized disturbance of blood supply, resulting in hypoxia in the NTS, would lead to an acute increase in arterial pressure. Male Wistar rats were used. Cardiovascular parameters were measured before and after specific branches of superficial dorsal medullary veins were occluded; we assumed these were drainage vessels from the NTS and would produce stagnant hypoxia. Hypoxyprobe-1, a marker for detecting cellular hypoxia in the post-mortem tissue, was used to reveal whether vessel occlusion induced hypoxia within the NTS. Following vessel occlusion, blood flow in the dorsal surface of the medulla oblongata including the NTS region showed an approximately 60% decrease and was associated with hypoxia in neurons located predominantly in the caudal part of the NTS as revealed using hypoxyprobe-1. Arterial pressure increased and this response was pronounced significantly in both magnitude and duration when baroreceptor reflex afferents were sectioned. These results suggest that localized hypoxia in the NTS increases arterial pressure. We suggest this represents a protective mechanism whereby the elevated systemic pressure is a compensatory mechanism to enhance cerebral perfusion. Whether this physiological mechanism has any relevance to neurogenic hypertension is discussed.

Vagal gustatory reflex circuits for intraoral food sorting behavior in the goldfish: cellular organization and neurotransmitters.

PubMed

Ikenaga, Takanori; Ogura, Tatsuya; Finger, Thomas E

2009-09-20

The sense of taste is crucial in an animal's determination as to what is edible and what is not. This gustatory function is especially important in goldfish, who utilize a sophisticated oropharyngeal sorting mechanism to separate food from substrate material. The computational aspects of this detection are carried out by the medullary vagal lobe, which is a large, laminated structure combining elements of both the gustatory nucleus of the solitary tract and the nucleus ambiguus. The sensory layers of the vagal lobe are coupled to the motor layers via a simple reflex arc. Details of this reflex circuit were investigated with histology and calcium imaging. Biocytin injections into the motor layer labeled vagal reflex interneurons that have radially directed dendrites ramifying within the layers of primary afferent terminals. Axons of reflex interneurons extend radially inward to terminate onto both vagal motoneurons and small, GABAergic interneurons in the motor layer. Functional imaging shows increases in intracellular Ca++ of vagal motoneurons following electrical stimulation in the sensory layer. These responses were suppressed under Ca(++)-free conditions and by interruption of the axons bridging between the sensory and motor layers. Pharmacological experiments showed that glutamate acting via (+/-)-alpha-amino-3-hydroxy- 5-ethylisoxazole-4-propioinc acid (AMPA)/kainate and N-methyl-D-aspartic acid (NMDA) receptors mediate neurotransmission between reflex interneurons and vagal motoneurons. Thus, the vagal gustatory portion of the viscerosensory complex is linked to branchiomotor neurons of the pharynx via a glutamatergic interneuronal system.

Vagal gustatory reflex circuits for intraoral food sorting behavior in the goldfish Cellular organization and neurotransmitters

PubMed Central

Ikenaga, Takanori; Ogura, Tatsuya; Finger, Thomas E.

2009-01-01

The sense of taste is crucial in an animal’s determination as to what is edible and what is not. This gustatory function is especially important in goldfish who utilize a sophisticated oropharyngeal sorting mechanism to separate food from substrate material. The computational aspects of this detection are carried out by the medullary vagal lobe which is a large, laminated structure combining elements of both the gustatory nucleus of the solitary tract and the nucleus ambiguus. The sensory layers of the vagal lobe are coupled to the motor layers via a simple reflex arc. Details of this reflex circuit were investigated with histology and calcium imaging. Biocytin injections into the motor layer labeled vagal reflex interneurons which have radially-directed dendrites ramifying within the layers of primary afferent terminals. Axons of reflex interneurons extend radially inward to terminate onto both vagal motoneurons and small, GABAergic interneurons in the motor layer. Functional imaging shows increases in intracellular Ca++ of vagal motoneurons following electrical stimulation in the sensory layer. These responses were suppressed under Ca++-free conditions and by interruption of the axons bridging between the sensory and motor layers. Pharmacological experiments showed that glutamate acting via (±)-α-amino-3-hydroxy-5-ethylisoxazole-4-propioinc acid (AMPA)/kainate and N-methyl-D-aspartic acid (NMDA) receptors mediates neurotransmission between reflex interneurons and vagal motoneurons. Thus the vagal gustatory portion of the viscerosensory complex is linked to branchiomotor neurons of the pharynx via a glutamatergic interneuronal system. PMID:19598285

Nitric oxide and superoxide transport in a cross section of the rat outer medulla. II. Reciprocal interactions and tubulovascular cross talk.

PubMed

Edwards, Aurélie; Layton, Anita T

2010-09-01

In a companion study (Edwards A and Layton AT. Am J Physiol Renal Physiol. doi:10.1152/ajprenal.00680.2009), we developed a mathematical model of nitric oxide (NO), superoxide (O(2)(-)), and total peroxynitrite (ONOO) transport in mid-outer stripe and mid-inner stripe cross sections of the rat outer medulla (OM). We examined how the three-dimensional architecture of the rat OM, together with low medullary oxygen tension (Po(2)), affects the distribution of NO, O(2)(-), and ONOO in the rat OM. In the current study, we sought to determine generation rate and permeability values that are compatible with measurements of medullary NO concentrations and to assess the importance of tubulovascular cross talk and NO-O(2)(-) interactions under physiological conditions. Our results suggest that the main determinants of NO concentrations in the rat OM are the rate of vascular and tubular NO synthesis under hypoxic conditions, and the red blood cell (RBC) permeability to NO (P(NO)(RBC)). The lower the P(NO)(RBC), the lower the amount of NO that is scavenged by hemoglobin species, and the higher the extra-erythrocyte NO concentrations. In addition, our results indicate that basal endothelial NO production acts to significantly limit NaCl reabsorption across medullary thick ascending limbs and to sustain medullary perfusion, whereas basal epithelial NO production has a smaller impact on NaCl transport and a negligible effect on vascular tone. Our model also predicts that O(2)(-) consumption by NO significantly reduces medullary O(2)(-) concentrations, but that O(2)(-) , when present at subnanomolar concentrations, has a small impact on medullary NO bioavailability.

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.

PubMed

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 sulfate and elevation of progesterone suggest inhibition of 17-hydroxylase and 21-hydroxylase activities by sorafenib.

Pathologic bone tissues in a Turkey vulture and a nonavian dinosaur: implications for interpreting endosteal bone and radial fibrolamellar bone in fossil dinosaurs.

PubMed

Chinsamy, Anusuya; Tumarkin-Deratzian, Allison

2009-09-01

We report on similar pathological bone microstructure in an extant turkey vulture (Cathartes aura) and a nonavian dinosaur from Transylvania. Both these individuals exhibit distinctive periosteal reactive bone deposition accompanied by endosteal bone deposits in the medullary cavity. Our findings have direct implications on the two novel bone tissues recently described among nonavian dinosaurs, radial fibrolamellar bone tissue and medullary bone tissue. On the basis of the observed morphology of the periosteal reactive bone in the turkey vulture and the Transylvanian dinosaur, we propose that the radial fibrolamellar bone tissues observed in mature dinosaurs may have had a pathological origin. Our analysis also shows that on the basis of origin, location, and morphology, pathologically derived endosteal bone tissue can be similar to medullary bone tissues described in nonavian dinosaurs. As such, we caution the interpretation of all endosteally derived bone tissue as homologous to avian medullary bone. (c) 2009 Wiley-Liss, Inc.

Caffeine in the milk prevents respiratory disorders caused by in utero caffeine exposure in rats.

PubMed

Bodineau, Laurence; Saadani-Makki, Fadoua; Jullien, Hugues; Frugière, Alain

2006-01-25

Consequences of postnatal caffeine exposure by the milk on ponto-medullary respiratory disturbances observed following an in utero caffeine exposure were analysed. Ponto-medullary-spinal cord preparations from newborn rats exposed to caffeine during gestation but not after the birth display an increase in respiratory frequency and an exaggeration of the hypoxic respiratory depression compared to not treated preparations. These data suggest that tachypneic and apneic episodes encountered in human newborns whose mother consumed caffeine during pregnancy are due in large part to central effect of caffeine at the ponto-medullary level. Both baseline respiratory frequency increase and emphasis of hypoxic respiratory depression are not encountered if rat dams consumed caffeine during nursing. Our hypothesis is that newborn rats exposed to caffeine during gestation but not after the birth would be in withdrawal situation whereas, when caffeine is present in drinking fluid of lactating dams, it goes down the milk and is able to prevent ponto-medullary respiratory disturbances.

[Incidence of familial non-medullary thyroid carcinoma in the patient register of the Clinic and Polyclinic of Nuclear Medicine, University of Würzburg].

PubMed

Körber, C; Geling, M; Werner, E; Mörtl, M; Mäder, U; Reiners, C; Farahati, J

2000-01-01

In this study the incidence rate of familial non-medullary thyroid carcinoma was investigated in the first and second grade relatives of patients registered at the Clinic and Polyclinic for Nuclear Medicine, University of Würzburg. In this study 596 patients with differentiated thyroid carcinoma were enclosed, who were treated between 01.01.81 and 31.12.95. The data concerning a familial occurrence were studied by a retrospective survey-based analysis. These data were compared to a literature analysis for familial non-medullary thyroid carcinoma. 14 patients of the 596 patients treated showed a familial occurrence (2.3%). All these patients suffered from papillary thyroid carcinoma. According to the prognostic factors (tumor state, lymph node involvement, metastatic disease) no differences could be evaluated in the different groups (sporadic versus familial non-medullary thyroid disease). A familial occurrence of differentiated thyroid carcinomas is not frequently observed, but should be considered due to further genetic diseases.

Thyroid paraganglioma. Report of 3 cases and description of an immunohistochemical profile useful in the differential diagnosis with medullary thyroid carcinoma, based on complementary DNA array results.

PubMed

Castelblanco, Esmeralda; Gallel, Pilar; Ros, Susana; Gatius, Sonia; Valls, Joan; De-Cubas, Aguirre A; Maliszewska, Agnieszka; Yebra-Pimentel, M Teresa; Menarguez, Javier; Gamallo, Carlos; Opocher, Giuseppe; Robledo, Mercedes; Matias-Guiu, Xavier

2012-07-01

Thyroid paraganglioma is a rare disorder that sometimes poses problems in differential diagnosis with medullary thyroid carcinoma. So far, differential diagnosis is solved with the help of some markers that are frequently expressed in medullary thyroid carcinoma (thyroid transcription factor 1, calcitonin, and carcinoembryonic antigen). However, some of these markers are not absolutely specific of medullary thyroid carcinoma and may be expressed in other tumors. Here we report 3 new cases of thyroid paraganglioma and describe our strategy to design a diagnostic immunohistochemical battery. First, we performed a comparative analysis of the expression profile of head and neck paragangliomas and medullary thyroid carcinoma, obtained after complementary DNA array analysis of 2 series of fresh-frozen samples of paragangliomas and medullary thyroid carcinoma, respectively. Seven biomarkers showing differential expression were selected (nicotinamide adenine dinucleotide dehydrogenase 1 alpha subcomplex, 4-like 2, NDUFA4L2; cytochrome c oxidase subunit IV isoform 2; vesicular monoamine transporter 2; calcitonin gene-related protein/calcitonin; carcinoembryonic antigen; and thyroid transcription factor 1) for immunohistochemical analysis. Two tissue microarrays were constructed from 2 different series of paraffin-embedded samples of paragangliomas and medullary thyroid carcinoma. We provide a classifying rule for differential diagnosis that combines negativity or low staining for calcitonin gene-related protein (histologic score, <10) or calcitonin (histologic score, <50) together with positivity of any of NADH dehydrogenase 1 alpha subcomplex, 4-like 2; cytochrome c oxidase subunit IV isoform 2; or vesicular monoamine transporter 2 to predict paragangliomas, showing a prediction error of 0%. Finally, the immunohistochemical battery was checked in paraffin-embedded blocks from 4 examples of thyroid paraganglioma (1 previously reported case and 3 new cases), showing also a prediction error of 0%. Our results suggest that the comparative expression profile, obtained by complementary DNA arrays, seems to be a good tool to design immunohistochemical batteries used in differential diagnosis. Copyright © 2012 Elsevier Inc. All rights reserved.

The autonomic higher order processing nuclei of the lower brain stem are among the early targets of the Alzheimer's disease-related cytoskeletal pathology.

PubMed

Rüb, U; Del Tredici, K; Schultz, C; Thal, D R; Braak, E; Braak, H

2001-06-01

The nuclei of the pontine parabrachial region (medial parabrachial nucleus, MPB; lateral parabrachial nucleus, LPB; subpeduncular nucleus, SPP) together with the intermediate zone of the medullary reticular formation (IRZ) are pivotal relay stations within central autonomic regulatory feedback systems. This study was undertaken to investigate the evolution of the Alzheimer's disease-related cytoskeletal pathology in these four sites of the lower brain stem. We examined the MPB, LPB, SPP and IRZ in 27 autopsy cases and classified the cortical Alzheimer-related cytoskeletal anomalies according to an established staging system (neurofibrillary tangle/neuropil threads [NFT/NT] stages I-VI). The lesions were visualized either with the antibody AT8, which is immunospecific for the abnormally phosphorylated form of the cytoskeletal protein tau, or with a modified Gallyas silver iodide stain. The MPB, SPB, and IRZ display cytoskeletal pathology in stage I and the LPB in stage II, whereby bothstages correspond to the preclinical phase of Alzheimer's disease (AD). In stages III-IV (incipient AD), the MPB and SPP are severely affected. In all of the stage III-IV cases, the lesions in the LPB and IRZ are well developed. In stages V and VI (clinical phase of AD), the MPB and SPP are filled with the abnormal intraneuronal material. At stages V-VI, the LPB is moderately involved and the IRZ shows severe damage. The pathogenesis of the AD-related cytoskeletal lesions in the nuclei of the pontine parabrachial region and in the IRZ conforms with the cortical NFT/NT staging sequence I-VI. In the event that the cytoskeletal pathology observed in this study impairs the function of the nerve cells involved, it is conceivable that autonomic mechanisms progressively deteriorate with advancing cortical NFT/NT stages. This relationship remains to be established, but it could provide insights into the illusive correlation between the AD-related cytoskeletal pathology and the function of affected neurons.

Somatotopy in the Medullary Dorsal Horn As a Basis for Orofacial Reflex Behavior

PubMed Central

Panneton, W. Michael; Pan, BingBing; Gan, Qi

2017-01-01

The somatotopy of the trigeminocervical complex of the rat was defined as a basis for describing circuitry for reflex behaviors directed through the facial motor nucleus. Thus, transganglionic transport of horseradish peroxidase conjugates applied to individual nerves/peripheral receptive fields showed that nerves innervating oropharyngeal structures projected most rostrally, followed by nerves innervating snout, periocular, and then periauricular receptive fields most caudally. Nerves innervating mucosae or glabrous receptive fields terminated densely in laminae I, II, and V of the trigeminocervical complex, while those innervating hairy skin terminated in laminae I–V. Projections to lamina II exhibited the most focused somatotopy when individual cases were compared. Retrograde transport of FluoroGold (FG) deposited into the facial motor nucleus resulted in labeled neurons almost solely in lamina V of the trigeminocervical complex. The distribution of these labeled neurons paralleled the somatotopy of primary afferent fibers, e.g., those labeled after FG injections into a functional group of motoneurons innervating lip musculature were found most rostrally while those labeled after injections into motoneurons innervating snout, periocular and preauricular muscles, respectively, were found at progressively more caudal levels. Anterograde transport of injections of biotinylated dextran amine into lamina V at different rostrocaudal levels of the trigeminocervical complex confirmed the notion that the somatotopy of orofacial sensory fields parallels the musculotopy of facial motor neurons. These data suggest that neurons in lamina V are important interneurons in a simple orofacial reflex circuit consisting of a sensory neuron, interneuron and motor neuron. Moreover, the somatotopy of primary afferent fibers from the head and neck confirms the “onion skin hypothesis” and suggests rostral cervical dermatomes blend seamlessly with “cranial dermatomes.” The transition area between subnucleus interpolaris and subnucleus caudalis is addressed while the paratrigeminal nucleus is discussed as an interface between the somatic and visceral nervous systems. PMID:29066998

Review analysis of medullary carcinoma thyroid--15-year Indian experience.

PubMed

Dorairajan, N; Saravanakumar, P; Karthikeyan, S; Siddharth, D; Kanna, Srinivasulu

2005-08-01

To emphasize the importance of adequate primary surgery in cases of medullary carcinoma of the thyroid, 44 cases of treated medullary carcinoma of thyroid were retrospectively reviewed in Government General Hospital, Chennai between 1987 and 2002. Patients who underwent total thyroidectomy with only central compartment dissection were compared with those who had undergone total thyroidectomy with meticulous triple compartment (bilateral lateral and central groups) nodal dissection. The group of total thyroidectomy with only central compartment dissection had high rate of lymph nodal recurrence and persistent hypercalcitoninaemia when compared with the group of total thyroidectomy with meticulous triple compartment nodal dissection. (Chi square value 4.503 with p<0.05).

Glucagon Like Peptide-1 Receptor Expression in the Human Thyroid Gland

PubMed Central

Gier, Belinda; Butler, Peter C.; Lai, Chi K.; Kirakossian, David; DeNicola, Matthew M.

2012-01-01

Background: Glucagon like peptide-1 (GLP-1) mimetic therapy induces medullary thyroid neoplasia in rodents. We sought to establish whether C cells in human medullary thyroid carcinoma, C cell hyperplasia, and normal human thyroid express the GLP-1 receptor. Methods: Thyroid tissue samples with medullary thyroid carcinoma (n = 12), C cell hyperplasia (n = 9), papillary thyroid carcinoma (n = 17), and normal human thyroid (n = 15) were evaluated by immunofluorescence for expression of calcitonin and GLP-1 receptors. Results: Coincident immunoreactivity for calcitonin and GLP-1 receptor was consistently observed in both medullary thyroid carcinoma and C cell hyperplasia. GLP-1 receptor immunoreactivity was also detected in 18% of papillary thyroid carcinoma (three of 17 cases). Within normal human thyroid tissue, GLP-1 receptor immunoreactivity was found in five of 15 of the examined cases in about 35% of the total C cells assessed. Conclusions: In humans, neoplastic and hyperplastic lesions of thyroid C cells express the GLP-1 receptor. GLP-1 receptor expression is detected in 18% papillary thyroid carcinomas and in C cells in 33% of control thyroid lobes. The consequence of long-term pharmacologically increased GLP-1 signaling on these GLP-1 receptor-expressing cells in the thyroid gland in humans remains unknown, but appropriately powered prospective studies to exclude an increase in medullary or papillary carcinomas of the thyroid are warranted. PMID:22031513

The TRH neuron: a hypothalamic integrator of energy metabolism.

PubMed

Lechan, Ronald M; Fekete, Csaba

2006-01-01

Thyrotropin-releasing hormone (TRH) has an important role in the regulation of energy homeostasis not only through effects on thyroid function orchestrated through hypophysiotropic neurons in the hypothalamic paraventricular nucleus (PVN), but also through central effects on feeding behavior, thermogenesis, locomotor activation and autonomic regulation. Hypophysiotropic TRH neurons are located in the medial and periventricular parvocellular subdivisions of the PVN and receive direct monosynaptic projections from two, separate, populations of leptin-responsive neurons in the hypothalamic arcuate nucleus containing either alpha-melanocyte-stimulating hormone (alpha-MSH) and cocaine- and amphetamine-regulated transcript (CART), peptides that promote weight loss and increase energy expenditure, or neuropeptide Y (NPY) and agouti-related protein (AGRP), peptides that promote weight gain and reduce energy expenditure. During fasting, the reduction in TRH mRNA in hypophysiotropic neurons mediated by suppression of alpha-MSH/CART simultaneously with an increase in NPY/AGRP gene expression in arcuate nucleus neurons contributes to the fall in circulating thyroid hormone levels, presumably by increasing the sensitivity of the TRH gene to negative feedback inhibition by thyroid hormone. Endotoxin administration, however, has the paradoxical effect of increasing circulating levels of leptin and melanocortin signaling and CART gene expression in arcuate nucleus neurons, but inhibiting TRH gene expression in hypophysiotropic neurons. This may be explained by an overriding inhibitory effect of endotoxin to increase type 2 iodothyroine deiodinase (D2) in a population of specialized glial cells, tanycytes, located in the base and infralateral walls of the third ventricle. By increasing the conversion of T4 into T3, tanycytes may increase local tissue concenetrations of thyroid hormone, and thereby induce a state of local tissue hyperthyroidism in the region of hypophysisotrophic TRH neurons. Other regions of the brain may also serve as metabolic sensors for hypophysiostropic TRH neurons including the ventrolateral medulla and dorsomedial nucleus of the hypothalamus that have direct monosynaptic projections to the PVN. TRH also exerts a number of effects within the central nervous system that may contribute to the regulation of energy homeostasis. Included are an increase in core body temperature mediated through neurons in the anterior hypothalamic-preoptic area that coordinate a variety of autonomic responses; arousal and locomotor activation through cholinergic and dopaminergic mechanisms on the septum and nucleus accumbens, respectively; and regulation of the cephalic phase of digestion. While the latter responses are largely mediated through cholinergic mechanisms via TRH neurons in the brainstem medullary raphe and dorsal motor nucleus of the vagus, effects of TRH on autonomic loci in the hypothalamic PVN may also be important. Contrary to the actions of T3 to increase appetite, TRH has central effects to reduce food intake in normal, fasting and stressed animals. The precise locus where TRH mediates this response is unknown. However, evidence that an anatomically separate population of nonhypophysiotropic TRH neurons in the anterior parvocellular subdivision of the PVN is integrated into the leptin regulatory control system by the same arcuate nucleus neuronal populations that innervate hypophysiotropic TRH neurons, raises the possibility that anterior parvocellular TRH neurons may be involved, possibly through interactions with the limbic nervous system.

Peptide Receptor Radionuclide Therapy (PRRT) of Medullary and Nonmedullary Thyroid Cancer Using Radiolabeled Somatostatin Analogues.

PubMed

Salavati, Ali; Puranik, Ameya; Kulkarni, Harshad R; Budiawan, Hendra; Baum, Richard P

2016-05-01

As therapeutic options in advanced medullary and non-iodine avid differentiated (nonmedullary) thyroid cancers are limited and associated with significant toxicity, targeting of somatostatin receptors (SSTRs) for internal radiation therapy provides a promising option. Theranostics (therapy and diagnosis) using radiolabeled somatostatin analogues has proved to be a milestone in the management of SSTR-expressing tumors. Peptide receptor radionuclide therapy using (177)Lu-labeled or (90)Y-labeled somatostatin analogues may have a significant role in the management of medullary and nonmedullary thyroid cancers in those patients where PET/CT with (68)Ga-labeled somatostatin analogues demonstrates significant SSTR expression. Copyright © 2016 Elsevier Inc. All rights reserved.

Unusual Metastasis of Medullary Thyroid Carcinoma to the Breast: A Cytological and Histopathological Correlation

PubMed Central

Tanwar, Parul; Gandhi, Jatin S; Sharma, Anila; Gupta, Manoj; Choudhary, Partha S

2018-01-01

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. PMID:29643661

Pontine Mechanisms of Respiratory Control

PubMed Central

Dutschmann, Mathias; Dick, Thomas E.

2015-01-01

Pontine respiratory nuclei provide synaptic input to medullary rhythmogenic circuits to shape and adapt the breathing pattern. An understanding of this statement depends on appreciating breathing as a behavior, rather than a stereotypic rhythm. In this review, we focus on the pontine-mediated inspiratory off-switch (IOS) associated with postinspiratory glottal constriction. Further, IOS is examined in the context of pontine regulation of glottal resistance in response to multimodal sensory inputs and higher commands, which in turn rules timing, duration, and patterning of respiratory airflow. In addition, network plasticity in respiratory control emerges during the development of the pons. Synaptic plasticity is required for dynamic and efficient modulation of the expiratory breathing pattern to cope with rapid changes from eupneic to adaptive breathing linked to exploratory (foraging and sniffing) and expulsive (vocalizing, coughing, sneezing, and retching) behaviors, as well as conveyance of basic emotions. The speed and complexity of changes in the breathing pattern of behaving animals implies that “learning to breathe” is necessary to adjust to changing internal and external states to maintain homeostasis and survival. PMID:23720253

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.

PubMed

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.

Distribution and cellular localization of imidazoleacetic acid-ribotide, an endogenous ligand at imidazol(in)e and adrenergic receptors, in rat brain

PubMed Central

Friedrich, Victor L.; Martinelli, Giorgio P.; Prell, George D.; Holstein, Gay R.

2007-01-01

Imidazoleacetic acid-ribotide (IAA-RP) is a putative neurotransmitter/modulator recently discovered in mammalian brain. The present study examines the distribution of IAA-RP in the rat CNS using a highly specific antiserum raised in rabbit against IAA-RP with immunostaining of aldehyde-fixed rat CNS. IAA-RP-immunoreactive neurons were present throughout the neuraxis; neuroglia were not labeled. In each region, only a subset of the neuronal pool was immunostained. In the forebrain, ribotide-immunolabeled neurons were common in neocortex, in hippocampal formation, and in subcortical structures including basal ganglia, thalamus and hypothalamus. Labeling was prominent limbic areas including olfactory bulb, basal forebrain, pyriform cortex and amygdala. In the mid- and hindbrain, immunolabled neurons were concentrated in specific nuclei and, in some areas, in specific subregions of those nuclei. Structures of the motor system, including cranial nerve motor nuclei, precerebellar nuclei, the substantia nigra, and the red nucleus were clearly labeled. Staining was intense in cells and/or puncta in the rostral and caudal ventrolateral medullary reticular formation, nucleus tractus solitarius and the caudal vestibular nuclear complex. Within neurons, the ribotide was found predominantly in somata and dendrites; some myelinated axons and occasional synaptic terminals were also immunostained. These data indicate that IAA-RP contributes to the neurochemical phenotype of many neuronal populations further support our suggestion that, in autonomic structures, the IAA-RP may serve as a chemical mediator in complex circuits involved in blood pressure regulation and, more generally, sympathetic drive. PMID:17210242

Repetitive Diving in Trained Rats Still Increases Fos Production in Brainstem Neurons after Bilateral Sectioning of the Anterior Ethmoidal Nerve

PubMed Central

McCulloch, Paul F.; Warren, Erik A.; DiNovo, Karyn M.

2016-01-01

This research was designed to investigate the role of the anterior ethmoidal nerve (AEN) during repetitive trained diving in rats, with specific attention to activation of afferent and efferent brainstem nuclei that are part of this reflexive response. The AEN innervates the nose and nasal passages and is thought to be an important component of the afferent limb of the diving response. Male Sprague-Dawley rats (N = 24) were trained to swim and dive through a 5 m underwater maze. Some rats (N = 12) had bilateral sectioning of the AEN, others a Sham surgery (N = 12). Twelve rats (6 AEN cut and 6 Sham) had 24 post-surgical dive trials over 2 h to activate brainstem neurons to produce Fos, a neuronal activation marker. Remaining rats were non-diving controls. Diving animals had significantly more Fos-positive neurons than non-diving animals in the caudal pressor area, ventral medullary dorsal horn, ventral paratrigeminal nucleus, nucleus tractus solitarius, rostral ventrolateral medulla, Raphe nuclei, A5, Locus Coeruleus, and Kölliker-Fuse area. There were no significant differences in brainstem Fos labeling in rats diving with and without intact AENs. Thus, the AENs are not required for initiation of the diving response. Other nerve(s) that innervate the nose and nasal passages, and/or suprabulbar activation of brainstem neurons, may be responsible for the pattern of neuronal activation observed during repetitive trained diving in rats. These results help define the central neuronal circuitry of the mammalian diving response. PMID:27148082

Immunocytochemical localization of luteinizing hormone-releasing hormone (LHRH) in the nervus terminalis and brain of the big brown bat, Eptesicus fuscus.

PubMed

Oelschläger, H A; Northcutt, R G

1992-01-15

Little is known about the immunohistochemistry of the nervous system in bats. This is particularly true of the nervus terminalis, which exerts strong influence on the reproductive system during ontogeny and in the adult. Luteinizing hormone-releasing hormone (LHRH) was visualized immunocytochemically in the nervus terminalis and brain of juvenile and adult big brown bats (Eptesicus fuscus). The peripheral LHRH-immunoreactive (ir) cells and fibers (nervus terminalis) are dispersed along the basal surface of the forebrain from the olfactory bulbs to the prepiriform cortex and the interpeduncular fossa. A concentration of peripheral LHRH-ir perikarya and fibers was found at the caudalmost part of the olfactory bulbs, near the medioventral forebrain sulcus; obviously these cells mediate between the bulbs and the remaining forebrain. Within the central nervous system (CNS), LHRH-ir perikarya and fibers were distributed throughout the olfactory tubercle, diagonal band, preoptic area, suprachiasmatic and supraoptic nuclei, the bed nuclei of stria terminalis and stria medullaris, the anterior lateral and posterior hypothalamus, and the tuber cinereum. The highest concentration of cells was found within the arcuate nucleus. Fibers were most concentrated within the median eminence, infundibular stalk, and the medial habenula. The data obtained suggest that this distribution of LHRH immunoreactivity may be characteristic for microchiropteran (insectivorous) bats. The strong projections of LHRH-containing nuclei in the basal forebrain (including the arcuate nucleus) to the habenula, may indicate close functional contact between these brain areas via feedback loops, which could be important for the processing of thermal and other environmental stimuli correlated with hibernation.

Dynamics of neuromodulatory feedback determines frequency modulation in a reduced respiratory network: a computational study.

PubMed

Toporikova, Natalia; Butera, Robert J

2013-02-01

Neuromodulators, such as amines and neuropeptides, alter the activity of neurons and neuronal networks. In this work, we investigate how neuromodulators, which activate G(q)-protein second messenger systems, can modulate the bursting frequency of neurons in a critical portion of the respiratory neural network, the pre-Bötzinger complex (preBötC). These neurons are a vital part of the ponto-medullary neuronal network, which generates a stable respiratory rhythm whose frequency is regulated by neuromodulator release from the nearby Raphe nucleus. Using a simulated 50-cell network of excitatory preBötC neurons with a heterogeneous distribution of persistent sodium conductance and Ca(2+), we determined conditions for frequency modulation in such a network by simulating interaction between Raphe and preBötC nuclei. We found that the positive feedback between the Raphe excitability and preBötC activity induces frequency modulation in the preBötC neurons. In addition, the frequency of the respiratory rhythm can be regulated via phasic release of excitatory neuromodulators from the Raphe nucleus. We predict that the application of a G(q) antagonist will eliminate this frequency modulation by the Raphe and keep the network frequency constant and low. In contrast, application of a G(q) agonist will result in a high frequency for all levels of Raphe stimulation. Our modeling results also suggest that high [K(+)] requirement in respiratory brain slice experiments may serve as a compensatory mechanism for low neuromodulatory tone. Copyright © 2012 Elsevier B.V. All rights reserved.

Single oral administration of flavan 3-ols induces stress responses monitored with stress hormone elevations in the plasma and paraventricular nucleus.

PubMed

Fujii, Yasuyuki; Suzuki, Kenta; Hasegawa, Yahiro; Nanba, Fumio; Toda, Toshiya; Adachi, Takahiro; Taira, Shu; Osakabe, Naomi

2018-06-11

We previously confirmed that postprandial alterations in the circulation and metabolism after a single oral dose of flavan 3-ols (mixture of catechin and catechin oligomers) were involved in an increase in sympathetic nervous activity. However, it is well known that, in response to various stresses, activation of the hypothalamic-pituitary-adrenal (HPA) axis occurs together with sympathetic nerve activity, which is associated with activation of the sympathetic-adrenal-medullary (SAM) axis. In this study, we examined whether the HPA axis was activated after a single dose of flavan 3-ols. We administered an oral dose of 10 or 50 mg/kg flavan 3-ols to male ICR mice, removed the brains, and fixed them in paraformaldehyde-phosphate buffer. Other animals that were treated similarly were decapitated, and blood was collected. In the paraventricular nucleus (PVN), c-fos mRNA expression increased significantly at 15 min after administration of either 10 or 50 mg/kg flavan 3-ols. Corticotropin-releasing hormone (CRH) mRNA expression levels significantly increased at 240 min after administration of 10 mg/kg flavan 3-ols, and at 60 min after administration of 50 mg/kg flavan 3-ols. Plasma corticosterone levels were also significantly increased at 240 min after ingestion of 50 mg/kg flavan 3-ols. In this experiment, we confirmed that the ingestion of flavan 3-ols acted as a stressor in mammals with activation both the SAM and HPA axes. Copyright © 2018 Elsevier B.V. All rights reserved.

Cerebellar afferents originating from the medullary reticular formation that are different from mossy, climbing or monoaminergic fibers in the rat.

PubMed

Luo, Yuanjun; Sugihara, Izumi

2014-05-30

Integration of cortical Purkinje cell inputs and brain stem inputs is essential in generating cerebellar outputs to the cerebellar nuclei (CN). Currently, collaterals of climbing and mossy fiber axons, noradrenergic, serotoninergic and cholinergic axons, and collaterals of rubrospinal axons are known to innervate the CN from the brain stem. We investigated whether other afferents to the CN from the medulla exist in the rat. Retrograde labeling revealed the presence of neurons that project to the CN but not to the cerebellar cortex in the median reticular formation in the rostrodorsal medulla (tentatively named 'caudal raphe interpositus area', CRI). Anterograde tracer injection into the CRI labeled abundant axonal terminals in the CN, mainly in the ventral parvocellular part of the posterior interposed and lateral nucleus. Axonal reconstruction showed that a single CRI axon projected to the CN with 170-1086 varicosities, more broadly and densely than collaterals of a mossy or climbing fiber axon. CRI axons had no or a few collaterals that projected to the granular and Purkinje cell layers of the cerebellar cortex with some small terminals, indicating that these axons are different from mossy fiber axons. CRI axons also had collaterals that projected to the medial vestibular nucleus and an ascending branch that was not reconstructed. The location of the CRI, electron microscopic observations, and immunostaining results all indicated that CRI axons are not monoaminergic. We conclude that CRI axons form a type of afferent projection to the CN that is different from mossy, climbing or monoaminergic fibers. Copyright © 2014 Elsevier B.V. All rights reserved.

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

PubMed

Fry, Brendan C; Edwards, Aurélie; Layton, Anita T

2015-05-01

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. Copyright © 2015 the American Physiological Society.

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

PubMed Central

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

Farnesoid X receptor is essential for the survival of renal medullary collecting duct cells under hypertonic stress.

PubMed

Xu, Sujuan; Huang, Shizheng; Luan, Zhilin; Chen, Tingyue; Wei, Yuanyi; Xing, Miaomiao; Li, Yaqing; Du, Chunxiu; Wang, Bing; Zheng, Feng; Wang, Nanping; Guan, Youfei; Gustafsson, Jan-Åke; Zhang, Xiaoyan

2018-05-22

Hypertonicity in renal medulla is critical for the kidney to produce concentrated urine. Renal medullary cells have to survive high medullary osmolarity during antidiuresis. Previous study reported that farnesoid X receptor (FXR), a nuclear receptor transcription factor activated by endogenous bile acids, increases urine concentrating ability by up-regulating aquaporin 2 expression in medullary collecting duct cells (MCDs). However, whether FXR is also involved in the maintenance of cell survival of MCDs under dehydration condition and hypertonic stress remains largely unknown. In the present study, we demonstrate that 24-hours water restriction selectively up-regulated renal medullary expression of FXR with little MCD apoptosis in wild-type mice. In contrast, water deprivation caused a massive apoptosis of MCDs in both global FXR gene-deficient mice and collecting duct-specific FXR knockout mice. In vitro studies showed that hypertonicity significantly increased FXR and tonicity response enhancer binding protein (TonEBP) expression in mIMCD3 cell line and primary cultured MCDs. Activation and overexpression of FXR markedly increased cell viability and decreased cell apoptosis under hyperosmotic conditions. In addition, FXR can increase gene expression and nuclear translocation of TonEBP. We conclude that FXR protects MCDs from hypertonicity-induced cell injury very likely via increasing TonEBP expression and nuclear translocation. This study provides insights into the molecular mechanism by which FXR enhances urine concentration via maintaining cell viability of MCDs under hyperosmotic condition.

Dilated intercellular spaces and chronic cough as an extra-oesophageal manifestation of gastrooesophageal reflux disease.

PubMed

Orlando, Roy C

2011-06-01

Chronic cough is one of the extra-oesophageal manifestations of gastrooesophageal reflux disease (GORD). It is presumed to occur either directly by microaspiration of acidic gastric contents into the airway or indirectly by a reflex triggered by contact of acidic refluxates with the oesophageal epithelium in GORD. How contact of the oesophageal epithelium with acidic refluxates promotes sensitization for chronic cough is unknown, but like heartburn, which is a necessary accompaniment, it requires acid activation of nociceptors within the oesophageal mucosa. Dilated intercellular spaces within the oesophageal epithelium, a reflection of an increase in paracellular permeability, is a histopathologic feature of both erosive and non-erosive forms of GORD. Since it correlates with the symptom of heartburn, it is hypothesized herein that the increase in paracellular permeability to acid reflected by dilated intercellular spaces in oesophageal epithelium also serves as mediator of the signals that produce the reflex-induced sensitization for cough--a sensitization that can occur centrally within the medullary Nucleus Tractus Solitarius or peripherally within the tracheobronchial tree. Copyright © 2010 Elsevier Ltd. All rights reserved.

Expression of TASK-1 in brainstem and the occurrence of central sleep apnea in rats.

PubMed

Wang, Jing; Zhang, Cheng; Li, Nan; Su, Li; Wang, Guangfa

2008-03-20

Recent studies revealed that unstable ventilation control is one of mechanisms underlying the occurrence of sleep apnea. Thus, we investigated whether TASK-1, an acid-sensitive potassium channel, plays a role in the occurrence of sleep apnea. First, the expression of TASK-1 transcriptions on brainstem was checked by in situ hybridization. Then, the correlation between the central apneic episodes and protein contents of TASK-1 measured by western blot was analyzed from 27 male rats. Results showed that TASK-1 mRNAs were widely distributed on the putative central chemoreceptors such as locus coeruleus, nucleus tractus solitarius and medullary raphe, etc. Both the total spontaneous apnea index (TSAI) and spontaneous apnea index in NREM sleep (NSAI) were positively correlated with TASK-1 protein contents (r=0.547 and 0.601, respectively, p<0.01). However, the post-sigh sleep apnea index (PAI) had no relationship with TASK-1 protein. Thus, we concluded that TASK-1 channels may function as central chemoreceptors that play a role in spontaneous sleep apneas in rats.

Substance P and central respiratory activity: a comparative in vitro study in NK1 receptor knockout and wild-type mice.

PubMed

Ptak, K; Hunt, S P; Monteau, R

2000-07-01

Neurokinin-1 receptors (NK1) are present within the respiratory medullary network and in the phrenic nucleus, which controls the diaphragm. We compared the efficacy of substance P (SP) at inducing changes in respiratory frequency or the amplitude of the respiratory motor output between NK1 knockout (NK1-/-) and wild-type mice, using the in vitro brainstem-spinal cord preparation. The in vitro respiratory frequency, as well as the variability of the rhythm and the amplitude of the motor output were similar in both lines. In wild-type mice, application of exogenous SP induced either an increase in respiratory frequency (superfusion of the medulla) or an increase of the inspiratory motor output, as defined by the integral of C4 cervical ventral root activity (superfusion of the spinal cord). These two effects were not apparent in NK1-/- mice. In conclusion, NK1 receptors mediate the respiratory responses to SP but the lack of NK1 receptors in newborn NK1-/- mice does not change the respiratory activity.

Recurrent intramedullary epidermoid cyst of conus medullaris

PubMed Central

Fleming, Christina; Kaliaperumal, Chandrasekaran; O’Sullivan, Michael

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. PMID:22669964

NEW DEVELOPMENTS IN THE DIAGNOSIS AND TREATMENT OF THYROID CANCER

PubMed Central

Schneider, David F.; Chen, Herbert

2013-01-01

Thyroid cancer exists in several forms. Differentiated thyroid cancers include papillary and follicular histologies. These tumors exist along a spectrum of differentiation, and their incidence continues to climb. A number of advances in the diagnosis and treatment of differentiated thyroid cancers now exist. These include molecular diagnostics and more advanced strategies for risk stratification. Medullary cancer arises from the parafollicular cells and not the follicular cells. Therefore, diagnosis and treatment differs from differentiated thyroid tumors. Genetic testing and newer adjuvant therapies has changed the diagnosis and treatment of medullary thyroid cancer. This review will focus on the epidemiology, diagnosis, work-up, and treatment of both differentiated and medullary thyroid cancers, focusing specifically on newer developments in the field. PMID:23797834

Vascularised endosteal bone tissue in armoured sauropod dinosaurs.

PubMed

Chinsamy, Anusuya; Cerda, Ignacio; Powell, Jaime

2016-04-26

The presence of well-vascularised, endosteal bone in the medullary region of long bones of nonavian dinosaurs has been invoked as being homologous to medullary bone, a specialised bone tissue formed during ovulation in birds. However, similar bone tissues can result as a pathological response in modern birds and in nonavian dinosaurs, and has also been reported in an immature nonavian dinosaur. Here we report on the occurrence of well-vascularised endosteally formed bone tissue in three skeletal elements of armoured titanosaur sauropods from the Upper Cretaceous of Argentina: i) within the medullary cavity of a metatarsal, ii) inside a pneumatic cavity of a posterior caudal vertebra, iii) in intra-trabecular spaces in an osteoderm. We show that considering the criteria of location, origin (or development), and histology, these endosteally derived tissues in the saltasaurine titanosaurs could be described as either medullary bone or pathological bone. Furthermore, we show that similar endosteally formed well-vascularised bone tissue is fairly widely distributed among nondinosaurian Archosauriformes, and are not restricted to long bones, but can occur in the axial, and dermal skeleton. We propose that independent evidence is required to verify whether vascularised endosteal bone tissues in extinct archosaurs are pathological or reproductive in nature.

Characterization of organic osmolytes in avian renal medulla: a nonurea osmotic gradient system.

PubMed

Lien, Y H; Pacelli, M M; Braun, E J

1993-06-01

We measured the organic osmolytes present in the renal cortex and medullary cones of adult female domestic fowl before and after 48 h of water deprivation. Urine osmolality increased from 198 +/- 82 to 569 +/- 42 mosmol/kgH2O after water deprivation. In water-deprived birds, the major organic osmolytes, myoinositol, betaine, and taurine, in the medullary cones increased by 40, 100, and 24%, respectively, compared with control birds. No sorbitol was detected, and glycerophosphorylcholine (GPC) content was not affected by water deprivation. In the renal cortex, only betaine content increased significantly (4.8 +/- 0.6 vs. 3.1 +/- 0.3 mmol/kg wet wt) after water deprivation. In this study, we demonstrated that birds, like mammals, accumulate organic osmolytes in response to the increased interstitial osmolality that occurs during antidiuresis. Because urea is nearly absent in the avian medullary interstitium, our observation that GPC is not osmoregulated in the avian kidney supports the idea that GPC is the "counteracting osmolyte" for urea in the mammalian kidney. Furthermore, the organic osmolytes present in avian medullary cones are remarkably similar to those of the mammalian outer medulla. This similarity may be relevant to the morphological analogy of the two regions.

Vascularised endosteal bone tissue in armoured sauropod dinosaurs

PubMed Central

Chinsamy, Anusuya; Cerda, Ignacio; Powell, Jaime

2016-01-01

The presence of well-vascularised, endosteal bone in the medullary region of long bones of nonavian dinosaurs has been invoked as being homologous to medullary bone, a specialised bone tissue formed during ovulation in birds. However, similar bone tissues can result as a pathological response in modern birds and in nonavian dinosaurs, and has also been reported in an immature nonavian dinosaur. Here we report on the occurrence of well-vascularised endosteally formed bone tissue in three skeletal elements of armoured titanosaur sauropods from the Upper Cretaceous of Argentina: i) within the medullary cavity of a metatarsal, ii) inside a pneumatic cavity of a posterior caudal vertebra, iii) in intra-trabecular spaces in an osteoderm. We show that considering the criteria of location, origin (or development), and histology, these endosteally derived tissues in the saltasaurine titanosaurs could be described as either medullary bone or pathological bone. Furthermore, we show that similar endosteally formed well-vascularised bone tissue is fairly widely distributed among nondinosaurian Archosauriformes, and are not restricted to long bones, but can occur in the axial, and dermal skeleton. We propose that independent evidence is required to verify whether vascularised endosteal bone tissues in extinct archosaurs are pathological or reproductive in nature. PMID:27112710

Comparative physiology and architecture associated with the mammalian urine concentrating mechanism: role of inner medullary water and urea transport pathways in the rodent medulla.

PubMed

Pannabecker, Thomas L

2013-04-01

Comparative studies of renal structure and function have potential to provide insights into the urine-concentrating mechanism of the mammalian kidney. This review focuses on the tubular transport pathways for water and urea that play key roles in fluid and solute movements between various compartments of the rodent renal inner medulla. Information on aquaporin water channel and urea transporter expression has increased our understanding of functional segmentation of medullary thin limbs of Henle's loops, collecting ducts, and vasa recta. A more complete understanding of membrane transporters and medullary architecture has identified new and potentially significant interactions between these structures and the interstitium. These interactions are now being introduced into our concept of how the inner medullary urine-concentrating mechanism works. A variety of regulatory pathways lead directly or indirectly to variable patterns of fluid and solute movements among the interstitial and tissue compartments. Animals with the ability to produce highly concentrated urine, such as desert species, are considered to exemplify tubular structure and function that optimize urine concentration. These species may provide unique insights into the urine-concentrating process.(1)

Comparative physiology and architecture associated with the mammalian urine concentrating mechanism: role of inner medullary water and urea transport pathways in the rodent medulla

PubMed Central

2013-01-01

Comparative studies of renal structure and function have potential to provide insights into the urine-concentrating mechanism of the mammalian kidney. This review focuses on the tubular transport pathways for water and urea that play key roles in fluid and solute movements between various compartments of the rodent renal inner medulla. Information on aquaporin water channel and urea transporter expression has increased our understanding of functional segmentation of medullary thin limbs of Henle's loops, collecting ducts, and vasa recta. A more complete understanding of membrane transporters and medullary architecture has identified new and potentially significant interactions between these structures and the interstitium. These interactions are now being introduced into our concept of how the inner medullary urine-concentrating mechanism works. A variety of regulatory pathways lead directly or indirectly to variable patterns of fluid and solute movements among the interstitial and tissue compartments. Animals with the ability to produce highly concentrated urine, such as desert species, are considered to exemplify tubular structure and function that optimize urine concentration. These species may provide unique insights into the urine-concentrating process.1 PMID:23364530

The secretogranin-II derived peptide secretoneurin modulates electric behavior in the weakly pulse type electric fish, Brachyhypopomus gauderio.

PubMed

Pouso, Paula; Quintana, Laura; López, Gabriela C; Somoza, Gustavo M; Silva, Ana C; Trudeau, Vance L

2015-10-01

Secretoneurin (SN) in the preoptic area and pituitary of mammals and fish has a conserved close association with the vasopressin and oxytocin systems, members of a peptide family that are key in the modulation of sexual and social behaviors. Here we show the presence of SN-immunoreactive cells and projections in the brain of the electric fish, Brachyhypopomus gauderio. Secretoneurin colocalized with vasotocin (AVT) and isotocin in cells and fibers of the preoptic area. In the rostral pars distalis of the pituitary, many cells were both SN and prolactin-positive. In the hindbrain, at the level of the command nucleus of the electric behavior (pacemaker nucleus; PN), some of SN-positive fibers colocalized with AVT. We also explored the potential neuromodulatory role of SN on electric behavior, specifically on the rate of the electric organ discharge (EOD) that signals arousal, dominance and subordinate status. Each EOD is triggered by the command discharge of the PN, ultimately responsible for the basal EOD rate. SN modulated diurnal basal EOD rate in freely swimming fish in a context-dependent manner; determined by the initial value of EOD rate. In brainstem slices, SN partially mimicked the in vivo behavioral effects acting on PN firing rate. Taken together, our results suggest that SN may regulate electric behavior, and that its effect on EOD rate may be explained by direct action of SN at the PN level through either neuroendocrine and/or endocrine mechanisms. Copyright © 2015 Elsevier Inc. All rights reserved.

Effect of extracellular acid–base disturbances on the intracellular pH of neurones cultured from rat medullary raphe or hippocampus

PubMed Central

Bouyer, Patrice; Bradley, Stefania Risso; Zhao, Jinhua; Wang, Wengang; Richerson, George B; Boron, Walter F

2004-01-01

Previous reports suggest that an important characteristic of chemosensitive neurones is an unusually large change of steady-state intracellular pH in response to a change in extracellular pH (ΔpHi/ΔpHo). To determine whether such a correlation exists between neurones from the medullary raphe (a chemosensitive brain region) and hippocampus (a non-chemosensitive region), we used BCECF to monitor pHi in cultured neurones subjected to extracellular acid–base disturbances. In medullary raphe neurones, respiratory acidosis (5% → 9% CO2) caused a rapid fall in pHi (ΔpHi ∼0.2) with no recovery and a large ΔpHi/ΔpHo of 0.71. Hippocampal neurones had a similar response, but with a slightly lower ΔpHi/ΔpHo (0.59). We further investigated a possible link between pHi regulation and chemosensitivity by following the pHi measurements on medullary raphe neurones with an immunocytochemistry for tryptophan hydroxylase (a marker of serotonergic neurones). We found that the ΔpHi/ΔpHo of 0.69 for serotonergic neurones (which are stimulated by acidosis) was not different from either the ΔpHi/ΔpHo of 0.75 for non-serotonergic neurones (most of which are not chemosensitive), or from the ΔpHi/ΔpHo of hippocampal neurones. For both respiratory alkalosis (5% → 3% CO2) and metabolic alkalosis (22 mm → 35 mm HCO3−), ΔpHi/ΔpHo was 0.42–0.53 for all groups of neurones studied. The only notable difference between medullary raphe and hippocampal neurones was in response to metabolic acidosis (22 mm → 14 mm HCO3−), which caused a large pHi decrease in ∼80% of medullary raphe neurones (ΔpHi/ΔpHo = 0.71), but relatively little pHi decrease in 70% of the hippocampal neurones (ΔpHi/ΔpHo = 0.09). Our comparison of medullary raphe and hippocampal neurones indicates that, except in response to metabolic acidosis, the neurones from the chemosensitive region do not have a uniquely high ΔpHi/ΔpHo. Moreover, regardless of whether neurones were cultured from the chemosensitive or the non-chemosensitive region, pHi did not recover during any of the acid–base stresses. PMID:15194736

MEDULLARY THICK ASCENDING LIMB BUFFER VASOCONSTRICTION OF RENAL OUTER-MEDULLARY VASA RECTA IN SALT-RESISTANT BUT NOT SALT-SENSITIVE RATS

PubMed Central

O’Connor, Paul M.; Cowley, Allen W.

2013-01-01

We have previously demonstrated that paracrine signaling occurs between medullary thick ascending limb (mTAL) and the contractile pericytes of outer-medullary vasa recta (VR) termed ‘tubular-vascular cross talk’. The aim of the current study was to determine whether tubular-vascular cross talk has a functional effect on vasoconstrictor responses to angiotensin II, and to determine whether this is altered in the Dahl salt-sensitive (SS) rat. Studies were performed on salt-resistant consomic SS.13BN and SS rats using a novel outer medullary tissue strip preparation in which freshly isolated VR within VR bundles were perfused either alone or in combination with nearby mTAL. In VR from SS.13BN rats, angiotensin II (1μM) increased VR bundle intracellular Ca2+ concentration ([Ca2+]VR) 19±9nM (n=8) and reduced focal diameter in perfused VR by (−20±7%;n=5). In the presence of nearby mTAL however, [Ca2+]VR (−9±8nM; n=8) and VR diameter (−1±4%, n=7) in SS.13BN rats was unchanged by angiotensin II. In contrast, in Dahl SS rats, angiotensin II resulted in rapid and sustained increase in [Ca2+]VR (89±48 n=7;50±24% n=8) and a reduction in VR diameter of (−17±7;n=7 and −11±4%;n=5) in both isolated VR and VR with nearby mTAL, respectively. In VR with mTAL from SS13BN rats, inhibiton of purinergic receptors resulted in an increase in [Ca2+]VR, indicating purinergic signaling buffers vasoconstriction. Importantly, our in vitro data were able to predict medullary blood flow responses to angiotensin II in SS and SS.13BN rats in vivo. We conclude that paracrine signaling from mTAL buffers angiotensin II vasoconstriction in Dahl salt-resistant SS.13BN rats but not SS rats. PMID:22926950

Baroreflex regulation of blood pressure during dynamic exercise

NASA Technical Reports Server (NTRS)

Raven, P. B.; Potts, J. T.; Shi, X.; Blomqvist, C. G. (Principal Investigator)

1997-01-01

From the work of Potts et al. Papelier et al. and Shi et al. it is readily apparent that the arterial (aortic and carotid) baroreflexes are reset to function at the prevailing ABP of exercise. The blood pressure of exercise is the result of the hemodynamic (cardiac output and TPR) responses, which appear to be regulated by two redundant neural control systems, "Central Command" and the "exercise pressor reflex". Central Command is a feed-forward neural control system that operates in parallel with the neural regulation of the locomotor system and appears to establish the hemodynamic response to exercise. Within the central nervous system it appears that the HLR may be the operational site for Central Command. Specific neural sites within the HLR have been demonstrated in animals to be active during exercise. With the advent of positron emission tomography (PET) and single-photon emission computed tomography (SPECT), the anatomical areas of the human brain related to Central Command are being mapped. It also appears that the Nucleus Tractus Solitarius and the ventrolateral medulla may serve as an integrating site as they receive neural information from the working muscles via the group III/IV muscle afferents as well as from higher brain centers. This anatomical site within the CNS is now the focus of many investigations in which arterial baroreflex function, Central Command and the "exercise pressor reflex" appear to demonstrate inhibitory or facilitatory interaction. The concept of whether Central Command is the prime mover in the resetting of the arterial baroreceptors to function at the exercising ABP or whether the resetting is an integration of the "exercise pressor reflex" information with that of Central Command is now under intense investigation. However, it would be justified to conclude, from the data of Bevegard and Shepherd, Dicarlo and Bishop, Potts et al., and Papelier et al. that the act of exercise results in the resetting of the arterial baroreflex. In addition, if, as we have proposed, the cardiopulmonary baroreceptors primarily monitors and reflexly regulates cardiac filling volume, it would seem from the data of Mack et al. and Potts et al. that the cardiopulmonary baroreceptor is also reset at the beginning of exercise. Therefore, investigations of the neural mechanisms of regulation involving Central Command and cardiopulmonary afferents, similar to those being undertaken for the arterial baroreflex, need to be established.

Renal cell carcinoma, unclassified with medullary phenotype: poorly differentiated adenocarcinomas overlapping with renal medullary carcinoma.

PubMed

Sirohi, Deepika; Smith, Steven C; Ohe, Chisato; Colombo, Piergiuseppe; Divatia, Mukul; Dragoescu, Ema; Rao, Priya; Hirsch, Michelle S; Chen, Ying-Bei; Mehra, Rohit; Amin, Mahul B

2017-09-01

Renal medullary carcinoma (RMC) is a highly aggressive renal cell carcinoma arising in the collecting system and requiring careful correlation with status of sickle cell trait. A panel of international experts has recently proposed provisional diagnostic terminology, renal cell carcinoma, unclassified, with medullary phenotype, based on encountering an extraordinarily rare tumor with RMC morphology and immunophenotype in an individual proven not to have a hemoglobinopathy. Herein, we extend this observation to a cohort of 5 such tumors, morphologically similar to RMC, lacking SMARCB1 expression by immunohistochemistry, but each without evidence of a hemoglobinopathy. The tumors arose in 4 men and 1 woman with a mean age of 44 years, occurring in 3 left and 2 right kidneys. Clinically, aggression was apparent with involvement of perinephric adipose tissue in all 5 cases, nodal metastasis in 4 of 5 cases, and death of disease in 4 of 5 cases within 3-27 months. Histologic sections showed poorly differentiated adenocarcinoma, often with solid and nested growth patterns, as well as infiltrative glandular, tubulopapillary, cribriform, or reticular growth. Rhabdoid and sarcomatoid cytomorphology was seen in a subset. All tumors showed PAX8 nuclear positivity and SMARCB1 loss, with OCT3/4 expression in 4 of 5 cases. In summary, this first series of renal cell carcinoma, unclassified, with medullary phenotype documents tumors with morphologic, immunophenotypic, and prognostic features of RMC occurring in individuals without sickle cell trait. Although greater biologic and molecular understanding is needed, the available evidence points to these cases representing a sporadic counterpart to sickle cell trait-associated RMC. Copyright © 2017 Elsevier Inc. All rights reserved.

Urinary concentrating defect in mice with selective deletion of phloretin-sensitive urea transporters in the renal collecting duct

PubMed Central

Fenton, Robert A.; Chou, Chung-Lin; Stewart, Gavin S.; Smith, Craig P.; Knepper, Mark A.

2004-01-01

To investigate the role of inner medullary collecting duct (IMCD) urea transporters in the renal concentrating mechanism, we deleted 3 kb of the UT-A urea transporter gene containing a single 140-bp exon (exon 10). Deletion of this segment selectively disrupted expression of the two known IMCD isoforms of UT-A, namely UT-A1 and UT-A3, producing UT-A1/3-/- mice. In isolated perfused IMCDs from UT-A1/3-/- mice, there was a complete absence of phloretin-sensitive or vasopressin-stimulated urea transport. On a normal protein intake (20% protein diet), UT-A1/3-/- mice had significantly greater fluid consumption and urine flow and a reduced maximal urinary osmolality relative to wild-type controls. These differences in urinary concentrating capacity were nearly eliminated when urea excretion was decreased by dietary protein restriction (4% by weight), consistent with the 1958 Berliner hypothesis stating that the chief role of IMCD urea transport in the concentrating mechanism is the prevention of urea-induced osmotic diuresis. Analysis of inner medullary tissue after water restriction revealed marked depletion of urea in UT-A1/3-/- mice, confirming the concept that phloretin-sensitive IMCD urea transporters play a central role in medullary urea accumulation. However, there were no significant differences in mean inner medullary Na+ or Cl- concentrations between UT-A1/3-/- mice and wild-type controls, indicating that the processes that concentrate NaCl were intact. Thus, these results do not corroborate the predictions of passive medullary concentrating models stating that NaCl accumulation in the inner medulla depends on rapid vasopressin-regulated urea transport across the IMCD epithelium. PMID:15123796

Longitudinal Volume Quantification of Deep Medullary Veins in Patients with Cerebral Venous Sinus Thrombosis : Venous Volume Assessment in Cerebral Venous Sinus Thrombosis Using SWI.

PubMed

Dempfle, A K; Harloff, A; Schuchardt, F; Bäuerle, J; Yang, S; Urbach, H; Egger, K

2017-06-06

Susceptibility-weighted imaging (SWI) visualizes small cerebral veins with high sensitivity and could, thus, enable quantification of hemodynamics of deep medullary veins. We aimed to evaluate volume changes of deep medullary veins in patients with acute cerebral venous sinus thrombosis (CVST) over time in comparison to healthy controls. All magnetic resonance imaging (MRI) experiments were executed at 3 T using a 32-channel head coil. Based on SWI and semiautomatic postprocessing (statistical parametric mapping [SPM8] and ANTs), the volume of deep medullary veins was quantified in 14 patients with acute CVST at baseline and the 6‑month follow-up, as well as in 13 healthy controls undergoing repeated MRI examination with an interscan interval of at least 1 month. Deep medullary venous volume change over time was significantly different between healthy controls and patient groups (p < 0.001). Patients with superior sagittal sinus thrombosis (SSST) showed a significant decline from baseline to follow-up measurements (9.8 ± 4.9 ml versus 7.5 ± 4.2 ml; p = 0.02), whereas in patients with transverse sinus thrombosis (TST) and healthy controls no significant volume changes were observable. Venous volume quantification was feasible and reproducible both in healthy volunteers and in patients. The decrease of venous volume in patients over time represents improvement of venous drainage, reduction of congestion, and normalization of microcirculation due to treatment. Thus, quantification of venous microcirculation could be valuable for estimation of prognosis and guidance of CVST therapy in the future.

Arterial changes in cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) in relation to pathogenesis of diffuse myelin loss of cerebral white matter: examination of cerebral medullary arteries by reconstruction of serial sections of an autopsy case.

PubMed

Okeda, Riki; Arima, Kunimasa; Kawai, Mitsuru

2002-11-01

There is little information regarding the pathogenesis underlying diffuse myelin loss in the cerebral white matter and sparing of the U fibers in cerebral autosomal-dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL), in which the medial smooth muscle cells of systemic arteries are characteristically involved. We sought to examine the precise extent and severity of changes in the cerebral arteries in an autopsy case of CADASIL in relation to pathogenesis of the diffuse myelin loss. We reconstructed 1000 serial sections of the frontal cerebral medullary arteries of an autopsy subject, which was the first identified Japanese case of CADASIL, as confirmed by the presence of ultrastructural deposits of granular osmiophilic material in the media of some visceral arteries and by genetic analysis. We reconstructed 11 medullary arteries of the frontal lobe showing diffuse myelin loss and atrophy of the white matter with sparing of the U fibers. All of these showed complete loss of medial smooth muscle cells over their entire length and severe adventitial fibrosis. Although intimal fibrosis or hyalinosis was present, luminal occlusion was scarce. These changes were also observed in the small and large arachnoidal arteries but were relatively mild in the latter and in the cortical and subcortical medullary arteries. These arterial changes resulted in transformation of the cerebral arteries, in particular almost all the medullary arteries, to a so-called earthen pipe state. This supports the reported findings of a reduction in vascular reactivity to fluctuations in CO2 levels and systemic blood pressure in CADASIL.

Maximum urine concentrating capability in a mathematical model of the inner medulla of the rat kidney.

PubMed

Marcano, Mariano; Layton, Anita T; Layton, Harold E

2010-02-01

In a mathematical model of the urine concentrating mechanism of the inner medulla of the rat kidney, a nonlinear optimization technique was used to estimate parameter sets that maximize the urine-to-plasma osmolality ratio (U/P) while maintaining the urine flow rate within a plausible physiologic range. The model, which used a central core formulation, represented loops of Henle turning at all levels of the inner medulla and a composite collecting duct (CD). The parameters varied were: water flow and urea concentration in tubular fluid entering the descending thin limbs and the composite CD at the outer-inner medullary boundary; scaling factors for the number of loops of Henle and CDs as a function of medullary depth; location and increase rate of the urea permeability profile along the CD; and a scaling factor for the maximum rate of NaCl transport from the CD. The optimization algorithm sought to maximize a quantity E that equaled U/P minus a penalty function for insufficient urine flow. Maxima of E were sought by changing parameter values in the direction in parameter space in which E increased. The algorithm attained a maximum E that increased urine osmolality and inner medullary concentrating capability by 37.5% and 80.2%, respectively, above base-case values; the corresponding urine flow rate and the concentrations of NaCl and urea were all within or near reported experimental ranges. Our results predict that urine osmolality is particularly sensitive to three parameters: the urea concentration in tubular fluid entering the CD at the outer-inner medullary boundary, the location and increase rate of the urea permeability profile along the CD, and the rate of decrease of the CD population (and thus of CD surface area) along the cortico-medullary axis.

Effect of Space Flight on Adrenal Medullary Function

NASA Technical Reports Server (NTRS)

Lelkes, Peter I.

1999-01-01

We hypothesize that microgravity conditions during space flight alter the expression and specific activities of the adrenal medullary CA synthesizing enzymes (CASE). Previously, we examined adrenals from six rats flown for six days aboard STS 54 and reported that microgravity induced a decrease in the expression and specific activity of rat adrenal medullary tyrosine hydroxylase, the rate limiting enzyme of CA synthesis, without affecting the expression of other CASE. In the past, we analyzed some of the > 300 adrenals from two previous Space Shuttle missions (PARE 03 and SLS 2). The preliminary results (a) attest to the good state of tissue preservation, thus proving the feasibility of subsequent large-scale evaluation, and (b) confirm and extend our previous findings. With this grant we will be able to expeditiously analyze all our specimens and to complete our studies in a timely fashion.

The Kenny syndrome, a rare type of growth deficiency with tubular stenosis, transient hypoparathyroidism and anomalies of refraction.

PubMed

Majewski, F; Rosendahl, W; Ranke, M; Nolte, K

1981-03-01

One family (3 cases) with the Kenny syndrome and a second family (3 cases) with features of Kenny syndrome but lacking medullary stenosis are reported. The main symptoms in both families are proportionate dwarfism, cortical thickening of tubular bones, variable anomalies of the calvaria, anemia, transient hypoparathyroidism and variable ocular anomalies. The latter include microphthalmia, and moderate-to-severe myopia or hyperopia. In the first family there was medullary stenosis of most tubular bones. In the second family two cases exhibited mild-to-moderate cortical thickening of tubular bones, but absent or mild medullary stenosis. Possible variability of the Kenny syndrome is discussed. Endocrine studies failed to demonstrate any permanent disturbance of parathormone or calcitonin metabolism, or GH deficiency. Pathogenesis remains unclear. Autosomal dominant inheritance seems to be likely.

Surgical management of medullary thyroid cancer.

PubMed

Mazeh, H; Sippel, R S

2012-12-01

Although thyroid cancer accounts for only 1.5% of all malignancies in the US it is the most rapidly increasing cancer in incidence and it is the most common endocrine malignancy that accounts for over 95% of the endocrine malignancies. Medullary thyroid cancer (MTC) originates from the parafollicular C cells and it represents 6-8% of all thyroid cancer cases. As many as 25% of the MTCs are familial and carry a specific germline mutation as compared to only than 10% familial inheritance in non-medullary thyroid cancers. While well-differentiated thyroid malignancies carry a very good prognosis, recurrence and survival rates of patients with MTC are significantly worse. The difference in cell origin and differentiation also results in different available adjunct therapy. The aim of this study is to review in detail the surgical management of patients with MTC.

PPG neurons of the lower brain stem and their role in brain GLP-1 receptor activation

PubMed Central

Cork, Simon C.

2015-01-01

Within the brain, glucagon-like peptide-1 (GLP-1) affects central autonomic neurons, including those controlling the cardiovascular system, thermogenesis, and energy balance. Additionally, GLP-1 influences the mesolimbic reward system to modulate the rewarding properties of palatable food. GLP-1 is produced in the gut and by hindbrain preproglucagon (PPG) neurons, located mainly in the nucleus tractus solitarii (NTS) and medullary intermediate reticular nucleus. Transgenic mice expressing glucagon promoter-driven yellow fluorescent protein revealed that PPG neurons not only project to central autonomic control regions and mesolimbic reward centers, but also strongly innervate spinal autonomic neurons. Therefore, these brain stem PPG neurons could directly modulate sympathetic outflow through their spinal inputs to sympathetic preganglionic neurons. Electrical recordings from PPG neurons in vitro have revealed that they receive synaptic inputs from vagal afferents entering via the solitary tract. Vagal afferents convey satiation to the brain from signals like postprandial gastric distention or activation of peripheral GLP-1 receptors. CCK and leptin, short- and long-term satiety peptides, respectively, increased the electrical activity of PPG neurons, while ghrelin, an orexigenic peptide, had no effect. These findings indicate that satiation is a main driver of PPG neuronal activation. They also show that PPG neurons are in a prime position to respond to both immediate and long-term indicators of energy and feeding status, enabling regulation of both energy balance and general autonomic homeostasis. This review discusses the question of whether PPG neurons, rather than gut-derived GLP-1, are providing the physiological substrate for the effects elicited by central nervous system GLP-1 receptor activation. PMID:26290108

PPG neurons of the lower brain stem and their role in brain GLP-1 receptor activation.

PubMed

Trapp, Stefan; Cork, Simon C

2015-10-15

Within the brain, glucagon-like peptide-1 (GLP-1) affects central autonomic neurons, including those controlling the cardiovascular system, thermogenesis, and energy balance. Additionally, GLP-1 influences the mesolimbic reward system to modulate the rewarding properties of palatable food. GLP-1 is produced in the gut and by hindbrain preproglucagon (PPG) neurons, located mainly in the nucleus tractus solitarii (NTS) and medullary intermediate reticular nucleus. Transgenic mice expressing glucagon promoter-driven yellow fluorescent protein revealed that PPG neurons not only project to central autonomic control regions and mesolimbic reward centers, but also strongly innervate spinal autonomic neurons. Therefore, these brain stem PPG neurons could directly modulate sympathetic outflow through their spinal inputs to sympathetic preganglionic neurons. Electrical recordings from PPG neurons in vitro have revealed that they receive synaptic inputs from vagal afferents entering via the solitary tract. Vagal afferents convey satiation to the brain from signals like postprandial gastric distention or activation of peripheral GLP-1 receptors. CCK and leptin, short- and long-term satiety peptides, respectively, increased the electrical activity of PPG neurons, while ghrelin, an orexigenic peptide, had no effect. These findings indicate that satiation is a main driver of PPG neuronal activation. They also show that PPG neurons are in a prime position to respond to both immediate and long-term indicators of energy and feeding status, enabling regulation of both energy balance and general autonomic homeostasis. This review discusses the question of whether PPG neurons, rather than gut-derived GLP-1, are providing the physiological substrate for the effects elicited by central nervous system GLP-1 receptor activation. Copyright © 2015 the American Physiological Society.

Motor cortex electrical stimulation augments sprouting of the corticospinal tract and promotes recovery of motor function

PubMed Central

Carmel, Jason B.; Martin, John H.

2014-01-01

The corticospinal system—with its direct spinal pathway, the corticospinal tract (CST) – is the primary system for controlling voluntary movement. Our approach to CST repair after injury in mature animals was informed by our finding that activity drives establishment of connections with spinal cord circuits during postnatal development. After incomplete injury in maturity, spared CST circuits sprout, and partially restore lost function. Our approach harnesses activity to augment this injury-dependent CST sprouting and to promote function. Lesion of the medullary pyramid unilaterally eliminates all CST axons from one hemisphere and allows examination of CST sprouting from the unaffected hemisphere. We discovered that 10 days of electrical stimulation of either the spared CST or motor cortex induces CST axon sprouting that partially reconstructs the lost CST. Stimulation also leads to sprouting of the cortical projection to the magnocellular red nucleus, where the rubrospinal tract originates. Coordinated outgrowth of the CST and cortical projections to the red nucleus could support partial re-establishment of motor systems connections to the denervated spinal motor circuits. Stimulation restores skilled motor function in our animal model. Lesioned animals have a persistent forelimb deficit contralateral to pyramidotomy in the horizontal ladder task. Rats that received motor cortex stimulation either after acute or chronic injury showed a significant functional improvement that brought error rate to pre-lesion control levels. Reversible inactivation of the stimulated motor cortex reinstated the impairment demonstrating the importance of the stimulated system to recovery. Motor cortex electrical stimulation is an effective approach to promote spouting of spared CST axons. By optimizing activity-dependent sprouting in animals, we could have an approach that can be translated to the human for evaluation with minimal delay. PMID:24994971

Reversible inactivation of rostral nucleus raphe pallidus attenuates acute autonomic responses but not their habituation to repeated audiogenic stress in rats.

PubMed

Nyhuis, Tara J; Masini, Cher V; Taufer, Kirsten L; Day, Heidi E W; Campeau, Serge

2016-01-01

The medullary nucleus raphe pallidus (RPa) mediates several autonomic responses evoked by acute stress exposure, including tachycardia and hyperthermia. The present study assessed whether the RPa contributes to the decline/habituation of these responses observed during repeated audiogenic stress. Adult male rats were implanted with cannulae aimed at the RPa, and abdominal E-mitters that wirelessly acquire heart rate and core body temperature. After surgical recovery, animals were injected with muscimol or vehicle (aCSF) in the RPa region, followed by 30 min of 95-dBA loud noise or no noise control exposures on 3 consecutive days at 24-h intervals. Forty-eight hours after the third exposure, animals were exposed to an additional, but injection-free, loud noise or no noise test to assess habituation of hyperthermia and tachycardia. Three days later, rats were restrained for 30-min to evaluate their ability to display normal acute autonomic responses following the repeated muscimol injection regimen. The results indicated that the inhibition of cellular activity induced by the GABAA-receptor agonist muscimol centered in the RPa region reliably attenuated acute audiogenic stress-evoked tachycardia and hyperthermia, compared with vehicle-injected rats. Animals in the stress groups exhibited similar attenuated tachycardia and hyperthermia during the injection-free fourth audiogenic stress exposure, and displayed similar and robust increases in these responses to the subsequent restraint test. These results suggest that cellular activity in neurons of the RPa region is necessary for the expression of acute audiogenic stress-induced tachycardia and hyperthermia, but may not be necessary for the acquisition of habituated tachycardic responses to repeated stress.

Area postrema projects to FoxP2 neurons of the pre-locus coeruleus and parabrachial nuclei: brainstem sites implicated in sodium appetite regulation.

PubMed

Stein, Matthew K; Loewy, Arthur D

2010-11-04

The area postrema (AP) is a circumventricular organ located in the dorsal midline of the medulla. It functions as a chemosensor for blood-borne peptides and solutes, and converts this information into neural signals that are transmitted to the nucleus tractus solitarius (NTS) and parabrachial nucleus (PB). One of its NTS targets in the rat is the aldosterone-sensitive neurons which contain the enzyme 11 β-hydroxysteroid dehydrogenase type 2 (HSD2). The HSD2 neurons are part of a central network involved in sodium appetite regulation, and they innervate numerous brain sites including the pre-locus coeruleus (pre-LC) and PB external lateral-inner (PBel-inner) cell groups of the dorsolateral pons. Both pontine cell groups express the transcription factor FoxP2 and become c-Fos activated following sodium depletion. Because the AP is a component in this network, we wanted to determine whether it also projects to the same sites as the HSD2 neurons. By using a combination of anterograde axonal and retrograde cell body tract-tracing techniques in individual rats, we show that the AP projects to FoxP2 immunoreactive neurons in the pre-LC and PBel-inner. Thus, the AP sends a direct projection to both the first-order medullary (HSD2 neurons of the NTS) and the second-order dorsolateral pontine neurons (pre-LC and PB-el inner neurons). All three sites transmit information related to systemic sodium depletion to forebrain sites and are part of the central neural circuitry that regulates the complex behavior of sodium appetite. Copyright © 2010 Elsevier B.V. All rights reserved.

Ponto-medullary nuclei involved in the generation of sequential pharyngeal swallowing and concomitant protective laryngeal adduction in situ

PubMed Central

Bautista, Tara G; Dutschmann, Mathias

2014-01-01

Both swallowing and respiration involve postinspiratory laryngeal adduction. Swallowing-related postinspiratory neurons are likely to be located in the nucleus of the solitary tract (NTS) and those involved in respiration are found in the Kölliker–Fuse nucleus (KF). The function of KF and NTS in the generation of swallowing and its coordination with respiration was investigated in perfused brainstem preparations of juvenile rats (n = 41). Orally injected water evoked sequential pharyngeal swallowing (s-PSW) seen as phasic, spindle-shaped bursting of vagal nerve activity (VNA) against tonic postinspiratory discharge. KF inhibition by microinjecting isoguvacine (GABAA receptor agonist) selectively attenuated tonic postinspiratory VNA (n = 10, P < 0.001) but had no effect on frequency or timing of s-PSW. KF disinhibition after bicuculline (GABAA receptor antagonist) microinjections caused an increase of the tonic VNA (n = 8, P < 0.01) resulting in obscured and delayed phasic s-PSW. Occurrence of spontaneous PSW significantly increased after KF inhibition (P < 0.0001) but not after KF disinhibition (P = 0.14). NTS isoguvacine microinjections attenuated the occurrence of all PSW (n = 5, P < 0.01). NTS bicuculline microinjections (n = 6) resulted in spontaneous activation of a disordered PSW pattern and long-lasting suppression of respiratory activity. Pharmacological manipulation of either KF or NTS also triggered profound changes in respiratory postinspiratory VNA. Our results indicate that the s-PSW comprises two functionally distinct components. While the primary s-PSW is generated within the NTS, a KF-mediated laryngeal adductor reflex safeguards the lower airways from aspiration. Synaptic interaction between KF and NTS is required for s-PSW coordination with respiration as well as for proper gating and timing of s-PSW. PMID:24639482

Neuronal Activation in the Central Nervous System of Rats in the Initial Stage of Chronic Kidney Disease-Modulatory Effects of Losartan and Moxonidine

PubMed Central

Palkovits, Miklós; Šebeková, Katarína; Klenovics, Kristina Simon; Kebis, Anton; Fazeli, Gholamreza; Bahner, Udo; Heidland, August

2013-01-01

The effect of mild chronic renal failure (CRF) induced by 4/6-nephrectomy (4/6NX) on central neuronal activations was investigated by c-Fos immunohistochemistry staining and compared to sham-operated rats. In the 4/6 NX rats also the effect of the angiotensin receptor blocker, losartan, and the central sympatholyticum moxonidine was studied for two months. In serial brain sections Fos-immunoreactive neurons were localized and classified semiquantitatively. In 37 brain areas/nuclei several neurons with different functional properties were strongly affected in 4/6NX. It elicited a moderate to high Fos-activity in areas responsible for the monoaminergic innervation of the cerebral cortex, the limbic system, the thalamus and hypothalamus (e.g. noradrenergic neurons of the locus coeruleus, serotonergic neurons in dorsal raphe, histaminergic neurons in the tuberomamillary nucleus). Other monoaminergic cell groups (A5 noradrenaline, C1 adrenaline, medullary raphe serotonin neurons) and neurons in the hypothalamic paraventricular nucleus (innervating the sympathetic preganglionic neurons and affecting the peripheral sympathetic outflow) did not show Fos-activity. Stress- and pain-sensitive cortical/subcortical areas, neurons in the limbic system, the hypothalamus and the circumventricular organs were also affected by 4/6NX. Administration of losartan and more strongly moxonidine modulated most effects and particularly inhibited Fos-activity in locus coeruleus neurons. In conclusion, 4/6NX elicits high activity in central sympathetic, stress- and pain-related brain areas as well as in the limbic system, which can be ameliorated by losartan and particularly by moxonidine. These changes indicate a high sensitivity of CNS in initial stages of CKD which could be causative in clinical disturbances. PMID:23818940

Mapping and Analysis of the Connectome of Sympathetic Premotor Neurons in the Rostral Ventrolateral Medulla of the Rat Using a Volumetric Brain Atlas

PubMed Central

Dempsey, Bowen; Le, Sheng; Turner, Anita; Bokiniec, Phil; Ramadas, Radhika; Bjaalie, Jan G.; Menuet, Clement; Neve, Rachael; Allen, Andrew M.; Goodchild, Ann K.; McMullan, Simon

2017-01-01

Spinally projecting neurons in the rostral ventrolateral medulla (RVLM) play a critical role in the generation of vasomotor sympathetic tone and are thought to receive convergent input from neurons at every level of the neuraxis; the factors that determine their ongoing activity remain unresolved. In this study we use a genetically restricted viral tracing strategy to definitively map their spatially diffuse connectome. We infected bulbospinal RVLM neurons with a recombinant rabies variant that drives reporter expression in monosynaptically connected input neurons and mapped their distribution using an MRI-based volumetric atlas and a novel image alignment and visualization tool that efficiently translates the positions of neurons captured in conventional photomicrographs to Cartesian coordinates. We identified prominent inputs from well-established neurohumoral and viscero-sympathetic sensory actuators, medullary autonomic and respiratory subnuclei, and supramedullary autonomic nuclei. The majority of inputs lay within the brainstem (88–94%), and included putative respiratory neurons in the pre-Bötzinger Complex and post-inspiratory complex that are therefore likely to underlie respiratory-sympathetic coupling. We also discovered a substantial and previously unrecognized input from the region immediately ventral to nucleus prepositus hypoglossi. In contrast, RVLM sympathetic premotor neurons were only sparsely innervated by suprapontine structures including the paraventricular nucleus, lateral hypothalamus, periaqueductal gray, and superior colliculus, and we found almost no evidence of direct inputs from the cortex or amygdala. Our approach can be used to quantify, standardize and share complete neuroanatomical datasets, and therefore provides researchers with a platform for presentation, analysis and independent reanalysis of connectomic data. PMID:28298886

Reversible inactivation of rostral nucleus raphe pallidus attenuates acute autonomic responses but not their habituation to repeated audiogenic stress in rats

PubMed Central

Nyhuis, Tara J.; Masini, Cher V.; Taufer, Kirsten L.; Day, Heidi E.W.; Campeau, Serge

2016-01-01

The medullary nucleus raphe pallidus (RPa) mediates several autonomic responses evoked by acute stress exposure, including tachycardia and hyperthermia. The present study assessed whether the RPa contributes to the decline/habituation of these responses observed during repeated audiogenic stress. Adult male rats were implanted with cannulae aimed at the RPa, and abdominal E-mitters that wirelessly acquire heart rate and core body temperature. After surgical recovery, animals were injected with muscimol or vehicle (aCSF) in the RPa region, followed by 30 minutes of 95-dBA loud noise or no noise control exposures on 3 consecutive days at 24-hr intervals. Forty-eight hours after the third exposure, animals were exposed to an additional, but injection-free, loud noise or no noise test to assess habituation of hyperthermia and tachycardia. Three days later, rats were restrained for 30-minutes to evaluate their ability to display normal acute autonomic responses following the repeated muscimol injection regimen. The results indicated that the inhibition of cellular activity induced by the GABAA-receptor agonist muscimol centered in the RPa region reliably attenuated acute audiogenic stress-evoked tachycardia and hyperthermia, compared with vehicle-injected rats. Animals in the stress groups exhibited similarly attenuated tachycardia and hyperthermia during the injection-free fourth audiogenic stress exposure, and displayed similar and robust increases in these responses to the subsequent restraint test. These results suggest that cellular activity in neurons of the RPa region is necessary for the expression of acute audiogenic stress-induced tachycardia and hyperthermia, but may not be necessary for the acquisition of habituated tachycardic responses to repeated stress. PMID:26998558

Inhibition of spinal reflexes by paramedian reticular nucleus.

PubMed

Chai, C Y; Lin, Y F; Wang, H Y; Wu, W C; Yen, C T; Kuo, J S; Wayner, M J

1990-10-01

The inhibitory actions of the paramedian reticular nucleus (PRN), and its neighbouring structures, i.e., midline raphe nuclei (MRN) and dorsal medullary depressor area (DMD) on the knee jerk (KnJ) and crossed extension movement (CEM) induced by central sciatic stimulation and on the L5 ventral root response (EVRR) evoked by central tibial stimulation, were studied in cats under urethane (400 mg/kg) and alpha-chloralose (40 mg/kg) anesthesia alone, IP or further paralyzed with atracurium besylate (0.5 mg/kg/30 min), IV. Electrical stimulation of the above areas with rectangular pulses (80 Hz, 1.0 msec, 100-200 microA) decreased systemic arterial blood pressure (SAP) in an average value of: 36 +/- 3 mmHg for PRN; 19 +/- 2 mmHg for MRN; and 23 +/- 3 mmHg for DMD. The KnJ and CEM were almost completely suppressed by simultaneous PRN stimulation. The EVRR, including mono- and polysynaptic spinal reflexes with transmission velocity from 10 to 60 m/sec or above, were also suppressed. MRN stimulation only inhibited the KnJ, CEM and polysynaptic spinal reflexes with transmission velocities between 25 and 60 m/sec, but facilitated spinal reflexes with conduction velocities below 10 m/sec. On the other hand, DMD stimulation resulted in small suppression of KnJ, CEM and inhibition of polysynaptic spinal reflexes with conduction velocities between 25 and 60 m/sec. Even though MRN and DMD partially inhibited polysynaptic spinal reflexes, the magnitude of such inhibition was much smaller than that produced by PRN (-20% and -22% vs. -48%). The above-mentioned PRN effects on SAP and EVRR persisted in chronic animals decerebellated 9-12 days before.(ABSTRACT TRUNCATED AT 250 WORDS)

Nucleus Ambiguus Cholinergic Neurons Activated by Acupuncture: Relation to Enkephalin

PubMed Central

Guo, Zhi-Ling; Li, Min; Longhurst, John C.

2012-01-01

Acupuncture regulates autonomic function. Our previous studies have shown that electroacupuncture (EA) at the Jianshi–Neiguan acupoints (P5–P6, underlying the median nerve) inhibits central sympathetic outflow and attenuates excitatory cardiovascular reflexes, in part, through an opioid mechanism. It is unknown if EA at these acupoints influences the parasympathetic system. Thus, using c-Fos expression, we examined activation of nucleus ambiguus (NAmb) neurons by EA, their relation to cholinergic (preganglionic parasympathetic) neurons and those containing enkephalin. To enhance detection of cell bodies containing enkephalin, colchicine (90–100 μg/kg) was administered into the subarachnoid space of cats 30 hr prior to EA or sham-operated controls for EA. Following bilateral barodenervation and cervical vagotomy, either EA for 30 min at P5–P6 acupoints or control stimulation (needle placement at P5–P6 without stimulation) was applied. While perikarya containing enkephalin were observed in some medullary nuclei (e.g., râphe), only enkephalin-containing neuronal processes were found in the NAmb. Compared to controls (n=4), more c-Fos immunoreactivity, located principally in close proximity to fibers containing enkephalin was noted in the NAmb of EA-treated cats (n=5; P<0.01). Moreover, neurons double-labeled with c-Fos and choline acetyltransferase in the NAmb were identified in EA-treated, but not the control animals. These data demonstrate for the first time that EA activates preganglionic parasympathetic neurons in the NAmb. Because of their close proximity, these EA-activated neurons likely interact with nerve fibers containing enkephalin. These results suggest that EA at the P5–P6 acupoints has the potential to influence parasympathetic outflow and cardiovascular function, likely through an enkephalinergic mechanism. PMID:22306033

Acute lymphoblastic leukemia terminating as histiocytic medullary reticulosis.

PubMed

Shreiner, D P

1975-02-24

A young man with acute lymphoblastic leukemia was treated with vincristine sulfate, prednisone, and intrathecally injected methotrexate sodium for central nervous system involvement. A good remission was induced, but three months later he had hepatosplenomegaly, an enlarging mediastinal mass, and progressive anemia. Histiocytic medullary reticulosis was confirmed by a bone marrow biopsy specimen. The patient died of respiratory failure because of infiltration of the lungs by malignant histiocytes.

Control of potassium excretion: a Paleolithic perspective.

PubMed

Halperin, Mitchell L; Cheema-Dhadli, Surinder; Lin, Shih-Hua; Kamel, Kamel S

2006-07-01

Regulation of potassium (K) excretion was examined in an experimental setting that reflects the dietary conditions for humans in Paleolithic times (high, episodic intake of K with organic anions; low intake of NaCl), because this is when major control mechanisms were likely to have developed. The major control of K secretion in this setting is to regulate the number of luminal K channels in the cortical collecting duct. Following a KCl load, the K concentration in the medullary interstitial compartment rose; the likely source of this medullary K was its absorption by the H/K-ATPase in the inner medullary collecting duct. As a result of the higher medullary K concentration, the absorption of Na and Cl was inhibited in the loop of Henle, and this led to an increased distal delivery of a sufficient quantity of Na to raise K excretion markedly, while avoiding a large natriuresis. In addition, because K in the diet was accompanied by 'future' bicarbonate, a role for bicarbonate in the control of K secretion via 'selecting' whether aldosterone would be a NaCl-conserving or a kaliuretic hormone is discussed. This way of examining the control of K excretion provides new insights into clinical disorders with an abnormal plasma K concentration secondary to altered K excretion, and also into the pathophysiology of calcium-containing kidney stones.

Nedd4 Family Interacting Protein 1 (Ndfip1) Is Required for Ubiquitination and Nuclear Trafficking of BRCA1-associated ATM Activator 1 (BRAT1) during the DNA Damage Response*

PubMed Central

Low, Ley-Hian; Chow, Yuh-Lit; Li, Yijia; Goh, Choo-Peng; Putz, Ulrich; Silke, John; Ouchi, Toru; Howitt, Jason; Tan, Seong-Seng

2015-01-01

During injury, cells are vulnerable to apoptosis from a variety of stress conditions including DNA damage causing double-stranded breaks. Without repair, these breaks lead to aberrations in DNA replication and transcription, leading to apoptosis. A major response to DNA damage is provided by the protein kinase ATM (ataxia telangiectasia mutated) that is capable of commanding a plethora of signaling networks for DNA repair, cell cycle arrest, and even apoptosis. A key element in the DNA damage response is the mobilization of activating proteins into the cell nucleus to repair damaged DNA. BRAT1 is one of these proteins, and it functions as an activator of ATM by maintaining its phosphorylated status while also keeping other phosphatases at bay. However, it is unknown how BRAT1 is trafficked into the cell nucleus to maintain ATM phosphorylation. Here we demonstrate that Ndfip1-mediated ubiquitination of BRAT1 leads to BRAT1 trafficking into the cell nucleus. Without Ndfip1, BRAT1 failed to translocate to the nucleus. Under genotoxic stress, cells showed increased expression of both Ndfip1 and phosphorylated ATM. Following brain injury, neurons show increased expression of Ndfip1 and nuclear translocation of BRAT1. These results point to Ndfip1 as a sensor protein during cell injury and Ndfip1 up-regulation as a cue for BRAT1 ubiquitination by Nedd4 E3 ligases, followed by nuclear translocation of BRAT1. PMID:25631046

STUDIES OF THE RENAL CONCENTRATING MECHANISM IN HUMANS. I. THE EFFECT OF HYPERTHYROIDISM,

DTIC Science & Technology

Summary: (1) The maximum urinary osmolality after dehydration and exogenous vasopressin was significantly decreased during thyrotoxicosis in... thyrotoxicosis , TcH2O during a moderate mannitol diuresis was unchanged in most patients. The data suggest that the decreased Umax and normal TcH2O...in thyrotoxic individuals is probably caused by an increase in medullary blood flow with a decrease in medullary osmolality. (2) Renal hemodynamics

Review analysis of medullary carcinoma of the thyroid: a 15-year Indian experience.

PubMed

Dorairajan, N; Siddharth, D; Kanna, Srinivasulu

2006-01-01

The aim of this study was to emphasize the importance of adequate primary surgery in cases of medullary carcinoma of the thyroid. We retrospectively reviewed 44 cases of medullary carcinoma of the thyroid treated in Government General Hospital, Chennai between 1987 and 2002. Patients who underwent total thyroidectomy with only central compartment dissection were compared with those who had undergone total thyroidectomy with meticulous triple compartment (bilateral lateral and central groups) nodal dissection. The group of total thyroidectomy with only central compartment dissection had a high rate of lymph nodal recurrence and persistent hypercalcitoninemia compared with the group with total thyroidectomy with meticulous triple compartment nodal dissection. (chi square, 4.503; P > 0.05). Primary surgery with total thyroidectomy with meticulous triple compartment dissection is superior to total thyroidectomy with central compartment dissection alone in terms of preventing nodal and local recurrences and achieving normal (basal and stimulated) serum calcitonin levels postoperatively.

Acute Transverse Myelitis at the Conus Medullaris Level After Rabies Vaccination in a Patient With Behçet's Disease

PubMed Central

Bir, Levent Sinan; Özdemir Eşmeli, Fatma; Cenikli, Utku; Erdoğan, Çağgdaş; Değirmenci, Eylem

2007-01-01

Case report: A 25-year-old man with Behçet's disease was admitted because of weakness of the lower limbs and difficulty in urination. He had received a rabies vaccination 2 months previous because he had been bitten by a dog. Findings: Clinical and laboratory findings supported acute transverse myelitis. A hyperintense lesion and expansion at the level of conus medullaris was detected on spinal magnetic resonance imaging. Conclusion: Although neurologic involvement is one of the main causes of mortality and morbidity in Behçet's disease, the factors that aggravate the involvement of the nervous system are still unclear. Vaccination may have been the factor that had activated autoimmune mechanisms in this case. To our knowledge, involvement of the conus medullaris in Behçet's disease after rabies vaccination has not been reported. PMID:17684898

Revised American Thyroid Association guidelines for the management of medullary thyroid carcinoma.

PubMed

Wells, Samuel A; Asa, Sylvia L; Dralle, Henning; Elisei, Rossella; Evans, Douglas B; Gagel, Robert F; Lee, Nancy; Machens, Andreas; Moley, Jeffrey F; Pacini, Furio; Raue, Friedhelm; Frank-Raue, Karin; Robinson, Bruce; Rosenthal, M Sara; Santoro, Massimo; Schlumberger, Martin; Shah, Manisha; Waguespack, Steven G

2015-06-01

The American Thyroid Association appointed a Task Force of experts to revise the original Medullary Thyroid Carcinoma: Management Guidelines of the American Thyroid Association. The Task Force identified relevant articles using a systematic PubMed search, supplemented with additional published materials, and then created evidence-based recommendations, which were set in categories using criteria adapted from the United States Preventive Services Task Force Agency for Healthcare Research and Quality. The original guidelines provided abundant source material and an excellent organizational structure that served as the basis for the current revised document. The revised guidelines are focused primarily on the diagnosis and treatment of patients with sporadic medullary thyroid carcinoma (MTC) and hereditary MTC. The Task Force developed 67 evidence-based recommendations to assist clinicians in the care of patients with MTC. The Task Force considers the recommendations to represent current, rational, and optimal medical practice.

Revised American Thyroid Association Guidelines for the Management of Medullary Thyroid Carcinoma

PubMed Central

Asa, Sylvia L.; Dralle, Henning; Elisei, Rossella; Evans, Douglas B.; Gagel, Robert F.; Lee, Nancy; Machens, Andreas; Moley, Jeffrey F.; Pacini, Furio; Raue, Friedhelm; Frank-Raue, Karin; Robinson, Bruce; Rosenthal, M. Sara; Santoro, Massimo; Schlumberger, Martin; Shah, Manisha; Waguespack, Steven G.

2015-01-01

Introduction: The American Thyroid Association appointed a Task Force of experts to revise the original Medullary Thyroid Carcinoma: Management Guidelines of the American Thyroid Association. Methods: The Task Force identified relevant articles using a systematic PubMed search, supplemented with additional published materials, and then created evidence-based recommendations, which were set in categories using criteria adapted from the United States Preventive Services Task Force Agency for Healthcare Research and Quality. The original guidelines provided abundant source material and an excellent organizational structure that served as the basis for the current revised document. Results: The revised guidelines are focused primarily on the diagnosis and treatment of patients with sporadic medullary thyroid carcinoma (MTC) and hereditary MTC. Conclusions: The Task Force developed 67 evidence-based recommendations to assist clinicians in the care of patients with MTC. The Task Force considers the recommendations to represent current, rational, and optimal medical practice. PMID:25810047

A Novel, Low-Volume Method for Organ Culture of Embryonic Kidneys That Allows Development of Cortico-Medullary Anatomical Organization

PubMed Central

Sebinger, David D. R.; Unbekandt, Mathieu; Ganeva, Veronika V.; Ofenbauer, Andreas; Werner, Carsten; Davies, Jamie A.

2010-01-01

Here, we present a novel method for culturing kidneys in low volumes of medium that offers more organotypic development compared to conventional methods. Organ culture is a powerful technique for studying renal development. It recapitulates many aspects of early development very well, but the established techniques have some disadvantages: in particular, they require relatively large volumes (1–3 mls) of culture medium, which can make high-throughput screens expensive, they require porous (filter) substrates which are difficult to modify chemically, and the organs produced do not achieve good cortico-medullary zonation. Here, we present a technique of growing kidney rudiments in very low volumes of medium–around 85 microliters–using silicone chambers. In this system, kidneys grow directly on glass, grow larger than in conventional culture and develop a clear anatomical cortico-medullary zonation with extended loops of Henle. PMID:20479933

[A case of bilateral medial medullary infarction caused by unilateral vertebral artery dissection].

PubMed

Akimoto, Takayoshi; Hara, Makoto; Saito, Mari; Takahashi, Keiko; Kamei, Satoshi

2015-01-01

A 34-year-old man developed right neck pain. Several hours later, he felt numbness of his extremities and presented at our hospital. He developed right hemiparesis and hypoesthesia of the right extremities. A few hours later, upbeat nystagmus and dysarthria appeared along with a sensory disturbance that spread to all extremities, and right hemiparesis progressed to tetraplegia. Brain MR diffusion-weighted images revealed a high-intensity lesion in the bilateral medial medulla oblongata and we diagnosed this bilateral medial medullary infarction. Three dimentional CT angiography revealed dissection of the right VA. We administered intravenous argatroban, edaravone, glycerin and oral clopidogrel. He was assessed as having modified Rankin scale 4 and was transferred to another hospital for rehabilitation on day 30. When the medial medulla oblongata is supplied by the unilateral VA, a unilateral VA dissection can cause bilateral medial medullary infarction.

The anatomical, cellular and synaptic basis of motor atonia during rapid eye movement sleep

PubMed Central

Chen, Michael C.

2016-01-01

Abstract Rapid eye movement (REM) sleep is a recurring part of the sleep–wake cycle characterized by fast, desynchronized rhythms in the electroencephalogram (EEG), hippocampal theta activity, rapid eye movements, autonomic activation and loss of postural muscle tone (atonia). The brain circuitry governing REM sleep is located in the pontine and medullary brainstem and includes ascending and descending projections that regulate the EEG and motor components of REM sleep. The descending signal for postural muscle atonia during REM sleep is thought to originate from glutamatergic neurons of the sublaterodorsal nucleus (SLD), which in turn activate glycinergic pre‐motor neurons in the spinal cord and/or ventromedial medulla to inhibit motor neurons. Despite work over the past two decades on many neurotransmitter systems that regulate the SLD, gaps remain in our knowledge of the synaptic basis by which SLD REM neurons are regulated and in turn produce REM sleep atonia. Elucidating the anatomical, cellular and synaptic basis of REM sleep atonia control is a critical step for treating many sleep‐related disorders including obstructive sleep apnoea (apnea), REM sleep behaviour disorder (RBD) and narcolepsy with cataplexy. PMID:27060683

High CO2/H+ dialysis in the caudal ventrolateral medulla (Loeschcke's area) increases ventilation in wakefulness.

PubMed

da Silva, Glauber S F; Li, Aihua; Nattie, Eugene

2010-04-15

Central chemoreception, the detection of CO(2)/H(+) within the brain and the resultant effect on ventilation, was initially localized at two areas on the ventrolateral medulla, one rostral (rVLM-Mitchell's) the other caudal (cVLM-Loeschcke's), by surface application of acidic solutions in anesthetized animals. Focal dialysis of a high CO(2)/H(+) artificial cerebrospinal fluid (aCSF) that produced a milder local pH change in unanesthetized rats (like that with a approximately 6.6mm Hg increase in arterial P(CO2)) delineated putative chemoreceptor regions for the rVLM at the retrotrapezoid nucleus and the rostral medullary raphe that function predominantly in wakefulness and sleep, respectively. Here we ask if chemoreception in the cVLM can be detected by mild focal stimulation and if it functions in a state dependent manner. At responsive sites just beneath Loeschcke's area, ventilation was increased by, on average, 17% (P<0.01) only in wakefulness. These data support our hypothesis that central chemoreception is a distributed property with some sites functioning in a state dependent manner. Copyright 2010 Elsevier B.V. All rights reserved.

More a finger than a nose: the trigeminal motor and sensory innervation of the Schnauzenorgan in the elephant-nose fish Gnathonemus petersii.

PubMed

Amey-Özel, Monique; von der Emde, Gerhard; Engelmann, Jacob; Grant, Kirsty

2015-04-01

The weakly electric fish Gnathonemus petersii uses its electric sense to actively probe the environment. Its highly mobile chin appendage, the Schnauzenorgan, is rich in electroreceptors. Physical measurements have demonstrated the importance of the position of the Schnauzenorgan in funneling the fish's self-generated electric field. The present study focuses on the trigeminal motor pathway that controls Schnauzenorgan movement and on its trigeminal sensory innervation and central representation. The nerves entering the Schnauzenorgan are very large and contain both motor and sensory trigeminal components as well as an electrosensory pathway. With the use of neurotracer techniques, labeled Schnauzenorgan motoneurons were found throughout the ventral main body of the trigeminal motor nucleus but not among the population of larger motoneurons in its rostrodorsal region. The Schnauzenorgan receives no motor or sensory innervation from the facial nerve. There are many anastomoses between the peripheral electrosensory and trigeminal nerves, but these senses remain separate in the sensory ganglia and in their first central relays. Schnauzenorgan trigeminal primary afferent projections extend throughout the descending trigeminal sensory nuclei, and a few fibers enter the facial lobe. Although no labeled neurons could be identified in the brain as the trigeminal mesencephalic root, some Schnauzenorgan trigeminal afferents terminated in the trigeminal motor nucleus, suggesting a monosynaptic, possibly proprioceptive, pathway. In this first step toward understanding multimodal central representation of the Schnauzenorgan, no direct interconnections were found between the trigeminal sensory and electromotor command system, or the electrosensory and trigeminal motor command. The pathways linking perception to action remain to be studied. © 2014 Wiley Periodicals, Inc.

Use of GDNF Releasing Nanofiber Nerve Guide Conduits for the Repair of Conus Medullaris/Cauda Equina Injury in the Nonhuman Primate

DTIC Science & Technology

2015-02-01

repair of conus medullaris/cauda equina injury in rhesus macaques using a biodegradable bridging graft that releasing the trophic factor, GDNF. All...and biodegradable nerve guidance channels as bridging grafts. The follow section describes the methods and protocols for laminectomy, ventral root...in saline until being grafted, 8. For use of a bridging biodegradable NGC segment, the NGCs were fabricated and comprised of electrospun

Medullary thyroid cancer: the functions of raf-1 and human achaete-scute homologue-1.

PubMed

Chen, Herbert; Kunnimalaiyaan, Muthusamy; Van Gompel, Jamie J

2005-06-01

Medullary thyroid cancer (MTC) is a prototypic neuroendocrine tumor of the thyroid C cells. Other than surgery, there are no curative therapies for MTC. In this review, we detail recent studies that suggest that targeting specific signaling pathways may be a viable strategy to control MTC tumor progression. Specifically, we discuss the role of the raf-1 and achaete-scute homologue-1 pathways in the MTC tumor growth and differentiation.

[True myelinic neuroma. Its associations (neurocrestopathies)].

PubMed

Cortijo, A T; Pons, S; Ortíz Medina, A; Grinberg, A

1975-01-01

A case of true mielinic neuroma is described. An exhaustive review of the literature on this subject, basically of the Bolande article is carried out by the authors. The mielinic neuromata are a partial aspect of the complexe neuro-crestopathic syndromes associating the cutaneous lesions to: 1) Medullary tyroid carcinoma, 2) pheocromocytoma and 3) neurofibromatous lesions. The observation related by the authors shows: 1) Ehlers-Danlos disease (not described previously), 2) skeletal abnormalities, 3) medullary tyroid carcinoma and 4) pheochromocytoma symptoms.

[Effects of medullary ischemia on respiratory and blood pressure induced by ligating basilar artery in cat].

PubMed

Zhuang, Xu; Guo, Jun-Xia; Zhang, Cheng-Wu; Zheng, Yu

2003-11-01

Observations on medullary ischemia region, the morphology of neurons and changes of respiration and blood pressure were made, in order to give evidences on how medullary ischemia affects respiration and circulation and give some advices on how to protect from it. Using cats as the experimental animals, the different parts of the basilar artery trunk were ligated. The changes in the density of blood vessels, the morphology of neurons in the brainstem, the electromyogram (EMG) of the diaphragm and the blood pressure of the femoral artery were investigated. The density of blood vessels notably decreased in the medulla after ligating the basilar artery trunk. The ischemic range induced by ligation of the different parts of the basilar artery trunk overlapped, mainly locating in the medulla rostral to the obex. The soma were swelled and the Nissl bodies decreased in some of neurons in the ischemic region of medulla. The duration of inspiration (T1) and expiration (TE) shortened, respiratory frequency (RF) increased, and mean blood pressure (MBP) decreased in the experimental groups (P < 0.05). There is an obvious overlap of the areas in which blood supplied by different parts of the basilar artery trunk. Medullary ischemia can involve in changes of respiration and blood pressure. The ischemic damage of neurons in the medulla might be the structural basis of the changes in the respiratory and circulatory functions.

Decreased adrenal medullary tyrosine hydroxylase mRNA in DMBA (7,12-dimethylbenz(a)anthracene)-induced mammary carcinoma

DOE Office of Scientific and Technical Information (OSTI.GOV)

Bunce, O.R.; Badary, O.A.; Abou El-Ela, S.

1991-03-15

Adrenal cortical hormones suppress initiation and promotion of DMBA-induced mammary tumorigenesis. The authors found a positive correlation between presence of DMBA-induced adrenal cortical necrosis and mammary tumor incidence. Because they find adrenal medullary as well as cortical lesions in tumor bearing (TB) DMBA-treated rats, they evaluated medullary function by quantitating hybridized cDNA- TH-S{sup 35} with in situ TH-mRNA u sing computer assisted quantitative autoradiographic technique. Virgin female Sprague-Dawley rats were given a 10 mg i.g. dose of DMBA. Three wks later, rats were placed on 20% polyunsaturated (PUFA) fat diets containing omega-6 and omega-3 fatty acids. All were killed 15more » wks post-DMBA. TH-mRNA levels in adrenal medullae of TB animals were decreased compared to non-TB rats. Histopathology indicated a high incidence of medullary necrosis in TB rats, whereas, adrenal necrosis did not occur in non-TB animals. Adrenal necrosis correlated positively with tumor burden, but no correlation was found between incidence of adrenal lesions and type of PUFA in the diet. The authors suggest that DMBA adrenal necrosis may reduce TH-mRNA in the medulla, compromise its catecholamine synthetic capability, and thereby contribute to the overall metabolic stress condition of TB rats.« less

Medullary nephrocalcinosis, distal renal tubular acidosis and polycythaemia in a patient with nephrotic syndrome.

PubMed

Karunarathne, Suneth; Udayakumara, Yapa; Govindapala, Dumitha; Fernando, Harshini

2012-07-26

Medullary nephrocalcinosis and distal renal tubular acidosis are closely associated and each can lead to the other. These clinical entities are rare in patients with nephrotic syndrome and polycythaemia is an unusual finding in such patients. We describe the presence of medullary nephrocalcinosis, distal renal tubular acidosis and polycythaemia in a patient with nephrotic syndrome due to minimal change disease. Proposed mechanisms of polycythaemia in patients with nephrotic syndrome and distal renal tubular acidosis include, increased erythropoietin production and secretion of interleukin 8 which in turn stimulate erythropoiesis. A 22 year old Sri Lankan Sinhala male with nephrotic syndrome due to minimal change disease was investigated for incidentally detected polycythaemia. Investigations revealed the presence of renal tubular acidosis type I and medullary nephrocalcinosis. Despite extensive investigation, a definite cause for polycythaemia was not found in this patient. Treatment with potassium and bicarbonate supplementation with potassium citrate led to correction of acidosis thereby avoiding the progression of nephrocalcinosis and harmful effects of chronic acidosis. The constellation of clinical and biochemical findings in this patient is unique but the pathogenesis of erythrocytosis is not clearly explained. The proposed mechanisms for erythrocytosis in other patients with proteinuria include increased erythropoietin secretion due to renal hypoxia and increased secretion of interleukin 8 from the kidney. This case illustrates that there may exist hitherto unknown connections between tubular and glomerular dysfunction in patients with nephrotic syndrome.

Carotid chemoreceptors tune breathing via multipath routing: reticular chain and loop operations supported by parallel spike train correlations.

PubMed

Morris, Kendall F; Nuding, Sarah C; Segers, Lauren S; Iceman, Kimberly E; O'Connor, Russell; Dean, Jay B; Ott, Mackenzie M; Alencar, Pierina A; Shuman, Dale; Horton, Kofi-Kermit; Taylor-Clark, Thomas E; Bolser, Donald C; Lindsey, Bruce G

2018-02-01

We tested the hypothesis that carotid chemoreceptors tune breathing through parallel circuit paths that target distinct elements of an inspiratory neuron chain in the ventral respiratory column (VRC). Microelectrode arrays were used to monitor neuronal spike trains simultaneously in the VRC, peri-nucleus tractus solitarius (p-NTS)-medial medulla, the dorsal parafacial region of the lateral tegmental field (FTL-pF), and medullary raphe nuclei together with phrenic nerve activity during selective stimulation of carotid chemoreceptors or transient hypoxia in 19 decerebrate, neuromuscularly blocked, and artificially ventilated cats. Of 994 neurons tested, 56% had a significant change in firing rate. A total of 33,422 cell pairs were evaluated for signs of functional interaction; 63% of chemoresponsive neurons were elements of at least one pair with correlational signatures indicative of paucisynaptic relationships. We detected evidence for postinspiratory neuron inhibition of rostral VRC I-Driver (pre-Bötzinger) neurons, an interaction predicted to modulate breathing frequency, and for reciprocal excitation between chemoresponsive p-NTS neurons and more downstream VRC inspiratory neurons for control of breathing depth. Chemoresponsive pericolumnar tonic expiratory neurons, proposed to amplify inspiratory drive by disinhibition, were correlationally linked to afferent and efferent "chains" of chemoresponsive neurons extending to all monitored regions. The chains included coordinated clusters of chemoresponsive FTL-pF neurons with functional links to widespread medullary sites involved in the control of breathing. The results support long-standing concepts on brain stem network architecture and a circuit model for peripheral chemoreceptor modulation of breathing with multiple circuit loops and chains tuned by tegmental field neurons with quasi-periodic discharge patterns. NEW & NOTEWORTHY We tested the long-standing hypothesis that carotid chemoreceptors tune the frequency and depth of breathing through parallel circuit operations targeting the ventral respiratory column. Responses to stimulation of the chemoreceptors and identified functional connectivity support differential tuning of inspiratory neuron burst duration and firing rate and a model of brain stem network architecture incorporating tonic expiratory "hub" neurons regulated by convergent neuronal chains and loops through rostral lateral tegmental field neurons with quasi-periodic discharge patterns.

Modification of medullary respiratory-related discharge patterns by behaviors and states of arousal.

PubMed

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 sniffing reflex is worthy of further note in that, based on power spectrum analyses of concurrently recorded ECoG activities, this particular discharge pattern was clearly associated with the activation of a 6-10 Hz theta rhythm. These findings indicated that bulbar RRU activity patterns are subject to change by not only behaviors and sleep/wakefulness cycles, but also a variety of modulatory influences and feedback/feedforward biases from other central and peripheral physiological control mechanisms.

Role of H2O2 in hypertension, renin-angiotensin system activation and renal medullary disfunction caused by angiotensin II

PubMed Central

Sousa, T; Oliveira, S; Afonso, J; Morato, M; Patinha, D; Fraga, S; Carvalho, F; Albino-Teixeira, A

2012-01-01

BACKGROUND AND PURPOSE Activation of the intrarenal renin-angiotensin system (RAS) and increased renal medullary hydrogen peroxide (H2O2) contribute to hypertension. We examined whether H2O2 mediated hypertension and intrarenal RAS activation induced by angiotensin II (Ang II). EXPERIMENTAL APPROACH Ang II (200 ng·kg−1·min−1) or saline were infused in Sprague Dawley rats from day 0 to day 14. Polyethylene glycol (PEG)-catalase (10 000 U·kg−1·day−1) was given to Ang II-treated rats, from day 7 to day 14. Systolic blood pressure was measured throughout the study. H2O2, angiotensin AT1 receptor and Nox4 expression and nuclear factor-κB (NF-κB) activation were evaluated in the kidney. Plasma and urinary H2O2 and angiotensinogen were also measured. KEY RESULTS Ang II increased H2O2, AT1 receptor and Nox4 expression and NF-κB activation in the renal medulla, but not in the cortex. Ang II raised plasma and urinary H2O2 levels, increased urinary angiotensinogen but reduced plasma angiotensinogen. PEG-catalase had a short-term antihypertensive effect and transiently suppressed urinary angiotensinogen. PEG-catalase decreased renal medullary expression of AT1 receptors and Nox4 in Ang II-infused rats. Renal medullary NF-κB activation was correlated with local H2O2 levels and urinary angiotensinogen excretion. Loss of antihypertensive efficacy was associated with an eightfold increase of plasma angiotensinogen. CONCLUSIONS AND IMPLICATIONS The renal medulla is a major target for Ang II-induced redox dysfunction. H2O2 appears to be the key mediator enhancing intrarenal RAS activation and decreasing systemic RAS activity. The specific control of renal medullary H2O2 levels may provide future grounds for the treatment of hypertension. PMID:22452317

Impact of renal medullary three-dimensional architecture on oxygen transport.

PubMed

Fry, Brendan C; Edwards, Aurélie; Sgouralis, Ioannis; Layton, Anita T

2014-08-01

We have developed a highly detailed mathematical model of solute transport in the renal medulla of the rat kidney to study the impact of the structured organization of nephrons and vessels revealed in anatomic studies. The model represents the arrangement of tubules around a vascular bundle in the outer medulla and around a collecting duct cluster in the upper inner medulla. Model simulations yield marked gradients in intrabundle and interbundle interstitial fluid oxygen tension (PO2), NaCl concentration, and osmolality in the outer medulla, owing to the vigorous active reabsorption of NaCl by the thick ascending limbs. In the inner medulla, where the thin ascending limbs do not mediate significant active NaCl transport, interstitial fluid composition becomes much more homogeneous with respect to NaCl, urea, and osmolality. Nonetheless, a substantial PO2 gradient remains, owing to the relatively high oxygen demand of the inner medullary collecting ducts. Perhaps more importantly, the model predicts that in the absence of the three-dimensional medullary architecture, oxygen delivery to the inner medulla would drastically decrease, with the terminal inner medulla nearly completely deprived of oxygen. Thus model results suggest that the functional role of the three-dimensional medullary architecture may be to preserve oxygen delivery to the papilla. Additionally, a simulation that represents low medullary blood flow suggests that the separation of thick limbs from the vascular bundles substantially increases the risk of the segments to hypoxic injury. When nephrons and vessels are more homogeneously distributed, luminal PO2 in the thick ascending limb of superficial nephrons increases by 66% in the inner stripe. Furthermore, simulations predict that owing to the Bohr effect, the presumed greater acidity of blood in the interbundle regions, where thick ascending limbs are located, relative to that in the vascular bundles, facilitates the delivery of O2 to support the high metabolic requirements of the thick limbs and raises NaCl reabsorption. Copyright © 2014 the American Physiological Society.

MR measures of renal perfusion, oxygen bioavailability and total renal blood flow in a porcine model: noninvasive regional assessment of renal function.

PubMed

Wentland, Andrew L; Artz, Nathan S; Fain, Sean B; Grist, Thomas M; Djamali, Arjang; Sadowski, Elizabeth A

2012-01-01

Magnetic resonance imaging (MRI) may be a useful adjunct to current methods of evaluating renal function. MRI is a noninvasive imaging modality that has the ability to evaluate the kidneys regionally, which is lacking in current clinical methods. Other investigators have evaluated renal function with MRI-based measurements, such as with techniques to measure cortical and medullary perfusion, oxygen bioavailability and total renal blood flow (TRBF). However, use of all three techniques simultaneously, and therefore the relationships between these MRI-derived functional parameters, have not been reported previously. To evaluate the ability of these MRI techniques to track changes in renal function, we scanned 11 swine during a state of hyperperfusion with acetylcholine and a saline bolus and subsequently scanned during a state of hypoperfusion with the prolonged use of isoflurane anesthesia. For each time point, measurements of perfusion, oxygen bioavailability and TRBF were acquired. Measurements of perfusion and oxygen bioavailability were compared with measurements of TRBF for all swine across all time points. Cortical perfusion, cortical oxygen bioavailability, medullary oxygen bioavailability and TRBF significantly increased with the acetylcholine challenge. Cortical perfusion, medullary perfusion, cortical oxygen bioavailability and TRBF significantly decreased during isoflurane anesthesia. Cortical perfusion (Spearman's correlation coefficient = 0.68; P < 1 × 10(-6)) and oxygen bioavailability (Spearman's correlation coefficient = -0.60; P < 0.0001) correlated significantly with TRBF, whereas medullary perfusion and oxygen bioavailability did not correlate with TRBF. Our results demonstrate expected changes given the pharmacologically induced changes in renal function. Maintenance of the medullary oxygen bioavailability in low blood flow states may reflect the autoregulation particular to this region of the kidney. The ability to non-invasively measure all three parameters of kidney function in a single MRI examination and to evaluate the relationships between these functional parameters is potentially useful for evaluating the state of the human kidneys in situ in future studies.

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

PubMed

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 (P<0.05) and more rapid recovery of intracellular pH in wild-type rats (ΔpHI 0.005 versus 0.002 U/s, P=0.046, respectively). Superoxide production was enhanced by low intracellular sodium (<10 mmol/L) in both thick 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.

The Gravity field of Comet 67 P/Churyumov-Gerasimenko Expressed in Bispherical Harmonics

NASA Astrophysics Data System (ADS)

Andert, T.; Barriot, J. P.; Paetzold, M.; Sichoix, L.; Tellmann, S.; Häusler, B.

2015-12-01

On 6 August 2014, after a ten years cruise, the ESA-Rosetta spacecraft arrived at comet 67P/Churyumov-Gerasimenko. At that time the spacecraft was commanded to drift along with the comet at distances between 100 km and 50 km, the distance was then successfully lowered to 30 km in September 2014 and to 10 km in November 2014 and bound orbits could be achieved. Based on Doppler tracking data the Rosetta radio science experiment (RSI) was able to determine the mass of the nucleus and its gravity field in spherical harmonics series in order to constrain density and the internal structure of the nucleus. The shape of the comet is complex, a representation of the gravity field as belonging to one single body in either spherical or ellipsoidal harmonics series will give the shape of the body more preference than its internal structure. The observed shape of the nucleus, however, offers the opportunity to interpret it as consisting of two different bodies, namely the "head" and the "feet" sections of 67P/Churyumov-Gerasimenko, both having a nearly ellipsoidal shape. In this new approach, the bispherical harmonics expansion, the comet nucleus has been approximated by two independent lobes, each lobe represented by its own spherical harmonics expansion. As a result of the bispherical harmonics representation, it is anticipated that the gravity field will gain higher accuracy and will be less dominated by the complex shape of the comet. We have derived the analytical expressions of the gravity potential and its derivatives of a body in bispherical coordinates and applied this concept to the comet Churyumov-Gerasimenko. The paper will present the bispherical harmonics representation of the gravity field and first results derived from this new concept.

The nucleus reticularis gigantocellularis modulates the cardiopulmonary responses to central and peripheral drives related to exercise.

PubMed

Richard, C A; Waldrop, T G; Bauer, R M; Mitchell, J H; Stremel, R W

1989-03-13

It is known that muscle afferents and the hypothalamic locomotor region (HLR) both project to the nucleus reticularis gigantocellularis (NGC) and that the NGC is capable of influencing cardiovascular and respiratory variables. Therefore, the role of NGC in the cardiovascular and respiratory response to exercise-related signals was investigated in anesthetized cats. These signals were generated by stimulation of: (1) spinal ventral roots to induce hindlimb muscle contraction (MC) and (2) the HLR. Bilateral electrolytic lesion of the NGC at the pontomedullary border caused tidal volume, respiratory frequency and heart rate responses to HLR stimulation to be greater than the responses recorded prior to lesioning. Lesioning had no effect on the ventilatory or cardiovascular responses to MC but did decrease phrenic responsiveness; lesion had no effect on any resting values. In this preparation, the pontomedullary NGC acts as an inhibitory influence on tidal volume, breathing frequency and heart rate responses to the central command for exercise. In addition, NGC modulation of ventilation would appear to be selective for certain respiratory muscle groups.

Resolution of brainstem edema after treatment of a dural tentorial arteriovenous fistula.

PubMed

Alvarez, Hortensia; Sasaki-Adams, Deanna; Castillo, Mauricio

2015-10-01

We report a patient with a petrosal arterio-venous dural fistula draining into the ponto-mesencephalic and medullary venous systems presenting with edema of the brain stem and complete reversal of magnetic resonance imaging (MRI) abnormalities after combined endovascular and surgical treatments. The venous anatomy of the posterior fossa and the significance of the venous involvement as the cause of clinical symptoms and imaging abnormalities in cerebro-medullary vascular lesions are discussed. © The Author(s) 2015.

Nodular Graves' disease with medullary thyroid cancer.

PubMed

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.

[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)].

PubMed

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.

[Medullary layer activity of the rat adrenals after a flight on the Kosmos-1129 biosatellite].

PubMed

Kvetnanský, R; Blazicek, P; Tigranian, R A

1982-01-01

After a 18.5-day space flight on Cosmos-1129 rat adrenals were investigated for the concentration of catecholamines and activity of enzymes involved in their synthesis, i.e. tyrosine hydroxylase, dopamine-beta-hydroxylase, and phenyl ethanol amine-N-methyl transferase. It was found that inflight the sympatho-adreno-medullary system of rats was not exposed to a prolonged or strong stressogenic effect. Postflight the rats showed an increased reactivity to the immobilization stress.

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.

PubMed

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.

A Case of a Composite Adrenal Medullary Tumor of Pheochromocytoma and Ganglioneuroma Masquerading as Acute Pancreatitis

PubMed Central

Choi, Eun-Kyoung; Kim, Wan-Ho

2006-01-01

Composite adrenal medullary tumors, composed of both pheochromocytoma and ganglioneuroma, are extremely rare, as are pheochromocytomas masquerading as acute relapsing pancreatitis. We recently experienced a case of a 48-year-old male with both these phenomena. The patient complained of an acute onset of intense abdominal discomfort. At the same time, pancreatic enzymes were increased in concentration. An abdominal computed tomographic scan revealed an enlarged pancreas and a 3-cm left adrenal incidentaloma. Biochemical and 131I-MIBG scintigraphic findings were compatible with a pheochromocytoma. Yet, he had no clinical manifestations suggesting pheochromocytoma. An adrenalectomy was performed and a composite adrenal medullary tumor of pheochromocytoma and ganglioneuroma was confirmed during a pathologic examination. This case illustrates two points: 1) acute abdominal intense discomfort and hyperamylasemia may be unusual presentations of pheochromocytomas; and 2) the possibility of the pheochromocytoma, albeit rare, should be considered when a relapsing pancreatitis of uncertain etiology develops. PMID:16913447

Morphometric study of the avian adrenal gland.

PubMed Central

Aire, T A

1980-01-01

The interrenal and medullary cords as well as the blood vessels and connective tissue proportions in the adrenal glands of the male Nigerian fowl (Gallus domesticus) and guinea-fowl (Numida meleagris) were studied by microstereological techniques. Laying domestic fowl of the Rhode Island Red breed were entirely defeathered and maintained in a hot, humid pen for a period of three months, after which the adrenal glands were also studied microstereologically. Interrenal cord width was also measured in all the birds studied. The interrenal cords of the subscapular zone were consistently wider than those cords in the inner zone of the adrenal glands. This clearly suggested morphological zoning. The proportion of interrenal tissue was significantly greater in the guinea-fowl than in the Nigerian fowl, but the medullary tissue and the blood vessels and connective tissue were not significantly different. Interrenal hypoplasia or medullary hyperplasia occurred in the defeathered Rhode Island Red fowl as compared to the control birds of the same breed and sex. The significance of these findings is discussed. PMID:7440402

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

PubMed

Wakasugi, Masaki; Kono, Hiroshi; Yasuhara, Yumiko; Tsujimura, Naoto; Nakahara, Yujiro; Matsumoto, Takashi; Takemoto, Hiroyoshi; Takachi, Ko; Nishioka, Kiyonori; Yoshida, Kyotaro; Oshima, Satoshi

2017-01-01

Medullary carcinoma is a rare type of colorectal adenocarcinoma, and omental infarction is a rare cause of acute abdomen. 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. 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. A rare case of medullary carcinoma of the ascending colon followed by infarction of the greater omentum mimicking anastomotic leakage is presented.

Effects of pH and medullary blood flow on oxygen transport and sodium reabsorption in the rat outer medulla.

PubMed

Chen, Jing; Edwards, Aurélie; Layton, Anita T

2010-06-01

We used a mathematical model of O(2) transport and the urine concentrating mechanism of the outer medulla of the rat kidney to study the effects of blood pH and medullary blood flow on O(2) availability and Na(+) reabsorption. The model predicts that in vivo paracellular Na(+) fluxes across medullary thick ascending limbs (mTALs) are small relative to transcellular Na(+) fluxes and that paracellular fluxes favor Na(+) reabsorption from the lumen along most of the mTAL segments. In addition, model results suggest that blood pH has a significant impact on O(2) transport and Na(+) reabsorption owing to the Bohr effect, according to which a lower pH reduces the binding affinity of hemoglobin for O(2). Thus our model predicts that the presumed greater acidity of blood in the interbundle regions, where mTALs are located, relative to that in the vascular bundles, facilitates the delivery of O(2) to support the high metabolic requirements of the mTALs and raises the concentrating capability of the outer medulla. Model results also suggest that increases in vascular and tubular flow rates result in disproportional, smaller increases in active O(2) consumption and mTAL active Na(+) transport, despite the higher delivery of O(2) and Na(+). That is, at a sufficiently high medullary O(2) supply, O(2) demand in the outer medulla does not adjust precisely to changes in O(2) delivery.

Hydronephrosis in the Wnt5a-ablated kidney is caused by an abnormal ureter-bladder connection.

PubMed

Yun, Kangsun; Perantoni, Alan O

The Wnt5a null mouse is a complex developmental model which, among its several posterior-localized axis defects, exhibits multiple kidney phenotypes, including duplex kidney and loss of the medullary zone. We previously reported that ablation of Wnt5a in nascent mesoderm causes duplex kidney formation as a result of aberrant development of the nephric duct and abnormal extension of intermediate mesoderm. However, these mice also display a loss of the medullary region late in gestation. We have now genetically isolated duplex kidney formation from the medullary defect by specifically targeting the progenitors for both the ureteric bud and metanephric mesenchyme. The conditional mutants fail to form a normal renal medulla but no longer exhibit duplex kidney formation. Approximately 1/3 of the mutants develop hydronephrosis in the kidneys either uni- or bilaterally when using Dll1Cre. The abnormal kidney phenotype becomes prominent at E16.5, which approximates the time when urine production begins in the mouse embryonic kidney, and is associated with a dramatic increase in apoptosis only in mutant kidneys with hydronephrosis. Methylene blue dye injection and histologic examination reveal that aberrant cell death likely results from urine toxicity due to an abnormal ureter-bladder connection. This study shows that Wnt5a is not required for development of the renal medulla and that loss of the renal medullary region in the Wnt5a-deleted kidney is caused by an abnormal ureter-bladder connection. Published by Elsevier B.V.

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

PubMed

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.

Risk Factors, Etiological Classification, Topographical Location, and Outcome in Medullary Infarctions.

PubMed

Gökçal, Elif; Baran, Gözde; Niftaliyev, Elvin; Güzel, Vildan; Asil, Talip

2017-07-01

An understanding of the etiological mechanisms is important for therapeutic decisions and prognostic evaluation of patients with ischemic stroke. The object of this study was to evaluate the risk factors, etiological subtypes, and topography of lesion in patients with medullary infarctions (MIs). Besides, we also investigated early neurological deterioration, new vascular events, and functional outcome of all patients at 3-month follow-up. We analyzed our database consisting of patients who were diagnosed with acute MI and who were admitted within 24 hours of onset. Etiological classification of stroke was made on the basis of the Trial of Org 1972 in Acute Stroke Treatment criteria. All of the infarctions were grouped into anteromedial, anterolateral, lateral, and posterior arterial territories and also categorized into those involving the upper, middle, or lower medulla oblongata. Early neurological deterioration, major vascular events within the first 3 months of follow-up and modified Rankin Score at 3 months were reviewed. A total of 65 patients with medullary infarctions were reviewed. Involved arterial territories differed according to the etiological classification. Large artery atherosclerosis was the most common etiological subtype; however, small vessel disease was the most common subtype in medial MIs. The lesions involving the anteromedial territory were common in the upper medullary region, whereas the lesions involving the posterior and lateral territories were common in the lower medulla oblangata. Recurrent stroke was seen in the posterior and lateral territories; however, early progression and poor functional outcome were mostly seen in lesions involving the anteromedial territories.

Nodular Graves’ disease with medullary thyroid cancer

PubMed Central

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. PMID:26430321

Bilateral medial medullary syndrome secondary to Takayasu arteritis.

PubMed

Deshpande, Anirudda; Chandran, Vijay; Pai, Aparna; Rao, Suryanarayana; Shetty, Ranjan

2013-08-13

Medial medullary syndrome (MMS) is a rare type of stroke which results due to occlusion of the anterior spinal artery or vertebral artery or its branches. In this case report we present a patient who developed MMS secondary to Takayasu arteritis (TA). TA is a chronic inflammatory arteritis primarily involving the arch of aorta and its branches, which in our patient resulted in occlusion of subclavian arteries as well as infarction of the medial medulla bilaterally. To our knowledge this is the first time that MMS has been found to occur secondary to TA.

Acute coronary syndrome: a rare case of multiple endocrine neoplasia syndromes with pheochromocytoma and medullary thyroid carcinoma.

PubMed

Maloberti, Alessadro; Meani, Paolo; Pirola, Roberto; Varrenti, Marisa; Boniardi, Marco; De Biase, Anna Maria; Vallerio, Paola; Bonacina, Edgardo; Mancia, Giuseppe; Loli, Paola; Giannattasio, Cristina

2015-09-01

Pheochromocytoma is a tumor arising from neuroectodermal chromaffin tissues in the adrenal gland or extra-adrenal paraganglia (paragangliomas). The prevalence of the tumor is 0.1%-0.6% in the hypertensive population, of which 10%-20% are malignant. Pheochromocytoma produces, stores, and secretes catecholamines, as well as leads to hypertensive crisis, arrhythmia, angina, and acute myocardial infarction without coronary artery diseases. We report a case of acute coronary syndrome (ACS) with a final diagnosis of multiple endocrine neoplasia with pheochromocytoma and medullary thyroid carcinoma (MTC).

Song decrystallization in adult zebra finches does not require the song nucleus NIf.

PubMed

Roy, Arani; Mooney, Richard

2009-08-01

In adult male zebra finches, transecting the vocal nerve causes previously stable (i.e., crystallized) song to slowly degrade, presumably because of the resulting distortion in auditory feedback. How and where distorted feedback interacts with song motor networks to induce this process of song decrystallization remains unknown. The song premotor nucleus HVC is a potential site where auditory feedback signals could interact with song motor commands. Although the forebrain nucleus interface of the nidopallium (NIf) appears to be the primary auditory input to HVC, NIf lesions made in adult zebra finches do not trigger song decrystallization. One possibility is that NIf lesions do not interfere with song maintenance, but do compromise the adult zebra finch's ability to express renewed vocal plasticity in response to feedback perturbations. To test this idea, we bilaterally lesioned NIf and then transected the vocal nerve in adult male zebra finches. We found that bilateral NIf lesions did not prevent nerve section-induced song decrystallization. To test the extent to which the NIf lesions disrupted auditory processing in the song system, we made in vivo extracellular recordings in HVC and a downstream anterior forebrain pathway (AFP) in NIf-lesioned birds. We found strong and selective auditory responses to the playback of the birds' own song persisted in HVC and the AFP following NIf lesions. These findings suggest that auditory inputs to the song system other than NIf, such as the caudal mesopallium, could act as a source of auditory feedback signals to the song motor network.

Stimulation of pontine reticular formation in monkeys with strabismus.

PubMed

Walton, Mark M G; Ono, Seiji; Mustari, Michael J

2013-10-29

Saccade disconjugacy in strabismus could result from any of a number of factors, including abnormalities of eye muscles, the plant, motoneurons, near response cells, or atypical tuning of neurons in saccade-related areas of the brain. This study was designed to investigate the possibility that saccade disconjugacy in strabismus is associated with abnormalities in paramedian pontine reticular formation (PPRF). We applied microstimulation to 22 sites in PPRF and 20 sites in abducens nucleus in three rhesus macaque monkeys (one normal, one esotrope, and one exotrope). When mean velocity was compared between the two eyes, a slight difference was found for 1/5 sites in the normal animal. Significant differences were found for 5/6 sites in an esotrope and 10/11 sites in an exotrope. For five sites in the strabismic monkeys, the directions of evoked movements differed by more than 40° between the two eyes. When stimulation was applied to abducens nucleus (20 sites), the ipsilateral eye moved faster for 4/6 sites in the normal animal and all nine sites in the esotrope. For the exotrope, however, the left eye always moved faster, even for three sites on the right side. For the strabismic animals, stimulation of abducens nucleus often caused a different eye to move faster than stimulation of PPRF. These data suggest that PPRF is organized at least partly monocularly in strabismus and that disconjugate saccades are at least partly a consequence of unbalanced saccadic commands being sent to the two eyes.

Production and actions of superoxide in the renal medulla.

PubMed

Zou, A P; Li, N; Cowley, A W

2001-02-01

The present study characterized the biochemical pathways responsible for superoxide (O(2)(-.)) production in different regions of the rat kidney and determined the role of O(2)(-.)in the control of renal medullary blood flow (MBF) and renal function. By use of dihydroethidium/DNA fluorescence spectrometry with microtiter plates, the production of O(2)(-. )was monitored when tissue homogenate from different kidney regions was incubated with substrates for the major O(2)(-.)-producing enzymes, such as NADH/NADPH oxidase, xanthine oxidase, and mitochondrial respiratory chain enzymes. The production of O(2)(-. )via NADH oxidase was greater (P<0.05) in the renal cortex and outer medulla (OM) than in the papilla. The mitochondrial enzyme activity for O(2)(-.)production was higher (P<0.05) in the OM than in the cortex and papilla. Compared with NADH oxidase and mitochondrial enzymes, xanthine oxidase and NADPH oxidase produced much less O(2)(-. )in the kidney under this condition. Overall, the renal OM exhibited the greatest enzyme activities for O(2)(-.)production. In anesthetized rats, renal medullary interstitial infusion of a superoxide dismutase inhibitor, diethyldithiocarbamate, markedly decreased renal MBF and sodium excretion. Diethyldithiocarbamate (5 mg/kg per minute by renal medullary interstitial infusion [RI]) reduced the renal medullary laser-Doppler flow signal from 0.6+/-0.04 to 0.4+/-0.03 V, a reduction of 33%, and both urine flow and sodium excretion decreased by 49%. In contrast, a membrane-permeable superoxide dismutase mimetic, 4-hydroxytetramethyl-piperidine-1-oxyl (TEMPOL, 30 micromol/kg per minute RI) increased MBF and sodium excretion by 34% and 69%, respectively. These effects of TEMPOL on renal MBF and sodium excretion were not altered by pretreatment with N(G)-nitro-L-arginine methyl ester (10 microgram/kg per minute RI). We conclude that (1) renal medullary O(2)(-. )is primarily produced in the renal OM; (2) both NADH oxidase and mitochondrial enzymes are responsible for the O(2)(-.)production in this kidney region; and (3) O(2)(-. )exerts a tonic regulatory action on renal MBF.

Thymic lymphocytes. III. Cooperative phenomenon in the proliferation of thymocytes under Con A stimulation.

PubMed

Papiernik, M; Jacobson, J B

1986-01-01

In the present paper, the response of thymocytes to Con A is analyzed in terms of a cooperative phenomenon between medullary thymocytes, cortical thymocytes, thymic accessory cells, and interleukin 2. Medullary thymocytes respond spontaneously to Con A and produce IL-2. The addition of exogenously produced IL-2 enhances their proliferation. Small numbers of cortical (PNA+) thymocytes do not respond to Con A, even in the presence of IL-2-containing supernatant. By increasing the number of PNA+ cells per well, sensitivity to Con A and IL-2 appears. This response may be linked either to the increase in a minor PNA+-responding population and/or to the enhanced contamination by medullary thymocytes and macrophages in non-responding PNA+ thymocyte population. In this hypothesis, either the contaminating cells respond by themselves and/or cooperate with PNA+ cells to induce their proliferation. Coculture of non-responding low numbers of PNA+ thymocytes with Con A- and IL-2-containing supernatant in the presence of PNA- cells containing thymic medullary thymocytes and macrophages always produces a higher response than that of each individual population. These results show that a cooperative phenomenon occurs in the cocultures of PNA+ and PNA- thymic cells. We can show using PNA+ and PNA- thymocytes with different Thy 1 alleles, that indeed both PNA+ and populations participate PNA-thymocytes with different Thy 1 alleles, that indeed both PNA+ and PNA- populations participate in the generation of proliferating cells. We can demonstrate, by lysis experiments with monoclonal antibodies and complement that at the end of coculture, most of the proliferating cells are Lyt 1+, and part are Lyt 2+ or L3T4+. We discuss the fact that the phenotype of the cells after activation does not allow us to deduce the phenotype of their precursors. Lysis of Ia+ cells prior to coculture, reduces the level of the proliferative response but does not modify the percentage of cooperation produced by the coculture. Cooperation with medullary mature thymocytes or the presence of active Ia- accessory cells possibly able to convert to Ia expression during coculture experiments may account for these results.

Neural targets for relieving parkinsonian rigidity and bradykinesia with pallidal deep brain stimulation

PubMed Central

Zhang, Jianyu; Ghosh, Debabrata; McIntyre, Cameron C.; Vitek, Jerrold L.

2012-01-01

Clinical evidence has suggested that subtle changes in deep brain stimulation (DBS) settings can have differential effects on bradykinesia and rigidity in patients with Parkinson's disease. In this study, we first investigated the degree of improvement in bradykinesia and rigidity during targeted globus pallidus DBS in three 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-treated rhesus macaques. Behavioral outcomes of DBS were then coupled with detailed, subject-specific computational models of neurons in the globus pallidus internus (GPi), globus pallidus externus (GPe), and internal capsule (IC) to determine which neuronal pathways when modulated with high-frequency electrical stimulation best correlate with improvement in motor symptoms. The modeling results support the hypothesis that multiple neuronal pathways can underlie the therapeutic effect of DBS on parkinsonian bradykinesia and rigidity. Across all three subjects, improvements in rigidity correlated most strongly with spread of neuronal activation into IC, driving a small percentage of fibers within this tract (<10% on average). The most robust effect on bradykinesia resulted from stimulating a combination of sensorimotor axonal projections within the GP, specifically at the site of the medial medullary lamina. Thus the beneficial effects of pallidal DBS for parkinsonian symptoms may occur from multiple targets within and near the target nucleus. PMID:22514292

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

PubMed

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.

Expression of CTLA-4 (CD152) on human medullary CD4+ thymocytes.

PubMed

Castan, J; Klauenberg, U; Kalmár, P; Fleischer, B; Bröker, B M

1998-06-01

CTLA-4 (CD152) is a T cell surface receptor with sequence homology to the co-stimulatory molecule CD28. The molecule, which is essential for the inhibitory regulation of the immune response, becomes transiently expressed on mature T cells after stimulation in vitro. In situ, CTLA-4+ T cells are enriched in the light zones of the germinal centers in human peripheral lymphoid organs. In this study we have studied expression of CTLA-4 in human thymus in situ. CTLA-4 was expressed on about one third of CD4+/CD8-/CD1- medullary thymocytes. CTLA-4 was acquired by a subset of immature (CD1+) thymocytes and lost from the mature (CD1-) subpopulation within 48 h of cell culture, suggesting that the expression on medullary thymocytes is transient. The demonstration of CTLA-4 on a substantial subpopulation of mature CD4+ thymocytes adds a new dimension to the understanding of this important molecule. When contemplating application of anti-CTLA-4 for therapy its potential influence on T cell maturation has to be taken into account.

Diagnosis of pheochromocytoma in the setting of Parkinson disease.

PubMed

Mehta, Shyamal H; Prakash, Rajan; Prisant, L Michael; Isales, Carlos M; Morgan, John C; Williams, Hadyn; Sethi, Kapil D

2009-06-01

A 59-year-old man with a 7-year history of Parkinson disease (PD) presented with episodes of sudden, severe headaches with neck pain, tachycardia, sweating and pallor. During these episodes, the patient showed marked elevations in blood pressure, regardless of posture. This was unusual, given that he had no prior history of hypertension. The array of symptoms raised suspicions of pheochromocytoma, but diagnosis was challenging, as the standard diagnostic biochemical tests were confounded by dopaminergic medications. Further work-up revealed left adrenal medullary hyperplasia. Several reports exist of pseudopheochromocytoma in patients on dopaminergic therapy, but this is the first documented case of pheochromocytoma syndrome due to adrenal medullary hyperplasia in a patient with PD. This case highlights the challenges of performing a diagnostic work-up in a PD patient with symptoms suggestive of pheochromocytoma, and illustrates the utility of (123)I-metaiodobenzylguanidine ((123)I-MIBG) single-photon emission CT in making a diagnosis.Investigations. Physical examination, laboratory tests, abdominal MRI scan, abdominal (123)I-MIBG scan, abdominal (18)F-fluorodeoxyglucose PET scan. Pheochromocytoma syndrome due to adrenal medullary hyperplasia.Management. Surgical excision of the left adrenal gland.

Histopathological examination of bone debris from reaming of interlocking intra-medullary nail fixation of long bone fractures with concomitant head injury.

PubMed

Khallaf, Fathy G; Kehinde, Elijah O

2015-12-01

The aim of study was to test, for the presence of osteoblasts in the reaming debris of intramedullary nailing of femoral and tibial fracture in patients with and without severe head injury. Two groups of patients were studied. Group A (n = 32) had long bone fractures in addition to having head injuries. Group B (n = 35) had only long bone fractures. The fractures in the 2 groups of patients was treated by inter medullary nailing. Osteoblasts in the debris of the inter medullary nailing was compared between the 2 groups of patients. The results demonstrated that histopathological specimens from reaming debris of fractured femur and tibia in patients with head injury showed osteoblasts in (82.9%) and in (27.5%) of patients with isolated long bone fractures (p < 0.001). Healing indicators in diaphyseal fractures and concomitant head injury confirm fast and adequate healing in these patients and the presence of plenty of osteoblasts in their reaming debris may reflect a proof of accelerated fracture healing environment.

Intramedullary placement of ventricular shunts: a review of using bone as a distal cerebrospinal absorption site in treating hydrocephalus.

PubMed

Kassem, Mohammad W; Chern, Joshua; Loukas, Marios; Tubbs, R Shane

2017-12-01

Intraosseous (IO) vascular access has been used since the Second World War and is warranted when there is an emergency and/or urgent need to replenish the vascular pool. Despite long-term and satisfactory results from delivering large quantities of intravenous fluid via the medullary space of bone, use of this space for a distant receptacle for cerebrospinal fluid (CSF) diversion has seldom been considered. The current paper reviews the literature regarding the bony medullary space as a receptacle for intravenous fluid and CSF. Previous authors have demonstrated the potential of the diploic space of the calvaria for CSF shunting. Pugh and colleagues tested the ability of the cranium to receive and absorb a small amount of tracer fluid. The literature suggests that intraosseous placement of ventricular diversionary shunts is an alternative to more traditional sites such as the pleural cavity and peritoneum. When these latter locations are not available or are contraindicated, placement in the medullary space of bone is another option available to the surgeon.

Expression of a monocarboxylate transporter in reticular cells of the mouse lymph node and its involvement in the uptake of exogenous particles.

PubMed

Zheng, Miao; Ishiguro-Oonuma, Toshina; Iwanaga, Toshihiko

2014-01-01

The monocarboxylate transporter (MCT)-1 plays an important role in the transfer of monocarboxylate metabolites such as lactate, ketone bodies, and acetic acid. The present study revealed the selective localization of MCT1 in reticular cells of the murine lymph node. An intense MCT1 immunoreactivity was found in the reticular cells forming a cellular network together with sinus-lining cells in the medullary sinuses and in cells covering the inside of subcapsular sinuses.Electron-microscopically, MCT1 was localized along the plasma membrane of the reticular cells.The medullary reticular cells vigorously ingested carboxylate-modified latex particles, but any reticular cells within the cortical lymphoid follicles and medullary cords neither expressed MCT1 nor incorporated latex particles. MCT1-immunoreactive reticular cells also expressed LYVE-1,which is a hyaluronan receptor abundant in both the lymphatic endothelium and hepatic sinusoidal epithelium. The selective localization of MCT1 and LYVE-1 suggests a high level of activity for lymphoid reticular cells in the uptake of carboxylate-modified and hyaluronate waste substances circulating in the body.

Fos Expression in Neurons of the Rat Vestibulo-Autonomic Pathway Activated by Sinusoidal Galvanic Vestibular Stimulation

PubMed Central

Holstein, Gay R.; Friedrich Jr., Victor L.; Martinelli, Giorgio P.; Ogorodnikov, Dmitri; Yakushin, Sergei B.; Cohen, Bernard

2012-01-01

The vestibular system sends projections to brainstem autonomic nuclei that modulate heart rate and blood pressure in response to changes in head and body position with regard to gravity. Consistent with this, binaural sinusoidally modulated galvanic vestibular stimulation (sGVS) in humans causes vasoconstriction in the legs, while low frequency (0.02–0.04 Hz) sGVS causes a rapid drop in heart rate and blood pressure in anesthetized rats. We have hypothesized that these responses occur through activation of vestibulo-sympathetic pathways. In the present study, c-Fos protein expression was examined in neurons of the vestibular nuclei and rostral ventrolateral medullary region (RVLM) that were activated by low frequency sGVS. We found c-Fos-labeled neurons in the spinal, medial, and superior vestibular nuclei (SpVN, MVN, and SVN, respectively) and the parasolitary nucleus. The highest density of c-Fos-positive vestibular nuclear neurons was observed in MVN, where immunolabeled cells were present throughout the rostro-caudal extent of the nucleus. c-Fos expression was concentrated in the parvocellular region and largely absent from magnocellular MVN. c-Fos-labeled cells were scattered throughout caudal SpVN, and the immunostained neurons in SVN were restricted to a discrete wedge-shaped area immediately lateral to the IVth ventricle. Immunofluorescence localization of c-Fos and glutamate revealed that approximately one third of the c-Fos-labeled vestibular neurons showed intense glutamate-like immunofluorescence, far in excess of the stain reflecting the metabolic pool of cytoplasmic glutamate. In the RVLM, which receives a direct projection from the vestibular nuclei and sends efferents to preganglionic sympathetic neurons in the spinal cord, we observed an approximately threefold increase in c-Fos labeling in the sGVS-activated rats. We conclude that localization of c-Fos protein following sGVS is a reliable marker for sGVS-activated neurons of the vestibulo-sympathetic pathway. PMID:22403566

A Rare Variant of Wallenberg’s Syndrome: Opalski syndrome

PubMed Central

KK, Parathan; P, Chitrambalam; Aiyappan, Senthil Kumar; N, Deepthi

2014-01-01

Lateral Medullary Syndrome (LMS) is a well-documented vascular syndrome of the posterior circulation territory. This syndrome is easily localised because of characteristic presentation, unique territory of blood supply and very small area of involvement. We present a case of Wallenberg’s syndrome which did not have all the classical components of the syndrome, like Horner’s syndrome. Opalski syndrome is a rare variant of Wallenberg syndrome, where lateral medullary syndrome is associated with ipsilateral hemiparesis. This case report highlights how differential involvement of the lateral part of medulla can result in varied presentation. PMID:25177595

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

Cancer.gov

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.

Bilateral Medial Medullary Infarction with Nondominant Vertebral Artery Occlusion.

PubMed

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.

Acute coronary syndrome: a rare case of multiple endocrine neoplasia syndromes with pheochromocytoma and medullary thyroid carcinoma

PubMed Central

Maloberti, Alessadro; Meani, Paolo; Pirola, Roberto; Varrenti, Marisa; Boniardi, Marco; De Biase, Anna Maria; Vallerio, Paola; Bonacina, Edgardo; Mancia, Giuseppe; Loli, Paola; Giannattasio, Cristina

2015-01-01

Pheochromocytoma is a tumor arising from neuroectodermal chromaffin tissues in the adrenal gland or extra-adrenal paraganglia (paragangliomas). The prevalence of the tumor is 0.1%-0.6% in the hypertensive population, of which 10%-20% are malignant. Pheochromocytoma produces, stores, and secretes catecholamines, as well as leads to hypertensive crisis, arrhythmia, angina, and acute myocardial infarction without coronary artery diseases. We report a case of acute coronary syndrome (ACS) with a final diagnosis of multiple endocrine neoplasia with pheochromocytoma and medullary thyroid carcinoma (MTC). PMID:26487970

Gender-specific reproductive tissue in ratites and Tyrannosaurus rex.

PubMed

Schweitzer, Mary H; Wittmeyer, Jennifer L; Horner, John R

2005-06-03

Unambiguous indicators of gender in dinosaurs are usually lost during fossilization, along with other aspects of soft tissue anatomy. We report the presence of endosteally derived bone tissues lining the interior marrow cavities of portions of Tyrannosaurus rex (Museum of the Rockies specimen number 1125) hindlimb elements, and we hypothesize that these tissues are homologous to specialized avian tissues known as medullary bone. Because medullary bone is unique to female birds, its discovery in extinct dinosaurs solidifies the link between dinosaurs and birds, suggests similar reproductive strategies, and provides an objective means of gender differentiation in dinosaurs.

Deficiency of Carbonic Anhydrase II Results in a Urinary Concentrating Defect

PubMed Central

Krishnan, Devishree; Pan, Wanling; Beggs, Megan R.; Trepiccione, Francesco; Chambrey, Régine; Eladari, Dominique; Cordat, Emmanuelle; Dimke, Henrik; Alexander, R. Todd

2018-01-01

Carbonic anhydrase II (CAII) is expressed along the nephron where it interacts with a number of transport proteins augmenting their activity. Aquaporin-1 (AQP1) interacts with CAII to increase water flux through the water channel. Both CAII and aquaporin-1 are expressed in the thin descending limb (TDL); however, the physiological role of a CAII-AQP1 interaction in this nephron segment is not known. To determine if CAII was required for urinary concentration, we studied water handling in CAII-deficient mice. CAII-deficient mice demonstrate polyuria and polydipsia as well as an alkaline urine and bicarbonaturia, consistent with a type III renal tubular acidosis. Natriuresis and hypercalciuria cause polyuria, however, CAII-deficient mice did not have increased urinary sodium nor calcium excretion. Further examination revealed dilute urine in the CAII-deficient mice. Urinary concentration remained reduced in CAII-deficient mice relative to wild-type animals even after water deprivation. The renal expression and localization by light microscopy of NKCC2 and aquaporin-2 was not altered. However, CAII-deficient mice had increased renal AQP1 expression. CAII associates with and increases water flux through aquaporin-1. Water flux through aquaporin-1 in the TDL of the loop of Henle is essential to the concentration of urine, as this is required to generate a concentrated medullary interstitium. We therefore measured cortical and medullary interstitial concentration in wild-type and CAII-deficient mice. Mice lacking CAII had equivalent cortical interstitial osmolarity to wild-type mice: however, they had reduced medullary interstitial osmolarity. We propose therefore that reduced water flux through aquaporin-1 in the TDL in the absence of CAII prevents the generation of a maximally concentrated medullary interstitium. This, in turn, limits urinary concentration in CAII deficient mice. PMID:29354070

Effect of dark chocolate on renal tissue oxygenation as measured by BOLD-MRI in healthy volunteers.

PubMed

Pruijm, Menno; Hofmann, Lucie; Charollais-Thoenig, Julie; Forni, Valentina; Maillard, Marc; Coristine, Andrew; Stuber, Matthias; Burnier, Michel; Vogt, Bruno

2013-09-01

Cocoa is rich in flavonoids, has anti-oxidative properties and increases the bioavailability of nitric oxide (NO). Adequate renal tissue oxygenation is crucial for the maintenance of renal function. The goal of this study was to investigate the effect of cocoa-rich dark chocolate (DC) on renal tissue oxygenation in humans, as compared to flavonoid-poor white chocolate (WC). Ten healthy volunteers with preserved kidney function (mean age ± SD 35 ± 12 years, 70% women, BMI 21 ± 3 kg/m2) underwent blood oxygenation level-dependent magnetic resonance imaging (BOLD-MRI) before and 2 hours after the ingestion of 1 g/kg of DC (70% cocoa). Renal tissue oxygenation was determined by the measurement of R2* maps on 4 coronal slices covering both kidneys. The mean R2* (= 1/T2*) values in the medulla and cortex were calculated, a low R2* indicating high tissue oxygenation. Eight participants also underwent BOLD-MRI at least 1 week later, before and 2 hours after the intake of 1 g/kg WC. The mean medullary R2* was lower after DC intake compared to baseline (28.2 ± 1.3 s-1 vs. 29.6 ± 1.3 s-1, p = 0.04), whereas cortical and medullary R2* values did not change after WC intake. The change in medullary R2* correlated with the level of circulating (epi)catechines, metabolites of flavonoids (r = 0.74, p = 0.037), and was independent of plasma renin activity. This study suggests for the first time an increase of renal medullary oxygenation after intake of dark chocolate. Whether this is linked to flavonoid-induced changes in renal perfusion or oxygen consumption, and whether cocoa has potentially renoprotective properties, merits further study.

Impact of mandibular invasion on prognosis in oral squamous cell carcinoma four centimeters or less in size.

PubMed

Fives, Cassie; Nae, Andreea; Roche, Phoebe; O'Leary, Gerard; Fitzgerald, Brendan; Feeley, Linda; Sheahan, Patrick

2017-04-01

Previous studies have reported variable results for the impact of bone invasion on survival in oral cancer. It is unclear whether bone invasion in small (≤4 cm) squamous cell carcinomas (SCC) of the oral cavity is an independent adverse prognosticator. Our objective was to investigate impact on survival of bone invasion in SCC of floor of mouth (FOM), lower alveolus (LA), and retromolar trigone (RMT) ≤4 cm in size. Retrospective study of 96 patients with SCC of the FOM, LA, and RMT undergoing primary surgical treatment. Original pathology reports and slides were reviewed by three pathologists. Level of bone invasion was categorized as cortical or medullary. Main outcome measures were local control (LC) and overall survival (OS). Bone invasion was present in 31 cases (32%). On review of pathology slides, all cases of bone invasion demonstrated medullary involvement. Median follow-up was 36 months for all patients, and 53 months for patients not dying from cancer. Among tumors ≤4 cm, bone invasion was associated with significantly worse LC (P =.04) and OS (P =.0005). Medullary invasion (hazard ratio: 2.2, 95% confidence interval: 1.1-4.4, P =.03), postoperative radiotherapy (hazard ratio: 0.3, 95% confidence interval: 0.1-0.5, P <.001), and positive pathologic nodal status (hazard ratio: 4.1, 95% confidence interval: 1.9-8.6, P <.001) were independent predictors of worse OS among the entire cohort. Mandibular medullary bone invasion is a poor prognosticator in oral cancers, irrespective of small size of primary tumor. Such cases should be considered for postoperative radiotherapy. 4. Laryngoscope, 127:849-854, 2017. © 2016 The American Laryngological, Rhinological and Otological Society, Inc.

Adrenal medullary hyperplasia is a precursor lesion for pheochromocytoma in MEN2 syndrome.

PubMed

Korpershoek, Esther; Petri, Bart-Jeroen; Post, Edward; van Eijck, Casper H J; Oldenburg, Rogier A; Belt, Eric J T; de Herder, Wouter W; de Krijger, Ronald R; Dinjens, Winand N M

2014-10-01

Adrenal medullary hyperplasias (AMHs) are adrenal medullary proliferations with a size < 1 cm, while larger lesions are considered as pheochromocytoma (PCC). This arbitrary distinction has been proposed decades ago, although the biological relationship between AMH and PCC has never been investigated. Both lesions are frequently diagnosed in multiple endocrine neoplasia type 2 (MEN2) patients in whom they are considered as two unrelated clinical entities. In this study, we investigated the molecular relationship between AMH and PCC in MEN2 patients. Molecular aberrations of 19 AMHs and 13 PCCs from 18 MEN2 patients were determined by rearranged during transfection (RET) proto-oncogene mutation analysis and loss of heterozygosity (LOH) analysis for chromosomal regions 1p13, 1p36, 3p, and 3q, genomic areas covering commonly altered regions in RET-related PCC. Identical molecular aberrations were found in all AMHs and PCCs, at similar frequencies. LOH was seen for chromosomes 1p13 in 8 of 18 (44%), 1p36 in 9 of 15 (60%), 3p12-13 in 12 of 18 (67%), and 3q23-24 in 10 of 16 (63%) of AMHs, and for chromosome 1p13 in 13 of 13 (100%), 1p36 in 7 of 11 (64%), 3p12-13 in 4 of 11 (36%), and 3q23-24 in 11 of 12 (92%) of PCCs. Our results indicate that AMHs are not hyperplasias and, in clinical practice, should be regarded as PCCs, which has an impact on diagnosis and treatment of MEN2 patients. We therefore propose to replace the term AMH by micro-PCC to indicate adrenal medullary proliferations of less than 1 cm.

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

PubMed Central

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

Song Decrystallization in Adult Zebra Finches Does Not Require the Song Nucleus NIf

PubMed Central

Roy, Arani; Mooney, Richard

2009-01-01

In adult male zebra finches, transecting the vocal nerve causes previously stable (i.e., crystallized) song to slowly degrade, presumably because of the resulting distortion in auditory feedback. How and where distorted feedback interacts with song motor networks to induce this process of song decrystallization remains unknown. The song premotor nucleus HVC is a potential site where auditory feedback signals could interact with song motor commands. Although the forebrain nucleus interface of the nidopallium (NIf) appears to be the primary auditory input to HVC, NIf lesions made in adult zebra finches do not trigger song decrystallization. One possibility is that NIf lesions do not interfere with song maintenance, but do compromise the adult zebra finch's ability to express renewed vocal plasticity in response to feedback perturbations. To test this idea, we bilaterally lesioned NIf and then transected the vocal nerve in adult male zebra finches. We found that bilateral NIf lesions did not prevent nerve section–induced song decrystallization. To test the extent to which the NIf lesions disrupted auditory processing in the song system, we made in vivo extracellular recordings in HVC and a downstream anterior forebrain pathway (AFP) in NIf-lesioned birds. We found strong and selective auditory responses to the playback of the birds' own song persisted in HVC and the AFP following NIf lesions. These findings suggest that auditory inputs to the song system other than NIf, such as the caudal mesopallium, could act as a source of auditory feedback signals to the song motor network. PMID:19515953

SOCCER: Comet Coma Sample Return Mission

NASA Technical Reports Server (NTRS)

Albee, A. L.; Uesugi, K. T.; Tsou, Peter

1994-01-01

Comets, being considered the most primitive bodies in the solar system, command the highest priority among solar system objects for studying solar nebula evolution and the evolution of life through biogenic elements and compounds. Sample Of Comet Coma Earth Return (SOCCER), a joint effort between NASA and the Institute of Space and Astronautical Science (ISAS) in Japan, has two primary science objectives: (1) the imaging of the comet nucleus and (2) the return to Earth of samples of volatile species and intact dust. This effort makes use of the unique strengths and capabilities of both countries in realizing this important quest for the return of samples from a comet. This paper presents an overview of SOCCER's science payloads, engineering flight system, and its mission operations.

Assessment of Erythroid and Granulocytic Hematopoietic Lineages in Patients with Non-Small-Cell Lung Carcinoma.

PubMed

Goldberg, V E; Polyakova, T Yu; Popova, N O; Vysotskaya, V V; Simolina, E I; Belevich, Yu V; Tuzikova, T P; Goldberg, A V; Zhdanov, V V; Miroshnichenko, L A; Udut, E V; Simanina, E V; Dygai, A M; Zyuz'kov, G N

2017-08-01

The toxic effects of combined cisplatin/docetaxel therapy cycles on erythroid and granulocytic hematopoietic lineages as well as their intercycle recovery were examined in patients with stage III-IV non-small-cell lung carcinoma. Responsiveness of the blood system to this therapy remained at a high level. Combined therapy pronouncedly activated the key elements of the erythroid and granulocytic hematopoietic lineages leading to accumulation of immature and mature myelokaryocytes in the bone marrow, enlargement of the medullary pool of mature neutrophils, and increase in the count of medullary erythroid and granulocytic precursor cells under conditions of their accelerated maturation.

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

PubMed

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.

A re-assessment of the effects of intracortical delivery of inosine on transmidline growth of corticospinal tract axons after unilateral lesions of the medullary pyramid

PubMed Central

Steward, Oswald; Sharp, Kelli; Yee, Kelly Matsudaira

2011-01-01

This study was undertaken as part of the NIH “Facilities of Research Excellence-Spinal Cord Injury”, which supports independent replication of published studies. Here, we repeat an experiment reporting that intracortical delivery of inosine promoted trans-midline growth of corticospinal tract (CST) axons in the spinal cord after unilateral injury to the medullary pyramid. Rats received unilateral transections of the medullary pyramid and 1 day later, a cannula assembly was implanted into the sensorimotor cortex contralateral to the pyramidotomy to deliver either inosine or vehicle. The cannula assembly was attached to an osmotic minipump that was implanted sub-cutaneously. Seventeen or 18 days post-injury, the CST was traced by making multiple injections of miniruby-BDA into the sensorimotor cortex. Rats were killed for tract tracing 14 days after the BDA injections. Sections through the cervical spinal cord were stained for BDA and immunostained for GAP43 and GFAP. Our results revealed no evidence for enhanced growth of CST axons across the midline of the dorsal column in rats that received intracortical infusion of inosine. Possible reasons for the failure to replicate are discussed. PMID:21946267

Treatment of medullary thyroid carcinoma with apatinib

PubMed Central

Cai, Sina; Deng, Huan; Chen, Yinkui; Wu, Xing; Guan, Xiaoqian

2017-01-01

Abstract Rationale: Medullary thyroid carcinoma (MTC) is a rare type thyroid carcinoma originating from the thyroid parafollicular cells (C cells). Chemotherapy has a limited efficacy for treating persistent or recurrent MTC. Patient concerns: A 46-year-old woman who underwent thyroidectomy for MTC in December 2007. She began experience recurring diarrhea in January 2015 and started to cough and feel shortness of breath in March 2016. Diagnoses: A chestcomputed tomography (CT) scan showed metastases in the bilateral lungs, pulmonary hilum, and mediastinal lymph nodes. Percutaneous biopsy of the pulmonary occupying lesions performed on March 21, 2016 indicated medullary carcinoma metastases at the right pulmonary hilum. Interventions: This patient was treated with oral apatinib (500 mg daily). Outcomes: The patient's symptoms of diarrhea, coughing, and shortness of breath disappeared. CT reexaminations for efficacy assessment at 1, 2, and 3 months after the treatment indicated partial remission. Systemic migrating bone and joint pains occurred during the treatment, which were considered to be adverse events of apatinib. Lessons: Treatment of MTC with apatinib has been shown to be effective in our case. Tyrosine kinase inhibitors (TKIs) that suppress rearranged during transfection (RET) and vascular endothelial growth factor receptor (VEGFR) should be considered as a effective therapeutic approaches. PMID:29390263

Medullary Sponge Kidney

MedlinePlus

... Process Research Training & Career Development Funded Grants & Grant History Research Resources Research at NIDDK Technology Advancement & Transfer Meetings & Workshops Health Information Diabetes Digestive ...

Brainstem and cervical spinal cord Fos immunoreactivity evoked by nerve growth factor injection into neck muscles in mice.

PubMed

Panfil, C; Makowska, A; Ellrich, J

2006-02-01

Although myofascial tenderness is thought to play a key role in the pathophysiology of tension-type headache, very few studies have addressed neck muscle nociception. The neuronal activation pattern following local nerve growth factor (NGF) administration into semispinal neck muscles in anaesthetized mice was investigated using Fos protein immunohistochemistry. In order to differentiate between the effects of NGF administration on c-fos expression and the effects of surgical preparation, needle insertion and intramuscular injection, the experiments were conducted in three groups. In the sham group (n=7) cannula needles were only inserted without any injection. In the saline (n=7) and NGF groups (n=7) 0.9% physiological saline solution or 0.8 microm NGF solution were injected in both muscles, respectively. In comparison with sham and saline conditions, NGF administration induced significantly stronger Fos immunoreactivity in the mesencephalic periaqueductal grey (PAG), the medullary lateral reticular nucleus (LRN), and superficial layers I and II of cervical spinal dorsal horns C1, C2 and C3. This activation pattern corresponds very well to central nervous system processing of deep noxious input. A knowledge of the central anatomical representation of neck muscle pain is an essential prerequisite for the investigation of neck muscle nociception in order to develop a future model of tension-type headache.

Defining the neurocircuitry of exercise hyperpnoea

PubMed Central

Paterson, David J

2014-01-01

One hundred years ago in this journal, Krogh and Lindhard published a seminal paper highlighting the importance of the brain in the control of breathing during exercise. This symposium report reviews the historical developments that have taken place since 1913, and attempts to place the detailed neurocircuitry thought to underpin exercise hyperpnoea into context by focusing on key structures that might form the command network. With the advent of enhanced neuroimaging and functional neurosurgical techniques, a unique window of opportunity has recently arisen to target potential circuits in humans. Animal studies have identified a priori sites of interest in mid-brain structures, in particular the subthalamic locomotor region (subthalamic nucleus, STN) and the periaqueductal grey (PAG), which have now been recorded from in humans during exercise. When all data are viewed in an integrative manner, the PAG, in particular the lateral PAG, and aspects of the dorsal lateral PAG, appear to be key communicating circuitry for ‘central command’. Moreover, the PAG also fulfils many requirements of a command centre. It has functional connectivity to higher centres (dorsal lateral prefrontal cortex) and the basal ganglia (in particular, the STN), and receives a sensory input from contracting muscle, but, importantly, it sends efferent information to brainstem nuclei involved in cardiorespiratory control. PMID:23918772

Lymphoepithelioma-like Carcinoma of the Breast: A Case Report

PubMed Central

Top, Ömer Erdinç; Vardar, Enver; Yağcı, Ayşe; Deniz, Senem; Öztürk, Rafet; Zengel, Baha

2014-01-01

Lymphoepithelioma-like carcinoma carries similar histopathological features with lymphoepithelioma typically located in the nasopharynx. Lymphoepithelioma-like carcinoma of the breast can be mistaken for breast lymphoma or medullary carcinoma due to the undifferentiated appearance of tumor cells and presence of prominent lymphoid component. Lymphoepithelioma-like carcinoma is rare, and the similarity between medullary carcinoma of the breast makes it difficult to distinguish these two tumors. In the presented case, neither lymph node nor distant metastases were detected. Breast lymphoepithelioma-like carcinoma is extremely rare with only 21 reported cases in the literature. Herein we present a 59-year-old woman with lymphoepithelioma-like carcinoma of the breast along with the cases previously published in the literature. PMID:28331666

Regional distribution of acid mucopolysaccharides in the kidney

PubMed Central

Castor, C. W.; Greene, J. A.

1968-01-01

Kidneys from 20 dogs were dissected into cortical and medullary components and analysed for acid mucopolysaccharide content. Heparitin sulfate accounted for approximately 80% of cortical acid mucopolysaccharide, 10% was chondroitin sulfate B, and 10% was low molecular weight hyaluronic acid. Medullary tissue exhibited a 4- to 5-fold higher concentration of acid mucopolysaccharide than did cortical tissue, and the dominant compound was moderately highly polymerized hyaluronic acid. While chondroitin sulfates A and (or) C were not detected in this study, the presence of minor amounts of these substances could not be excluded. A model experiment indicated that hyaluronic acid retards sodium diffusion, apparently due to its viscous properties rather than its electronegativity. PMID:4233982

Renal medullary carcinoma and sickle cell trait: A systematic review.

PubMed

Alvarez, Ofelia; Rodriguez, Maria M; Jordan, Lanetta; Sarnaik, Sharada

2015-10-01

Sickle cell trait (SCT) carries a small risk of renal medullary carcinoma (RMC). We conducted a systematic literature review and reported new four RMC cases (total N = 217). Eighty eight percent had SCT and 8% had sickle cell disease; 50% were children. Males had 2.4× risk than females. Isolated hematuria or in combination with abdominal or flank pain was the presenting sign in 66% cases. Tumor-related mortality was 95%. Four non-metastatic patients were long-term disease-free survivors. Although risk appears to be very low, individuals with SCT should be informed about the low risk of RMC with the hope of early diagnosis. Hematuria should prompt immediate investigation. © 2015 Wiley Periodicals, Inc.

Urea transporter knockout mice and their renal phenotypes.

PubMed

Fenton, Robert A; Yang, Baoxue

2014-01-01

Urea transporter gene knockout mice have been created for the study of the urine-concentrating mechanism. The major findings in studies of the renal phenotype of these mice are as follows: (1) Urea accumulation in the inner medullary interstitium is dependent on intrarenal urea recycling mediated by urea transporters; (2) urea transporters are essential for preventing urea-induced osmotic diuresis and thus for water conservation; (3) NaCl concentration in the inner medullary interstitium is not significantly affected by the absence of IMCD, descending limb of Henle and descending vasa recta urea transporters. Studies in urea transporter knockout mouse models have highlighted the essential role of urea for producing maximally concentrated urine.

Recurrent Medullary Thyroid Carcinoma on 68Ga-Prostate-Specific Membrane Antigen PET/CT: Exploring New Theranostic Avenues.

PubMed

Arora, Saurabh; Damle, Nishikant Avinash; Parida, Girish Kumar; Singhal, Abhinav; Nalli, Harish; Dattagupta, Shreya; Bal, Chandrasekar

2018-05-01

The prostate-specific membrane antigen (PSMA) is highly expressed in prostate cancer cells. Few other malignancies have shown expression of PSMA. We present a case of 35-year-old man with medullary thyroid carcinoma, post total thyroidectomy and bilateral neck dissection, now presenting with rising calcitonin levels (doubling time 9 months) and local neck recurrence with negative I-MIBG scan. We decided to perform Ga-PSMA-HBED-CC PET/CT scan to assess PSMA expression and explore the therapeutic option in view of rising serum calcitonin. It revealed intense PSMA uptake in the soft tissue mass in left thyroid bed and cervical lymph nodes.

Neonatal cholestasis and focal medullary dysplasia of the kidneys in a case of microcephalic osteodysplastic primordial dwarfism.

PubMed Central

Berger, A; Haschke, N; Kohlhauser, C; Amman, G; Unterberger, U; Weninger, M

1998-01-01

We report on a male infant who presented with intrauterine growth retardation, severe postnatal failure to thrive, microcephaly, facial dysmorphism, and skeletal dysplasia. The clinical and radiological findings are consistent with former descriptions of microcephalic osteodysplastic primordial dwarfism (MOPD) type I/III. In addition to previously published features, multiple fractures of the long bones, severe neonatal cholestasis, and histological dysplasia of the kidneys were found. The boy died at the age of 8 months. The new finding of focal renal medullary dysplasia further supports the hypothesis of a basic defect in tissue differentiation in the pathogenesis of this rare condition. Images PMID:9475098

[Somatostatin receptor scintigraphy in medullary thyroid carcinomas, GEP and carcinoid tumors].

PubMed

Eising, E G; Farahati, J; Bier, D; Knust, E J; Reiners, C

1995-02-01

For this study, 24 patients with medullary thyroid cancer (MTC) and 10 with carcinoid-/GEP-tumours underwent scintigraphy with 123I-Tyr3-octreotide or 111In-DTPA-D-Phe1-octreotide (Octreoscan) or 99mTc-V-DMSA. Calcitonin and CEA were elevated in MTC patients, the other had tumour lesions on CT. Octreoscan-scintigraphy was positive in 68% of all suspicious cases. On the other hand, 123I-Tyr3-octreotide showed only rarely positive results. 99mTc-V-DMSA-scans in MTC patients were positive in 23%. Liver metastases could be seen only with Octreoscan in the non-MTC-group. These results showed better sensitivity of 111In-labelled octreotide.

Pressor response to L-cysteine injected into the cisterna magna of conscious rats involves recruitment of hypothalamic vasopressinergic neurons.

PubMed

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.

Palaeobiological implications of the bone histology of Pterodaustro guinazui.

PubMed

Chinsamy, Anusuya; Codorniú, Laura; Chiappe, Luis

2009-09-01

This study provides a comprehensive investigation of the bone microstructure of multiple bones of the Early Cretaceous filter-feeder, Pterodaustro guinazui, from the Largacito Formation of Central Argentina. We provide information regarding the bone histology of multiple elements from single skeletons, as well as a variety of bones from different individuals. In addition, we analysed changes in bone microstructure through ontogeny in growth series of several long bones of the taxon. Our investigation of skeletal and ontogenetic variation in Pterodaustro gives insights into the developmental growth dynamics of this unusual ctenochasmatid pterodactyloid from early ontogeny through to adulthood and also provides information pertaining to histological variability within and between bones of individuals. This study also documents the presence of what appears to be medullary bone tissue within the medullary cavity of a large femur of Pterodaustro. This suggests that, like birds, reproductively active female pterosaurs may have deposited a special bone tissue (medullary bone) to cope with the demand of calcium during eggshelling. Our study supports the hypothesis that small Jurassic pterodactyloids took several years to reach adult body size. More specifically, we provide data that suggests that Pterodaustro attained sexual maturity at about 2 years of age, and continued to grow for a further 3-4 years doubling in size before attaining skeletal maturity. (c) 2009 Wiley-Liss, Inc.

Longitudinal assessment of mouse renal injury using high-resolution anatomic and magnetization transfer MR imaging.

PubMed

Wang, Feng; Jiang, Rosie; Takahashi, Keiko; Gore, John; Harris, Raymond C; Takahashi, Takamune; Quarles, C Chad

2014-11-01

The purpose of this study is to evaluate the utility of high-resolution non-invasive endogenous high-field MRI methods for the longitudinal structural and quantitative assessments of mouse kidney disease using the model of unilateral ureter obstruction (UUO). T1-weighted, T2-weighted and magnetization transfer (MT) imaging protocols were optimized to improve the regional contrast in mouse kidney. Conventional T1 and T2 weighted images were collected in UUO mice on day 0 (~3h), day 1, day 3 and day 6 after injury, on a 7 T small animal MRI system. Cortical and medullary thickness, corticomedullary contrast and Magnetization Transfer Ratio (MTR) were assessed longitudinally. Masson trichrome staining was used to histologically assess changes in tissue microstructure. Over the course of UUO progression there were significant (p<0.05) changes in thickness of cortex and outer medulla, and regional changes in T2 signal intensity and MTR values. Histological changes included tubular cell death, tubular dilation, urine retention, and interstitial fibrosis, assessed by histology. The MRI measures of renal cortical and medullary atrophy, cortical-medullary differentiation and MTR changes provide an endogenous, non-invasive and quantitative evaluation of renal morphology and tissue composition during UUO progression. Copyright © 2014 Elsevier Inc. All rights reserved.

Substance P in the dorsal vagal complex inhibits medullary TRH-induced gastric acid secretion in rats.

PubMed

Yang, H; Taché, Y

1997-05-01

Neurons that contain substance P (SP) and thyrotropin-releasing hormone (TRH) in medullary midline raphe nuclei project to the dorsal vagal complex (DVC). The modulatory role of SP on basal gastric acid secretion (GAS) and TRH on DVC-induced stimulation of GAS was studied in urethan-anesthetized rats. The stable SP agonist, DiMe-C7 ([pGlu5, MePhe8, MeGly9]SP5-11, 50 and 100 pmol), injected unilaterally into the DVC reduced the GAS response (47 +/- 12 mumol/60 min) to coinjected TRH analog, RX 77368 (25 pmol), by 53% and 85%, respectively, whereas DiMe-C7 (100 pmol) alone had no effect on basal and pentagastrin-stimulated GAS. DiMe-C7 (100 pmol/site) inhibited the GAS response to kainic acid injected into the raphe pallidus (Rpa) when it was injected bilaterally into the DVC but not the hypoglossal nuclei. The SP nourokinin-1-receptor antagonist, CP-96,345, injected bilaterally into the DVC (1 nmol/ site) increased basal GAS (33 +/- 8 mumol/90 min) and potentiated the GAS response to kainic acid injected into the Rpa by 40%. These results suggest that SP acts on neurokinin-1 receptors in the DVC to reduce medullary TRH-induced stimulation of GAS in rats.

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

PubMed

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.

Treatment of medullary thyroid carcinoma with apatinib: A case report and literature review.

PubMed

Cai, Sina; Deng, Huan; Chen, Yinkui; Wu, Xing; Guan, Xiaoqian

2017-12-01

Medullary thyroid carcinoma (MTC) is a rare type thyroid carcinoma originating from the thyroid parafollicular cells (C cells). Chemotherapy has a limited efficacy for treating persistent or recurrent MTC. A 46-year-old woman who underwent thyroidectomy for MTC in December 2007. She began experience recurring diarrhea in January 2015 and started to cough and feel shortness of breath in March 2016. A chestcomputed tomography (CT) scan showed metastases in the bilateral lungs, pulmonary hilum, and mediastinal lymph nodes. Percutaneous biopsy of the pulmonary occupying lesions performed on March 21, 2016 indicated medullary carcinoma metastases at the right pulmonary hilum. This patient was treated with oral apatinib (500 mg daily). The patient's symptoms of diarrhea, coughing, and shortness of breath disappeared. CT reexaminations for efficacy assessment at 1, 2, and 3 months after the treatment indicated partial remission. Systemic migrating bone and joint pains occurred during the treatment, which were considered to be adverse events of apatinib. Treatment of MTC with apatinib has been shown to be effective in our case. Tyrosine kinase inhibitors (TKIs) that suppress rearranged during transfection (RET) and vascular endothelial growth factor receptor (VEGFR) should be considered as a effective therapeutic approaches. Copyright © 2017 The Authors. Published by Wolters Kluwer Health, Inc. All rights reserved.

Transventricular Transvelar Approach to Trochlear Nerve Schwannoma: Novel Technique to Lesions of Inferior Pineal Region.

PubMed

Farrokhi, Majid Reza; Ghaffarpasand, Fariborz; Taghipour, Mousa; Derakhshan, Nima

2018-06-01

The schwannoma of the trochlear nerve is rare and originates mostly from the distal parts in the interpeduncular cistern. A lesion on the proximal segment in the inferior pineal region is extremely rare. Because of the rarity of the disease, the surgical approach to this region for the resection of trochlear nerve schwannoma has not been well documented in the literature. We herein describe a novel approach to successfully resect the trochlear nerve schwannoma. A 12-year-old boy presented with occipital headache, abnormal gait, and disturbed conjoined eye movement. He was diagnosed with a lesion in the inferior pineal region compressing the superior medullary velum into the roof of the fourth ventricle. A bilateral midline suboccipital craniotomy was performed, and the fourth ventricle was exposed. The lesion was approached through the fourth ventricle superior medullary velum (transventricular transvelar approach). The lesion was totally resected, and his histopathology examination revealed trochlear schwannoma. The patient's symptoms resolved, and he had no recurrence at 12-year follow-up with normal eye movement and vision. The transventricular transvelar approach is feasible and safe to treat a lesion of the lower part of the pineal region being pushed through the superior medullary velum. Copyright © 2018 Elsevier Inc. All rights reserved.

Serum cholecystokinin and neurotensin during follow-up of pancreas, prostate and medullary thyroid tumors.

PubMed

Pichon, M F; Coquin, G; Fauveau, C; Rey, A

1999-01-01

Growth of pancreatic carcinoma cells is stimulated by cholecystokinin (CCK) and neurotensin (NT). Prostatic carcinoma cells can secrete neurotensin. The CCK gene has been described in thyroid medullary carcinomas (MCT). Serum CCK and NT were measured by RIAs during monitoring of 19 pancreas tumours, 10 prostate adenocarcinomas and 10 thyroid medullary cancers (MCT). No correlations were found between CCK and NT in the three tumour types, nor with CA 19.9, PSA, CEA or calcitonin. In pancreas adenocarcinomas (n = 12), initial median CCK was > 8pg/ml (non significant differences between stages T, N or M). Median NT was > 80 pg/ml in all but M0 and stage I-II cases, and significantly higher in M1 and stages IV (P = 0.002). Non significant differences were found for CCK and NT according to clinical stages. In prostate cancers, median CCK was significantly more elevated after relapse (P = 0.040). Median NT was significantly more elevated in disease-free patients (P = 0.04). In MCT, CCK and NT were not related to clinical stages. In pancreas and prostate cancers serum CCK may follow tumour load and disease progression. NT was lower in progressive disease. The contribution of these peptides in human tumour growth, since they may have therapeutic implication, warrants further investigation.

MIBG scintiscan

MedlinePlus

Adrenal medullary imaging; Meta-iodobenzylguanidine scintiscan; Pheochromocytoma - MIBG; Neuroblastoma - MIBG; Carcinoid MIBG ... answer. It is also used to help diagnose neuroblastoma and can be used for carcinoid tumors.

Renal papillary necrosis

MedlinePlus

... asking your provider. Alternative Names Necrosis - renal papillae; Renal medullary necrosis Images Kidney anatomy Kidney - blood and urine flow References Bushinsky DA, Monk RD. Nephrolithiasis and nephrocalcinosis. ...

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

PubMed

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 (P<.05). SWAL-QOL Scale scores increased more significantly in the sensory approach combined with traditional swallowing therapy 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 medullary infarction. A sensory approach appears to be better than a motor approach. Copyright © 2016 American Congress of Rehabilitation Medicine. Published by Elsevier Inc. All rights reserved.

A new perspective on the pathogenesis of chronic renal disease in captive cheetahs (Acinonyx jubatus)

PubMed Central

Prozesky, Leon; Lawrence, John

2018-01-01

The sustainability of captive cheetah populations is limited by high mortality due to chronic renal disease. This necropsy study, conducted on 243 captive cheetahs from one institution, investigated the relationships between focal palatine erosions, gastritis, enterocolitis, glomerulosclerosis, chronic renal infarcts, renal cortical and medullary fibrosis, and renal medullary amyloidosis at death. Associations between the individual renal lesions and death due to chronic renal disease and comparisons of lesion prevalence between captive bred and wild born and between normal and king coated cheetahs were also assessed. All lesions were significantly positively correlated with age at death. Renal medullary fibrosis was the only lesion associated with the likelihood of death being due to chronic renal disease, and cheetahs with this lesion were younger, on average, than cheetahs with other renal lesions. Alimentary tract lesions were not associated with amyloidosis. All lesions, except for palatine erosions, were more common in wild born than in captive bred cheetahs; the former were older at death than the latter. Having a king coat had no clear effect on disease prevalence. These results suggest that age and renal medullary fibrosis are the primary factors influencing the pathogenesis of chronic renal disease in captive cheetahs. Apart from amyloidosis, these findings are analogous to those described in chronic renal disease in domestic cats, which is postulated to result primarily from repetitive hypoxic injury of renal tubules, mediated by age and stress. Cheetahs may be particularly susceptible to acute renal tubular injury due to their propensity for stress and their extended life span in captivity, as well as their adaptation for fecundity (rather than longevity) and adrenaline-mediated high speed prey chases. The presence of chronic renal disease in subadult cheetahs suggests that prevention, identification and mitigation of stress are critical to the successful prevention of chronic renal disease in captive cheetahs. PMID:29513736

A new perspective on the pathogenesis of chronic renal disease in captive cheetahs (Acinonyx jubatus).

PubMed

Mitchell, Emily P; Prozesky, Leon; Lawrence, John

2018-01-01

The sustainability of captive cheetah populations is limited by high mortality due to chronic renal disease. This necropsy study, conducted on 243 captive cheetahs from one institution, investigated the relationships between focal palatine erosions, gastritis, enterocolitis, glomerulosclerosis, chronic renal infarcts, renal cortical and medullary fibrosis, and renal medullary amyloidosis at death. Associations between the individual renal lesions and death due to chronic renal disease and comparisons of lesion prevalence between captive bred and wild born and between normal and king coated cheetahs were also assessed. All lesions were significantly positively correlated with age at death. Renal medullary fibrosis was the only lesion associated with the likelihood of death being due to chronic renal disease, and cheetahs with this lesion were younger, on average, than cheetahs with other renal lesions. Alimentary tract lesions were not associated with amyloidosis. All lesions, except for palatine erosions, were more common in wild born than in captive bred cheetahs; the former were older at death than the latter. Having a king coat had no clear effect on disease prevalence. These results suggest that age and renal medullary fibrosis are the primary factors influencing the pathogenesis of chronic renal disease in captive cheetahs. Apart from amyloidosis, these findings are analogous to those described in chronic renal disease in domestic cats, which is postulated to result primarily from repetitive hypoxic injury of renal tubules, mediated by age and stress. Cheetahs may be particularly susceptible to acute renal tubular injury due to their propensity for stress and their extended life span in captivity, as well as their adaptation for fecundity (rather than longevity) and adrenaline-mediated high speed prey chases. The presence of chronic renal disease in subadult cheetahs suggests that prevention, identification and mitigation of stress are critical to the successful prevention of chronic renal disease in captive cheetahs.

Quantification of vascular damage in acute kidney injury with fluorine magnetic resonance imaging and spectroscopy.

PubMed

Moore, Jeremy K; Chen, Junjie; Pan, Hua; Gaut, Joseph P; Jain, Sanjay; Wickline, Samuel A

2018-06-01

To design a fluorine MRI/MR spectroscopy approach to quantify renal vascular damage after ischemia-reperfusion injury, and the therapeutic response to antithrombin nanoparticles (NPs) to protect kidney function. A total of 53 rats underwent 45 min of bilateral renal artery occlusion and were treated at reperfusion with either plain perfluorocarbon NPs or NPs functionalized with a direct thrombin inhibitor (PPACK:phenyalanine-proline-arginine-chloromethylketone). Three hours after reperfusion, kidneys underwent ex vivo fluorine MRI/MR spectroscopy at 4.7 T to quantify the extent and volume of trapped NPs, as an index of vascular damage and ischemia-reperfusion injury. Microscopic evaluation of structural damage and NP trapping in non-reperfused renal segments was performed. Serum creatinine was quantified serially over 7 days. The damaged renal cortico-medullary junction trapped a significant volume of NPs (P = 0.04), which correlated linearly (r = 0.64) with the severity of kidney injury 3 h after reperfusion. Despite global large vessel reperfusion, non-reperfusion in medullary peritubular capillaries was confirmed by MRI and microscopy, indicative of continuing hypoxia due to vascular compromise. Treatment of animals with PPACK NPs after acute kidney injury did not accelerate kidney functional recovery. Quantification of ischemia-reperfusion injury after acute kidney injury with fluorine MRI/MR spectroscopy of perfluorocarbon NPs objectively depicts the extent and severity of vascular injury and its linear relationship to renal dysfunction. The lack of kidney function improvement after early posttreatment thrombin inhibition confirms the rapid onset of ischemia-reperfusion injury as a consequence of vascular damage and non-reperfusion. The prolongation of medullary ischemia renders cortico-medullary tubular structures susceptible to continued necrosis despite restoration of large vessel flow, which suggests limitations to acute interventions after acute kidney injury, designed to interdict renal tubular damage. Magn Reson Med 79:3144-3153, 2018. © 2017 International Society for Magnetic Resonance in Medicine. © 2017 International Society for Magnetic Resonance in Medicine.

Changes in Level of the Conus after Corrective Surgery for Scoliosis: MRI-Based Preliminary Study in 31 Patients

PubMed Central

Hong, Jae-Young; Park, Jung-Ho; Hur, Chang-Yong; Hong, Suk-Joo; Modi, Hitesh N

2011-01-01

Background Detection of postoperative spinal cord level change can provide basic information about the spinal cord status, and electrophysiological studies regarding this point should be conducted in the future. Methods To determine the changes in the spinal cord level postoperatively and the possible associated factors, we prospectively studied 31 patients with scoliosis. All the patients underwent correction and posterior fusion using pedicle screws and rods between January 2008 and March 2009. The pre- and postoperative conus medullaris levels were determined by matching the axial magnetic resonance image to the sagittal scout image. The patients were divided according to the change in the postoperative conus medullaris level. The change group was defined as the patients who showed a change of more than one divided section in the vertebral column postoperatively, and the parameters of the change and non-change groups were compared. Results The mean pre- and postoperative Cobb's angle of the coronal curve was 76.80° ± 17.19° and 33.23° ± 14.39°, respectively. Eleven of 31 patients showed a lower conus medullaris level postoperatively. There were no differences in the pre- and postoperative magnitude of the coronal curve, lordosis and kyphosis between the groups. However, the postoperative degrees of correction of the coronal curve and lumbar lordosis were higher in the change group. There were also differences in the disease entities between the groups. A higher percentage of patients with Duchene muscular dystrophy had a change in level compared to that of the patients with cerebral palsy (83.3% vs. 45.5%, respectively). Conclusions The conus medullaris level changed postoperatively in the patients with severe scoliosis. Overall, the postoperative degree of correction of the coronal curve was higher in the change group than that in the non-change group. The degrees of correction of the coronal curve and lumbar lordosis were related to the spinal cord level change after scoliosis correction. PMID:21369475

Measurement of arterial transit time and renal blood flow using pseudocontinuous ASL MRI with multiple post-labeling delays: Feasibility, reproducibility, and variation.

PubMed

Kim, Dong Won; Shim, Woo Hyun; Yoon, Seong Kuk; Oh, Jong Yeong; Kim, Jeong Kon; Jung, Hoesu; Matsuda, Tsuyoshi; Kim, Dongeun

2017-09-01

To evaluate the feasibility, reproducibility, and variation of renal perfusion and arterial transit time (ATT) using pseudocontinuous arterial spin labeling magnetic resonance imaging (PCASL MRI) in healthy volunteers. PCASL MRI at 3T was performed in 25 healthy volunteers on two different occasions. The ATT and ATT-corrected renal blood flow (ATT-cRBF) were calculated at four different post-labeling delay points (0.5, 1.0, 1.5, and 2.0 s) and evaluated for each kidney and subject. The intraclass correlation (ICC) and Bland-Altman plot were used to assess the reproducibility of the PCASL MRI technique. The within-subject coefficient of variance was determined. Results were obtained for 46 kidneys of 23 subjects with a mean age of 38.6 ± 9.8 years and estimated glomerular filtration rate (eGFR) of 89.1 ± 21.2 ml/min/1.73 m 2 . Two subjects failed in the ASL MRI examination. The mean cortical and medullary ATT-cRBF for the subjects were 215 ± 65 and 81 ± 21 ml/min/100 g, respectively, and the mean cortical and medullary ATT were 1141 ± 262 and 1123 ± 245 msec, correspondingly. The ICC for the cortical ATT-cRBF was 0.927 and the within-subject coefficient of variance was 14.4%. The ICCs for the medullary ATT-cRBF and the cortical and medullary ATT were poor. The Bland-Altman plot for cortical RBF showed good agreement between the two measurements. PCASL MRI is a feasible and reproducible method for measuring renal cortical perfusion. In contrast, ATT for the renal cortex and medulla has poor reproducibility and high variation. 2 Technical Efficacy: Stage 2 J. MAGN. RESON. IMAGING 2017;46:813-819. © 2017 International Society for Magnetic Resonance in Medicine.

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

PubMed

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), 65.8% patients above the age of 80 (p < 0.05), 100% of the patients with hemoglobin below 90 g/L and 20 patients with a ASA grade of 3 (p < 0.05). 78.5% patients with A2 fracture and 75% of A3 fractures needed blood transfusion (p > 0.05). Length of hospital stay in non-transfusion group was 13 days and in transfusion group was 19 days (p < 0.05). 55.1% operated within 36 h and 47.6% operated after 36 h of admission needed transfusion (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.

Expression of receptor-type protein tyrosine phosphatase in developing and adult renal vasculature

PubMed Central

Takahashi, Keiko; Kim, Rachel; Lauhan, Colette; Park, Yuna; Nguyen, Nghiep G.; Vestweber, Dietmar; Dominguez, Melissa G.; Valenzuela, David M.; Murphy, Andrew J.; Yancopoulos, George D.; Gale, Nicholas W.; Takahashi, Takamune

2017-01-01

Renal vascular development is a coordinated process that requires ordered endothelial cell proliferation, migration, intercellular adhesion, and morphogenesis. In recent decades, studies have defined the pivotal role of endothelial receptor tyrosine kinases (RPTKs) in the development and maintenance of renal vasculature. However, the expression and the role of receptor tyrosine phosphatases (RPTPs) in renal endothelium are poorly understood, though coupled and counterbalancing roles of RPTKs and RPTPs are well defined in other systems. In this study, we evaluated the promoter activity and immunolocalization of two endothelial RPTPs, VE-PTP and PTPμ, in developing and adult renal vasculature using the heterozygous LacZ knock-in mice and specific antibodies. In adult kidneys, both VE-PTP and PTPμ were expressed in the endothelium of arterial, glomerular, and medullary vessels, while their expression was highly limited in peritubular capillaries and venous endothelium. VE-PTP and PTPμ promoter activity was also observed in medullary tubular segments in adult kidneys. In embryonic (E12.5, E13.5, E15.5, E17.5) and postnatal (P0, P3, P7) kidneys, these RPTPs were expressed in ingrowing renal arteries, developing glomerular microvasculature (as early as the S-shaped stage), and medullary vessels. Their expression became more evident as the vasculatures matured. Peritubular capillary expression of VE-PTP was also noted in embryonic and postnatal kidneys. Compared to VE-PTP, PTPμ immunoreactivity was relatively limited in embryonic and neonatal renal vasculature and evident immunoreactivity was observed from the P3 stage. These findings indicate 1) VE-PTP and PTPμ are expressed in endothelium of arterial, glomerular, and medullary renal vasculature, 2) their expression increases as renal vascular development proceeds, suggesting that these RPTPs play a role in maturation and maintenance of these vasculatures, and 3) peritubular capillary VE-PTP expression is down-regulated in adult kidneys, suggesting a role of VE-PTP in the development of peritubular capillaries. PMID:28542220

Germ line mutation analysis in families with multiple endocrine neoplasia type 2A or familial medullary thyroid carcinoma.

PubMed

Karga, H J; Karayianni, M K; Linos, D A; Tseleni, S C; Karaiskos, K D; Papapetrou, P D

1998-10-01

The RET proto-oncogene has been identified as the multiple endocrine neoplasia type 2 disease gene. An association between specific RET mutation and disease phenotype has been reported. We present the phenotype-genotype of 12 Greek families with multiple endocrine neoplasia type 2A (MEN 2A) or familial medullary thyroid carcinoma (FMTC). Seventy members were studied and DNA analysis for RET mutations was performed in fifty-eight of them. Exons 10, 11, 13, 14 and 16 of the RET proto-oncogene were analyzed by single strand conformation polymorphism analysis, direct DNA sequencing and/or restriction enzyme analysis. No mutations of the RET proto-oncogene were identified in 1 of 9 families with MEN 2A and in the 3 families with FMTC. In 7 MEN 2A families, the mutation was demonstrated in codon 634 and in 1 family it was demonstrated in codon 620. There was a low frequency, about 8%, of hyperparathyroidism associated with MEN 2A. The specific causative mutations for pararthyroid disease were C634R or C634Y. Among the MEN 2A individuals there was one case with de novo C634R mutation and one case, C634Y, with cutaneous lichen amyloidosis which predated by 24 years the diagnosis of MEN 2A. In 2 children who were MEN 2A gene carriers, microscopic medullary thyroid carcinomas were found. These data show a low frequency of hyperparathyroidism in our cases and provide further evidence that individuals with C634R as well as with C634Y mutations of the RET proto-oncogene could be at risk for parathyroid disease. Cutaneous lichen amyloidosis could be an early feature of MEN 2A. Additionally, direct DNA testing provided an opportunity to resect medullary thyroid carcinoma at an early stage.

Differentiated and Medullary Thyroid Cancer: Surgical Management of Cervical Lymph Nodes

PubMed Central

Asimakopoulos, P.; Nixon, I.J.; Shaha, A.R.

2017-01-01

Thyroid cancer metastasises to the central and lateral compartments of the neck frequently and early. The impact of nodal metastases on outcome is affected by the histological subtype of the primary tumour and the patient’s age, as well as the size, number and location of those metastases. The impact of extranodal extension has recently been highlighted as an important prognosticating factor. Although clinically evident nodal disease in the lateral neck compartments has a significant impact on both survival and recurrence, microscopic metastases to the central or the lateral neck in well-differentiated thyroid cancer do not significantly affect outcome. Here we discuss the surgical management of neck metastases in well-differentiated and medullary thyroid carcinoma. PMID:28094086

Spinally projecting preproglucagon axons preferentially innervate sympathetic preganglionic neurons

PubMed Central

Llewellyn-Smith, I.J.; Marina, N.; Manton, R.N.; Reimann, F.; Gribble, F.M.; Trapp, S.

2015-01-01

Glucagon-like peptide-1 (GLP-1) affects central autonomic neurons, including those controlling the cardiovascular system, thermogenesis, and energy balance. Preproglucagon (PPG) neurons, located mainly in the nucleus tractus solitarius (NTS) and medullary reticular formation, produce GLP-1. In transgenic mice expressing glucagon promoter-driven yellow fluorescent protein (YFP), these brainstem PPG neurons project to many central autonomic regions where GLP-1 receptors are expressed. The spinal cord also contains GLP-1 receptor mRNA but the distribution of spinal PPG axons is unknown. Here, we used two-color immunoperoxidase labeling to examine PPG innervation of spinal segments T1–S4 in YFP-PPG mice. Immunoreactivity for YFP identified spinal PPG axons and perikarya. We classified spinal neurons receiving PPG input by immunoreactivity for choline acetyltransferase (ChAT), nitric oxide synthase (NOS) and/or Fluorogold (FG) retrogradely transported from the peritoneal cavity. FG microinjected at T9 defined cell bodies that supplied spinal PPG innervation. The deep dorsal horn of lower lumbar cord contained YFP-immunoreactive neurons. Non-varicose, YFP-immunoreactive axons were prominent in the lateral funiculus, ventral white commissure and around the ventral median fissure. In T1–L2, varicose, YFP-containing axons closely apposed many ChAT-immunoreactive sympathetic preganglionic neurons (SPN) in the intermediolateral cell column (IML) and dorsal lamina X. In the sacral parasympathetic nucleus, about 10% of ChAT-immunoreactive preganglionic neurons received YFP appositions, as did occasional ChAT-positive motor neurons throughout the rostrocaudal extent of the ventral horn. YFP appositions also occurred on NOS-immunoreactive spinal interneurons and on spinal YFP-immunoreactive neurons. Injecting FG at T9 retrogradely labeled many YFP-PPG cell bodies in the medulla but none of the spinal YFP-immunoreactive neurons. These results show that brainstem PPG neurons innervate spinal autonomic and somatic motor neurons. The distributions of spinal PPG axons and spinal GLP-1 receptors correlate well. SPN receive the densest PPG innervation. Brainstem PPG neurons could directly modulate sympathetic outflow through their spinal inputs to SPN or interneurons. PMID:25450967

Progressive Changes in a Distributed Neural Circuit Underlie Breathing Abnormalities in Mice Lacking MeCP2.

PubMed

Huang, Teng-Wei; Kochukov, Mikhail Y; Ward, Christopher S; Merritt, Jonathan; Thomas, Kaitlin; Nguyen, Tiffani; Arenkiel, Benjamin R; Neul, Jeffrey L

2016-05-18

Rett syndrome (RTT) is a neurodevelopmental disorder caused by mutations in Methyl-CpG-binding protein 2 (MECP2). Severe breathing abnormalities are common in RTT and are reproduced in mouse models of RTT. Previously, we found that removing MeCP2 from the brainstem and spinal cord in mice caused early lethality and abnormal breathing. To determine whether loss of MeCP2 in functional components of the respiratory network causes specific breathing disorders, we used the Cre/LoxP system to differentially manipulate MeCP2 expression throughout the brainstem respiratory network, specifically within HoxA4-derived tissues, which include breathing control circuitry within the nucleus tractus solitarius and the caudal part of ventral respiratory column but do not include more rostral parts of the breathing control circuitry. To determine whether respiratory phenotypes manifested in animals with MeCP2 removed from specific pons medullary respiratory circuits, we performed whole-body plethysmography and electrophysiological recordings from in vitro brainstem slices from mice lacking MeCP2 in different circuits. Our results indicate that MeCP2 expression in the medullary respiratory network is sufficient for normal respiratory rhythm and preventing apnea. However, MeCP2 expression within components of the breathing circuitry rostral to the HoxA4 domain are neither sufficient to prevent the hyperventilation nor abnormal hypoxic ventilatory response. Surprisingly, we found that MeCP2 expression in the HoxA4 domain alone is critical for survival. Our study reveals that MeCP2 is differentially required in select respiratory components for different aspects of respiratory functions, and collectively for the integrity of this network functions to maintain proper respiration. Breathing abnormalities are a significant clinical feature in Rett syndrome and are robustly reproduced in the mouse models of this disease. Previous work has established that alterations in the function of MeCP2, the protein encoded by the gene mutated in Rett syndrome, within the hindbrain are critical for control of normal breathing. Here we show that MeCP2 function plays distinct roles in specific brainstem regions in the genesis of various aspects of abnormal breathing. This provides insight into the pathogenesis of these breathing abnormalities in Rett syndrome, which could be used to target treatments to improve these symptoms. Furthermore, it provides further knowledge about the fundamental neural circuits that control breathing. Copyright © 2016 the authors 0270-6474/16/365572-15$15.00/0.

Origin and plasticity of the subdivisions of the inferior olivary complex.

PubMed

Hidalgo-Sánchez, Matías; Backer, Stéphanie; Puelles, Luis; Bloch-Gallego, Evelyne

2012-11-15

The precerebellar nuclei (PCN) originate from the rhombic lip, a germinal neuroepithelium adjacent to the roof plate of the fourth ventricle. We first report here that, in chicken, the Brn3a-expressing postmitotic medullary cells that produce the inferior olive (ION, the source of cerebellar climbing fibres) originate from a dorso-ventral domain roughly coinciding with the hindbrain vestibular column. Whereas Foxd3 expression labels the whole mature ION but is only detected in a subpopulation of ION neuroblasts initiating their migration, we report that Brn3a allows the visualization of the whole population of ION neurons from the very beginning of their migration. We show that Brn3a-positive neurons migrate tangentially ventralwards through a characteristic dorso-ventral double submarginal stream. Cath1 expressing progenitors lying just dorsal to the ION origin correlated dorso-ventral topography with the prospective cochlear column (caudal to it) and generate precerebellar nuclei emitting mossy-fiber cerebellar afferents. We used the chick-quail chimaera technique with homotopic grafts at HH10 to determine the precise fate map of ION precursors across the caudal cryptorhombomeric subdivisions of the medullary hindbrain (r8-r11). We demonstrate that each crypto-rhombomere contributes to two lamellae of the ION, while each ION sub-nucleus originates from at least two contiguous crypto-rhombomeres. We then questioned how rhombomere identity is related to the plasticity of cell type specification in the dorsal hindbrain. The potential plasticity of ectopically HH10 grafted ION progenitors to change their original fate in alternative rostrocaudal environments was examined. Heterotopic grafts from the presumptive ION territory to the pontine region (r4-r5) caused a change of fate, since the migrated derivatives adopted a pontine phenotype. The reverse experiment caused pontine progenitors to produce derivatives appropriately integrated into the ION complex. Grafts of ION progenitor domains to myelomeres (my) 2-3 also showed complete fate regulation, reproducing spinal cord-like structures, whereas the reverse experiment revealed the inability of my2-3 to generate ION cell types. This was not the case with more caudal, relatively less specified myelomeres (my5-6). Interestingly, when heterotopically grafted cells are integrated dorsally, they do not change their phenotype. Our results support the hypothesis that positional information present in the hindbrain and spinal cord at early neural tube stages controls the specific fates of ventrally migrating PCN precursors. Copyright © 2012 Elsevier Inc. All rights reserved.

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

NASA Technical Reports Server (NTRS)

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.

FSP1+ fibroblast subpopulation is essential for the maintenance and regeneration of medullary thymic epithelial cells

PubMed Central

Sun, Lina; Sun, Chenming; Liang, Zhanfeng; Li, Hongran; Chen, Lin; Luo, Haiying; Zhang, Hongmei; Ding, Pengbo; Sun, Xiaoning; Qin, Zhihai; Zhao, Yong

2015-01-01

Thymic epithelial cells (TECs) form a 3-dimentional network supporting thymocyte development and maturation. Besides epithelium and thymocytes, heterogeneous fibroblasts are essential components in maintaining thymic microenvironments. However, thymic fibroblast characteristics, development and function remain to be determined. We herein found that thymic non-hematopoietic CD45-FSP1+ cells represent a unique Fibroblast specific protein 1 (FSP1)—fibroblast-derived cell subset. Deletion of these cells in FSP1-TK transgenic mice caused thymus atrophy due to the loss of TECs, especially mature medullary TECs (MHCIIhigh, CD80+ and Aire+). In a cyclophosphamide-induced thymus injury and regeneration model, lack of non-hematopoietic CD45-FSP1+ fibroblast subpopulation significantly delayed thymus regeneration. In fact, thymic FSP1+ fibroblasts released more IL-6, FGF7 and FSP1 in the culture medium than their FSP1- counterparts. Further experiments showed that the FSP1 protein could directly enhance the proliferation and maturation of TECs in the in vitro culture systems. FSP1 knockout mice had significantly smaller thymus size and less TECs than their control. Collectively, our studies reveal that thymic CD45-FSP1+ cells are a subpopulation of fibroblasts, which is crucial for the maintenance and regeneration of TECs especially medullary TECs through providing IL-6, FGF7 and FSP1. PMID:26445893

Ikarisoside A inhibits acetylcholine-induced catecholamine secretion and synthesis by suppressing nicotinic acetylcholine receptor-ion channels in cultured bovine adrenal medullary cells.

PubMed

Li, Xiaojia; Toyohira, Yumiko; Horisita, Takafumi; Satoh, Noriaki; Takahashi, Keita; Zhang, Han; Iinuma, Munekazu; Yoshinaga, Yukari; Ueno, Susumu; Tsutsui, Masato; Sata, Takeyoshi; Yanagihara, Nobuyuki

2015-12-01

Ikarisoside A is a natural flavonol glycoside derived from plants of the genus Epimedium, which have been used in Traditional Chinese Medicine as tonics, antirheumatics, and aphrodisiacs. Here, we report the effects of ikarisoside A and three other flavonol glycosides on catecholamine secretion and synthesis in cultured bovine adrenal medullary cells. We found that ikarisoside A (1-100 μM), but not icariin, epimedin C, or epimedoside A, concentration-dependently inhibited the secretion of catecholamines induced by acetylcholine, a physiological secretagogue and agonist of nicotinic acetylcholine receptors. Ikarisoside A had little effect on catecholamine secretion induced by veratridine and 56 mM K(+). Ikarisoside A (1-100 μM) also inhibited (22)Na(+) influx and (45)Ca(2+) influx induced by acetylcholine in a concentration-dependent manner similar to that of catecholamine secretion. In Xenopus oocytes expressing α3β4 nicotinic acetylcholine receptors, ikarisoside A (0.1-100 μM) directly inhibited the current evoked by acetylcholine. It also suppressed (14)C-catecholamine synthesis and tyrosine hydroxylase activity induced by acetylcholine at 1-100 μM and 10-100 μM, respectively. The present findings suggest that ikarisoside A inhibits acetylcholine-induced catecholamine secretion and synthesis by suppression of nicotinic acetylcholine receptor-ion channels in bovine adrenal medullary cells.

BIOPSY PROVEN MEDULLARY SPONGE KIDNEY: Clinical findings, histopathology, and role of osteogenesis in stone and plaque formation

PubMed Central

Evan, Andrew P.; Worcester, Elaine M.; Williams, James C.; Sommer, Andre J.; Lingeman, James E.; Phillips, Carrie L.; Coe, Fredric L.

2015-01-01

Medullary sponge kidney (MSK) is associated with recurrent stone formation, but the clinical phenotype is unclear because patients with other disorders may be incorrectly labeled MSK. We studied 12 patients with histologic findings pathognomonic of MSK. All patients had an endoscopically recognizable pattern of papillary malformation, which may be segmental or diffuse. Affected papillae are enlarged and billowy, due to markedly enlarged inner medullary collecting ducts (IMCD), which contain small, mobile ductal stones. Patients had frequent dilation of Bellini ducts, with occasional mineral plugs. Stones may form over white (Randall’s) plaque, but most renal pelvic stones are not attached, and have a similar morphology as ductal stones, which are a mixture of calcium oxalate and apatite. Patients had no abnormalities of urinary acidification or acid excretion; the most frequent metabolic abnormality was idiopathic hypercalciuria. Although both Runx2 and Osterix are expressed in papillae of MSK patients, no mineral deposition was seen at the sites of gene expression, arguing against a role of these genes in this process. Similar studies in idiopathic calcium stone formers showed no expression of these genes at sites of Randall’s plaque. The most likely mechanism for stone formation in MSK appears to be crystallization due to urinary stasis in dilated IMCD with subsequent passage of ductal stones into the renal pelvis where they may serve as nuclei for stone formation. PMID:25615853

Magnetic resonance elastography can monitor changes in medullary stiffness in response to treatment in the swine ischemic kidney

PubMed Central

Zhang, Xin; Zhu, Xiangyang; Ferguson, Christopher M.; Jiang, Kai; Burningham, Tyson; Lerman, Amir; Lerman, Lilach O.

2018-01-01

Object Low-energy shockwave (SW) therapy attenuates damage in the stenotic kidney (STK) caused by atherosclerotic renal artery stenosis (ARAS). We hypothesized that magnetic resonance elastography (MRE) would detect attenuation of fibrosis following SW in unilateral ARAS kidneys. Materials and Methods Domestic pigs were randomized to control, unilateral ARAS, and ARAS treated with 6 sessions of SW over 3 consecutive weeks (n=7 each) starting after 3 weeks of ARAS or sham. Four weeks after SW treatment, renal fibrosis was evaluated with MRE in-vivo or trichrome staining ex-vivo. Blood pressure, single-kidney renal-blood-flow (RBF) and glomerular-filtration-rate (GFR) were assessed. Results MRE detected increased stiffness in the STK medulla (15.3±2.1 vs. 10.1±0.8 kPa, p<0.05) that moderately correlated with severity of fibrosis (R2=0.501, p<0.01), but did not identify mild STK cortical or contralateral kidney fibrosis. Trichrome staining showed that medullary fibrosis was increased in ARAS and alleviated by SW (10.4±1.8% vs. 2.9±0.2%, p<0.01). SW slightly decreased blood pressure and normalized STK RBF and GFR in ARAS. In the contralateral kidney, SW reversed the increase in RBF and GFR. Conclusion MRE might be a tool for noninvasive monitoring of medullary fibrosis in response to treatment in kidney disease. PMID:29289980

Inherited medullary thyroid cancer and the duty to warn: revisiting Pate v. Threlkel in light of HIPAA.

PubMed

Rosenthal, M Sara; Pierce, Heather Hanson

2005-02-01

Familial medullary thyroid cancer (FMTC) is one of the few autosomal dominant cancers for which genetic testing provides a clear medical indication for prophylactic and/or curative therapy, and for which prophylactic thyroidectomy, followed by thyroid hormone replacement, presents a relatively low morbidity risk. Medullary thyroid cancer (MTC) is a particularly aggressive type of thyroid cancer, and screening by traditional biochemical markers yields a high proportion of advanced stage diagnoses in individuals from FMTC families. This is particularly hazardous since there are no curative systemic treatments for MTC. Genetic testing for germline mutations of the RET proto-oncogene provides a reliable method of identifying at-risk family members in those FMTC families in which a mutation has been identified in the proband. Prophylactic thyroidectomy in such at-risk family members has significantly reduced the proportion of advanced stage MTC diagnoses in MTC families. Since a clear medical benefit exists for genetic testing in family members, and a clear danger to family members exists in the absence of genetic counseling, establishing genetic diagnosis as standard of care has critical legal and ethical implications for medical providers caring for probands and family members. The "duty to warn," reinforced by the courts in the legal case of Pate v. Threlkel, may override recent confidentiality legislation, known as the HIPAA Privacy Rules, which came into effect April 12, 2003.

Targeted Therapy Shows Benefit in Rare Type of Thyroid Cancer

Cancer.gov

Treatment with the multitargeted agent vandetanib (Caprelsa) improved progression-free survival in patients with medullary thyroid cancer (MTC), according to findings from a randomized clinical trial.

Medullary Sponge Kidney and Urinary Calculi Aeromedical Concerns

NASA Technical Reports Server (NTRS)

Jones, Jeffrey A.; Cherian, Sebastian F.; Barr, Yael R.; Stocco, Amber

2008-01-01

Medullary Sponge Kidney (MSK) is a benign disorder associated with renal stones in 60% of patients. Patients frequently have episodic painless hematuria but are otherwise asymptomatic unless renal calculi or infections complicate the disease. Nephrolithiasis is a relative, but frequently enforced, contraindication to space or other high performance flight. Two case reports of asymptomatic NASA flight crew with MSK and three cases of military aviators diagnosed with MSK are reviewed, all cases resulted in waiver and return to flight status after treatment and a vigorous follow up and prophylaxis protocol. MSK in aviation and space flight necessitates a highly case-by-case dependent evaluation and treatment process to rule out other potential confounding factors that might also contribute to stone formation and in order to re-qualify the aviator for flight duties.

Update on the management of unusual neuroendocrine tumors: pheochromocytoma and paraganglioma, medullary thyroid cancer and adrenocortical carcinoma.

PubMed

Strosberg, Jonathan R

2013-02-01

Pheochromocytomas, paragangliomas, and medullary thyroid carcinomas (MTCs) originate in cells that share a common neuroectodermal origin. Like other neuroendocrine neoplasms, they are characterized by a propensity to secrete amines (epinephrine and norepinephrine) and peptide hormones (calcitonin). Improved understanding of underlying molecular pathways, such as mutations of the RET (rearranged during transfection) proto-oncogene, has led to new rational targeted therapies. Adrenocortical carcinomas (ACCs) originate in the steroid hormone-producing adrenal cortex. While tumors of the adrenal cortex are not, strictly speaking, part the "diffuse neuroendocrine system," they are often included in neuroendocrine tumor guidelines due to their orphan status. In this update on management of unusual neuroendocrine tumors, we review the biology and treatment of these rare neoplasms. Copyright © 2013 Elsevier Inc. All rights reserved.

Comparison of 1.5 and 3 T BOLD MR to study oxygenation of kidney cortex and medulla in human renovascular disease.

PubMed

Gloviczki, Monika L; Glockner, James; Gomez, Sabas I; Romero, Juan C; Lerman, Lilach O; McKusick, Michael; Textor, Stephen C

2009-09-01

Imaging of the kidney using blood oxygen level dependent MR presents a major opportunity to examine differences in tissue oxygenation within the cortex and medulla applicable to human disease. We sought to define the differences between regions within kidneys and to optimize selection of regions of interest for study with 1.5 and 3 Tesla systems. Studies in 38 subjects were performed under baseline conditions and after administration of furosemide intravenously to examine changes in R2* as a result of suppressing oxygen consumption related to medullary tubular solute transport. These studies were carried out in patients with atherosclerotic renal artery stenosis (n = 24 kidneys) or essential hypertension or nonstenotic kidneys (n = 39). All patients but one were treated with agents to block the renin angiotensin system (ACE inhibitors or angiotensin receptor blockers). For each kidney, 3 levels (upper pole, hilum, and lower pole) were examined, including 3 individual segments (anterior, lateral, and posterior). Low basal R2* levels in kidney cortex (12.06 +/- 0.84 s(-1)) at 1.5 Tesla reflected robust blood flow and oxygenation and agreed closely with values obtained at 3.0 Tesla (13.62 +/- 0.56 s(-1), NS). Coefficients of variation ranged between 15% and 20% between segments and levels at both field strengths. By contrast, inner medullary R2* levels were higher at 3 T (31.66 +/- 0.74 s(-1)) as compared with 1.5 T (22.19 +/- 1.52 s(-1), P < 0.01). Medullary R2* values fell after furosemide administration reflecting reduced deoxyhemoglobin levels associated with blocked energy-dependent transport. The fall in medullary R2* at 3.0 Tesla (-12.61 +/- 0.97 s(-1)) was greater than observed at 1.5 T (-6.07 +/- 1.38 s(-1), P < 0.05). Cortical R2* levels remained low after furosemide and did not vary with field strength. Correlations between measurements of defined cortical and medullary regions of interest within kidneys were greater at each sampling level and segment at 3.0 T as compared to 1.5 T. For patients studied with 3.0 T, furosemide administration induced a lesser fall in R2* in poststenotic kidneys at 3.0 T (-10.61 +/- 1.61 s(-1)) versus nonstenotic kidneys (-13.21 +/- 0.72 s(-1), P < 0.05). This difference was not evident in comparisons made at 1.5 T. The magnitude of furosemide-suppressible oxygen consumption at 3.0 T (-43%) corresponded more closely with reported experimental differences observed during direct measurement with tissue electrodes (45%-50%) than changes measured at 1.5 T. These results indicate that blood oxygen level dependent MR measurements at high field strength can better distinguish discrete cortical and inner medullary regions of the kidney and approximate measured differences in oxygen tension. Maneuvers that reduce oxygen consumption related to tubular solute transport allow functional evaluation of the interstitial compartment as a function of tissue oxygenation. Impaired response to alterations in oxygen consumption can be detected at 3 T more effectively than at 1.5 T and may provide real-time tools to examine developing parenchymal injury associated with impaired oxygenation.

Ibuprofen does not reverse ventilatory acclimatization to chronic hypoxia.

PubMed

De La Zerda, D J; Stokes, J A; Do, J; Go, A; Fu, Z; Powell, F L

2017-07-27

Ventilatory acclimatization to hypoxia involves an increase in the acute hypoxic ventilatory response that is blocked by non-steroidal anti-inflammatory drugs administered during sustained hypoxia. We tested the hypothesis that inflammatory signals are necessary to sustain ventilatory acclimatization to hypoxia once it is established. Adult, rats were acclimatized to normoxia or chronic hypoxia (CH, [Formula: see text] =70Torr) for 11-12days and treated with ibuprofen or saline for the last 2days of hypoxia. Ventilation, metabolic rate, and arterial blood gas responses to O 2 and CO 2 were not affected by ibuprofen after acclimatization had been established. Immunohistochemistry and image analysis showed acute (1h) hypoxia activated microglia in a medullary respiratory center (nucleus tractus solitarius, NTS) and this was blocked by ibuprofen administered from the beginning of hypoxic exposure. Microglia returned to the control state after 7days of CH and were not affected by ibuprofen administered for 2 more days of CH. In contrast, NTS astrocytes were activated by CH but not acute hypoxia and activation was not reversed by administering ibuprofen for the last 2days of CH. Hence, ibuprofen cannot reverse ventilatory acclimatization or astrocyte activation after they have been established by sustained hypoxia. The results are consistent with a model for microglia activation or other ibuprofen-sensitive processes being necessary for the induction but not maintenance of ventilatory acclimatization to hypoxia. Copyright © 2017 Elsevier B.V. All rights reserved.

Direct visualization of anatomic subfields within the superior aspect of the human lateral thalamus by MRI at 7T.

PubMed

Kanowski, M; Voges, J; Buentjen, L; Stadler, J; Heinze, H-J; Tempelmann, C

2014-09-01

The morphology of the human thalamus shows high interindividual variability. Therefore, direct visualization of landmarks within the thalamus is essential for an improved definition of electrode positions for deep brain stimulation. The aim of this study was to provide anatomic detail in the thalamus by using inversion recovery TSE imaging at 7T. The MR imaging protocol was optimized on 1 healthy subject to segment thalamic nuclei from one another. Final images, acquired with 0.5(2)-mm2 in-plane resolution and 3-mm section thickness, were compared with stereotactic brain atlases to assign visualized details to known anatomy. The robustness of the visualization of thalamic nuclei was assessed with 4 healthy subjects at lower image resolution. Thalamic subfields were successfully delineated in the dorsal aspect of the lateral thalamus. T1-weighting was essential. MR images had an appearance very similar to that of myelin-stained sections seen in brain atlases. Visualized intrathalamic structures were, among others, the lamella medialis, the external medullary lamina, the reticulatum thalami, the nucleus centre médian, the boundary between the nuclei dorso-oralis internus and externus, and the boundary between the nuclei dorso-oralis internus and zentrolateralis intermedius internus. Inversion recovery-prepared TSE imaging at 7T has a high potential to reveal fine anatomic detail in the thalamus, which may be helpful in enhancing the planning of stereotactic neurosurgery in the future. © 2014 by American Journal of Neuroradiology.

Organization of ascending spinal projections in Caiman crocodilus.

PubMed

Ebbesson, S O; Goodman, D C

1981-01-01

Ascending spinal projections in the caiman (Caiman crocodilus) were demonstrated with Nauta and Fink-Heimer methods following hemisections of the third spinal segment in a series of twelve animals. These results were compared with earlier data in the literature obtained from a turtle, a snake, and a lizard using the same experimental and histological procedures. The results show remarkable similarities considering that each species represents a different reptilian order with different evolutionary history and habitat. However, the caiman displays several important peculiarities. Although the dorsal funiculus of the caiman contains the largest number of ascending spinal projections of the four species examined, this funiculus has not differentiated into cuneate and gracile fasciculi as is the case in the tegu lizard. The ventro-lateral ascending spinal projections follow a fundamentally similar general morphologic pattern in the four species with only minor variations. The anatomical arrangement in the caiman and tegu lizard appears most similar in the high cervical and the medullary regions; however, this is not the case in midbrain and thalamic regions where considerably more extensive projections are seen in the caiman. In the caiman an extensive spinal connection to the ventro-lateral nucleus of the dorsal thalamus is present; this connection is reminiscent of the mammalian spinal projection to the ventro-basal complex. The caiman has in common with the other three reptilian species a small projection to another dorsal thalamic region that is apparently homologous to the mammalian intralaminar nuclei, which are the destination of the mammalian paleospinothalamic tract.

Vestibulo-Sympathetic Responses

PubMed Central

Yates, Bill J; Bolton, Philip S.; Macefield, Vaughan G.

2014-01-01

Evidence accumulated over 30 years, from experiments on animals and human subjects, has conclusively demonstrated that inputs from the vestibular otolith organs contribute to the control of blood pressure during movement and changes in posture. This review considers the effects of gravity on the body axis, and the consequences of postural changes on blood distribution in the body. It then separately considers findings collected in experiments on animals and human subjects demonstrating that the vestibular system regulates blood distribution in the body during movement. Vestibulosympathetic reflexes differ from responses triggered by unloading of cardiovascular receptors such as baroreceptors and cardiopulmonary receptors, as they can be elicited before a change in blood distribution occurs in the body. Dissimilarities in the expression of vestibulosympathetic reflexes in humans and animals are also described. In particular, there is evidence from experiments in animals, but not humans, that vestibulosympathetic reflexes are patterned, and differ between body regions. Results from neurophysiological and neuroanatomical studies in animals are discussed that identify the neurons that mediate vestibulosympathetic responses, which include cells in the caudal aspect of the vestibular nucleus complex, interneurons in the lateral medullary reticular formation, and bulbospinal neurons in the rostral ventrolateral medulla (RVLM). Recent findings showing that cognition can modify the gain of vestibulosympathetic responses are also presented, and neural pathways that could mediate adaptive plasticity in the responses are proposed, including connections of the posterior cerebellar vermis with the vestibular nuclei and brainstem nuclei that regulate blood pressure. PMID:24715571

Central circuitries for body temperature regulation and fever.

PubMed

Nakamura, Kazuhiro

2011-11-01

Body temperature regulation is a fundamental homeostatic function that is governed by the central nervous system in homeothermic animals, including humans. The central thermoregulatory system also functions for host defense from invading pathogens by elevating body core temperature, a response known as fever. Thermoregulation and fever involve a variety of involuntary effector responses, and this review summarizes the current understandings of the central circuitry mechanisms that underlie nonshivering thermogenesis in brown adipose tissue, shivering thermogenesis in skeletal muscles, thermoregulatory cardiac regulation, heat-loss regulation through cutaneous vasomotion, and ACTH release. To defend thermal homeostasis from environmental thermal challenges, feedforward thermosensory information on environmental temperature sensed by skin thermoreceptors ascends through the spinal cord and lateral parabrachial nucleus to the preoptic area (POA). The POA also receives feedback signals from local thermosensitive neurons, as well as pyrogenic signals of prostaglandin E(2) produced in response to infection. These afferent signals are integrated and affect the activity of GABAergic inhibitory projection neurons descending from the POA to the dorsomedial hypothalamus (DMH) or to the rostral medullary raphe region (rMR). Attenuation of the descending inhibition by cooling or pyrogenic signals leads to disinhibition of thermogenic neurons in the DMH and sympathetic and somatic premotor neurons in the rMR, which then drive spinal motor output mechanisms to elicit thermogenesis, tachycardia, and cutaneous vasoconstriction. Warming signals enhance the descending inhibition from the POA to inhibit the motor outputs, resulting in cutaneous vasodilation and inhibited thermogenesis. This central thermoregulatory mechanism also functions for metabolic regulation and stress-induced hyperthermia.

Minocycline attenuates bone cancer pain in rats by inhibiting NF-κB in spinal astrocytes

PubMed Central

Song, Zhen-peng; Xiong, Bing-rui; Guan, Xue-hai; Cao, Fei; Manyande, Anne; Zhou, Ya-qun; Zheng, Hua; Tian, Yu-ke

2016-01-01

Aim: To investigate the mechanisms underlying the anti-nociceptive effect of minocycline on bone cancer pain (BCP) in rats. Methods: A rat model of BCP was established by inoculating Walker 256 mammary carcinoma cells into tibial medullary canal. Two weeks later, the rats were injected with minocycline (50, 100 μg, intrathecally; or 40, 80 mg/kg, ip) twice daily for 3 consecutive days. Mechanical paw withdrawal threshold (PWT) was used to assess pain behavior. After the rats were euthanized, spinal cords were harvested for immunoblotting analyses. The effects of minocycline on NF-κB activation were also examined in primary rat astrocytes stimulated with IL-1β in vitro. Results: BCP rats had marked bone destruction, and showed mechanical tactile allodynia on d 7 and d 14 after the operation. Intrathecal injection of minocycline (100 μg) or intraperitoneal injection of minocycline (80 mg/kg) reversed BCP-induced mechanical tactile allodynia. Furthermore, intraperitoneal injection of minocycline (80 mg/kg) reversed BCP-induced upregulation of GFAP (astrocyte marker) and PSD95 in spinal cord. Moreover, intraperitoneal injection of minocycline (80 mg/kg) reversed BCP-induced upregulation of NF-κB, p-IKKα and IκBα in spinal cord. In IL-1β-stimulated primary rat astrocytes, pretreatment with minocycline (75, 100 μmol/L) significantly inhibited the translocation of NF-κB to nucleus. Conclusion: Minocycline effectively alleviates BCP by inhibiting the NF-κB signaling pathway in spinal astrocytes. PMID:27157092

Minocycline attenuates bone cancer pain in rats by inhibiting NF-κB in spinal astrocytes.

PubMed

Song, Zhen-Peng; Xiong, Bing-Rui; Guan, Xue-Hai; Cao, Fei; Manyande, Anne; Zhou, Ya-Qun; Zheng, Hua; Tian, Yu-Ke

2016-06-01

To investigate the mechanisms underlying the anti-nociceptive effect of minocycline on bone cancer pain (BCP) in rats. A rat model of BCP was established by inoculating Walker 256 mammary carcinoma cells into tibial medullary canal. Two weeks later, the rats were injected with minocycline (50, 100 μg, intrathecally; or 40, 80 mg/kg, ip) twice daily for 3 consecutive days. Mechanical paw withdrawal threshold (PWT) was used to assess pain behavior. After the rats were euthanized, spinal cords were harvested for immunoblotting analyses. The effects of minocycline on NF-κB activation were also examined in primary rat astrocytes stimulated with IL-1β in vitro. BCP rats had marked bone destruction, and showed mechanical tactile allodynia on d 7 and d 14 after the operation. Intrathecal injection of minocycline (100 μg) or intraperitoneal injection of minocycline (80 mg/kg) reversed BCP-induced mechanical tactile allodynia. Furthermore, intraperitoneal injection of minocycline (80 mg/kg) reversed BCP-induced upregulation of GFAP (astrocyte marker) and PSD95 in spinal cord. Moreover, intraperitoneal injection of minocycline (80 mg/kg) reversed BCP-induced upregulation of NF-κB, p-IKKα and IκBα in spinal cord. In IL-1β-stimulated primary rat astrocytes, pretreatment with minocycline (75, 100 μmol/L) significantly inhibited the translocation of NF-κB to nucleus. Minocycline effectively alleviates BCP by inhibiting the NF-κB signaling pathway in spinal astrocytes.

Brainstem Regions Involved in the Expiration Reflex. A c-fos Study in Anesthetized Cats

PubMed Central

Poliacek, Ivan; Halasova, Erika; Jakus, Jan; Murin, Peter; Barani, Helena; Stransky, Albert; Bolser, Donald C

2009-01-01

Expression of the immediate-early gene c-fos, a marker of neuronal activation, was employed to localize brainstem neuronal populations functionally related to the expiration reflex (ER). Twelve spontaneously breathing, non-decerebrate, pentobarbital anesthetized cats were used. The level of Fos-like immunoreactivity (FLI) in 6 animals with repetitive ERs mechanically induced from the glottis (296±9 ERs) was compared to FLI in 6 control non-stimulated cats. Respiratory rate, arterial blood pressure, and end tidal CO2 concentration remained stable during the experiment. In the medulla, increased FLI was found in the region of nucleus tractus solitarii (p<0.001), in the ventrolateral medulla along with the lateral tegmental field (p<0.01), and in the vestibular nuclei (p<0.01). In the pons, increased FLI was detected in the caudal extensions of the lateral parabrachial and Kölliker-Fuse nuclei (p<0.05). Within the rostral mesencephalon FLI was enhanced in the midline area (p<0.05). A lower level of ER-related FLI compared to control animals was detected in the pontine raphe region (p<0.05) and the lateral division of mesencephalic periaqueductal gray (p<0.05). The results suggest that the ER is coordinated by a complex long loop of medullary-pontine-mesencephalic neuronal circuits, some of which may differ from those of other respiratory reflexes. The FLI related to the expulsive behavior ER differs from that induced by laryngeal stimulation and laryngeal adductor responses, particularly in ventrolateral medulla and mesencephalon. PMID:17964550

Thyroid Surgery

MedlinePlus

... thyroid surgery, requiring treatment with thyroid hormone (see Hypothyroidism brochure ). This is especially true if you had ... Disease Graves’ Eye Disease Hashimoto’s Thyroiditis Hyperthyroidism (Overactive) Hypothyroidism (Underactive) Iodine Deficiency Low Iodine Diet Medullary Thyroid ...

Anatomy of the Spine

MedlinePlus

... is called the conus medullaris. There is a thread that continues from the conus called the filum ... bodies, the facet joint created by their articular processes, the intervertebral disc between them and the associated ...

Does the position of conus medullaris change with increased thoracolumbar kyphosis in ankylosing spondylitis patients?

PubMed Central

Qu, Zhe; Qian, Bang-ping; Qiu, Yong; Zhang, Yun-peng; Hu, Jun; Zhu, Ze-zhang

2017-01-01

Abstract To date, only a few reports described the potential factors influencing the position of conus medullaris. One previous study revealed no significant change of conus locations in patients with idiopathic scoliosis; however, the effect of ankylosing spondylitis (AS)-related thoracolumbar kyphosis on conus position remains unexplored. Therefore, we aimed to investigate the variation of conus medullaris terminations in patients with thoracolumbar kyphosis secondary to AS when compared with normal subjects, and evaluated the relationship between conus positions and the magnitude of kyphosis. In this study, MR images of 96 AS patients with thoracolumbar kyphosis, including 86 males and 10 females with an average of 34.6 years (range, 17–65 years), and 100 age-matched normal controls were reviewed to determine the conus terminations in relation to spinal levels. Sagittal parameters of the AS group measured on radiograph included: global kyphosis (GK), thoracic kyphosis (TK), lumbar lordosis (LL), and thoracolumbar junction (TLJ). Finally, conus tips located at the mean level of the lower 3rd of L1 in both groups, there was no significant difference of the conus distributions between AS and control group (P = 0.49). In addition, conus medullaris displayed similar positions in AS patients among various apical region groups (P = 0.88), and no significant difference was found when AS population was stratified into GK ranges of 30° (P = 0.173). Also, no remarkable correlation of the conus positions with GK (r = −0.15, P = 0.15), TK (r = −0.10, P = 0.34), LL (r = −0.10, P = 0.32), and TLJ (r = −0.06, P = 0.54) was identified. This study showed the conus terminations displayed a wide range of distributions in AS patients with thoracolumbar kyphosis, which was similar to normal subjects. Moreover, the conus located at a relatively fixed position and would not be affected by the change of kyphosis magnitude, which is an important knowledge that surgeons should acquire in surgical correction of the deformity in these patients. PMID:28178137

Does the position of conus medullaris change with increased thoracolumbar kyphosis in ankylosing spondylitis patients?

PubMed

Qu, Zhe; Qian, Bang-Ping; Qiu, Yong; Zhang, Yun-Peng; Hu, Jun; Zhu, Ze-Zhang

2017-02-01

To date, only a few reports described the potential factors influencing the position of conus medullaris. One previous study revealed no significant change of conus locations in patients with idiopathic scoliosis; however, the effect of ankylosing spondylitis (AS)-related thoracolumbar kyphosis on conus position remains unexplored. Therefore, we aimed to investigate the variation of conus medullaris terminations in patients with thoracolumbar kyphosis secondary to AS when compared with normal subjects, and evaluated the relationship between conus positions and the magnitude of kyphosis. In this study, MR images of 96 AS patients with thoracolumbar kyphosis, including 86 males and 10 females with an average of 34.6 years (range, 17-65 years), and 100 age-matched normal controls were reviewed to determine the conus terminations in relation to spinal levels. Sagittal parameters of the AS group measured on radiograph included: global kyphosis (GK), thoracic kyphosis (TK), lumbar lordosis (LL), and thoracolumbar junction (TLJ). Finally, conus tips located at the mean level of the lower 3rd of L1 in both groups, there was no significant difference of the conus distributions between AS and control group (P = 0.49). In addition, conus medullaris displayed similar positions in AS patients among various apical region groups (P = 0.88), and no significant difference was found when AS population was stratified into GK ranges of 30° (P = 0.173). Also, no remarkable correlation of the conus positions with GK (r = -0.15, P = 0.15), TK (r = -0.10, P = 0.34), LL (r = -0.10, P = 0.32), and TLJ (r = -0.06, P = 0.54) was identified. This study showed the conus terminations displayed a wide range of distributions in AS patients with thoracolumbar kyphosis, which was similar to normal subjects. Moreover, the conus located at a relatively fixed position and would not be affected by the change of kyphosis magnitude, which is an important knowledge that surgeons should acquire in surgical correction of the deformity in these patients.

Influence of Parathyroidectomy on Bone Calcium Concentration: Evaluation with Spectral CT in Patients with Secondary Hyperparathyroidism Undergoing Hemodialysis-A Prospective Feasibility Study.

PubMed

Ma, Qiang; Yang, Zhenghan; Han, Xue; Liu, Fen; Su, Dechun; Xing, Haidong

2017-07-01

Purpose To use spectral computed tomography (CT) to evaluate the influence of parathyroidectomy (PTX) on calcium concentration in trabecular bone and cortical bone in patients undergoing hemodialysis with secondary hyperparathyroidism. Materials and Methods This study was performed with institutional review board approval. Written consent was obtained from each patient. Thirty-eight men (mean age ± standard deviation, 55.69 years ± 8.05; range, 42-72 years) undergoing maintenance hemodialysis who underwent PTX and 40 patients (mean age, 56.71 years ± 9.53; range, 45-74 years) who did not undergo PTX received prospective follow-up for 2 years. Bone calcium concentration was measured in the cortical compartment of the bilateral proximal femur and the medullary compartment of the lumbar vertebral bodies (L1 through L3) on the basis of calcium-based material decomposition images of a spectral CT examination. The differences between baseline and end-of-study PTX parameters were analyzed with the paired Student t test. Results For patients who underwent PTX, mean cortical bone calcium concentration increased from 220.69 mg/cm 3 ± 25.79 to 257.43 mg/cm 3 ± 25.46 (t = 8.546, P < .001), whereas medullary bone calcium concentration decreased from 64.75 mg/cm 3 ± 15.07 to 61.42 mg/cm 3 ± 15.77 (t = 22.293, P < .001) from baseline to follow-up. In patients who did not undergo PTX, mean cortical bone calcium concentration decreased from 296.08 mg/cm 3 ± 36.35 to 258.35 mg/cm 3 ± 31.46 (t = 7.420, P < .001), but medullary bone calcium concentration increased from 61.13 mg/cm 3 ± 13.85 to 62.94 mg/cm 3 ± 14.80 (t = 2.370, P = .023) from baseline to follow-up. Conclusion During the course of chronic renal failure, different bone elements involve various pathologic changes. PTX could reverse long-term cortical bone loss reflected in calcium concentration measured with spectral CT; however, it could induce medullary bone loss. © RSNA, 2017 Online supplemental material is available for this article.

Role of medullary astroglial glutamine synthesis in tooth pulp hypersensitivity associated with frequent masseter muscle contraction.

PubMed

Watase, Tetsuro; Shimizu, Kohei; Ohara, Kinuyo; Komiya, Hiroki; Kanno, Kohei; Hatori, Keisuke; Noma, Noboru; Honda, Kuniya; Tsuboi, Yoshiyuki; Katagiri, Ayano; Shinoda, Masamichi; Ogiso, Bunnai; Iwata, Koichi

2018-01-01

Background The mechanisms underlying tooth pulp hypersensitivity associated with masseter muscle hyperalgesia remain largely underinvestigated. In the present study, we aimed to determine whether masseter muscle contraction induced by daily electrical stimulation influences the mechanical head-withdrawal threshold and genioglossus electromyography activity caused by the application of capsaicin to the upper first molar tooth pulp. We further investigated whether astroglial glutamine synthesis is involved in first molar tooth pulp hypersensitivity associated with masseter muscle contraction. Methods The first molar tooth pulp was treated with capsaicin or vehicle in masseter muscle contraction or sham rats, following which the astroglial glutamine synthetase inhibitor methionine sulfoximine or Phosphate buffered saline (PBS) was applied. Astroglial activation was assessed via immunohistochemistry. Results The mechanical head-withdrawal threshold of the ipsilateral masseter muscle was significantly decreased in masseter muscle contraction rats than in sham rats. Genioglossus electromyography activity was significantly higher in masseter muscle contraction rats than sham rats. Glial fibrillary acidic protein-immunoreactive cell density was significantly higher in masseter muscle contraction rats than in sham rats. Administration of methionine sulfoximine induced no significant changes in the density of glial fibrillary acidic protein-immunoreactive cells relative to PBS treatment. However, mechanical head-withdrawal threshold was significantly higher in masseter muscle contraction rats than PBS-treated rats after methionine sulfoximine administration. Genioglossus electromyography activity following first molar tooth pulp capsaicin treatment was significantly lower in methionine sulfoximine-treated rats than in PBS-treated rats. In the ipsilateral region, the total number of phosphorylated extracellular signal-regulated protein kinase immunoreactive cells in the medullary dorsal horn was significantly smaller upon first molar tooth pulp capsaicin application in methionine sulfoximine-treated rats than in PBS-treated rats. Conclusions Our results suggest that masseter muscle contraction induces astroglial activation, and that this activation spreads from caudal to the obex in the medullary dorsal horn, resulting in enhanced neuronal excitability associated with astroglial glutamine synthesis in medullary dorsal horn neurons receiving inputs from the tooth pulp. These findings provide significant insight into the mechanisms underlying tooth pulp hypersensitivity associated with masseter muscle contraction.

Renal Cell Carcinoma, Unclassified with Medullary Phenotype and Synchronous Renal Clear Cell Carcinoma Present in a Patient with No Sickle Cell Trait/Disease: Diagnostic and Therapeutic Challenges.

PubMed

Lai, Jenny Z; Lai, H Henry; Cao, Dengfeng

2018-06-01

Renal medullary carcinoma (RMC) is an aggressive high-grade renal cell carcinoma (RCC) associated almost exclusively with sickle cell trait or sickle cell disease. However, RCC with RMC features has rarely been reported in patients with no sickle cell trait or disease. Renal cell carcinoma unclassified with medullary phenotype (RCCU-MP) is a newly-coined term used by an international panel of experts to describe renal cell carcinoma showing morphologic and immunohistochemical features of renal medullary carcinoma in patients without sickle cell trait/disease. So far, only one study in the English literature has described five such cases. Here, we report a case with unique clinical and pathological features in a 76-year-old male patient without sickle cell trait. The patient had a history of colon cancer with liver and lung metastases and was found to have a new renal mass in his right kidney during the follow up. A right nephrectomy was performed and showed two separate masses (tumor 1 and tumor 2). Tumor 1 had histologic features of RMC and the tumor cells were positive for CK7, Pax8, and OCT4 and showed loss of nuclear INI1 expression. Tumor 1 was diagnosed as RCCU-MP (6.3 cm, pT3aNx, WHO/ISUP nuclear grade 3). Tumor 2 showed features of clear cell type of RCC (0.6 cm, pT1aNx, WHO/ISUP grade 2) with intact nuclear INI1 expression. Three-months post-nephrectomy, the patient developed lung metastasis of RCCU-MP. To the best of our knowledge, this was the first documented case with synchronous RCCU-MP and clear cell RCC presenting in a patient without sickle cell trait. Careful histologic assessment with a panel of immunohistochemical biomarkers was helpful to render a correct diagnosis for early aggressive treatment. Copyright© 2018, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.

Influence of graded levels of calcium and vitamin K in the diets of laying hens during the growing phase and their effects on the laying phase.

PubMed

Souza, C; Santos, T C; Murakami, A E; Iwaki, L C V; Mello, J F

2017-10-01

The aim of this study was to evaluate the effect of dietary supplementation of vitamin K (vit K) and Ca in the diets of laying hens on bone and blood parameters and performance during the growing phase and the effects on the laying phase up to 32 weeks. The study utilized 120 Hy-Line W-36 pullets in the growing phase (13-18 weeks), 80 laying hens in the production phase (20-32 weeks), distributed in a completely randomized design in a 2 × 5 factorial arrangement, two levels of Ca (0.8 and 1.4%) and five levels of vit K supplementation (0, 2, 8, 16 and 32 mg/kg) with four experimental units. An experimental diet was fed during the growing phase, and the commercial diet was fed during the production phase and were analysed for biochemistry and bone variables at 18 and 32 weeks. In pullets, a significant interaction of levels of vit K and Ca was observed for total serum calcium (mg/dl), Seedor index, Ca in the bones (%) and medullary bone (%). Pullets at 18 weeks of age, receiving diets with 1.4% Ca, displayed a quadratic effect of vit K with better results for these variables with 17.86, 14.59, 14.48 and 16.80 mg/kg of vit K, respectively. For level 0.8% Ca no effect of vit K was observed. The treatments during the growing phase had no effect on egg production, performance and biochemistry serum until 32 weeks. Medullary bone (%), there was a significant interaction for 1.4% Ca and a quadratic effect for vit K, with greater medullary bone areas observed with 6.09 mg/kg vit K in the diet. Supplementation with vit K in a diet with 1.4% Ca during the growing phase allowed for an increase in the area of medullary bone at 18 weeks, which was maintained until 32 weeks. Journal of Animal Physiology and Animal Nutrition © 2016 Blackwell Verlag GmbH.

Kidney Dysplasia

MedlinePlus

... Disease Ectopic Kidney Medullary Sponge Kidney Kidney Dysplasia Kidney Dysplasia What is kidney dysplasia? Kidney dysplasia is a condition in which ... Kidney dysplasia in one kidney What are the kidneys and what do they do? The kidneys are ...

Ectopic Kidney

MedlinePlus

... Ectopic Kidney Medullary Sponge Kidney Kidney Dysplasia Ectopic Kidney What is an ectopic kidney? An ectopic kidney is a birth defect in ... has an ectopic kidney. 1 What are the kidneys and what do they do? The kidneys are ...

Medullary cystic kidney disease

MedlinePlus

... Tests that may be done include: 24-hour urine volume and electrolytes Blood urea nitrogen (BUN) Complete blood count (CBC) Creatinine blood test Creatinine clearance -- blood and urine Uric acid blood test Urine specific gravity (will ...

The cystic dilation of ventriculus terminalis with neurological symptoms: Three case reports and a literature review.

PubMed

Lotfinia, Iraj; Mahdkhah, Ata

2018-05-23

The ventriculus terminalis (VT) is a very small ependymal-lined residual lumen in the conus medullaris. It is normally present in all subjects during fetal development. VT in adults appears as an unusual pathology with an uncertain pathogenesis. In this paper, we described three case reports of symptomatic fifth ventricle cystic dilations. All of them were female and their mean age was 59 years. We treated them surgically and all three patients were improved based on clinical and imaging assessments. Our cases suggested that surgical decompression was a safe and effective treatment in symptomatic patients and the neurosurgeons should be aware of such rare situations. A complete list of differential diagnosis about other cystic dilations of the conus medullaris should be emphasized to select the correct clinical approach.

Magnetization transfer and adiabatic R 1ρ MRI in the brainstem of Parkinson's disease.

PubMed

Tuite, Paul J; Mangia, Silvia; Tyan, Andrew E; Lee, Michael K; Garwood, Michael; Michaeli, Shalom

2012-06-01

In addition to classic midbrain pathology, Parkinson's disease (PD) is accompanied by changes in pontine and medullary brainstem structures. These additional abnormalities may underlie non-motor features as well as play a role in motor disability. Using novel magnetic resonance imaging (MRI) methods based on rotating frame adiabatic R(1ρ) (i.e., measurements of longitudinal relaxation during adiabatic full passage pulses) and modified magnetization transfer (MT) MRI mapping, we sought to identify brainstem alterations in nine individuals with mild-moderate PD (off medication) and ten age-matched controls at 4 T. We discovered significant differences in MRI parameters between midbrain and medullary brainstem structures in control subjects as compared to PD patients. These findings support the presence of underlying functional/structural brainstem changes in mild-moderate PD. Copyright © 2012 Elsevier Ltd. All rights reserved.

One lesson from arthroplasty to osseointegration in search for better fixation of in-bone implanted prosthesis

PubMed Central

Pitkin, Mark

2011-01-01

Direct transcutaneous prosthetic attachment (osseointegration) consists of implanting directly into the residuum bone a metal pylon whose external fraction connects the residuum to the external prosthesis. Since the introduction of osseointegration about 20 years ago, the obvious challenge associated with this technology has been the skin-pylon interface as a source of infections. In comparison, the bone-device interface was considered less problematic because of the knowledge and experience inherited from dental implantology and total joint replacement (arthroplasty). Current methods of pylon fixation in osseointegration follow arthroplasty’s paradigm of positioning the pylon’s shaft inside the bone’s medullary canal. However, adopting the medullary canal as a holding compartment for the pylon’s shaft creates the problem of shaft loosening, which has not yet been solved in arthroplasty. PMID:18712634

Expression and regulation of CNTF receptor-alpha in the in situ and in oculo grafted adult rat adrenal medulla.

PubMed

Förander, P; Brené, S; Strömberg, I

2000-02-28

Cultured and transplanted adrenal medullary cells respond to ciliary neurotrophic factor (CNTF) with neurite formation and improved cell survival although the presence of the CNTF receptor-alpha (CNTFRalpha) has been unclear. This study show that CNTFRalpha mRNA was expressed in the postnatal day 1 as well as in the adult rat adrenal medulla. The highest CNTFRalpha mRNA signal was found in the ganglion cells of the adrenal medulla. After transplantation of adrenal medullary tissue the CNTFRalpha mRNA levels were down-regulated in the chromaffin cells. CNTF treatment of grafts did not normalize the receptor levels, but treatment with nerve growth factor (NGF) did. Thus, we demonstrate that CNTFRalpha mRNA is expressed in adrenal medulla, the levels becomes down-regulated after transplantation, but normalized after treatment with NGF.

A regulatory role for TGF-β signaling in the establishment and function of the thymic medulla.

PubMed

Hauri-Hohl, Mathias; Zuklys, Saulius; Holländer, Georg A; Ziegler, Steven F

2014-06-01

Medullary thymic epithelial cells (mTECs) are critical in establishing and maintaining the appropriate microenvironment for negative selection and maturation of immunocompetent T cells with a self-tolerant T cell antigen receptor repertoire. Cues that direct proliferation and maturation of mTECs are provided by members of the tumor necrosis factor (TNF) superfamily expressed on developing thymocytes. Here we demonstrate a negative role of the morphogen TGF-β in tempering these signals under physiological conditions, limiting both growth and function of the thymic medulla. Eliminating TGF-β signaling specifically in TECs or by pharmacological means increased the size of the mTEC compartment, enhanced negative selection and functional maturation of medullary thymocytes as well as the production of regulatory T cells, thus reducing the autoreactive potential of peripheral T cells.

Apical P2XR contribute to [Ca2+]i signaling and Isc in mouse renal MCD.

PubMed

Li, Liuzhe; Lynch, I Jeanette; Zheng, Wencui; Cash, Melanie N; Teng, Xueling; Wingo, Charles S; Verlander, Jill W; Xia, Shen-Ling

2007-08-03

We examined P2X receptor expression and distribution in the mouse collecting duct (CD) and their functional role in Ca(2+) signaling. Both P2X(1) and P2X(4) were detected by RT-PCR and Western blot. Immunohistochemistry demonstrated apical P2X(1) and P2X(4) immunoreactivity in principal cells in the outer medullary CD (OMCD) and inner medullary CD (IMCD). Luminal ATP induced an increase in Ca(2+) signaling in native medullary CD (MCD) as measured by fluorescence imaging. ATP also induced an increase in Ca(2+) signaling in MCD cells grown in primary culture but not in the presence of P2XR antagonist PPNDS. Short circuit current (I(sc)) measurement with mouse IMCD cells showed that P2XR agonist BzATP induced a larger I(sc) than did P2YR agonist UTP in the apical membrane. Our data reveal for the first time that P2X(1) and P2X(4) are cell-specific with prominent immunoreactivity in the apical area of MCD cells. The finding that P2XR blockade inhibits ATP-induced Ca(2+) signaling suggests that activation of P2XR is a key step in Ca(2+)-dependent purinergic signaling. The result that activation of P2XR produces large I(sc) indicates the necessity of P2XR in renal CD ion transport.

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

PubMed

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.

Inhibitory effects of pine nodule extract and its component, SJ-2, on acetylcholine-induced catecholamine secretion and synthesis in bovine adrenal medullary cells.

PubMed

Li, Xiaojia; Horishita, Takafumi; Toyohira, Yumiko; Shao, Hui; Bai, Jie; Bo, Haixia; Song, Xinbo; Ishikane, Shin; Yoshinaga, Yukari; Satoh, Noriaki; Tsutsui, Masato; Yanagihara, Nobuyuki

2017-04-01

Extract of pine nodules (matsufushi) formed by bark proliferation on the surface of trees of Pinus tabulaeformis or Pinus massoniana has been used as an analgesic for joint pain, rheumatism, neuralgia, dysmenorrhea and other complaints in Chinese traditional medicine. Here we report the effects of matsufushi extract and its components on catecholamine secretion and synthesis in cultured bovine adrenal medullary cells. We found that matsufushi extract (0.0003-0.005%) and its component, SJ-2 (5-hydroxy-3-methoxy-trans-stilbene) (0.3-100 μM), but not the other three, concentration-dependently inhibited catecholamine secretion induced by acetylcholine, a physiological secretagogue. Matsufushi extract (0.0003-0.005%) and SJ-2 (0.3-100 μM) also inhibited 45 Ca 2+ influx induced by acetylcholine in a concentration-dependent manner, similar to its effect on catecholamine secretion. They also suppressed 14 C-catecholamine synthesis and tyrosine hydroxylase activity induced by acetylcholine. In Xenopus oocytes expressing α3β4 nicotinic acetylcholine receptors, matsufushi extract (0.00003-0.001%) and SJ-2 (1-100 μM) directly inhibited the current evoked by acetylcholine. The present findings suggest that SJ-2, as well as matsufushi extract, inhibits acetylcholine-induced catecholamine secretion and synthesis by suppression of nicotinic acetylcholine receptor-ion channels in bovine adrenal medullary cells. Copyright © 2017 The Authors. Production and hosting by Elsevier B.V. All rights reserved.

Magnetic resonance elastography can monitor changes in medullary stiffness in response to treatment in the swine ischemic kidney.

PubMed

Zhang, Xin; Zhu, Xiangyang; Ferguson, Christopher Martyn; Jiang, Kai; Burningham, Tyson; Lerman, Amir; Lerman, Lilach Orly

2018-06-01

Low-energy shockwave (SW) therapy attenuates damage in the stenotic kidney (STK) caused by atherosclerotic renal artery stenosis (ARAS). We hypothesized that magnetic resonance elastography (MRE) would detect attenuation of fibrosis following SW in unilateral ARAS kidneys. Domestic pigs were randomized to control, unilateral ARAS, and ARAS treated with 6 sessions of SW over 3 consecutive weeks (n = 7 each) starting after 3 weeks of ARAS or sham. Four weeks after SW treatment, renal fibrosis was evaluated with MRE in vivo or trichrome staining ex vivo. Blood pressure, single-kidney renal-blood-flow (RBF) and glomerular-filtration-rate (GFR) were assessed. MRE detected increased stiffness in the STK medulla (15.3 ± 2.1 vs. 10.1 ± 0.8 kPa, p < 0.05) that moderately correlated with severity of fibrosis (R 2  = 0.501, p < 0.01), but did not identify mild STK cortical or contralateral kidney fibrosis. Trichrome staining showed that medullary fibrosis was increased in ARAS and alleviated by SW (10.4 ± 1.8% vs. 2.9 ± 0.2%, p < 0.01). SW slightly decreased blood pressure and normalized STK RBF and GFR in ARAS. In the contralateral kidney, SW reversed the increase in RBF and GFR. MRE might be a tool for noninvasive monitoring of medullary fibrosis in response to treatment in kidney disease.

Architecture of interstitial nodal spaces in the rodent renal inner medulla.

PubMed

Gilbert, Rebecca L; Pannabecker, Thomas L

2013-09-01

Every collecting duct (CD) of the rat inner medulla is uniformly surrounded by about four abutting ascending vasa recta (AVR) running parallel to it. One or two ascending thin limbs (ATLs) lie between and parallel to each abutting AVR pair, opposite the CD. These structures form boundaries of axially running interstitial compartments. Viewed in transverse sections, these compartments appear as four interstitial nodal spaces (INSs) positioned symmetrically around each CD. The axially running compartments are segmented by interstitial cells spaced at regular intervals. The pairing of ATLs and CDs bounded by an abundant supply of AVR carrying reabsorbed water, NaCl, and urea make a strong argument that the mixing of NaCl and urea within the INSs and countercurrent flows play a critical role in generating the inner medullary osmotic gradient. The results of this study fully support that hypothesis. We quantified interactions of all structures comprising INSs along the corticopapillary axis for two rodent species, the Munich-Wistar rat and the kangaroo rat. The results showed remarkable similarities in the configurations of INSs, suggesting that the structural arrangement of INSs is a highly conserved architecture that plays a fundamental role in renal function. The number density of INSs along the corticopapillary axis directly correlated with a loop population that declines exponentially with distance below the outer medullary-inner medullary boundary. The axial configurations were consistent with discrete association between near-bend loop segments and INSs and with upper loop segments lying distant from INSs.

Architecture of interstitial nodal spaces in the rodent renal inner medulla

PubMed Central

Gilbert, Rebecca L.

2013-01-01

Every collecting duct (CD) of the rat inner medulla is uniformly surrounded by about four abutting ascending vasa recta (AVR) running parallel to it. One or two ascending thin limbs (ATLs) lie between and parallel to each abutting AVR pair, opposite the CD. These structures form boundaries of axially running interstitial compartments. Viewed in transverse sections, these compartments appear as four interstitial nodal spaces (INSs) positioned symmetrically around each CD. The axially running compartments are segmented by interstitial cells spaced at regular intervals. The pairing of ATLs and CDs bounded by an abundant supply of AVR carrying reabsorbed water, NaCl, and urea make a strong argument that the mixing of NaCl and urea within the INSs and countercurrent flows play a critical role in generating the inner medullary osmotic gradient. The results of this study fully support that hypothesis. We quantified interactions of all structures comprising INSs along the corticopapillary axis for two rodent species, the Munich-Wistar rat and the kangaroo rat. The results showed remarkable similarities in the configurations of INSs, suggesting that the structural arrangement of INSs is a highly conserved architecture that plays a fundamental role in renal function. The number density of INSs along the corticopapillary axis directly correlated with a loop population that declines exponentially with distance below the outer medullary-inner medullary boundary. The axial configurations were consistent with discrete association between near-bend loop segments and INSs and with upper loop segments lying distant from INSs. PMID:23825077

Hyperpolarized 13 C,15 N2 -Urea MRI for assessment of the urea gradient in the porcine kidney.

PubMed

Hansen, Esben S S; Stewart, Neil J; Wild, Jim M; Stødkilde-Jørgensen, Hans; Laustsen, Christoffer

2016-12-01

A decline in cortico-medullary osmolality gradient of the kidney may serve as an early indicator of pathological disruption of the tubular reabsorption process. The purpose of this study was to investigate the feasibility of hyperpolarized 13 C, 15 N 2 -urea MRI as a biomarker of renal function in healthy porcine kidneys resembling the human physiology. Five healthy female Danish domestic pigs (weight 30 kg) were scanned at 3 Tesla (T) using a 13 C 3D balanced steady-state MR pulse sequence following injection of hyperpolarized 13 C, 15 N 2 -urea via a femoral vein catheter. Images were acquired at different time points after urea injection, and following treatment with furosemide. A gradient in cortico-medullary urea was observed with an intramedullary accumulation 75 s after injection of hyperpolarized 13 C, 15 N 2 -urea, whereas images acquired at earlier time points postinjection were dominated by cortical perfusion. Furosemide treatment resulted in an increased urea accumulation in the cortical space, leading to a reduction of the medullary-to-cortical signal ratio of 49%. This study demonstrates that hyperpolarized 13 C, 15 N 2 -urea MRI is capable of identifying the intrarenal accumulation of urea and can differentiate acute renal functional states in multipapillary kidneys, highlighting the potential for human translation. Magn Reson Med 76:1895-1899, 2016. © 2016 International Society for Magnetic Resonance in Medicine. © 2016 International Society for Magnetic Resonance in Medicine.

Cheiro-Oral Syndrome: A Clinical Analysis and Review of Literature

PubMed Central

2009-01-01

Purpose After a century, cheiro-oral syndrome (COS) was harangued and emphasized for its localizing value and benign course in recent two decades. However, an expanding body of case series challenged when COS may arise from an involvement of ascending sensory pathways between cortex and pons and terminate into poor outcome occasionally. Materials and Methods To analyze the location, underlying etiologies and prognosis in 76 patients presented with COS collected between 1989 and 2007. Results Four types of COS were categorized, namely unilateral (71.1%), typically bilateral (14.5%), atypically bilateral (7.9%) and crossed COS (6.5%). The most common site of COS occurrence was at pons (27.6%), following by thalamus (21.1%) and cortex (15.8%). Stroke with small infarctions or hemorrhage was the leading cause. Paroxysmal paresthesia was predicted for cortical involvement and bilateral paresthesia for pontine involvement, whereas crossed paresthesia for medullary involvement. However, the majority of lesions cannot be localized by clinical symptoms alone, and were demonstrated only by neuroimaging. Deterioration was ensued in 12% of patients, whose lesions were large cortical infarction, medullary infarction, and bilateral subdural hemorrhage. Conclusion COS arises from varied sites between medulla and cortex, and is usually caused by small stroke lesion. Neurological deterioration occurs in 12% of patients and relates to large vessel occlusion, medullary involvement or cortical stroke. Since the location and deterioration of COS cannot be predicted by clinical symptoms alone, COS should be considered an emergent condition for aggressive investigation until fatal cause is substantially excluded. PMID:20046417

Mitochondrial proteomic analysis reveals deficiencies in oxygen utilization in medullary thick ascending limb of Henle in the Dahl salt-sensitive rat

PubMed Central

Zheleznova, Nadezhda N.; Yang, Chun; Ryan, Robert P.; Halligan, Brian D.; Liang, Mingyu; Greene, Andrew S.

2012-01-01

The renal medullary thick ascending limb (mTAL) of the Dahl salt-sensitive (SS) rat is the site of enhanced NaCl reabsorption and excess superoxide production. In the present studies we isolated mitochondria from mTAL of SS and salt-resistant control strain SS.13BN rats on 0.4 and 8% salt diet for 7 days and performed a proteomic analysis. Purity of mTAL and mitochondria isolations exceeded 93.6 and 55%, respectively. Using LC/MS spectral analysis techniques we identified 96 mitochondrial proteins in four biological mTAL mitochondria samples, run in duplicate, as defined by proteins with a false discovery rate <5% and scan count ≥2. Seven of these 96 proteins, including IDH2, ACADM, SCOT, Hsp60, ATPA, EFTu, and VDAC2 were differentially expressed between the two rat strains. Oxygen consumption and high-resolution respirometry analyses showed that mTAL cells and the mitochondria in the outer medulla of SS rats fed high-salt diet exhibited lower rates of oxygen utilization compared with those from SS.13BN rats. These studies advance the conventional proteomic paradigm of focusing exclusively upon whole tissue homogenates to a focus upon a single cell type and specific subcellular organelle. The results reveal the importance of a largely unexplored role for deficiencies of mTAL mitochondrial metabolism and oxygen utilization in salt-induced hypertension and renal medullary oxidative stress. PMID:22805345

Renal BOLD-MRI relates to kidney function and activity of the renin-angiotensin-aldosterone system in hypertensive patients.

PubMed

Vink, Eva E; de Boer, Anneloes; Hoogduin, Hans J M; Voskuil, Michiel; Leiner, Tim; Bots, Michiel L; Joles, Jaap A; Blankestijn, Peter J

2015-03-01

The renin-angiotensin-aldosterone system (RAAS) and the sympathetic nervous system are key factors in the pathophysiology of hypertension. Renal hypoxia is the putative mechanism stimulating both systems. Blood oxygen level-dependent MRI (BOLD-MRI) provides a noninvasive tool to determine renal oxygenation in humans. The aim of the current study was to investigate the relation between blood pressure (BP) and kidney function with renal BOLD-MRI. Moreover, the relation between direct and indirect variables of the RAAS and sympathetic nervous system and renal BOLD-MRI was studied. Seventy-five hypertensive patients (38 men) were included. Antihypertensive medication was temporarily stopped. Patients collected urine during 24 h (sodium, catecholamines), blood samples were taken (creatinine, renin, aldosterone), a captopril challenge test was performed, and ambulatory BP was measured. Mean age was 58 (±11) years, day-time BP was 167 (±19)/102 (±16) mmHg, and estimated glomerular filtration rate was 75 (±18) ml/min per 1.73 m). In multivariable regression analysis, renal medullary R2*-values inversely related to estimated glomerular filtration rate (P = 0.02). Moreover, the BP-lowering effect of captopril positively related to cortical (P = 0.02) and medullary (P = 0.008) R2*-values, as well as to P90 (P = 0.02). In patients with hypertension, kidney function relates to medullary R2*-values. Activation of the RAAS is also positively related to the renal R2*-values.

Systemic AA amyloidosis in island foxes (Urocyon littoralis): Severity and risk factors

PubMed Central

Gaffney, Patricia M.; Witte, Carmel; Clifford, Deana L.; Imai, Denise M.; O’Brien, Timothy D.; Trejo, Margarita; Liberta, Falk; Annamalai, Karthikeyan; Fändrich, Marcus; Masliah, Eliezer; Munson, Linda; Sigurdson, Christina J.

2016-01-01

Systemic amyloid A (AA) amyloidosis is highly prevalent (34%) in endangered island foxes (Urocyon littoralis) and poses a risk to species recovery. Although elevated serum amyloid A from prolonged or recurrent inflammation predisposes to AA amyloidosis, additional risk factors are poorly understood. Here we define the severity of glomerular and medullary renal amyloid and identify risk factors for AA amyloidosis in 321 island foxes necropsied from 1987 through 2010. In affected kidneys, amyloid more commonly accumulated in the medullary interstitium than in the glomeruli [98% (78/80) versus 56% (45/80), respectively, p < 0.0001], and medullary deposition was more commonly severe [19% (20/105)] as compared to glomeruli [7% (7/105), p = 0.01]. Univariate odds ratios (ORs) of severe renal AA amyloidosis were greater for short- and long-term captive foxes compared to free-ranging (OR=3.2, 3.7, respectively, overall p = 0.05) and females compared to males (OR = 2.9, p = 0.05). Multivariable logistic regression revealed independent risk factors for amyloid development were increasing age class (OR = 3.8, p < 0.0001), San Clemente Island subspecies compared to San Nicolas Island subspecies (OR = 5.3, p = 0.0003), captivity (OR = 5.1, p = 0.0001), and nephritis (OR = 2.3, p = 0.01). The increased risk associated with the San Clemente subspecies or captivity suggests roles for genetic as well as exogenous risk factors in the development of AA amyloidosis. PMID:26419399

An Adapting Auditory-motor Feedback Loop Can Contribute to Generating Vocal Repetition

PubMed Central

Brainard, Michael S.; Jin, Dezhe Z.

2015-01-01

Consecutive repetition of actions is common in behavioral sequences. Although integration of sensory feedback with internal motor programs is important for sequence generation, if and how feedback contributes to repetitive actions is poorly understood. Here we study how auditory feedback contributes to generating repetitive syllable sequences in songbirds. We propose that auditory signals provide positive feedback to ongoing motor commands, but this influence decays as feedback weakens from response adaptation during syllable repetitions. Computational models show that this mechanism explains repeat distributions observed in Bengalese finch song. We experimentally confirmed two predictions of this mechanism in Bengalese finches: removal of auditory feedback by deafening reduces syllable repetitions; and neural responses to auditory playback of repeated syllable sequences gradually adapt in sensory-motor nucleus HVC. Together, our results implicate a positive auditory-feedback loop with adaptation in generating repetitive vocalizations, and suggest sensory adaptation is important for feedback control of motor sequences. PMID:26448054

A Symbiotic Brain-Machine Interface through Value-Based Decision Making

PubMed Central

Mahmoudi, Babak; Sanchez, Justin C.

2011-01-01

Background In the development of Brain Machine Interfaces (BMIs), there is a great need to enable users to interact with changing environments during the activities of daily life. It is expected that the number and scope of the learning tasks encountered during interaction with the environment as well as the pattern of brain activity will vary over time. These conditions, in addition to neural reorganization, pose a challenge to decoding neural commands for BMIs. We have developed a new BMI framework in which a computational agent symbiotically decoded users' intended actions by utilizing both motor commands and goal information directly from the brain through a continuous Perception-Action-Reward Cycle (PARC). Methodology The control architecture designed was based on Actor-Critic learning, which is a PARC-based reinforcement learning method. Our neurophysiology studies in rat models suggested that Nucleus Accumbens (NAcc) contained a rich representation of goal information in terms of predicting the probability of earning reward and it could be translated into an evaluative feedback for adaptation of the decoder with high precision. Simulated neural control experiments showed that the system was able to maintain high performance in decoding neural motor commands during novel tasks or in the presence of reorganization in the neural input. We then implanted a dual micro-wire array in the primary motor cortex (M1) and the NAcc of rat brain and implemented a full closed-loop system in which robot actions were decoded from the single unit activity in M1 based on an evaluative feedback that was estimated from NAcc. Conclusions Our results suggest that adapting the BMI decoder with an evaluative feedback that is directly extracted from the brain is a possible solution to the problem of operating BMIs in changing environments with dynamic neural signals. During closed-loop control, the agent was able to solve a reaching task by capturing the action and reward interdependency in the brain. PMID:21423797

An agonist–antagonist cerebellar nuclear system controlling eyelid kinematics during motor learning

PubMed Central

Sánchez-Campusano, Raudel; Gruart, Agnès; Fernández-Mas, Rodrigo; Delgado-García, José M.

2012-01-01

The presence of two antagonistic groups of deep cerebellar nuclei neurons has been reported as necessary for a proper dynamic control of learned motor responses. Most models of cerebellar function seem to ignore the biomechanical need for a double activation–deactivation system controlling eyelid kinematics, since most of them accept that, for closing the eyelid, only the activation of the orbicularis oculi (OO) muscle (via the red nucleus to the facial motor nucleus) is necessary, without a simultaneous deactivation of levator palpebrae motoneurons (via unknown pathways projecting to the perioculomotor area). We have analyzed the kinetic neural commands of two antagonistic types of cerebellar posterior interpositus neuron (IPn) (types A and B), the electromyographic (EMG) activity of the OO muscle, and eyelid kinematic variables in alert behaving cats during classical eyeblink conditioning, using a delay paradigm. We addressed the hypothesis that the interpositus nucleus can be considered an agonist–antagonist system controlling eyelid kinematics during motor learning. To carry out a comparative study of the kinetic–kinematic relationships, we applied timing and dispersion pattern analyses. We concluded that, in accordance with a dominant role of cerebellar circuits for the facilitation of flexor responses, type A neurons fire during active eyelid downward displacements—i.e., during the active contraction of the OO muscle. In contrast, type B neurons present a high tonic rate when the eyelids are wide open, and stop firing during any active downward displacement of the upper eyelid. From a functional point of view, it could be suggested that type B neurons play a facilitative role for the antagonistic action of the levator palpebrae muscle. From an anatomical point of view, the possibility that cerebellar nuclear type B neurons project to the perioculomotor area—i.e., more or less directly onto levator palpebrae motoneurons—is highly appealing. PMID:22435053

Thyroid Cancer—Health Professional Version

Cancer.gov

There are four types of thyroid cancer. These are papillary, follicular, medullary, and anaplastic thyroid cancer. Papillary is the most common type of thyroid cancer. Find evidence-based information on thyroid cancer treatment, screening, research, genetics, and statistics.

A rare case of a medullary, multifocal lesion in the distal radius

PubMed Central

Aktas, Birol; Ozturan, Burak; Kilic, Bulent; Ozkan, Korhan

2017-01-01

In multifocal findings, the possibility of multifocal osteoid osteomas should be considered and this case helps us to be attentive for the unusual radiographical presentation of osteoid osteoma. PMID:28748099

The cementless anatomic medullary locking femoral component: an independent clinical and radiographic assessment

PubMed Central

Chess, David G.; Grainger, R. Wayne; Phillips, Tom; Zarzour, Zane D.; Sheppard, Bruce R.

1996-01-01

Objective To review the clinical performance of the anatomic medullary locking (AML) femoral stem in total hip arthroplasty. Design A clinical and radiographic review. Setting A tertiary lower limb joint replacement centre. Patients Two hundred and twenty-one patients with noninflammatory gonarthrosis. Interventions Two hundred and twenty-seven primary total hip arthroplasties with the noncemented AML component completed by two surgeons. Main Outcome Measures Independent review by two experienced reviewers of the postoperative Harris hip score, radiographs of component fixation, size and degree of diaphyseal fill. Results Harris hip score was 84 (range from 43 to 98); component fixation showed bone ingrowth in 41%, stable fixation with fibrous ingrowth in 56% and unstable fixation in 3%; severe thigh pain in 4% of cases correlated with unstable fixation, and there was mild thigh pain in 20% of cases. Conclusion The AML femoral stem performs well in replacement arthroplasty compared with other noncemented stems. PMID:8857987

Cushing Disease in a patient with Multiple Endocrine Neoplasia type 2B.

PubMed

Kasturi, Kannan; Fernandes, Lucas; Quezado, Martha; Eid, Mary; Marcus, Leigh; Chittiboina, Prashant; Rappaport, Mark; Stratakis, Constantine A; Widemann, Brigitte; Lodish, Maya

2017-06-01

Multiple endocrine neoplasia type 2B (MEN2B) is a rare autosomal-dominant cancer syndrome characterized in part by metastatic medullary thyroid cancer (MTC) and pheochromocytoma. Cushing disease is a rare cause of endogenous hypercortisolism in children. We describe a 21-year-old African-American male who was diagnosed at age 10 with an ACTH-secreting pituitary microadenoma. At age 16 he developed medullary thyroid cancer and was found to have multiple endocrine neoplasia type 2B with the characteristic M918T mutation of the RET proto-oncogene. Following thyroidectomy, he was initiated on Vandetanib, a tyrosine kinase inhibitor, and has since had stable disease over the last 5 years. Our patient is the first individual with MEN2B to be described with Cushing disease. The RET oncogene may play a role in pituitary tumorigenesis; alternatively, the coexistence of these two entities may represent an extremely rare coincidence.

Cytologic diagnosis of medullary carcinoma of the thyroid gland.

PubMed

Papaparaskeva, K; Nagel, H; Droese, M

2000-06-01

The cytomorphologic features in fine-needle aspiration (FNA) biopsies from 91 histologiacally verified medullary carcinomas of the thyroid (MCT) were investigated. FNA was able to diagnose neoplasms with indications of surgical removal in 98.9% of cases and moreover, was accurate in specific tumor typing in 89% of cases. The most important cytologic criteria of MCT with FNA are: dispersed cell-pattern of polygonal or triangular cells, azurophilic cytoplasmic granules, and extremely eccentrically placed nuclei with coarse granular chromatin and amyloid. These and other cytologic features of MCT are discussed in detail. Fourteen cases of thyroid tumors originally diagnosed as MCT by cytology are illustrated to discuss the differential diagnosis of MCT and its potential pitfalls. If MCT is cytologically presumed but amyloid and azurophilic cytoplasmic granules are not demonstrated, the use of immunostaining is necessary for a correct tumor typing. The application of immunocytochemistry in MCT is discussed. Copyright 2000 Wiley-Liss, Inc.

Renal potassium physiology: integration of the renal response to dietary potassium depletion.

PubMed

Kamel, Kamel S; Schreiber, Martin; Halperin, Mitchell L

2018-01-01

We summarize the current understanding of the physiology of the renal handling of potassium (K + ), and present an integrative view of the renal response to K + depletion caused by dietary K + restriction. This renal response involves contributions from different nephron segments, and aims to diminish the rate of excretion of K + as a result of: decreasing the rate of electrogenic (and increasing the rate of electroneutral) reabsorption of sodium in the aldosterone-sensitive distal nephron (ASDN), decreasing the abundance of renal outer medullary K + channels in the luminal membrane of principal cells in the ASDN, decreasing the flow rate in the ASDN, and increasing the reabsorption of K + in the cortical and medullary collecting ducts. The implications of this physiology for the association between K + depletion and hypertension, and K + depletion and formation of calcium kidney stones are discussed. Copyright © 2017 International Society of Nephrology. Published by Elsevier Inc. All rights reserved.

A Shunt Model of the Inner Medullary Nephron with Pre-Bend Transitions

NASA Astrophysics Data System (ADS)

Gonzalez, M. T.; Hegarty, A. F.; Thomas, S. R.

2009-09-01

Mathematical models of the renal medulla face the problem of representing water and solute transfer among tens of thousands of nephrons and blood vessels of various lengths, arranged in countercurrent fashion. Published models fall into two broad categories with respect to this issue: multi-nephron models, which explicitly represent a large number of individual nephrons, or lumped models with virtual shunts that represent the turning back of nephrons and vessels at varying depths. Shunt models have the advantage of a compact description and relatively rapid execution time but are ill-suited to faithfully represent features such as prebend transitions of epithelial permeabilities in nephrons of different lengths. A new shunt model approach that can accommodate pre-bend transitions of nephrons at all medullary depths is presented in this work together with the results of simulation of predicted flows and concentrations.

Spinal capillary hemangiomas: Two cases reports and review of the literature

PubMed Central

Tunthanathip, Thara; Rattanalert, Sanguansin; Oearsakul, Thakul; Kanjanapradit, Kanet

2017-01-01

Hemangiomas have rarely been found in the spinal cord. A few cases of spinal capillary hemangioma have been reported since 1987. The authors reported the two cases of capillary hemangioma including the tumor at conus medullaris and the another mimicked von Hippel-Lindau disease. A 15-year-old man was presented with coccydynia and left leg pain. A magnetic resonance imaging (MRI) revealed an intradural extramedullary enhancing mass at conus medullaris. Another case, a 31-year-old man was presented with a history of familial history of brain tumor, retinal hemangioma both eyes, multiple pancreatic cyst and syringobulbia with syringohydromyelia. On MRI, a well-circumscribed intramedullary nodule was detected at C5-6 level and multiple subpial nodule along cervicothoracic spinal cord. All patients underwent surgery, and the histological diagnosis confirmed capillary hemangioma. Although rare and indistinguishable from other tumors, capillary hemangioma should be in the differential diagnosis of the spinal cord tumor. PMID:28761543

Cortical bone thickening in Type A posterior atlas arch defects: experimental report.

PubMed

Sanchis-Gimeno, Juan A; Llido, Susanna; Guede, David; Martinez-Soriano, Francisco; Ramon Caeiro, Jose; Blanco-Perez, Esther

2017-03-01

To date, no information about the cortical bone microstructural properties in atlas vertebrae with posterior arch defects has been reported. To test if there is an increased cortical bone thickening in atlases with Type A posterior atlas arch defects in an experimental model. Micro-computed tomography (CT) study on cadaveric atlas vertebrae. We analyzed the cortical bone thickness, the cortical volume, and the medullary volume (SkyScan 1172 Bruker micro-CT NV, Kontich, Belgium) in cadaveric dry vertebrae with a Type A atlas arch defect and normal control vertebrae. The micro-CT study revealed significant differences in cortical bone thickness (p=.005), cortical volume (p=.003), and medullary volume (p=.009) values between the normal and the Type A vertebrae. Type A congenital atlas arch defects present a cortical bone thickening that may play a protective role against atlas fractures. Copyright © 2016 Elsevier Inc. All rights reserved.

Splendore-Hoeppli phenomenon in a cat with osteomyelitis caused by Streptococcus species.

PubMed

França, Silvia de Araujo; Braga, Juliana Fortes Vilarinho; Moreira, Matheus Vilardo Loes; Silva, Vitor Cesar Martins; Souza, Erick Ferry; Pereira, Luiz Carlos; Rezende, Cleuza Maria de Faria; Ecco, Roselene

2014-02-01

A 9-month-old male neutered mixed-breed cat had a history of chronic lameness of the right hind limb, which was non-responsive to antibiotic treatment. Hematologic analysis revealed marked neutrophilia and mild monocytosis. Radiography revealed extensive loss of cortical bone, and replacement with irregular and disorganized bone. There was loss of the normal cortico-medullary distinction, and the medullary cavity had an irregular radiodensity suggestive of osteomyelitis. Surgical curettage and antibiotics did not improve the clinical condition, and amputation was performed. Grossly, the skin over the right tibia was ulcerated with a viscous and granular exudate. At histopathology, there was marked diffuse pyogranulomatous dermatitis, myositis, periostitis and osteomyelitis associated with Splendore-Hoeppli phenomenon. In addition, there was marrow osteoproliferation and multifocal cortical loss, reabsorption, fibroplasia and endosteal bone formation. Gram staining revealed myriad slightly elongated Gram-positive bacteria, arranged in pairs or single chains, confirmed by polymerase chain reaction as Streptococcus species.

Single-Cell RNA Sequencing of Lymph Node Stromal Cells Reveals Niche-Associated Heterogeneity.

PubMed

Rodda, Lauren B; Lu, Erick; Bennett, Mariko L; Sokol, Caroline L; Wang, Xiaoming; Luther, Sanjiv A; Barres, Ben A; Luster, Andrew D; Ye, Chun Jimmie; Cyster, Jason G

2018-05-15

Stromal cells (SCs) establish the compartmentalization of lymphoid tissues critical to the immune response. However, the full diversity of lymph node (LN) SCs remains undefined. Using droplet-based single-cell RNA sequencing, we identified nine peripheral LN non-endothelial SC clusters. Included are the established subsets, Ccl19 hi T-zone reticular cells (TRCs), marginal reticular cells, follicular dendritic cells (FDCs), and perivascular cells. We also identified Ccl19 lo TRCs, likely including cholesterol-25-hydroxylase + cells located at the T-zone perimeter, Cxcl9 + TRCs in the T-zone and interfollicular region, CD34 + SCs in the capsule and medullary vessel adventitia, indolethylamine N-methyltransferase + SCs in the medullary cords, and Nr4a1 + SCs in several niches. These data help define how transcriptionally distinct LN SCs support niche-restricted immune functions and provide evidence that many SCs are in an activated state. Copyright © 2018 Elsevier Inc. All rights reserved.

Radionuclide bone scanning of osteosarcoma: falsely extended uptake patterns.

PubMed

Chew, F S; Hudson, T M

1982-07-01

The pathologic specimens of 18 osteosarcomas of long bones were examined to correlate histologic abnormalities with abnormalities seen on preoperative 99mTc pyrophosphate or methylene diphosphonate bone scans. Seven scans accurately represented the extent of the tumor. Eleven scans disclosed increased activity extending beyond the radiographic abnormalities. In eight of these, there was no occult tumor extension and in the other three, the scan activity did not accurately portray the skip metastases that were present. Therefore, these 11 scans demonstrated the falsely extended pattern of uptake beyond the true limits of the tumors. Pathologic slides were available for 10 of the 11 areas of bone that exhibited extended uptake. In two instances, there was no pathologic abnormality. In the other eight cases we found marrow hyperemia, medullary reactive bone, or periosteal new bone. This is the first description of these histologic abnormalities of medullary bone in areas of extended uptake on radionuclide bone scans.

THE ROLE OF SEROTONIN IN RESPIRATORY FUNCTION AND DYSFUNCTION

PubMed Central

Hilaire, Gérard; Voituron, Nicolas; Menuet, Clément; Ichiyama, Ronaldo M.; Subramanian, Hari H.; Dutschmann, Mathias

2010-01-01

Serotonin (5-HT) is a neuro-modulator–transmitter influencing global brain function. Past and present findings illustrate a prominent role for 5-HT in the modulation of ponto-medullary autonomic circuits. 5-HT is also involved in the control of neurotrophic processes during pre- and postnatal development of neural circuits. The functional implications of 5-HT is particularly illustrated in the alterations to the serotonergic system, as seen in a wide range of neurological disorders. This article reviews the role of 5-HT in the development and control of respiratory networks in the ponto-medullary brainstem. The review further examines the role of 5-HT in breathing disorders occurring at different stages of life, in particular, the neonatal neurodevelopmental diseases such as Rett, sudden infant death and Prader-Willi syndromes, adult diseases such as sleep apnoea and mental illness linked to neurodegeneration. PMID:20801236

Spectrum of Spinal Cord, Spinal Root, and Brain MRI Abnormalities in Congenital Zika Syndrome with and without Arthrogryposis.

PubMed

Aragao, M F V V; Brainer-Lima, A M; Holanda, A C; van der Linden, V; Vasco Aragão, L; Silva Júnior, M L M; Sarteschi, C; Petribu, N C L; Valença, M M

2017-05-01

Arthrogryposis is among the malformations of congenital Zika syndrome. Similar to the brain, there might exist a spectrum of spinal cord abnormalities. The purpose of this study was to explore and describe in detail the MR imaging features found in the spinal cords, nerve roots, and brains of children with congenital Zika syndrome with and without arthrogryposis. Twelve infants with congenital Zika syndrome (4 with arthrogryposis and 8 without) who had undergone brain and spinal cord MR imaging were retrospectively selected. Qualitative and quantitative analyses were performed and compared between groups. At visual inspection, both groups showed reduced thoracic spinal cord thickness: 75% (6/8) of the group without arthrogryposis and 100% (4/4) of the arthrogryposis group. However, the latter had the entire spinal cord reduced and more severely reduced conus medullaris anterior roots (respectively, P = .002 and .007). Quantitative differences were found for conus medullaris base and cervical and lumbar intumescences diameters (respectively, P = .008, .048, .008), with more prominent reduction in arthrogryposis. Periventricular calcifications were more frequent in infants with arthrogryposis ( P = .018). Most infants had some degree of spinal cord thickness reduction, predominant in the thoracic segment (without arthrogryposis) or in the entire spinal cord (with arthrogryposis). The conus medullaris anterior roots were reduced in both groups (thinner in arthrogryposis). A prominent anterior median fissure of the spinal cord was absent in infants without arthrogryposis. Brain stem hypoplasia was present in all infants with arthrogryposis, periventricular calcifications, in the majority, and polymicrogyria was absent. © 2017 by American Journal of Neuroradiology.

Architecture of the human renal inner medulla and functional implications

PubMed Central

Wei, Guojun; Rosen, Seymour; Dantzler, William H.

2015-01-01

The architecture of the inner stripe of the outer medulla of the human kidney has long been known to exhibit distinctive configurations; however, inner medullary architecture remains poorly defined. Using immunohistochemistry with segment-specific antibodies for membrane fluid and solute transporters and other proteins, we identified a number of distinctive functional features of human inner medulla. In the outer inner medulla, aquaporin-1 (AQP1)-positive long-loop descending thin limbs (DTLs) lie alongside descending and ascending vasa recta (DVR, AVR) within vascular bundles. These vascular bundles are continuations of outer medullary vascular bundles. Bundles containing DTLs and vasa recta lie at the margins of coalescing collecting duct (CD) clusters, thereby forming two regions, the vascular bundle region and the CD cluster region. Although AQP1 and urea transporter UT-B are abundantly expressed in long-loop DTLs and DVR, respectively, their expression declines with depth below the outer medulla. Transcellular water and urea fluxes likely decline in these segments at progressively deeper levels. Smooth muscle myosin heavy chain protein is also expressed in DVR of the inner stripe and the upper inner medulla, but is sparsely expressed at deeper inner medullary levels. In rodent inner medulla, fenestrated capillaries abut CDs along their entire length, paralleling ascending thin limbs (ATLs), forming distinct compartments (interstitial nodal spaces; INSs); however, in humans this architecture rarely occurs. Thus INSs are relatively infrequent in the human inner medulla, unlike in the rodent where they are abundant. UT-B is expressed within the papillary epithelium of the lower inner medulla, indicating a transcellular pathway for urea across this epithelium. PMID:26290371

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

PubMed

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.

Influence of physical activity on tibial bone material properties in laying hens

DOE Office of Scientific and Technical Information (OSTI.GOV)

Rodriguez-Navarro, A. B.; McCormack, H. M.; Fleming, R. H.

Laying hens develop a type of osteoporosis that arises from a loss of structural bone, resulting in high incidence of fractures. In this study, a comparison of bone material properties was made for lines of hens created by divergent selection to have high and low bone strength and housed in either individual cages, with restricted mobility, or in an aviary system, with opportunity for increased mobility. Improvement of bone biomechanics in the high line hens and in aviary housing was mainly due to increased bone mass, thicker cortical bone and more medullary bone. However, bone material properties such as corticalmore » and medullary bone mineral composition and crystallinity as well as collagen maturity did not differ between lines. However, bone material properties of birds from the different type of housing were markedly different. The cortical bone in aviary birds had a lower degree of mineralization and bone mineral was less mature and less organized than in caged birds. Here, these differences can be explained by increased bone turnover rates due to the higher physical activity of aviary birds that stimulates bone formation and bone remodeling. Multivariate statistical analyses shows that both cortical and medullary bone contribute to breaking strengthThe cortical thickness was the single most important contributor while its degree of mineralization and porosity had a smaller contribution. Lastly, bone properties had poorer correlations with mechanical properties in cage birds than in aviary birds presumably due to the greater number of structural defects of cortical bone in cage birds.« less

Influence of physical activity on tibial bone material properties in laying hens

DOE PAGES

Rodriguez-Navarro, A. B.; McCormack, H. M.; Fleming, R. H.; ...

2017-11-03

Laying hens develop a type of osteoporosis that arises from a loss of structural bone, resulting in high incidence of fractures. In this study, a comparison of bone material properties was made for lines of hens created by divergent selection to have high and low bone strength and housed in either individual cages, with restricted mobility, or in an aviary system, with opportunity for increased mobility. Improvement of bone biomechanics in the high line hens and in aviary housing was mainly due to increased bone mass, thicker cortical bone and more medullary bone. However, bone material properties such as corticalmore » and medullary bone mineral composition and crystallinity as well as collagen maturity did not differ between lines. However, bone material properties of birds from the different type of housing were markedly different. The cortical bone in aviary birds had a lower degree of mineralization and bone mineral was less mature and less organized than in caged birds. Here, these differences can be explained by increased bone turnover rates due to the higher physical activity of aviary birds that stimulates bone formation and bone remodeling. Multivariate statistical analyses shows that both cortical and medullary bone contribute to breaking strengthThe cortical thickness was the single most important contributor while its degree of mineralization and porosity had a smaller contribution. Lastly, bone properties had poorer correlations with mechanical properties in cage birds than in aviary birds presumably due to the greater number of structural defects of cortical bone in cage birds.« less

Neonatal hyperleptinaemia programmes adrenal medullary function in adult rats: effects on cardiovascular parameters

PubMed Central

Trevenzoli, I H; Valle, M M R; Machado, F B; Garcia, R M G; Passos, M C F; Lisboa, P C; Moura, E G

2007-01-01

Epidemiological studies have shown a strong correlation between stressful events (nutritional, hormonal or environmental) in early life and development of adult diseases such as obesity, diabetes and cardiovascular failure. It is known that gestation and lactation are crucial periods for healthy growth in mammals and that the sympathoadrenal system is markedly influenced by environmental conditions during these periods. We previously demonstrated that neonatal hyperleptinaemia in rats programmes higher body weight, higher food intake and hypothalamic leptin resistance in adulthood. Using this model of programming, we investigated adrenal medullary function and effects on cardiovascular parameters in male rats in adulthood. Leptin treatment during the first 10 days of lactation (8μg 100 g−1 day−1, s.c.) resulted in lower body weight (6.5%, P < 0.05), hyperleptinaemia (10-fold, P < 0.05) and higher catecholamine content in adrenal glands (18.5%, P < 0.05) on the last day of treatment. In adulthood (150 days), the rats presented higher body weight (5%, P < 0.05), adrenal catecholamine content (3-fold, P < 0.05), tyrosine hydroxylase expression (35%, P < 0.05) and basal and caffeine-stimulated catecholamine release (53% and 100%, respectively, P < 0.05). Systolic blood pressure and heart rate were also higher in adult rats (7% and 6%, respectively, P < 0.05). Our results show that hyperleptinaemia in early life increases adrenal medullary function in adulthood and that this may alter cardiovascular parameters. Thus, we suggest that imprinting factors which increase leptin and catecholamine levels during the neonatal period could be involved in development of adult chronic diseases. PMID:17218354

Treatment of giant intradural (perimedullary) arteriovenous fistulas.

PubMed

Halbach, V V; Higashida, R T; Dowd, C F; Fraser, K W; Edwards, M S; Barnwell, S L

1993-12-01

Ten patients with giant intradural spinal arteriovenous fistulas (perimedullary Types II and III) were treated with embolization alone (three patients) or in combination with surgery (seven patients). Their ages at the time of treatment ranged from 2 to 40 years, with a mean of 19.5 years. The indications for treatment included progressive myelopathy in five patients, spinal subarachnoid hemorrhage in four, and acute paraplegia in one. Associated conditions included Rendu-Osler-Weber syndrome in two patients, and Cobb's syndrome in two patients. In one patient, the cause of the fistula may have been related to epidural anesthesia traumatizing a low tethered cord. Angiographically, the fistulas were subclassified in three groups: a single-hole fistula supplied by a single feeding medullary artery (three patients); a single-hole fistula supplied by multiple medullary arteries (three patients); and multiple separate fistulas supplied by multiple medullary arteries (four patients). Eight patients were classified as perimedullary Type III and two as perimedullary Type II. Embolic agents were delivered from transarterial routes in 14 procedures and transvenous routes in 2 procedures. A total of 16 embolizations and 8 operations were performed in 10 patients. Seven patients were cured of their fistula (as demonstrated by angiography), two patients had 5% residual filling and are scheduled for future therapy. One refused a follow-up angiographic examination. Complications related to embolization included rupture of the anterior spinal artery by a detachable balloon, resulting in transient worsening of paraplegia with recovery to baseline. Transient worsening of symptoms after surgery was common, but all patients returned to baseline or better. Dramatic improvement was observed in four patients.(ABSTRACT TRUNCATED AT 250 WORDS)

Meth math: modeling temperature responses to methamphetamine.

PubMed

Molkov, Yaroslav I; Zaretskaia, Maria V; Zaretsky, Dmitry V

2014-04-15

Methamphetamine (Meth) can evoke extreme hyperthermia, which correlates with neurotoxicity and death in laboratory animals and humans. The objective of this study was to uncover the mechanisms of a complex dose dependence of temperature responses to Meth by mathematical modeling of the neuronal circuitry. On the basis of previous studies, we composed an artificial neural network with the core comprising three sequentially connected nodes: excitatory, medullary, and sympathetic preganglionic neuronal (SPN). Meth directly stimulated the excitatory node, an inhibitory drive targeted the medullary node, and, in high doses, an additional excitatory drive affected the SPN node. All model parameters (weights of connections, sensitivities, and time constants) were subject to fitting experimental time series of temperature responses to 1, 3, 5, and 10 mg/kg Meth. Modeling suggested that the temperature response to the lowest dose of Meth, which caused an immediate and short hyperthermia, involves neuronal excitation at a supramedullary level. The delay in response after the intermediate doses of Meth is a result of neuronal inhibition at the medullary level. Finally, the rapid and robust increase in body temperature induced by the highest dose of Meth involves activation of high-dose excitatory drive. The impairment in the inhibitory mechanism can provoke a life-threatening temperature rise and makes it a plausible cause of fatal hyperthermia in Meth users. We expect that studying putative neuronal sites of Meth action and the neuromediators involved in a detailed model of this system may lead to more effective strategies for prevention and treatment of hyperthermia induced by amphetamine-like stimulants.

Rapamycin inhibition of mTORC1 reverses lithium-induced proliferation of renal collecting duct cells

PubMed Central

Gao, Yang; Romero-Aleshire, Melissa J.; Cai, Qi; Price, Theodore J.

2013-01-01

Nephrogenic diabetes insipidus (NDI) is the most common renal side effect in patients undergoing lithium therapy for bipolar affective disorders. Approximately 2 million US patients take lithium of whom ∼50% will have altered renal function and develop NDI (2, 37). Lithium-induced NDI is a defect in the urinary concentrating mechanism. Lithium therapy also leads to proliferation and abundant renal cysts (microcysts), commonly in the collecting ducts of the cortico-medullary region. The mTOR pathway integrates nutrient and mitogen signals to control cell proliferation and cell growth (size) via the mTOR Complex 1 (mTORC1). To address our hypothesis that mTOR activation may be responsible for lithium-induced proliferation of collecting ducts, we fed mice lithium chronically and assessed mTORC1 signaling in the renal medulla. We demonstrate that mTOR signaling is activated in the renal collecting ducts of lithium-treated mice; lithium increased the phosphorylation of rS6 (Ser240/Ser244), p-TSC2 (Thr1462), and p-mTOR (Ser2448). Consistent with our hypothesis, treatment with rapamycin, an allosteric inhibitor of mTOR, reversed lithium-induced proliferation of medullary collecting duct cells and reduced levels of p-rS6 and p-mTOR. Medullary levels of p-GSK3β were increased in the renal medullas of lithium-treated mice and remained elevated following rapamycin treatment. However, mTOR inhibition did not improve lithium-induced NDI and did not restore the expression of collecting duct proteins aquaporin-2 or UT-A1. PMID:23884148

Poorly Differentiated Medullary Phenotype Predicts Poor Survival in Early Lymph Node-Negative Gastro-Esophageal Adenocarcinomas.

PubMed

Treese, Christoph; Sanchez, Pedro; Grabowski, Patricia; Berg, Erika; Bläker, Hendrik; Kruschewski, Martin; Haase, Oliver; Hummel, Michael; Daum, Severin

2016-01-01

5-year survival rate in patients with early adenocarcinoma of the gastro-esophageal junction or stomach (AGE/S) in Caucasian patients is reported to be 60-80%. We aimed to identify prognostic markers for patients with UICC-I without lymph-node involvement (N0). Clinical data and tissue specimen from patients with AGE/S stage UICC-I-N0, treated by surgery only, were collected retrospectively. Tumor size, lymphatic vessel or vein invasion, grading, classification systems (WHO, Lauren, Ming), expression of BAX, BCL-2, CDX2, Cyclin E, E-cadherin, Ki-67, TP53, TP21, SHH, Survivin, HIF1A, TROP2 and mismatch repair deficiency were analyzed using tissue microarrays and correlated with overall and tumor related survival. 129 patients (48 female) with a mean follow-up of 129.1 months were identified. 5-year overall survival was 83.9%, 5-year tumor related survival was 95.1%. Poorly differentiated medullary cancer subtypes (p<0.001) and positive vein invasion (p<0.001) were identified as risk factors for decreased overall-and tumor related survival. Ki-67 (p = 0.012) and TP53 mutation (p = 0.044) were the only immunohistochemical markers associated with worse overall survival but did not reach significance for decreased tumor related survival. In the presented study patients with AGE/S in stage UICC-I-N0 had a better prognosis as previously reported for Caucasian patients. Poorly differentiated medullary subtype was associated with reduced survival and should be considered when studying prognosis in these patients.

Meth math: modeling temperature responses to methamphetamine

PubMed Central

Molkov, Yaroslav I.; Zaretskaia, Maria V.

2014-01-01

Methamphetamine (Meth) can evoke extreme hyperthermia, which correlates with neurotoxicity and death in laboratory animals and humans. The objective of this study was to uncover the mechanisms of a complex dose dependence of temperature responses to Meth by mathematical modeling of the neuronal circuitry. On the basis of previous studies, we composed an artificial neural network with the core comprising three sequentially connected nodes: excitatory, medullary, and sympathetic preganglionic neuronal (SPN). Meth directly stimulated the excitatory node, an inhibitory drive targeted the medullary node, and, in high doses, an additional excitatory drive affected the SPN node. All model parameters (weights of connections, sensitivities, and time constants) were subject to fitting experimental time series of temperature responses to 1, 3, 5, and 10 mg/kg Meth. Modeling suggested that the temperature response to the lowest dose of Meth, which caused an immediate and short hyperthermia, involves neuronal excitation at a supramedullary level. The delay in response after the intermediate doses of Meth is a result of neuronal inhibition at the medullary level. Finally, the rapid and robust increase in body temperature induced by the highest dose of Meth involves activation of high-dose excitatory drive. The impairment in the inhibitory mechanism can provoke a life-threatening temperature rise and makes it a plausible cause of fatal hyperthermia in Meth users. We expect that studying putative neuronal sites of Meth action and the neuromediators involved in a detailed model of this system may lead to more effective strategies for prevention and treatment of hyperthermia induced by amphetamine-like stimulants. PMID:24500434

Kidney outer medulla mitochondria are more efficient compared to cortex mitochondria as a strategy to sustain ATP production in a suboptimal environment.

PubMed

Schiffer, Tomas A; Gustafsson, Håkan; Palm, Fredrik

2018-05-30

The kidneys receive approximately 25% of cardiac output, which is a prerequisite in order to maintain sufficient glomerular filtration rate. However, both intrarenal regional renal blood flow and tissue oxygen levels are heterogeneous with decreasing levels in the inner part of the medulla. These differences in combination with the heterogeneous metabolic activity of the different nephron segment located in the different parts of the kidney may constitute a functional problem when challenged. The proximal tubule and the medullary thick ascending limb of Henle are considered to have the highest metabolic rate, which is relating to the high mitochondria content needed to sustain sufficient ATP production from oxidative phosphorylation in order to support high electrolyte transport activity in these nephron segments. Interestingly, the cells located in kidney medulla functions at the verge of hypoxia and the mitochondria may have adapted to the surrounding environment. However, little is known about intrarenal differences in mitochondria function. We therefore investigated functional differences between mitochondria isolated from kidney cortex and medulla of healthy normoglycemic rats were estimated using high-resolution respirometry. The results demonstrate that medullary mitochondria had a higher degree of coupling, are more efficient and have higher oxygen affinity, which would make them more suitable to function in an environment with limited oxygen supply. Furthermore, these results support the hypothesis that mitochondria of medullary cells have adapted to the normal hypoxic in vivo situation as a strategy of sustaining ATP production in a suboptimal environment.

Bilateral medial medullary infarction: a systematic review.

PubMed

Pongmoragot, Jitphapa; Parthasarathy, Sujatha; Selchen, Daniel; Saposnik, Gustavo

2013-08-01

Bilateral infarction of the medial medulla (MMI) is rare. Limited information is available on clinical characteristics, etiology, and prognosis. High-resolution neuroimaging has a major role in elucidating the underlying stroke mechanism. The aim of this systematic review was to analyze the clinical presentations, stroke mechanisms, and outcomes in patients with bilateral MMI. We performed a systematic review of the literature from 1992-2011 that reported on clinical presentations, stroke mechanism, and/or outcomes in patients with magnetic resonance imaging-proven bilateral MMI. Medline, EMBASE, and Web of Science Scholars Portal were searched without language restriction. Two reviewers independently assessed identified studies to determine eligibility, validity, and quality. The primary outcome was inpatient mortality; a secondary outcome was case fatality at 12 months. We identified 138 articles from Medline, EMBASE, and Scholars Portal including the MeSH terms "brainstem infarction," "medulla," and "bilateral." Twenty-nine articles met our inclusion criteria, including a total of 38 cases with bilateral MMI, and included in our study. These 38 patients had a mean age of 62.2 years and were predominately male (74.2%). The most common clinical presentations were motor weakness in 78.4%, dysarthria in 48.6%, and hypoglossal palsy in 40.5%. The most common vascular pathology was vertebral artery atherosclerosis, in 38.5%. The clinical outcome was poor (mortality, 23.8%; dependency, 61.9%). Bilateral medial medullary infarction is a rare stroke syndrome. Clinical presentations were mostly rostral medullary lesions. Large-artery atherosclerosis and branch disease were the most common stroke mechanisms. The clinical outcome was usually poor. Copyright © 2013 National Stroke Association. Published by Elsevier Inc. All rights reserved.

Medial medullary infarction: clinical, imaging, and outcome study in 86 consecutive patients.

PubMed

Kim, Jong S; Han, Young S

2009-10-01

Clinical-imaging correlation and long-term clinical outcomes remain to be investigated in medial medullary infarction (MMI). We studied clinical, MRI, and angiographic data of 86 consecutive MMI patients. The lesions were correlated with clinical findings, and long-term outcomes, divided into mild and severe (modified Rankin scale >3), were assessed by telephone interview. Central poststroke pain (CPSP) was defined as persistent pain with visual numeric scale > or = 4. The lesions were located mostly in the rostral medulla (rostral 76%, rostral+middle 16%), while ventro-dorsal lesion patterns include ventral (V, 20%), ventral+middle (VM, 33%), and ventral+middle+dorsal (VMD, 41%). Clinical manifestations included motor dysfunction in 78 patients (91%), sensory dysfunction in 59 (73%), and vertigo/dizziness in 51 (59%), each closely related to involvement of ventral, middle, and dorsal portions, respectively (P<0.001, each). Vertebral artery (VA) atherosclerotic disease relevant to the infarction occurred in 53 (62%) patients, mostly producing atheromatous branch occlusion (ABO). Small vessel disease (SVD) occurred in 24 (28%) patients. ABO was more closely related to VMD (versus V+VM) than was SVD (P=0.035). During follow-up (mean 71 months), 11 patients died, and recurrent strokes occurred in 11. Old age (P=0.001) and severe motor dysfunction at admission (P=0.001) were factors predicting poor prognosis. CPSP, occurring in 21 patients, was closely (P=0.013) related to poor clinical outcome. MMI usually presents with a rostral medullary lesion, with a good clinical ventro-dorsal imaging correlation, caused most frequently by ABO followed by SVD. A significant proportion of patients remain dependent or have CPSP.

Renal Atp6ap2/(Pro)renin Receptor Is Required for Normal Vacuolar H+-ATPase Function but Not for the Renin-Angiotensin System.

PubMed

Trepiccione, Francesco; Gerber, Simon D; Grahammer, Florian; López-Cayuqueo, Karen I; Baudrie, Véronique; Păunescu, Teodor G; Capen, Diane E; Picard, Nicolas; Alexander, R Todd; Huber, Tobias B; Chambrey, Regine; Brown, Dennis; Houillier, Pascal; Eladari, Dominique; Simons, Matias

2016-11-01

ATPase H + -transporting lysosomal accessory protein 2 (Atp6ap2), also known as the (pro)renin receptor, is a type 1 transmembrane protein and an accessory subunit of the vacuolar H + -ATPase (V-ATPase) that may also function within the renin-angiotensin system. However, the contribution of Atp6ap2 to renin-angiotensin-dependent functions remains unconfirmed. Using mice with an inducible conditional deletion of Atp6ap2 in mouse renal epithelial cells, we found that decreased V-ATPase expression and activity in the intercalated cells of the collecting duct impaired acid-base regulation by the kidney. In addition, these mice suffered from marked polyuria resistant to desmopressin administration. Immunoblotting revealed downregulation of the medullary Na + -K + -2Cl - cotransporter NKCC2 in these mice compared with wild-type mice, an effect accompanied by a hypotonic medullary interstitium and impaired countercurrent multiplication. This phenotype correlated with strong autophagic defects in epithelial cells of medullary tubules. Notably, cells with high accumulation of the autophagosomal substrate p62 displayed the strongest reduction of NKCC2 expression. Finally, nephron-specific Atp6ap2 depletion did not affect angiotensin II production, angiotensin II-dependent BP regulation, or sodium handling in the kidney. Taken together, our results show that nephron-specific deletion of Atp6ap2 does not affect the renin-angiotensin system but causes a combination of renal concentration defects and distal renal tubular acidosis as a result of impaired V-ATPase activity. Copyright © 2016 by the American Society of Nephrology.

Production and actions of the anandamide metabolite prostamide E2 in the renal medulla.

PubMed

Ritter, Joseph K; Li, Cao; Xia, Min; Poklis, Justin L; Lichtman, Aron H; Abdullah, Rehab A; Dewey, William L; Li, Pin-Lan

2012-09-01

Medullipin has been proposed to be an antihypertensive lipid hormone released from the renal medulla in response to increased arterial pressure and renal medullary blood flow. Because anandamide (AEA) possesses characteristics of this purported hormone, the present study tested the hypothesis that AEA or one of its metabolites represents medullipin. AEA was demonstrated to be enriched in the kidney medulla compared with cortex. Western blotting and enzymatic analyses of renal cortical and medullary microsomes revealed opposite patterns of enrichment of two AEA-metabolizing enzymes, with fatty acid amide hydrolase higher in the renal cortex and cyclooxygenase-2 (COX-2) higher in the renal medulla. In COX-2 reactions with renal medullary microsomes, prostamide E2, the ethanolamide of prostaglandin E₂, was the major product detected. Intramedullarily infused AEA dose-dependently increased urine volume and sodium and potassium excretion (15-60 nmol/kg/min) but had little effect on mean arterial pressure (MAP). The renal excretory effects of AEA were blocked by intravenous infusion of celecoxib (0.1 μg/kg/min), a selective COX-2 inhibitor, suggesting the involvement of a prostamide intermediate. Plasma kinetic analysis revealed longer elimination half-lives for AEA and prostamide E2 compared with prostaglandin E₂. Intravenous prostamide E2 reduced MAP and increased renal blood flow (RBF), actions opposite to those of angiotensin II. Coinfusion of prostamide E2 inhibited angiotensin II effects on MAP and RBF. These results suggest that AEA and/or its prostamide metabolites in the renal medulla may represent medullipin and function as a regulator of body fluid and MAP.

Impaired neural structure and function contributing to autonomic symptoms in congenital central hypoventilation syndrome.

PubMed

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.

Hypofractionated Radiation Therapy After Mastectomy in Preventing Recurrence in Patients With Stage IIa-IIIa Breast Cancer

ClinicalTrials.gov

2018-06-08

Ductal Breast Carcinoma; Invasive Breast Carcinoma; Lobular Breast Carcinoma; Medullary Breast Carcinoma; Stage II Breast Cancer; Stage IIA Breast Cancer; Stage IIB Breast Cancer; Stage IIIA Breast Cancer; Tubular Breast Carcinoma

A novel slice preparation to study medullary oromotor and autonomic circuits in vitro

PubMed Central

Nasse, Jason S.

2014-01-01

Background The medulla is capable of controlling and modulating ingestive behavior and gastrointestinal function. These two functions, which are critical to maintaining homeostasis, are governed by an interconnected group of nuclei dispersed throughout the medulla. As such, in vitro experiments to study the neurophysiologic details of these connections have been limited by spatial constraints of conventional slice preparations. New method This study demonstrates a novel method of sectioning the medulla so that sensory, integrative, and motor nuclei that innervate the gastrointestinal tract and the oral cavity remain intact. Results: Immunohistochemical staining against choline-acetyl-transferase and dopamine-β-hydroxylase demonstrated that within a 450 μm block of tissue we are able to capture sensory, integrative and motor nuclei that are critical to oromotor and gastrointestinal function. Within slice tracing shows that axonal projections from the NST to the reticular formation and from the reticular formation to the hypoglossal motor nucleus (mXII) persist. Live-cell calcium imaging of the slice demonstrates that stimulation of either the rostral or caudal NST activates neurons throughout the NST, as well as the reticular formation and mXII. Comparison with existing methods This new method of sectioning captures a majority of the nuclei that are active when ingesting a meal. Tradition planes of section, i.e. coronal, horizontal or sagittal, contain only a limited portion of the substrate. Conclusions Our results demonstrate that both anatomical and physiologic connections of oral and visceral sensory nuclei that project to integrative and motor nuclei remain intact with this new plane of section. PMID:25196216

Select spinal lesions reveal multiple ascending pathways in the rat conveying input from the male genitalia

PubMed Central

Hubscher, C H; Reed, W R; Kaddumi, E G; Armstrong, J E; Johnson, R D

2010-01-01

The specific white matter location of all the spinal pathways conveying penile input to the rostral medulla is not known. Our previous studies using rats demonstrated the loss of low but not high threshold penile inputs to medullary reticular formation (MRF) neurons after acute and chronic dorsal column (DC) lesions of the T8 spinal cord and loss of all penile inputs after lesioning the dorsal three-fifths of the cord. In the present study, select T8 lesions were made and terminal electrophysiological recordings were performed 45–60 days later in a limited portion of the nucleus reticularis gigantocellularis (Gi) and Gi pars alpha. Lesions included subtotal dorsal hemisections that spared only the lateral half of the dorsal portion of the lateral funiculus on one side, dorsal and over-dorsal hemisections, and subtotal transections that spared predominantly just the ventromedial white matter. Electrophysiological data for 448 single unit recordings obtained from 32 urethane-anaesthetized rats, when analysed in groups based upon histological lesion reconstructions, revealed (1) ascending bilateral projections in the dorsal, dorsolateral and ventrolateral white matter of the spinal cord conveying information from the male external genitalia to MRF, and (2) ascending bilateral projections in the ventrolateral white matter conveying information from the pelvic visceral organs (bladder, descending colon, urethra) to MRF. Multiple spinal pathways from the penis to the MRF may correspond to different functions, including those processing affective/pleasure/motivational, nociception, and mating-specific (such as for erection and ejaculation) inputs. PMID:20142271

Photostimulation of Phox2b medullary neurons activates cardiorespiratory function in conscious rats.

PubMed

Kanbar, Roy; Stornetta, Ruth L; Cash, Devin R; Lewis, Stephen J; Guyenet, Patrice G

2010-11-01

Hypoventilation is typically treated with positive pressure ventilation or, in extreme cases, by phrenic nerve stimulation. This preclinical study explores whether direct stimulation of central chemoreceptors could be used as an alternative method to stimulate breathing. To determine whether activation of the retrotrapezoid nucleus (RTN), which is located in the rostral ventrolateral medulla (RVLM), stimulates breathing with appropriate selectivity. A lentivirus was used to induce expression of the photoactivatable cationic channel channelrhodopsin-2 (ChR2) by RVLM Phox2b-containing neurons, a population that consists of central chemoreceptors (the ccRTN neurons) and blood pressure (BP)-regulating neurons (the C1 cells). The transfected neurons were activated with pulses of laser light. Respiratory effects were measured by plethysmography or diaphragmatic EMG recording and cardiovascular effects by monitoring BP, renal sympathetic nerve discharge, and the baroreflex. The RVLM contained 600 to 900 ChR2-transfected neurons (63% C1, 37% ccRTN). RVLM photostimulation significantly increased breathing rate (+42%), tidal volume (21%), minute volume (68%), and peak expiratory flow (48%). Photostimulation increased diaphragm EMG amplitude (19%) and frequency (21%). Photostimulation increased BP (4 mmHg) and renal sympathetic nerve discharge (43%) while decreasing heart rate (15 bpm). Photostimulation of ChR2-transfected RVLM Phox2b neurons produces a vigorous stimulation of breathing accompanied by a small sympathetically mediated increase in BP. These results demonstrate that breathing can be relatively selectively activated in resting unanesthetized mammals via optogenetic manipulation of RVLM neurons presumed to be central chemoreceptors. This methodology could perhaps be used in the future to enhance respiration in humans.

Fine structure of the uterus in tapeworm Tetrabothrius erostris (Cestoda: Tetrabothriidea).

PubMed

Korneva, Janetta V; Jones, Malcolm K; Kuklin, Vadim V

2014-12-01

The uterine organization in Tetrabothrius erostris (Tetrabothriidea) was investigated by the methods of transmission and scanning electron microscopy. In sexually mature proglottids, the uterine wall consists of a syncytial epithelium (1.4-2.5 μm thick, except in regions containing nuclei). The ribosomes, mitochondria and numerous cisternae of granular endoplasmic reticulum with concentric or parallel profiles with electron lucent material are observed in the epithelium. The uterine wall is characterized by the abundance of lipid droplets that are localized inside the long protrusions of the uterine epithelium (called fungiform papillae) up to 15-17 μm and in the surrounding medullary parenchyma. The protrusions with lipid droplets in the proximal ends of the uterus are located closely to each other. A basal matrix (up to 0.6 μm thick) supports the uterine epithelium. The musculature consisting of 1-2 muscle layers is well developed; large myocytons are connected with the myofibrils and have a nucleus that reaches 4 μm in size. In gravid proglottids, the epithelium without nuclei is reduced to 0.2-1.6 μm thick. The number of protrusions of the uterine epithelium and lipid droplets in the epithelial layer decreases. Sparse small muscle bundles underlay the uterine wall at this stage; the basal matrix is feebly marked. The matrotrophy or the support by nutrition from the parent organism to embryos is discussed for T. erostris which belongs to oligolecital cestodes and possesses numerous lipid droplets in the uterine wall during the development of embryos.

A novel slice preparation to study medullary oromotor and autonomic circuits in vitro.

PubMed

Nasse, Jason S

2014-11-30

The medulla is capable of controlling and modulating ingestive behavior and gastrointestinal function. These two functions, which are critical to maintaining homeostasis, are governed by an interconnected group of nuclei dispersed throughout the medulla. As such, in vitro experiments to study the neurophysiologic details of these connections have been limited by spatial constraints of conventional slice preparations. This study demonstrates a novel method of sectioning the medulla so that sensory, integrative, and motor nuclei that innervate the gastrointestinal tract and the oral cavity remain intact. Immunohistochemical staining against choline-acetyl-transferase and dopamine-β-hydroxylase demonstrated that within a 450 μm block of tissue we are able to capture sensory, integrative and motor nuclei that are critical to oromotor and gastrointestinal function. Within slice tracing shows that axonal projections from the NST to the reticular formation and from the reticular formation to the hypoglossal motor nucleus (mXII) persist. Live-cell calcium imaging of the slice demonstrates that stimulation of either the rostral or caudal NST activates neurons throughout the NST, as well as the reticular formation and mXII. This new method of sectioning captures a majority of the nuclei that are active when ingesting a meal. Tradition planes of section, i.e. coronal, horizontal or sagittal, contain only a limited portion of the substrate. Our results demonstrate that both anatomical and physiologic connections of oral and visceral sensory nuclei that project to integrative and motor nuclei remain intact with this new plane of section. Published by Elsevier B.V.

Studies on the cellular localization of spinal cord substance P receptors.

PubMed

Helke, C J; Charlton, C G; Wiley, R G

1986-10-01

Substance P-immunoreactivity and specific substance P binding sites are present in the spinal cord. Receptor autoradiography showed the discrete localization of substance P binding sites in both sensory and motor regions of the spinal cord and functional studies suggested an important role for substance P receptor activation in autonomic outflow, nociception, respiration and somatic motor function. In the current studies, we investigated the cellular localization of substance P binding sites in rat spinal cord using light microscopic autoradiography combined with several lesioning techniques. Unilateral injections of the suicide transport agent, ricin, into the superior cervical ganglion reduced substance P binding and cholinesterase-stained preganglionic sympathetic neurons in the intermediolateral cell column. However, unilateral electrolytic lesions of ventral medullary substance P neurons which project to the intermediolateral cell column did not alter the density of substance P binding in the intermediolateral cell column. Likewise, 6-hydroxydopamine and 5,7-dihydroxytryptamine, which destroy noradrenergic and serotonergic nerve terminals, did not reduce the substance P binding in the intermediolateral cell column. It appears, therefore, that the substance P binding sites are located postsynaptically on preganglionic sympathetic neurons rather than presynaptically on substance P-immunoreactive processes (i.e. as autoreceptors) or on monoamine nerve terminals. Unilateral injections of ricin into the phrenic nerve resulted in the unilateral destruction of phrenic motor neurons in the cervical spinal cord and caused a marked reduction in the substance P binding in the nucleus. Likewise, sciatic nerve injections of ricin caused a loss of associated motor neurons in the lateral portion of the ventral horn of the lumbar spinal cord and a reduction in the substance P binding. Sciatic nerve injections of ricin also destroyed afferent nerves of the associated dorsal root ganglia and increased the density of substance P binding in the dorsal horn. Capsaicin, which destroys small diameter primary sensory neurons, similarly increased the substance P binding in the dorsal horn. These studies show that the cellular localization of substance P binding sites can be determined by analysis of changes in substance P binding to discrete regions of spinal cord after selective lesions of specific groups of neurons. The data show the presence of substance P binding sites on preganglionic sympathetic neurons in the intermediolateral cell column and on somatic motor neurons in the ventral horn, including the phrenic motor nucleus.(ABSTRACT TRUNCATED AT 400 WORDS)

Thyroid Cancer—Patient Version

Cancer.gov

Thyroid cancer can be of four main types. Anaplastic thyroid cancer is hard to cure with current treatments, whereas papillary (the most common), follicular, and medullary thyroid cancer can usually be cured. Start here to find information on thyroid cancer treatment, screening, research, and statistics.

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

PubMed Central

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), and glutamine and dopamine were significantly below pre-CBD levels (P < 0.05). Serotonin, substance P, and epinephrine were variable but not significantly (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

Role of whole-body 64-slice multidetector computed tomography in treatment planning for multiple myeloma.

PubMed

Razek, Ahmed Abdel Khalek Abdel; Ezzat, Amany; Azmy, Emad; Tharwat, Nehal

2013-08-01

The authors evaluated the role of whole-body 64-slice multidetector computed tomography (WB-MDCT) in treatment planning for multiple myeloma. This was a prospective study of 28 consecutive patients with multiple myeloma (19 men, nine women; age range, 51-73 years; mean age, 60 years) who underwent WB-MDCT and conventional radiography (CR) of the skeleton. The images were interpreted for the presence of bony lesions, medullary lesions, fractures and extraosseous lesions. We evaluated any changes in treatment planning as a result of WB-MDCT findings. WB-MDCT was superior to CR for detecting bony lesions (p=0.001), especially of the spine (p=0.001) and thoracic cage (p=0.006). WB-MDCT upstaged 14 patients, with a significant difference in staging (p=0.002) between WB-MDCT and CR. Medullary involvement either focal (n=6) or diffuse (n=3) had a positive correlation with the overall score (r=0.790) and stage (r=0.618) of disease. Spine fractures were better detected at WB-MDCT (n=4) than at CR (n=2). Extraosseous soft tissue lesions (n=7) were detected only at WB-MDCT. Findings detected at the WB-MDCT led to changes in the patient's treatment plan in 39% of cases. Upstaging of seven patients (25%) altered the medical treatment plan, and four of 28 (14%) patients required additional radiotherapy (7%) and vertebroplasty (7%). We conclude that WB-MDCT has an impact on treatment planning and prognosis in patients with multiple myeloma, as it has high rate of detecting cortical and medullary bone lesions, spinal fracture and extraosseous lesions. This information may alter treatment planning in multiple myeloma due to disease upstaging and detection of spine fracture and extraosseous spinal lesions.

Cambial variations of Piper (Piperaceae) in Taiwan.

PubMed

Yang, Sheng-Zehn; Chen, Po-Hao

2017-12-01

Cambial variations in lianas of Piperaceae in Taiwan have not been studied previously. The stem anatomy of seven Piper species from Taiwan was examined to document cambial variations and better distinguish the species when leaves are absent. A key for the seven species is provided, based on the internal stem anatomy. The seven Piper species climb via adventitious roots, and in cross section, the stems were generally eccentric and oblate, although a transversely elliptic stem was found in P. kadsura (Choisy) Ohwi and P. sintenense Hatus. A cambial variant with secondary growth of external primary vascular bundles and xylem in plates was observed in all species except Piper betle L., which developed another cambium variant with xylem furrowed deeply by parenchyma proliferation. The sclerenchymatous ring surrounding the medullary vascular bundles was always continuous except in P. betle, where it was discontinuous. Mucilage canals varied from absent to present in the center of the pith, or present in the pith and inner cortex. Different sizes of vessels dispersed throughout the stem were ring or diffuse porous. The numbers of medullary and peripheral vascular bundles were distinctive and the widths of rays were noticeably different in each species. Differences in the growth rate of the medullary vascular bundles produced two development types of vascular bundles, although in both types, the peripheral vascular bundles gradually lengthen and become separated from each other by wide rays. We documented the internal stem anatomy of six previously unstudied species of Piper, including three endemic species, P. kwashoense Hayata, P. sintenense, and P. taiwanense Lin and Lu, and found that P. betle had deeply furrowed xylem, which had not been reported for the species before. The descriptions and photographs of seven Piper species will also provide a basis for further morphological studies.

Periconal arterial anastomotic circle and posterior lumbosacral watershed zone of the spinal cord.

PubMed

Gailloud, Philippe; Gregg, Lydia; Galan, Peter; Becker, Daniel; Pardo, Carlos

2015-11-01

The existence of spinal cord watershed territories was suggested in the 1950s. Segmental infarcts within the junctional territories of adjacent radiculomedullary contributors and isolated spinal gray matter ischemia constitute two well-recognized types of watershed injury. This report describes the existence of another watershed territory related to the particular configuration of the spinal vasculature in the region of the conus medullaris. The anatomical bases underlying the concept of a posterior lumbosacral watershed zone are demonstrated with angiographic images obtained in a 16-year-old child. The clinical importance of this watershed zone is illustrated with MRI and angiographic data of three patients with a conus medullaris infarction. In all three cases of spinal ischemia an intersegmental artery providing a significant radiculomedullary contribution for the lower cord was compromised by a compressive mechanism responsible for decreased spinal cord perfusion (diaphragmatic crus syndrome in two cases, disk herniation in one). The ischemic injury, located at the junction of the anterior and posterior spinal artery territories along the dorsal aspect of the conus medullaris, was consistent with a watershed mechanism. This zone is at risk because of the caudocranial direction of flow within the most caudal segment of the posterior spinal arterial network which, from a functional standpoint, depends on the anterior spinal artery. The posterior thoracolumbar watershed zone of the spinal cord represents an area at increased risk of ischemic injury, particularly in the context of partial flow impairment related to arterial compression mechanisms. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.

A computational model for simulating solute transport and oxygen consumption along the nephrons

PubMed Central

Vallon, Volker; Edwards, Aurélie

2016-01-01

The goal of this study was to investigate water and solute transport, with a focus on sodium transport (TNa) and metabolism along individual nephron segments under differing physiological and pathophysiological conditions. To accomplish this goal, we developed a computational model of solute transport and oxygen consumption (QO2) along different nephron populations of a rat kidney. The model represents detailed epithelial and paracellular transport processes along both the superficial and juxtamedullary nephrons, with the loop of Henle of each model nephron extending to differing depths of the inner medulla. We used the model to assess how changes in TNa may alter QO2 in different nephron segments and how shifting the TNa sites alters overall kidney QO2. Under baseline conditions, the model predicted a whole kidney TNa/QO2, which denotes the number of moles of Na+ reabsorbed per moles of O2 consumed, of ∼15, with TNa efficiency predicted to be significantly greater in cortical nephron segments than in medullary segments. The TNa/QO2 ratio was generally similar among the superficial and juxtamedullary nephron segments, except for the proximal tubule, where TNa/QO2 was ∼20% higher in superficial nephrons, due to the larger luminal flow along the juxtamedullary proximal tubules and the resulting higher, flow-induced transcellular transport. Moreover, the model predicted that an increase in single-nephron glomerular filtration rate does not significantly affect TNa/QO2 in the proximal tubules but generally increases TNa/QO2 along downstream segments. The latter result can be attributed to the generally higher luminal [Na+], which raises paracellular TNa. Consequently, vulnerable medullary segments, such as the S3 segment and medullary thick ascending limb, may be relatively protected from flow-induced increases in QO2 under pathophysiological conditions. PMID:27707705

Retention of differentiated characteristics by cultures of defined rabbit kidney epithelia.

PubMed

Wilson, P D; Anderson, R J; Breckon, R D; Nathrath, W; Schrier, R W

1987-02-01

Rabbit nephron segments of proximal convoluted tubules (PCT); proximal straight tubules (PST); cortical and medullary thick ascending limbs of Henle's loop (CAL, MAL); and cortical, outer medullary, and inner medullary collecting tubules (CCT, OMCT, IMCT) were individually microdissected and grown in monolayer culture in hormone supplemented, defined media. Factors favoring a rapid onset of proliferation included young donor age, distal tubule origin, and the addition of 3% fetal calf serum to the medium. All primary cultures had polarized morphology with apical microvilli facing the medium and basement membrane-like material adjacent to the dish. Differentiated properties characteristic of the tubular epithelium of origin retained in cultures included ultrastructural characteristics and cytochemically demonstrable marker enzyme proportions. PCT and PST were rich in alkaline phosphatase; CAL stained strongly for NaK-ATPase; CCT contained two cell populations with regard to cytochrome oxidase reaction. A CCT-specific anti-keratin antibody (aLEA) was immunolocalized in CCT cultures, and a PST cytokeratin antibody stained PST cultures. The biochemical response of adenylate cyclase to putative stimulating agents was the same in primary cultures as in freshly isolated tubules. In PCT and PST adenylate cyclase activity was stimulated by parathyroid hormone (PTH) but not by arginine vasopressin (AVP); CAL and MAL adenylate cyclase was stimulated by neither PTH nor AVP; CCT, OMCT, and IMCT adenylate cyclase was stimulated by AVP but not by PTH. NaF stimulated adenylate cyclase activity in every cultured segment. It is concluded that primary cultures of individually microdissected rabbit PCT, PST, CAL, MAL, CCT, OMCT, and IMCT retain differentiated characteristics with regard to ultrastructure, marker enzymes, cytoskeletal proteins, and hormone response of adenylate cyclase and provide a new system for studying normal and abnormal functions of the heterogeneous tubular epithelia in the kidney.

Factors Affecting the Occurrence of Spinal Reflexes in Brain Dead Cases.

PubMed

Hosseini, Mahsa Sadat; Ghorbani, Fariba; Ghobadi, Omid; Najafizadeh, Katayoun

2015-08-01

Brain death is defined as the permanent absence of all cortical and brain stem reflexes. A wide range of spontaneous or reflex movements that are considered medullary reflexes are observed in heart beating cases that appear brain dead, which may create uncertainty about the diagnosis of brain death and cause delays in deceased-donor organ donation process. We determined the frequency and type of medullary reflexes and factors affecting their occurrence in brain dead cases. During 1 year, 122 cases who fulfilled the criteria for brain death were admitted to the special intensive care unit for organ procurement of Masih Daneshvari Hospital. Presence of spinal reflexes was evaluated by trained coordinators and was recorded in a form in addition to other information including demographic characteristics, cause of brain death, time from detection of brain death, history of craniotomy, vital signs, serum electrolyte levels, and parameters of arterial blood gas determination. Most cases (63%) included in this study were male, and mean age was 33 ± 15 y. There was > 1 spinal reflex observed in 40 cases (33%). The most frequent reflex was plantar response (17%) following by myoclonus (10%), triple flexion reflex (9%), pronator extension reflex (8%), and undulating toe reflex (7%). Mean systolic blood pressure was significantly higher in cases who exhibited medullary reflexes than other cases (126 ± 19 mm Hg vs 116 ± 17 mm Hg; P = .007). Spinal reflexes occur frequently in brain dead cases, especially when they become hemodynamically stable after treatment in the organ procurement unit. Observing these movements by caregivers and family members has a negative effect on obtaining family consent and organ donation. Increasing awareness about spinal reflexes is necessary to avoid suspicion about the brain death diagnosis and delays in organ donation.

Histone Deacetylase Inhibitors: A Novel Therapeutic Weapon Against Medullary Thyroid Cancer?

PubMed

Damaskos, Christos; Garmpis, Nikolaos; Valsami, Serena; Spartalis, Eleftherios; Antoniou, Efstathios A; Tomos, Periklis; Karamaroudis, Stefanos; Zoumpou, Theofano; Pergialiotis, Vasilios; Stergios, Konstantinos; Michaelides, Constantinos; Kontzoglou, Konstantinos; Perrea, Despina; Nikiteas, Nikolaos; Dimitroulis, Dimitrios

2016-10-01

Medullary thyroid cancer (MTC) is highly malignant, metastatic and recurrent, remaining generally incurable, and responsible for approximately 14% of all thyroid carcinoma-related deaths. MTC can metastasize to lymph nodes, trachea and distant organs, such as brain, lungs, liver and bones. MTC cells are resistant to chemotherapy and traditional external therapies are not showing definite clinical benefits. Scientists are trying to understand the molecular background of carcinogenesis and histone deacetylase (HDAC) seems to play a potential role to gene transcription. On the other hand, HDAC inhibitors (HDACI) hamper the HDAC action giving promising results as new anticancer drugs. The purpose of this review was to evaluate the current status of research considering the role of HDACIs in MTC treatment and to present the latest trends in MTC treatment protocols. This literature review was accomplished using the MEDLINE database. The key words/phrases were; HDACI, medullary thyroid cancer, HDACI in the therapy of neuroendocrine tumors, HDACI in MTC. Forty-one articles were selected from the total number of the search's results. Only sixteen papers focus on the use of HDACIs in the treatment of MTC. In order to extract our conclusions, we took into account some studies whose main topic does not strictly refer to the MTC but they contain noteworthy and useful information. Only English articles published up to August 2016 were assessed and used for writing this review. Molecules, such as valproid acid (VPA), vorinostat, suberoyl bis-hydroxamic acid (SBHA), depsipeptide, belinostat, m-carboxycinnamic acid bis-hydroxamine (CBHA) and AB3 have shown promising antitumor effects against MTC. HDACIs represent a promising field for targeted therapy both for its anticancer properties, as well as for augmenting radiotherapeutic modalities. More trials are needed. Copyright© 2016 International Institute of Anticancer Research (Dr. John G. Delinassios), All rights reserved.

[Disruption of the arteria nutricia tibiae by reamed and unreamed intramedullary nailing. Study of the vascular architecture of the human tibial intramedullary cavity].

PubMed

Paar, O; mon O'Dey, D; Magin, M N; Prescher, A

2000-01-01

By reason of the pseudarthrotic healing of fractures due to vascular complications after reamed and unreamed intramedullary nailing, the intraosseous course and branching of the tibial nutrient artery and its impairment by nailing procedures needs an actual analysis. The nutrient vessel of 24 tibiae taken from fresh corpses were prepared by injection of Technovit and lead oxide. After this procedure the medullary cavities of 12 bones were opened by a frontal cut. These specimens were subjected to routine maceration. The other 12 tibiae were naed with the unreamed (6) and the reamed nailing (6) techniques. X-rays were also taken routinely. After penetration of the tibial compact bone the main trunk of the nutrient vessel runs through a perforated osseous tunnel (pars tecta arteriae nutriciae tibiae). At its end the vessel divides into a descending branch (obligate) and two ascending branches (facultative). The descending branch lies near to the centromedial region of the medullary cavity which is termed as the pars liberal arteriae nutriciae tibiae. All branches pass through supporting horizontal osseous lamellas. Due to this topography the reamed nailing technique destroyed the nutrient vessel completely in all specimens. In contrast to this observation the unreamed nailing destroyed the vessel completely only in 1 (16.7%) and partially in 3 (50%) bones; 2 (33.3%) specimens exhibited no destruction of the vessel. The unreamed as well as the reamed nailing technique can destroy the intramedullary course of the tibial nutrient artery. Fractures as well as displacement osteotomies or corticotomies are able to diminish the medullary blood supply seriously, if they are localised within the area of the tactic an of the tibial nutrient artery.

The effect of localized injection of adjuvant material on the draining lymph node

PubMed Central

Taub, R. N.; Krantz, Adrienne R.; Dresser, D. W.

1970-01-01

The histological accompaniments of adjuvant activity were studied in popliteal nodes of CBA mice at various intervals after footpad injection. Substances tested possessed either extrinsic adjuvanticity but little or no antigenicity (alum, vitamin A alcohol), antigenicity but no extrinsic adjuvanticity (bovine γA-like globulin), both (Freund's complete adjuvant, killed B. pertussis organisms, alum-precipitated BGG), or neither (paraffin oil BP). Substances possessing extrinsic adjuvanticity produced marked persistent enlargement of the draining lymph node, with prominent expansion, hypercellularity and blast transformation in the paracortical areas by the 4th day after injection. This was followed by germinal centre formation and medullary plasmacytosis occurring between the 4th and 10th day. Substances possessing little or no antigenicity produced a feeble germinal centre response and minimal medullary expansion. Bovine γA-like globulin, which lacks extrinsic adjuvanticity, produced a prominent germinal centre and medullary response but a minimal paracortical response. Only mild, transient lymph node enlargement, lasting 1–2 days, was seen after paraffin oil BP. Passive immunization of CBA mice with CBA anti-pertussis hyperimmune serum inhibited the adjuvant action of pertussis, and diminished and delayed the histological changes in the draining lymph node. These data suggested that paracortical expansion and hyperplasia were characteristic histological accompaniments to the injection of substances with extrinsic adjuvanticity. Because paracortical hypercellularity was observed in some instances to precede blast cell transformation, it is suggested that paracortical expansion induced by adjuvants is partly due to an augmented cellular traffic, with a net flux of recirculating lymphocytes into these areas. ImagesFIG. 1FIG. 2FIG. 5FIG. 6FIG. 8FIG. 10FIG. 11 PMID:4190416

Tissue distribution of very late activation antigens-1/6 and very late activation antigen ligands in the normal thymus and in thymoma.

PubMed Central

Ruco, L. P.; Paradiso, P.; Pittiglio, M.; Diodoro, M. G.; Gearing, A. J.; Mainiero, F.; Gismondi, A.; Santoni, A.; Baroni, C. D.

1993-01-01

The expression of very late activation antigens (VLAs)-1/6 was correlated with that of the VLA ligands fibronectin, laminin, collagen, and vascular cell adhesion molecule-1 in sections of normal thymus, in thymocyte suspensions, and in 10 cases of thymoma. Capsular epithelial cells are VLA-2+, VLA-3+, and VLA-6+ and face the thymic basement membrane, which is rich in fibronectin, laminin, and collagen type IV. Cortical epithelial cells are VLA-2+ and are embedded in a reticular meshwork of nonorganized extracellular matrix (ECM) that is rich in fibronectin. Cortical thymocytes, identified as CD3dim cells by using immunofluorescence in suspension, are highly positive for VLA-4, a fibronectin ligand. Most cortical macrophages are positive for vascular cell adhesion molecule-1, a molecule recognized by VLA-4. Medullary epithelial cells are VLA-2+/VLA-3+ and are codistributed with fibrous strands of organized ECM that are positive for fibronectin, collagen, and laminin. Medullary thymocytes, identified as CD3bright cells, are positive for VLA-4 and VLA-6, a ligand for laminin. Our findings suggest that intrathymic thymocyte maturation is associated with changes in expression of VLA molecules, which are apparently correlated with the presence of VLA ligands in the tissue microenvironment. Thymomas were classified as cortical (three), common (five), or medullary (two) type. Expression of VLA molecules and distribution of ECM in the three histological subtypes were reminiscent of those observed in the respective regions of the normal thymus. All cases of thymoma were characterized by overexpression of VLA molecules on neoplastic cells, which was associated with increased deposition of organized ECM rich in fibronectin, laminin, and collagen. Images Figure 1 Figure 3 PMID:8456937

Architecture of the human renal inner medulla and functional implications.

PubMed

Wei, Guojun; Rosen, Seymour; Dantzler, William H; Pannabecker, Thomas L

2015-10-01

The architecture of the inner stripe of the outer medulla of the human kidney has long been known to exhibit distinctive configurations; however, inner medullary architecture remains poorly defined. Using immunohistochemistry with segment-specific antibodies for membrane fluid and solute transporters and other proteins, we identified a number of distinctive functional features of human inner medulla. In the outer inner medulla, aquaporin-1 (AQP1)-positive long-loop descending thin limbs (DTLs) lie alongside descending and ascending vasa recta (DVR, AVR) within vascular bundles. These vascular bundles are continuations of outer medullary vascular bundles. Bundles containing DTLs and vasa recta lie at the margins of coalescing collecting duct (CD) clusters, thereby forming two regions, the vascular bundle region and the CD cluster region. Although AQP1 and urea transporter UT-B are abundantly expressed in long-loop DTLs and DVR, respectively, their expression declines with depth below the outer medulla. Transcellular water and urea fluxes likely decline in these segments at progressively deeper levels. Smooth muscle myosin heavy chain protein is also expressed in DVR of the inner stripe and the upper inner medulla, but is sparsely expressed at deeper inner medullary levels. In rodent inner medulla, fenestrated capillaries abut CDs along their entire length, paralleling ascending thin limbs (ATLs), forming distinct compartments (interstitial nodal spaces; INSs); however, in humans this architecture rarely occurs. Thus INSs are relatively infrequent in the human inner medulla, unlike in the rodent where they are abundant. UT-B is expressed within the papillary epithelium of the lower inner medulla, indicating a transcellular pathway for urea across this epithelium. Copyright © 2015 the American Physiological Society.

Different skeletal effects of the peroxisome proliferator activated receptor (PPAR)α agonist fenofibrate and the PPARγ agonist pioglitazone

PubMed Central

Syversen, Unni; Stunes, Astrid K; Gustafsson, Björn I; Obrant, Karl J; Nordsletten, Lars; Berge, Rolf; Thommesen, Liv; Reseland, Janne E

2009-01-01

Background All the peroxisome proliferator activated receptors (PPARs) are found to be expressed in bone cells. The PPARγ agonist rosiglitazone has been shown to decrease bone mass in mice and thiazolidinediones (TZDs) have recently been found to increase bone loss and fracture risk in humans treated for type 2 diabetes mellitus. The aim of the study was to examine the effect of the PPARα agonist fenofibrate (FENO) and the PPARγ agonist pioglitazone (PIO) on bone in intact female rats. Methods Rats were given methylcellulose (vehicle), fenofibrate or pioglitazone (35 mg/kg body weight/day) by gavage for 4 months. BMC, BMD, and body composition were measured by DXA. Histomorphometry and biomechanical testing of excised femurs were performed. Effects of the compounds on bone cells were studied. Results The FENO group had higher femoral BMD and smaller medullary area at the distal femur; while trabecular bone volume was similar to controls. Whole body BMD, BMC, and trabecular bone volume were lower, while medullary area was increased in PIO rats compared to controls. Ultimate bending moment and energy absorption of the femoral shafts were reduced in the PIO group, while similar to controls in the FENO group. Plasma osteocalcin was higher in the FENO group than in the other groups. FENO stimulated proliferation and differentiation of, and OPG release from, the preosteoblast cell line MC3T3-E1. Conclusion We show opposite skeletal effects of PPARα and γ agonists in intact female rats. FENO resulted in significantly higher femoral BMD and lower medullary area, while PIO induced bone loss and impairment of the mechanical strength. This represents a novel effect of PPARα activation. PMID:19331671

Dorsomedial pontine neurons with descending projections to the medullary reticular formation express orexin-1 and adrenergic alpha2A receptor mRNA.

PubMed

Volgin, Denys V; Malinowska, Monika; Kubin, Leszek

2009-08-14

Neurons located in the dorsomedial pontine rapid eye movement (REM) sleep-triggering region send axons to the medial medullary reticular formation (mMRF). This pathway is believed to be important for the generation of REM sleep motor atonia, but other than that they are glutamatergic little is known about neurochemical signatures of these pontine neurons important for REM sleep. We used single-cell reverse transcription and polymerase chain reaction (RT-PCR) to determine whether dorsomedial pontine cells with projections to the mMRF express mRNA for selected membrane receptors that mediate modulatory influences on REM sleep. Fluorescein (FITC)-labeled latex microspheres were microinjected into the mMRF of 26-34-day-old rats under pentobarbital anesthesia. After 5-6 days, rats were sacrificed, pontine slices were obtained and neurons were dissociated from 400 to 600 microm micropunches extracted from dorsomedial pontine reticular formation. We found that 32 out of 51 FITC-labeled cells tested (63+/-7% (SE)) contained the orexin type 1 receptor (ORX1r) mRNA, 27 out of 73 (37+/-6%) contained the adrenergic alpha(2A) receptor (alpha(2A)r) RNA, and 6 out of 31 (19+/-7%) contained both mRNAs. The percentage of cells positive for the ORX1r mRNA was significantly lower (p<0.04) for the dorsomedial pontine cells that were not retrogradely labeled from the mMRF (32+/-11%), whereas alpha(2A)r mRNA was present in a similar percentage of FITC-labeled and unlabeled neurons. Our data suggest that ORX and adrenergic pathways converge on a subpopulation of cells of the pontine REM sleep-triggering region that have descending projections to the medullary region important for the motor control during REM sleep.

Genetics Home Reference: medullary cystic kidney disease type 1

MedlinePlus

... They lead to the production of an altered protein. It is unclear how this change causes kidney disease. ... cystic kidney disease type 1 lie in a large VNTR in MUC1 missed by massively parallel sequencing. Nat Genet. 2013 Mar;45(3):299-303. ...

Pate v. Threlkel.

PubMed

1994-08-01

The Florida District Court of Appeal for the First District held that a physician has no duty to the children of a patient with a genetic disease to warn the patient that the disease is inherited so that the children can be tested and treated if need be. Dr. Threlkel had operated on the mother of Heidi Pate for medullary thyroid cancer three years before Pate's own medullary thyroid cancer was diagnosed and treated. Because Pate was not his patient and did not fit within any exception to the requirement that there be a physician patient relationship, the doctor owed no legal duty to her. The court distinguished this case from cases that involve the transmission of infectious or contagious disease through close contact, and from cases that involve the transmission of genetic disease due to the failure to diagnose it or to disclose the risk of it and thus prevent the birth of a genetically impaired child. In those cases a duty to warn does extend to family members.

Medullary ischemia due to vertebral arteritis associated with Behçet syndrome: a case report.

PubMed

Kaido, Takanobu; Otsuki, Taisuke; Ogawa, Masafumi; Takahashi, Akio; Kaneko, Yuu; Yamamoto, Toshiyuki; Nakata, Yasuhiro

2012-09-01

Here we report an extremely rare case of Behçet syndrome (BS) that showed acute onset of Wallenberg syndrome and was treated successfully by corticosteroids. A 51-year-old woman with BS had a sudden onset of Wallenberg syndrome. Three days after the onset, she was transferred to our institute. In the magnetic resonance imaging (MRI) study on admission, T2-weighted and fluid-attenuated inversion recovery images showed a high intensity area in the left paramedian region of the medulla oblongata. Contrast-enhanced T1-weighted images showed enhancement in the vessel wall of the left vertebral artery. We diagnosed her as having Wallenberg syndrome due to the acute vertebral arteritis associated with BS. After initiation of high-dose steroid therapy, her symptoms gradually improved. Two months after admission, she was discharged from our institute with mild hemihypesthesia. We hypothesized that vertebral arteritis due to BS had caused hypoperfusion of the medullary perforators causing Wallenberg syndrome in our patient.

Constitutive RET tyrosine kinase activation in hereditary medullary thyroid cancer: clinical opportunities.

PubMed

Machens, A; Lorenz, K; Dralle, H

2009-07-01

The ground-breaking discovery of genotype-phenotype relationships in hereditary medullary thyroid cancer has greatly facilitated early prophylactic thyroidectomy. Its timing depends not solely on a positive gene test but, more importantly, on the type of the REarranged during Transfection (RET) mutation and its underlying mode of RET receptor tyrosine kinase activation. In the past decade, the therapeutic corridor opened by molecular information has been defined down to a remarkable level of detail. Based on mutational risk profiles, preemptive thyroidectomy is recommended at 6 months of age for carriers of highest-risk mutations, before the age of 5 years for carriers of high-risk mutations, and before the age of 5 or 10 years for carriers of least-high-risk mutations. Additional lymph node dissection may not be needed in the absence of increased preoperative basal calcitonin levels. Better comprehension of RET function should enable the design of targeted therapies for RET carriers beyond surgical cure in whom the DNA-based 'window of opportunity' has been missed.

Role of prophylactic thyroidectomy in RET 790 familial medullary thyroid carcinoma.

PubMed

Bihan, Hélène; Baudin, Eric; Meas, Taly; Leboulleux, Sophie; Al Ghuzlan, Abir; Hannoteaux, Véronique; Travagli, Jean-Paul; Valleur, Patrice; Guillausseau, Pierre-Jean; Cohen, Régis

2012-04-01

We describe a family harboring RET 790 mutation and review the role of prophylactic thyroidectomy for medullary thyroid carcinoma. We evaluated in detail both clinical and biological follow-up and reviewed literature reports. Among 86 family members, 15 of 22 members screened harbored the 790 mutation. Abnormal calcitonin levels were found in 8/15. Total thyroidectomy with lymph node dissection cured the 5 operated patients (range, 45-76 years). Tumor staging was pT1N0M0. Among 10 carriers who did not undergo surgery, 3 patients had abnormal calcitonin levels. For the others, calcitonin levels remained <30 pg/mL. Two asymptomatic carriers were older than 70 years. Four subjects were lost to follow-up. In RET codon 790 mutations families, a case-by-case decision instead of systematic prophylactic thyroidectomy should be discussed. Difficulties of follow-up should be taken into account and represent the main challenge. Copyright © 2011 Wiley Periodicals, Inc.

Lack of effectiveness of laser therapy applied to the nerve course and the correspondent medullary roots

PubMed Central

Sousa, Fausto Fernandes de Almeida; Ribeiro, Thaís Lopes; Fazan, Valéria Paula Sassoli; Barbieri, Claudio Henrique

2013-01-01

OBJECTIVE: To investigate the influence of low intensity laser irradiation on the regeneration of the fibular nerve of rats after crush injury. METHODS: Twenty-five rats were used, divided into three groups: 1) intact nerve, no treatment; 2) crushed nerve, no treatment; 3) crush injury, laser irradiation applied on the medullary region corresponding to the roots of the sciatic nerve and subsequently on the course of the damaged nerve. Laser irradiation was carried out for 14 consecutive days. RESULTS: Animals were evaluated by functional gait analysis with the peroneal functional index and by histomorphometric analysis using the total number of myelinated nerve fibers and their density, total number of Schwann cells, total number of blood vessels and the occupied area, minimum diameter of the fiber diameter and G-quotient. CONCLUSION: According to the statistical analysis there was no significant difference among groups and the authors conclude that low intensity laser irradiation has little or no influence on nerve regeneration and functional recovery. Laboratory investigation. PMID:24453650

Apatinib-treated advanced medullary thyroid carcinoma: a case report.

PubMed

Chen, Kan; Gao, Yun; Shi, Fei; Cao, Guangqiang; Bao, Jiandong

2018-01-01

Medullary thyroid carcinoma (MTC) is a rare malignancy originating from calcitonin-producing parafollicular C cells of the thyroid. Neither radiotherapy nor chemotherapy has demonstrated durable objective responses in patients with advanced MTC. Vandetanib and cabozantinib are the 2 tyrosine kinase inhibitors recently approved by the US Food and Drug Administration, which are not affordable for most Chinese patients. Herein, we report a case of an MTC patient who responded to apatinib, a Chinese homemade tyrosine kinase inhibitor-targeted vascular endothelial growth factor receptor. The patient was treated with thyroid lobectomy but developed MTC with extensive metastasis. The levels of serum calcitonin and carcino-embryonic antigen were much higher than the normal range. Apatinib was given at a dose of 500 mg daily and adjusted according to tolerance. Sixteen weeks following apatinib administration, the patient achieved a partial response, which lasted more than 9 weeks. No severe toxicity or drug-related side effect was observed during the treatment. Therefore, apatinib could be a new option for the treatment of advanced MTC.

The normal and pathologic renal medulla: a comprehensive overview.

PubMed

López, José I; Larrinaga, Gorka; Kuroda, Naoto; Angulo, Javier C

2015-04-01

The renal medulla comprises an intricate system of tubules, blood vessels and interstitium that is not well understood by most general pathologists. We conducted an extensive review of the literature on the renal medulla, in both normal and pathologic conditions. We set out in detail the points of key interest to pathologists: normal and pathological development, physiology, microscopic anatomy, histology and immunohistochemistry; and the specific and most common other types of disease associated with this part of the kidney: developmental abnormalities, (multicystic dysplastic kidney, autosomal dominant and recessive polycystic kidney diseases, medullary cystic kidney disease), inflammatory conditions (xanthogranulomatous pyelonephritis, malakoplakia), hyperplasia and dysplasia, and neoplastic processes (oncocytoma, atypical oncocytic tumors, chromophobe cell carcinoma, collecting duct carcinoma, urothelial carcinoma, other carcinomas, renal medullary fibroma and metastatic tumors). This condensed overview of the origin, function and pathology of the renal medulla, both in terms of development, inflammation and neoplastic processes, should help focus the interest of clinical pathologists on this widely overlooked part of the kidney. Copyright © 2014 Elsevier GmbH. All rights reserved.

Enlargement of sacral subcutaneous meningocele associated with retained medullary cord.

PubMed

Shirozu, Noritoshi; Morioka, Takato; Inoha, Satoshi; Imamoto, Naoyuki; Sasaguri, Takakazu

2018-04-27

A retained medullary cord (RMC) is a rare closed spinal dysraphism with a robust elongated neural structure continuous from the conus and extending to the dural cul-de-sac. Four cases of RMC extending down to the base of an associated subcutaneous meningocele at the sacral level have been reported. We report an additional case of RMC, in whom serial MRI examination revealed an enlargement of the meningocele associated with RMC over a 3-month period between 8 and 11 months of age, when he began to stand. At the age of 12 months, untethering of the cord was performed. Histologically, the presence of ependyma-lined central canals in the dense neuroglial cores was noted in all cord-like structures in the intradural and intrameningocele sacs and at the attachment to the meningocele. It is conceivable that the hydrodynamic pressure with standing position and the check valve phenomenon were involved in meningocele enlargement. We should be mindful of these potential morphological changes.

Acute deterioration in occult Chiari malformation following missile spinal trauma. Case report.

PubMed

Shahlaie, Kiarash; Hartman, Jonathan; Utter, Garth H; Schrot, Rudolph J

2008-04-01

Patients with Chiari malformation (CM) Type I typically experience chronic, slowly progressive symptoms. Rarely, however, do they suffer acute neurological deterioration following an iatrogenic decrease in caudal cerebrospinal fluid pressure due to, for example, a lumbar puncture. To our knowledge, acute neurological deterioration following missile spinal injury in CM has not been previously described. The authors report on a 16-year-old girl who was shot in the abdomen and lumbar spine. Although neurologically intact on initial workup, she developed precipitous quadriplegia and apnea in a delayed fashion. Tonsillar herniation with medullary compression and cerebellar infarction was diagnosed on magnetic resonance imaging. Suboccipital decompression resulted in significant neurological improvement. Well-formed tonsillar ectopia diagnosed at surgery suggested a preexisting CM. The authors conclude that missile spinal trauma can precipitate medullary compression and acute neurological decline, especially in patients with preexisting tonsillar ectopia. Immediate operative decompression to relieve impaction at the cervicomedullary junction can result in significant neurological recovery.

Mandibular pseudocarcinomatous hyperplasia.

PubMed

Warter, A; Walter, P; Meyer, C; Barrière, P; Galatir, L; Wilk, A

2000-08-01

Three unusual cases of pseudocarcinomatous (pseudoepitheliomatous) hyperplasia (PH) affecting chronic osteomyelitic mandibular sequestra are reported to highlight the differences with the various squamous neoplasms which occur in that site. In two patients carrying a mandibular graft following the excision of an ameloblastoma, mucosal ulcers resulted in chronic osteomyelitis. In a third patient, an apical dental infection was associated with fistulated osteomyelitis. Histology of the three sequestra showed an intraosseous squamous proliferation. It was characterized by a peripheral involvement of medullary spaces, the more mature epithelial layer covering the bone trabeculae without intervening stroma, and the basal type epithelial layer surrounding a central fibrovascular core. There were no histological or cytological signs of malignancy. PH shows an inverted pattern when compared with the centro-medullary tumoural islands seen in the various oral or odontogenic squamous neoplasms which occur in the jaws. The lack of signs of malignancy distinguish PH from common squamous cell carcinomas. A short clinical course is an important feature in the distinction of PH from the well differentiated squamous cell carcinomas which may develop in fistulated chronic osteomyelitis.

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

PubMed

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.

Medullary thyroid carcinoma: ectopic production of peptides with ACTH-like, corticotrophin releasing factor-like and prolactin production-stimulating activities.

PubMed

Birkenhäger, J C; Upton, G V; Seldenrath, H J; Krieger, D T; Tashjian, A H

1976-10-01

A 45-year-old women had medullary tyroid carcinoma associated with Cushing's syndrome and galactorrhoea. Elevated plasma immunoreactive ACTH and cortisol were partially suppressed by intravenous dexamethasone, appreciably raised by lysine vasopressin, and urinary excretion of 17-oxogenic steroids slightly elevated by metyrapone. A large arterio-venous increase in plasma corticotrophin releasing factor-like activity across the thyroid gland was observed and tumour tissue contained corticotrophin releasing factor-like activity. Biologically active ACTH was not detected in tumour extracts before incubation with trypsin, but after trypsinization a value of 3.2 mU per gram was obtained. Arterial plasma contained biologically active ACTH (1.5 mU/100 ml) prior to trypsinization. Venous effluent from the thyroid gland contained biologically active (9.6 mU/100 ml) and immunoreactive ACTH (970 pg/ml) before trypsinization. Tumour extracts also contained prolactin production-stimulating activity. These findings can explain the Cushing's syndrome and the galactorrhoea both of which disappeared completely after thyroidectomy.

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

PubMed

Patel, Bidish K; Roy, Arun; Badhe, Bhawana A; Siddaraju, Neelaiah

2016-01-01

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 Hürthle cells. Our case highlights an unusual instance of MTC in concurrence with HT that can create a tricky situation for cytopathologists.

Neural imaging in songbirds using fiber optic fluorescence microscopy

NASA Astrophysics Data System (ADS)

Nooshabadi, Fatemeh; Hearn, Gentry; Lints, Thierry; Maitland, Kristen C.

2012-02-01

The song control system of juvenile songbirds is an important model for studying the developmental acquisition and generation of complex learned vocal motor sequences, two processes that are fundamental to human speech and language. To understand the neural mechanisms underlying song production, it is critical to characterize the activity of identified neurons in the song control system when the bird is singing. Neural imaging in unrestrained singing birds, although technically challenging, will advance our understanding of neural ensemble coding mechanisms in this system. We are exploring the use of a fiber optic microscope for functional imaging in the brain of behaving and singing birds in order to better understand the contribution of a key brain nucleus (high vocal center nucleus; HVC) to temporal aspects of song motor control. We have constructed a fluorescence microscope with LED illumination, a fiber bundle for transmission of fluorescence excitation and emission light, a ~2x GRIN lens, and a CCD for image acquisition. The system has 2 μm resolution, 375 μm field of view, 200 μm working distance, and 1 mm outer diameter. As an initial characterization of this setup, neurons in HVC were imaged using the fiber optic microscope after injection of quantum dots or fluorescent retrograde tracers into different song nuclei. A Lucid Vivascope confocal microscope was used to confirm the imaging results. Long-term imaging of the activity of these neurons in juvenile birds during singing may lead us to a better understanding of the central motor codes for song and the central mechanism by which auditory experience modifies song motor commands to enable vocal learning and imitation.

Motor-circuit communication matrix from spinal cord to brainstem neurons revealed by developmental origin.

PubMed

Pivetta, Chiara; Esposito, Maria Soledad; Sigrist, Markus; Arber, Silvia

2014-01-30

Accurate motor-task execution relies on continuous comparison of planned and performed actions. Motor-output pathways establish internal circuit collaterals for this purpose. Here we focus on motor collateral organization between spinal cord and upstream neurons in the brainstem. We used a newly developed mouse genetic tool intersectionally with viruses to uncover the connectivity rules of these ascending pathways by capturing the transient expression of neuronal subpopulation determinants. We reveal a widespread and diverse network of spinal dual-axon neurons, with coincident input to forelimb motor neurons and the lateral reticular nucleus (LRN) in the brainstem. Spinal information to the LRN is not segregated by motor pool or neurotransmitter identity. Instead, it is organized according to the developmental domain origin of the progenitor cells. Thus, excerpts of most spinal information destined for action are relayed to supraspinal centers through exquisitely organized ascending connectivity modules, enabling precise communication between command and execution centers of movement. Copyright © 2014 Elsevier Inc. All rights reserved.

Neural control of breathing and CO2 homeostasis

PubMed Central

Guyenet, P.G.; Bayliss, D.A

2015-01-01

Summary Recent advances have clarified how the brain detects CO2 to regulate breathing (central respiratory chemoreception). These mechanisms are reviewed and their significance is presented in the general context of CO2/pH homeostasis through breathing. At rest, respiratory chemoreflexes initiated at peripheral and central sites mediate rapid stabilization of arterial PCO2 and pH. Specific brainstem neurons (e.g., retrotrapezoid nucleus, RTN; serotonergic) are activated by PCO2 and stimulate breathing. RTN neurons detect CO2 via intrinsic proton receptors (TASK-2, GPR4), synaptic input from peripheral chemoreceptors and signals from astrocytes. Respiratory chemoreflexes are arousal state-dependent whereas chemoreceptor stimulation produces arousal. When abnormal, these interactions lead to sleep-disordered breathing. During exercise, “central command” and reflexes from exercising muscles produce the breathing stimulation required to maintain arterial PCO2 and pH despite elevated metabolic activity. The neural circuits underlying central command and muscle afferent control of breathing remain elusive and represent a fertile area for future investigation. PMID:26335642

Copper Cu 64 Anti-CEA Monoclonal Antibody M5A PET in Diagnosing Patients With CEA Positive Cancer

ClinicalTrials.gov

2018-06-15

Breast Cancer; Colon Cancer; Extrahepatic Bile Duct Cancer; Gallbladder Cancer; Gastrointestinal Cancer; Liver and Intrahepatic Biliary Tract Cancer; Lung Cancer; Metastatic Cancer; Pancreatic Cancer; Rectal Cancer; Thyroid Gland Medullary Carcinoma; Unspecified Adult Solid Tumor, Protocol Specific

Extrathyroidal Extension Is Associated with Compromised Survival in Patients with Thyroid Cancer.

PubMed

Youngwirth, Linda M; Adam, Mohamed A; Scheri, Randall P; Roman, Sanziana A; Sosa, Julie A

2017-05-01

Patients with thyroid cancer who have extrathyroidal extension (ETE) are considered to have more advanced tumors. However, data on the impact of ETE on patient outcomes remain limited. The purpose of this study was to evaluate the association between ETE and survival in patients with thyroid cancer. The National Cancer Database (1998-2012) was queried for all adult patients with differentiated thyroid cancer and medullary thyroid cancer. Patients were divided into three groups: no ETE (T1 and T2 tumors), minimal ETE (T3 tumors <4 cm), and extensive ETE (T4 tumors <4 cm). Patient demographic, clinical, and pathologic factors were evaluated for all patients. A Cox proportional hazards model was developed for each histology to identify factors associated with survival. In total, 241,118 patients with differentiated thyroid cancer met the inclusion criteria; 86.9% had no ETE, 9.1% minimal ETE, and 4.0% extensive ETE. Compared with patients with no ETE, patients with minimal and extensive ETE were more likely to have larger tumors (1.4 cm vs. 1.8 cm and 2.0 cm, respectively), lymphovascular invasion (8.6% vs. 28.0% and 35.1%, respectively), positive margins after thyroidectomy (6.1% vs. 35.2% and 45.9%, respectively), and regional lymph node metastases (32.5% vs. 67.0% and 74.6%, respectively; all p < 0.01). After adjustment, minimal ETE (hazard ratio [HR] = 1.13; p < 0.01) and extensive ETE (HR = 1.74; p < 0.01) were associated with compromised survival for patients with differentiated thyroid cancer. In total, 3415 patients with medullary thyroid cancer met the inclusion criteria; 87.9% had no ETE, 7.1% minimal ETE, and 5.0% extensive ETE. Compared with patients with no ETE, patients with minimal and extensive ETE were more likely to have larger tumors (1.7 cm vs. 2.2 cm and 2.2 cm, respectively), lymphovascular invasion (19.2% vs. 68.9% and 79.3%, respectively), positive margins after thyroidectomy (5.8% vs. 44.1% and 51.9%, respectively), and regional lymph node metastases (39.0% vs. 90.5% and 94.4%, respectively; all p < 0.01). After adjustment, extensive ETE (HR = 1.63; p = 0.01) was associated with compromised survival for patients with medullary thyroid cancer. In patients with differentiated and medullary thyroid cancers, ETE is associated with compromised survival. Given these findings, ETE should be included in the thyroid cancer treatment guidelines.

Development of Chronic Mandibular Osteomyelitis in a Miniswine Model

DTIC Science & Technology

1993-01-01

endotracheal intubation was then accomplished and medullary cavity to control bleeding and to produce anesthesia maintained with N,0/O,/Forane (ANA- some...Dis 122:410, 1970 experimental animal in dental research. Arch Oral Biol 7:17, 5. Norden CW, Shinners E, Niederriter K: Clindamycin treatment 1962 of

Bittersweet: Real-Time, Dynamic Changes in Blood Glucose Levels during an Acute Ozone Exposure in Rats

EPA Science Inventory

In humans and rats, acute exposures to ozone have been shown to activate the sympathetic-adrenal-medullary and hypothalamic-pituitary-adrenal axes to induce multi-organ metabolic alterations including impaired glucose homeostasis. These findings have largely been gleaned from on...

Soft tissue and cellular preservation in vertebrate skeletal elements from the Cretaceous to the present

PubMed Central

Schweitzer, Mary Higby; Wittmeyer, Jennifer L; Horner, John R

2006-01-01

Soft tissues and cell-like microstructures derived from skeletal elements of a well-preserved Tyrannosaurus rex (MOR 1125) were represented by four components in fragments of demineralized cortical and/or medullary bone: flexible and fibrous bone matrix; transparent, hollow and pliable blood vessels; intravascular material, including in some cases, structures morphologically reminiscent of vertebrate red blood cells; and osteocytes with intracellular contents and flexible filipodia. The present study attempts to trace the occurrence of these four components in bone from specimens spanning multiple geological time periods and varied depositional environments. At least three of the four components persist in some skeletal elements of specimens dating to the Campanian. Fibrous bone matrix is more altered over time in morphology and less likely to persist than vessels and/or osteocytes. Vessels vary greatly in preservation, even within the same specimen, with some regions retaining pliability and other regions almost crystalline. Osteocytes also vary, with some retaining long filipodia and transparency, while others present with short and stubby filipodia and deeply pigmented nuclei, or are pigmented throughout with no nucleus visible. Alternative hypotheses are considered to explain the origin/source of observed materials. Finally, a two-part mechanism, involving first cross-linking of molecular components and subsequent mineralization, is proposed to explain the surprising presence of still-soft elements in fossil bone. These results suggest that present models of fossilization processes may be incomplete and that soft tissue elements may be more commonly preserved, even in older specimens, than previously thought. Additionally, in many cases, osteocytes with defined nuclei are preserved, and may represent an important source for informative molecular data. PMID:17148248

Changes in glutamate receptor subunits within the medulla in goats after section of the carotid sinus nerves

PubMed Central

Miller, Justin Robert; Neumueller, Suzanne; Muere, Clarissa; Olesiak, Samantha; Pan, Lawrence; Bukowy, John D.; Daghistany, Asem O.; Hodges, Matthew R.

2014-01-01

The mechanisms which contribute to the time-dependent recovery of resting ventilation and the ventilatory CO2 chemoreflex after carotid body denervation (CBD) are poorly understood. Herein we tested the hypothesis that there are time-dependent changes in the expression of specific AMPA, NMDA, and/or neurokinin-1 (NK1R) receptors within respiratory-related brain stem nuclei acutely or chronically after CBD in adult goats. Brain stem tissues were collected acutely (5 days) or chronically (30 days) after sham or bilateral CBD, immunostained with antibodies targeting AMPA (GluA1 or GluA2), NMDA (GluN1), or NK-1 receptors, and optical density (OD) compared. Physiological measurement confirmed categorization of each group and showed ventilatory effects consistent with bilateral CBD (Miller et al. J Appl Physiol 115: 1088–1098, 2013). Acutely after CBD, GluA1 OD was unchanged or slightly increased, but GluA2 and GluN1 OD were reduced 15–30% within the nucleus tractus solitarius (NTS) and in other medullary respiratory nuclei. Chronically after CBD, GluA1 was reduced (P < 0.05) within the caudal NTS and in other nuclei, but there was significant recovery of GluA2 and GluN1 OD. NK1 OD was not significantly different from control after CBD. We conclude that the initial decrease in GluA2 and GluN1 after CBD likely contributes to hypoventilation and the reduced CO2 chemoreflex. The partial recovery of ventilation and the CO2 chemoreflex after CBD parallel a time-dependent return of these receptors to near control levels but likely depend upon additional initiating and maintenance factors for neuroplasticity. PMID:24790015

Bidirectional plasticity of pontine pneumotaxic postinspiratory drive: implication for a pontomedullary respiratory central pattern generator.

PubMed

Poon, Chi-Sang; Song, Gang

2014-01-01

The "pneumotaxic center" in the rostral dorsolateral pons as delineated by Lumsden nine decades ago is known to play an important role in promoting the inspiratory off-switch (IOS) for inspiratory-expiratory phase transition as a fail-safe mechanism for preventing apneusis in the absence of vagal input. Traditionally, the pontine pneumotaxic mechanism has been thought to contribute a tonic descending input that lowers the IOS threshold in medullary respiratory central pattern generator (rCPG) circuits, but otherwise does not constitute part of the rCPG. Recent evidence indicates that descending input from the Kölliker-Fuse nucleus (KFN) within the pneumotaxic center is essential for gating the postinspiratory phase of the three-phase respiratory rhythm to control the IOS in vagotomized animals. A critical question arising is whether such a descending pneumotaxic input from KFN that drives postinspiratory activity is tonic (null hypothesis) or rhythmic with postinspiratory phase modulation (alternative hypothesis). Here, we show that multifarious evidence reported in the literature collectively indicates that the descending pneumotaxic input may exhibit NMDA receptor-dependent short-term plasticity in the form of a biphasic neural differentiator that bidirectionally and phase-selectively modulates postinspiratory phase duration in response to vagal and peripheral chemoreceptor inputs independent of the responses in inspiratory and late-expiratory activities. The phase-selectivity property of the descending pneumotaxic input implicates a population of pontine early-expiratory (postinspiratory/expiratory-decrementing) neurons as the most likely neural correlate of the pneumotaxic mechanism that drives post-I activity, suggesting that the pontine pneumotaxic mechanism may be an integral part of a pontomedullary rCPG that underlies the three-phase respiratory rhythm. © 2014 Elsevier B.V. All rights reserved.

Decreased spinal synaptic inputs to phrenic motor neurons elicit localized inactivity-induced phrenic motor facilitation

PubMed Central

Streeter, K.A.; Baker-Herman, T.L.

2014-01-01

Phrenic motor neurons receive rhythmic synaptic inputs throughout life. Since even brief disruption in phrenic neural activity is detrimental to life, on-going neural activity may play a key role in shaping phrenic motor output. To test the hypothesis that spinal mechanisms sense and respond to reduced phrenic activity, anesthetized, ventilated rats received micro-injections of procaine in the C2 ventrolateral funiculus (VLF) to transiently (~30 min) block axon conduction in bulbospinal axons from medullary respiratory neurons that innervate one phrenic motor pool; during procaine injections, contralateral phrenic neural activity was maintained. Once axon conduction resumed, a prolonged increase in phrenic burst amplitude was observed in the ipsilateral phrenic nerve, demonstrating inactivity-induced phrenic motor facilitation (iPMF). Inhibition of tumor necrosis factor alpha (TNFα) and atypical PKC (aPKC) activity in spinal segments containing the phrenic motor nucleus impaired ipsilateral iPMF, suggesting a key role for spinal TNFα and aPKC in iPMF following unilateral axon conduction block. A small phrenic burst amplitude facilitation was also observed contralateral to axon conduction block, indicating crossed spinal phrenic motor facilitation (csPMF). csPMF was independent of spinal TNFα and aPKC. Ipsilateral iPMF and csPMF following unilateral withdrawal of phrenic synaptic inputs were associated with proportional increases in phrenic responses to chemoreceptor stimulation (hypercapnia), suggesting iPMF and csPMF increase phrenic dynamic range. These data suggest that local, spinal mechanisms sense and respond to reduced synaptic inputs to phrenic motor neurons. We hypothesize that iPMF and csPMF may represent compensatory mechanisms that assure adequate motor output is maintained in a physiological system in which prolonged inactivity ends life. PMID:24681155

Autonomic control of the heart is altered in Sprague-Dawley rats with spontaneous hydronephrosis

PubMed Central

Arnold, Amy C.; Shaltout, Hossam A.; Gilliam-Davis, Shea; Kock, Nancy D.

2011-01-01

The renal medulla plays an important role in cardiovascular regulation, through interactions with the autonomic nervous system. Hydronephrosis is characterized by substantial loss of renal medullary tissue. However, whether alterations in autonomic control of the heart are observed in this condition is unknown. Thus we assessed resting hemodynamics and baroreflex sensitivity (BRS) for control of heart rate in urethane/chloralose-anesthetized Sprague-Dawley rats with normal or hydronephrotic kidneys. While resting arterial pressure was similar, heart rate was higher in rats with hydronephrosis (290 ± 12 normal vs. 344 ± 11 mild/moderate vs. 355 ± 13 beats/min severe; P < 0.05). The evoked BRS to increases, but not decreases, in pressure was lower in hydronephrotic rats (1.06 ± 0.06 normal vs. 0.72 ± 0.10 mild/moderate vs. 0.63 ± 0.07 ms/mmHg severe; P < 0.05). Spectral analysis methods confirmed reduced parasympathetic function in hydronephrosis, with no differences in measures of indirect sympathetic activity among conditions. As a secondary aim, we investigated whether autonomic dysfunction in hydronephrosis is associated with activation of the renin-angiotensin system (RAS). There were no differences in circulating angiotensin peptides among conditions, suggesting that the impaired autonomic function in hydronephrosis is independent of peripheral RAS activation. A possible site for angiotensin II-mediated BRS impairment is the solitary tract nucleus (NTS). In normal and mild/moderate hydronephrotic rats, NTS administration of the angiotensin II type 1 receptor antagonist candesartan significantly improved the BRS, suggesting that angiotensin II provides tonic suppression to the baroreflex. In contrast, angiotensin II blockade produced no significant effect in severe hydronephrosis, indicating that at least within the NTS baroreflex suppression in these animals is independent of angiotensin II. PMID:21460193

Photostimulation of Phox2b Medullary Neurons Activates Cardiorespiratory Function in Conscious Rats

PubMed Central

Kanbar, Roy; Stornetta, Ruth L.; Cash, Devin R.; Lewis, Stephen J.; Guyenet, Patrice G.

2010-01-01

Rationale: Hypoventilation is typically treated with positive pressure ventilation or, in extreme cases, by phrenic nerve stimulation. This preclinical study explores whether direct stimulation of central chemoreceptors could be used as an alternative method to stimulate breathing. Objectives: To determine whether activation of the retrotrapezoid nucleus (RTN), which is located in the rostral ventrolateral medulla (RVLM), stimulates breathing with appropriate selectivity. Methods: A lentivirus was used to induce expression of the photoactivatable cationic channel channelrhodopsin-2 (ChR2) by RVLM Phox2b-containing neurons, a population that consists of central chemoreceptors (the ccRTN neurons) and blood pressure (BP)-regulating neurons (the C1 cells). The transfected neurons were activated with pulses of laser light. Respiratory effects were measured by plethysmography or diaphragmatic EMG recording and cardiovascular effects by monitoring BP, renal sympathetic nerve discharge, and the baroreflex. Measurements and Main Results: The RVLM contained 600 to 900 ChR2-transfected neurons (63% C1, 37% ccRTN). RVLM photostimulation significantly increased breathing rate (+42%), tidal volume (21%), minute volume (68%), and peak expiratory flow (48%). Photostimulation increased diaphragm EMG amplitude (19%) and frequency (21%). Photostimulation increased BP (4 mmHg) and renal sympathetic nerve discharge (43%) while decreasing heart rate (15 bpm). Conclusions: Photostimulation of ChR2-transfected RVLM Phox2b neurons produces a vigorous stimulation of breathing accompanied by a small sympathetically mediated increase in BP. These results demonstrate that breathing can be relatively selectively activated in resting unanesthetized mammals via optogenetic manipulation of RVLM neurons presumed to be central chemoreceptors. This methodology could perhaps be used in the future to enhance respiration in humans. PMID:20622037

Direct pyrogenic input from prostaglandin EP3 receptor-expressing preoptic neurons to the dorsomedial hypothalamus

PubMed Central

Nakamura, Yoshiko; Nakamura, Kazuhiro; Matsumura, Kiyoshi; Kobayashi, Shigeo; Kaneko, Takeshi; Morrison, Shaun F.

2008-01-01

Fever is induced by the neuronal mechanism in the brain. Prostaglandin (PG) E2 acts as a pyrogenic mediator in the preoptic area (POA) probably through the EP3 subtype of PGE receptor expressed on GABAergic neurons, and this PGE2 action triggers neuronal pathways for sympathetic thermogenesis in peripheral effector organs including brown adipose tissue (BAT). To explore pyrogenic efferent pathways from the POA, we here determined projection targets of EP3 receptor-expressing POA neurons with a special focus on rat hypothalamic regions including the dorsomedial hypothalamic nucleus (DMH), which is known as a center for autonomic responses to stress. Among injections of cholera toxin b-subunit (CTb), a retrograde tracer, into hypothalamic regions at the rostrocaudal level of the DMH, injections into the DMH, lateral hypothalamic area (LH), and dorsal hypothalamic area (DH) resulted in EP3 receptor immunolabeling in substantial populations of CTb-labeled neurons in the POA. Bilateral microinjections of muscimol, a GABAA receptor agonist, into the DMH and a ventral region of the DH, but not those into the LH, inhibited thermogenic (BAT sympathetic nerve activity, BAT temperature, core body temperature, and expired CO2) and cardiovascular (arterial pressure and heart rate) responses to an intra-POA PGE2 microinjection. Further immunohistochemical observations revealed close association of POA-derived GABAergic axon swellings with DMH neurons projecting to the medullary raphe regions where sympathetic premotor neurons for febrile and thermoregulatory responses are localized. These results suggest that a direct projection of EP3 receptor-expressing POA neurons to the DMH/DH region mediates febrile responses via a GABAergic mechanism. PMID:16367780

Orexin neurons are indispensable for prostaglandin E2-induced fever and defence against environmental cooling in mice

PubMed Central

Takahashi, Yoshiko; Zhang, Wei; Sameshima, Kohei; Kuroki, Chiharu; Matsumoto, Ami; Sunanaga, Jinko; Kono, Yu; Sakurai, Takeshi; Kanmura, Yuichi; Kuwaki, Tomoyuki

2013-01-01

We recently showed using prepro-orexin knockout (ORX-KO) mice and orexin neuron-ablated (ORX-AB) mice that orexin neurons in the hypothalamus, but not orexin peptides per se, are indispensable for stress-induced thermogenesis. To examine whether orexin neurons are more generally involved in central thermoregulatory mechanisms, we applied other forms of thermogenic perturbations, including brain prostaglandin E2 (PGE2) injections which mimic inflammatory fever and environmental cold exposure, to ORX-KO mice, ORX-AB mice and their wild-type (WT) litter mates. ORX-AB mice, but not ORX-KO mice, exhibited a blunted PGE2-induced fever and intolerance to cold (5°C) exposure, and these findings were similar to the results previously obtained with stress-induced thermogenesis. PGE2-induced shivering was also attenuated in ORX-AB mice. Both mutants responded similarly to environmental heating (39°C). In WT and ORX-KO mice, the administration of PGE2 and cold exposure activated orexin neurons, as revealed by increased levels of expression of c-fos. Injection of retrograde tracer into the medullary raphe nucleus revealed direct and indirect projection from the orexin neurons, of which the latter seemed to be preserved in the ORX-AB mice. In addition, we found that glutamate receptor antagonists (d-(–)-2-amino-5-phosphonopentanoic acid and 6-cyano-7-nitroquinoxaline-2,3-dione) but not orexin receptor antagonists (SB334867 and OX2 29) successfully inhibited PGE2-induced fever in WT mice. These results suggest that orexin neurons are important in general thermogenic processes, and their importance is not restricted to stress-induced thermogenesis. In addition, these results indicate the possible involvement of glutamate in orexin neurons implicated in PGE2-induced fever. PMID:23959674

Orexin neurons are indispensable for prostaglandin E2-induced fever and defence against environmental cooling in mice.

PubMed

Takahashi, Yoshiko; Zhang, Wei; Sameshima, Kohei; Kuroki, Chiharu; Matsumoto, Ami; Sunanaga, Jinko; Kono, Yu; Sakurai, Takeshi; Kanmura, Yuichi; Kuwaki, Tomoyuki

2013-11-15

We recently showed using prepro-orexin knockout (ORX-KO) mice and orexin neuron-ablated (ORX-AB) mice that orexin neurons in the hypothalamus, but not orexin peptides per se, are indispensable for stress-induced thermogenesis. To examine whether orexin neurons are more generally involved in central thermoregulatory mechanisms, we applied other forms of thermogenic perturbations, including brain prostaglandin E2 (PGE2) injections which mimic inflammatory fever and environmental cold exposure, to ORX-KO mice, ORX-AB mice and their wild-type (WT) litter mates. ORX-AB mice, but not ORX-KO mice, exhibited a blunted PGE2-induced fever and intolerance to cold (5°C) exposure, and these findings were similar to the results previously obtained with stress-induced thermogenesis. PGE2-induced shivering was also attenuated in ORX-AB mice. Both mutants responded similarly to environmental heating (39°C). In WT and ORX-KO mice, the administration of PGE2 and cold exposure activated orexin neurons, as revealed by increased levels of expression of c-fos. Injection of retrograde tracer into the medullary raphe nucleus revealed direct and indirect projection from the orexin neurons, of which the latter seemed to be preserved in the ORX-AB mice. In addition, we found that glutamate receptor antagonists (D-(-)-2-amino-5-phosphonopentanoic acid and 6-cyano-7-nitroquinoxaline-2,3-dione) but not orexin receptor antagonists (SB334867 and OX2 29) successfully inhibited PGE2-induced fever in WT mice. These results suggest that orexin neurons are important in general thermogenic processes, and their importance is not restricted to stress-induced thermogenesis. In addition, these results indicate the possible involvement of glutamate in orexin neurons implicated in PGE2-induced fever.

Sex-Specific Consequences of Neonatal Stress on Cardio-Respiratory Inhibition Following Laryngeal Stimulation in Rat Pups

PubMed Central

Baldy, Cécile; Chamberland, Simon

2017-01-01

Abstract The presence of liquid near the larynx of immature mammals triggers prolonged apneas with significant O2 desaturations and bradycardias. When excessive, this reflex (the laryngeal chemoreflex; LCR) can be fatal. Our understanding of the origins of abnormal LCR are limited; however, perinatal stress and male sex are risk factors for cardio-respiratory failure in infants. Because exposure to stress during early life has deleterious and sex-specific consequences on brain development it is plausible that respiratory reflexes are vulnerable to neuroendocrine dysfunction. To address this issue, we tested the hypothesis that neonatal maternal separation (NMS) is sufficient to exacerbate LCR-induced cardio-respiratory inhibition in anesthetized rat pups. Stressed pups were separated from their mother 3 h/d from postnatal days 3 to 12. At P14–P15, pups were instrumented to monitor breathing, O2 saturation (Spo2), and heart rate. The LCR was activated by water injections near the larynx (10 µl). LCR-induced apneas were longer in stressed pups than controls; O2 desaturations and bradycardias were more profound, especially in males. NMS increased the frequency and amplitude of spontaneous EPSCs (sEPSCs) in the dorsal motor nucleus of the vagus (DMNV) of males but not females. The positive relationship between corticosterone and testosterone observed in stressed pups (males only) suggests that disruption of neuroendocrine function by stress is key to sex-based differences in abnormal LCR. Because testosterone application onto medullary slices augments EPSC amplitude only in males, we propose that testosterone-mediated enhancement of synaptic connectivity within the DMNV contributes to the male bias in cardio-respiratory inhibition following LCR activation in stressed pups. PMID:29308430

Short-term sustained hypoxia induces changes in the coupling of sympathetic and respiratory activities in rats

PubMed Central

Moraes, Davi J A; Bonagamba, Leni G H; Costa, Kauê M; Costa-Silva, João H; Zoccal, Daniel B; Machado, Benedito H

2014-01-01

Individuals experiencing sustained hypoxia (SH) exhibit adjustments in the respiratory and autonomic functions by neural mechanisms not yet elucidated. In the present study we evaluated the central mechanisms underpinning the SH-induced changes in the respiratory pattern and their impact on the sympathetic outflow. Using a decerebrated arterially perfused in situ preparation, we verified that juvenile rats exposed to SH (10% O2) for 24 h presented an active expiratory pattern, with increased abdominal, hypoglossal and vagal activities during late-expiration (late-E). SH also enhanced the activity of augmenting-expiratory neurones and depressed the activity of post-inspiratory neurones of the Bötzinger complex (BötC) by mechanisms not related to changes in their intrinsic electrophysiological properties. SH rats exhibited high thoracic sympathetic activity and arterial pressure levels associated with an augmented firing frequency of pre-sympathetic neurones of the rostral ventrolateral medulla (RVLM) during the late-E phase. The antagonism of ionotropic glutamatergic receptors in the BötC/RVLM abolished the late-E bursts in expiratory and sympathetic outputs of SH rats, indicating that glutamatergic inputs to the BötC/RVLM are essential for the changes in the expiratory and sympathetic coupling observed in SH rats. We also observed that the usually silent late-E neurones of the retrotrapezoid nucleus/parafacial respiratory group became active in SH rats, suggesting that this neuronal population may provide the excitatory drive essential to the emergence of active expiration and sympathetic overactivity. We conclude that short-term SH induces the activation of medullary expiratory neurones, which affects the pattern of expiratory motor activity and its coupling with sympathetic activity. PMID:24614747

Interaction of medullary P2 and glutamate receptors mediates the vasodilation in the hindlimb of rat.

PubMed

Korim, Willian Seiji; Ferreira-Neto, Marcos L; Pedrino, Gustavo R; Pilowsky, Paul M; Cravo, Sergio L

2012-12-01

In the nucleus tractus solitarii (NTS) of rats, blockade of extracellular ATP breakdown to adenosine reduces arterial blood pressure (AP) increases that follow stimulation of the hypothalamic defense area (HDA). The effects of ATP on NTS P2 receptors, during stimulation of the HDA, are still unclear. The aim of this study was to determine whether activation of P2 receptors in the NTS mediates cardiovascular responses to HDA stimulation. Further investigation was taken to establish if changes in hindlimb vascular conductance (HVC) elicited by electrical stimulation of the HDA, or activation of P2 receptors in the NTS, are relayed in the rostral ventrolateral medulla (RVLM); and if those responses depend on glutamate release by ATP acting on presynaptic terminals. In anesthetized and paralyzed rats, electrical stimulation of the HDA increased AP and HVC. Blockade of P2 or glutamate receptors in the NTS, with bilateral microinjections of suramin (10 mM) or kynurenate (50 mM) reduced only the evoked increase in HVC by 75 % or more. Similar results were obtained with the blockade combining both antagonists. Blockade of P2 and glutamate receptors in the RVLM also reduced the increases in HVC to stimulation of the HDA by up to 75 %. Bilateral microinjections of kynurenate in the RVLM abolished changes in AP and HVC to injections of the P2 receptor agonist α,β-methylene ATP (20 mM) into the NTS. The findings suggest that HDA-NTS-RVLM pathways in control of HVC are mediated by activation of P2 and glutamate receptors in the brainstem in alerting-defense reactions.

Soft tissue and cellular preservation in vertebrate skeletal elements from the Cretaceous to the present.

PubMed

Schweitzer, Mary Higby; Wittmeyer, Jennifer L; Horner, John R

2007-01-22

Soft tissues and cell-like microstructures derived from skeletal elements of a well-preserved Tyrannosaurus rex (MOR 1125) were represented by four components in fragments of demineralized cortical and/or medullary bone: flexible and fibrous bone matrix; transparent, hollow and pliable blood vessels; intravascular material, including in some cases, structures morphologically reminiscent of vertebrate red blood cells; and osteocytes with intracellular contents and flexible filipodia. The present study attempts to trace the occurrence of these four components in bone from specimens spanning multiple geological time periods and varied depositional environments. At least three of the four components persist in some skeletal elements of specimens dating to the Campanian. Fibrous bone matrix is more altered over time in morphology and less likely to persist than vessels and/or osteocytes. Vessels vary greatly in preservation, even within the same specimen, with some regions retaining pliability and other regions almost crystalline. Osteocytes also vary, with some retaining long filipodia and transparency, while others present with short and stubby filipodia and deeply pigmented nuclei, or are pigmented throughout with no nucleus visible. Alternative hypotheses are considered to explain the origin/source of observed materials. Finally, a two-part mechanism, involving first cross-linking of molecular components and subsequent mineralization, is proposed to explain the surprising presence of still-soft elements in fossil bone. These results suggest that present models of fossilization processes may be incomplete and that soft tissue elements may be more commonly preserved, even in older specimens, than previously thought. Additionally, in many cases, osteocytes with defined nuclei are preserved, and may represent an important source for informative molecular data.

Interagency Evaluation of the Section 1206 Global Train and Equip Program

DTIC Science & Technology

2009-08-31

Capabilities, Joint Staff, U.S. Africa Command, U.S. Central Command, U.S Joint Forces Command, U.S. Pacific Command, U.S. Southern Command, U.S. Special...Intensity Conflict & Interdependent Capabilities; Commanders of U.S. Africa Command, U.S. Central Command, U.S. Joint Forces Command, U.S. Pacific... Central Command, commented that coordinating the Section 1206 project proposal with the partner nation prior to submission would inflate the

5. Command center doors at command center entry, building 501, ...

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

5. Command center doors at command center entry, building 501, looking north - Offutt Air Force Base, Strategic Air Command Headquarters & Command Center, Command Center, 901 SAC Boulevard, Bellevue, Sarpy County, NE

Renal Medullary Solute Depletion Resulting from Psychogenic Polydipsia in a Rhesus Monkey

DTIC Science & Technology

1988-01-01

O ADH would normally indicate nerphrovenic served to have poivdipsia and an unthnftv diabetes insipidus . however, oae would expect the appearance...rral~rirnimram: 1082 12 �-173 response to proloinied diuresis. and resuited in a lack ! iuinix !A Diabetes in.inlaius In KAirk K%\\ t.i .’m o)I renal

Evaluation of the 90-Day Inhalation Toxicity of Petroleum and Oil Shale JP-5 Jet Fuel

DTIC Science & Technology

1985-04-01

urothelium over the surface of the renal papillus, moderate to severe deposits of mineralized debris in medullary tubules (probably at the loop of Henle...and tubular degenera- tion. Hyperplastic areas along the pelvic urothelium were thought to result from mechanical irritation by mineralized de- bris

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

PubMed

Batista, Rafael Loch; Toscanini, Andrea Cecilia; Brandão, Lenine Garcia; Cunha-Neto, Malebranche Berardo C

2013-05-01

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.

Selective arterial chemoembolization for hepatic metastases from medullary thyroid carcinoma.

PubMed

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.

Bilateral neuroblastoma in situ associated with microcephaly.

PubMed Central

Park, W. S.; Chi, J. G.

1993-01-01

We present an autopsy case of a two-day-old female infant with a very unusual combination of neuroblastoma in situ in both adrenals and microcephaly. This baby was born to a 28-year-old mother after 38 weeks of gestation, and died of respiratory difficulty 2 days later. At autopsy, the baby weighted 1,840gm, and the brain was extraordinarily small with a weight of 125gm. The gyral pattern was simplified and irregular. Microscopically massive migration defects, pachygyria, micropolygyria, leptomeningeal glioneuronal islands, small corticospinal tract and heterotopic Purkinje cells in the cerebellum were found. In addition, there were medullary nodules in both adrenals. They measured 0.7 x 0.4cm and 0.7 x 0.3cm, respectively. These nodules showed the typical histological features of undifferentiated neuroblastoma. The tumor nodules were confined to the medullary portion and did not extend to the cortex or contiguous structures meeting the criteria of neuroblastoma in situ. Based on these unusual and seemingly unrelated sets of findings, it is suggested that the histogenesis of neuroblastoma in situ could be a part of the generalized dysontogenic process. PMID:8397936

Lack of association of the serotonin transporter polymorphism with the sudden infant death syndrome in the San Diego Dataset.

PubMed

Paterson, David S; Rivera, Keith D; Broadbelt, Kevin G; Trachtenberg, Felicia L; Belliveau, Richard A; Holm, Ingrid A; Haas, Elisabeth A; Stanley, Christina; Krous, Henry F; Kinney, Hannah C; Markianos, Kyriacos

2010-11-01

Dysfunction of medullary serotonin (5-HT)-mediated respiratory and autonomic function is postulated to underlie the pathogenesis of the majority of sudden infant death syndrome (SIDS) cases. Several studies have reported an increased frequency of the LL genotype and L allele of the 5-HT transporter (5-HTT) gene promoter polymorphism (5-HTTLPR), which is associated with increased transcriptional activity and 5-HT transport in vitro, in SIDS cases compared with controls. These findings raise the possibility that this polymorphism contributes to or exacerbates existing medullary 5-HT dysfunction in SIDS. In this study, we tested the hypothesis that the frequency of LL genotype and L allele are higher in 179 SIDS cases compared with 139 controls of multiple ethnicities in the San Diego SIDS Dataset. We observed no significant association of genotype or allele with SIDS cases either in the total cohort or on stratification for ethnicity. These observations do not support previous findings that the L allele and/or LL genotype of the 5-HTTLPR are associated with SIDS.

Predominant RET Germline Mutations in Exons 10, 11, and 16 in Iranian Patients with Hereditary Medullary Thyroid Carcinoma

PubMed Central

Hedayati, Mehdi; Zarif Yeganeh, Marjan; Sheikhol Eslami, Sara; Rezghi Barez, Shekoofe; Hoghooghi Rad, Laleh; Azizi, Fereidoun

2011-01-01

Medullary thyroid carcinoma occurs in both sporadic (75%) and hereditary (25%) forms. The missense mutations of RET proto-oncogene in MTC development have been well demonstrated. To investigate the spectrum of predominant RET germline mutations in exons 10, 11, and 16 in hereditary MTC in Iranian population, 217 participants were included. Genomic DNAs were extracted from the leukocytes using the standard Salting Out/Proteinase K method. Mutation detection was performed through PCR-RFLP and DNA sequencing. In 217 participants, 43 missense mutations were identified in exons 10 (6%), 11 (13%), and 16 (0.9%). Moreover, a novel germline mutation was detected in exon 11 (S686N). Also four different polymorphisms were found in intron 16 in eight patients. The obtained data showed the frequency profile of RET mutations in Iranian individuals with MTC (19.8%). The most frequent mutation in our population was C634G whereas in most population it was C634R. Altogether, these results underline the importance of the genetic background of family members of any patient with MTC. PMID:21765987

Renal medullary carcinoma: molecular, pathological and clinical evidence for treatment with topoisomerase-inhibiting therapy.

PubMed

Schaeffer, Edward M; Guzzo, Thomas J; Furge, Kyle A; Netto, George; Westphal, Michael; Dykema, Karl; Yang, Ximing; Zhou, Ming; Teh, Bin Tean; Pavlovich, Christian P

2010-07-01

Aetiology (case series) Level of Evidence 4. To present the molecular rationale and potential clinical benefit of topoisomerase II (TopoII)-inhibiting therapy for renal medullary carcinoma (RMC), a rare but extremely lethal form of kidney cancer that classically afflicts young men with sickle-cell trait. The current therapeutic approach with these aggressive tumours is radical nephrectomy followed by systemic chemotherapy, but the prognosis remains dismal. The whole-genome expression was analysed in four RMC tumours. We also report a case of metastatic RMC in which a complete response was achieved for 9 months using a TopoII-inhibiting therapy. Expanded whole-genome expression analysis showed increases of TopoII in all cases. There was also overall deregulation of DNA remodelling and repair, and an ontological association between RMC and urothelial carcinoma. Using a TopoII-inhibiting agent, there was a complete response for 9 months in a patient with metastatic RMC. This report provides molecular evidence for the rational use of TopoII inhibitors in the treatment of RMC.

Suspected panosteitis in a camel.

PubMed

Levine, David G; Smith, Jennifer J; Richardson, Dean W; Brown, Valerie; Beech, Jill; Habecker, Perry; Adam, Emma

2007-08-01

A 6-month-old male Bactrian camel was examined because of a 3-week history of lameness of the left hind limb. Lameness was initially detected in the left hind limb but resolved and was detected in the right hind limb during treatment. Lameness increased during periods of rapid growth. Radiography revealed multiple small opacities of the medullary cavity of several long bones throughout treatment. Core bone biopsies of lesions in the tibiae revealed lamellar bone with areas of loose connective tissue, osteoblasts in the medullary cavity, and periosteal new bone formation, all which were consistent with panosteitis. Palliative treatment was attempted with epidural and transdermal administration of analgesics. Flunixin meglumine was administered PO, which coincided with an abrupt increase in serum creatinine concentration. Performance of multiple diagnostic bone biopsies led to remission of clinical signs of pain. Panosteitis should be a differential diagnosis for shifting limb lameness in young camels. Bone biopsies can be useful for diagnosis of panosteitis and possible relief of pain associated with the disease. Bactrian camels may be susceptible to the renal toxicity of flunixin meglumine, especially when dehydrated.

Immunocytochemical localization of metabotropic (mGluR2/3 and mGluR4a) and ionotropic (GluR2/3) glutamate receptors in adrenal medullary ganglion cells.

PubMed

Sarría, R; Díez, J; Losada, J; Doñate-Oliver, F; Kuhn, R; Grandes, P

2006-02-01

The localization of metabotropic glutamate receptors of groups II (mGluR2/3) and III (mGluR4a) and the subunits 2 and 3 of alfa-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) ionotropic glutamate receptors (GluR2/3) was investigated with immunocytochemical methods in the rat adrenal gland. MGluR2/3, mGluR4a and GluR2/3 immunoreactivities were observed in large-sized, centrally located type I adrenal medullary ganglion neurons. Furthermore, the small-sized type II adrenal ganglion neurons identified by their immunoreactivity to brain nitric oxide synthase (bNOS), also expressed mGluR2/3, mGluR4a and GluR2/3. These cells were disposed in the peripheral portion of the adrenal medulla. None of the type I neurons were positively labeled for bNOS. These morphological observations suggest that activation of glutamate receptors in ganglion neurons may be instrumental in the control of adrenal endocrine systems as well as blood regulation.

The construction and partial characterization of plasmids containing complementary DNA sequences to human calcitonin precursor polyprotein.

PubMed Central

Allison, J; Hall, L; MacIntyre, I; Craig, R K

1981-01-01

(1) Total poly(A)-containing RNA isolated from human thyroid medullary carcinoma tissue was shown to direct the synthesis in the wheat germ cell-free system of a major (Mr 21000) and several minor forms of human calcitonin precursor polyproteins. Evidence for processing of these precursor(s) by the wheat germ cell-free system is also presented. (2) A small complementary DNA (cDNA) plasmid library has been constructed in the PstI site of the plasmid pAT153, using total human thyroid medullary carcinoma poly(A)-containing RNA as the starting material. (3) Plasmids containing abundant cDNA sequences were selected by hybridization in situ, and two of these (ph T-B3 and phT-B6) were characterized by hybridization--translation and restriction analysis. Each was shown to contain human calcitonin precursor polyprotein cDNA sequences. (4) RNA blotting techniques demonstrate that the human calcitonin precursor polyprotein is encoded within a mRNA containing 1000 bases. (5) The results demonstrate that human calcitonin is synthesized as a precursor polyprotein. Images Fig. 1. Fig. 2. Fig. 3. PMID:6896146

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

PubMed

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.

Neural differentiation of caudal cell mass (secondary neurulation) in chick embryos: Hamburger and Hamilton Stages 16-45.

PubMed

Yang, Hee-Jin; Wang, Kyu-Chang; Chi, Je G; Lee, Myung-Sook; Lee, Yun-Jin; Kim, Seung-Ki; Cho, Byung-Kyu

2003-04-14

In an attempt to understand the events in the secondary neurulation in embryonic stage, we investigated morphological changes in the tail bud of normal developing chick embryos. Hamburger and Hamilton stage 16-45 embryos were harvested and processed for light microscopic studies. The secondary neural tube is formed by aggregation of the caudal cell mass. Cells are arranged into a cord-like mass (medullary cord), which is continuous with the primary neural tube. Multiple small cavities develop in the medullary cord, and these cavities coalesce into one single lumen. The process of coalescence is completed by stage 35, and the whole neural tube is transformed into one tube with a single continuous lumen. At this stage, the terminal portion of the neural tube is bulged dorsally. Thereafter, the caudal portion of the neural tube regresses, and the proximal portion develops into normal spinal cord. Transient occlusion of the central canal was observed at stage 40 in one sample. The sequence of events elucidated in this study can be used as base-line data for experiments concerning congenital malformations involving secondary neurulation.

Mixed-mode oscillations and population bursting in the pre-Bötzinger complex

PubMed Central

Bacak, Bartholomew J; Kim, Taegyo; Smith, Jeffrey C; Rubin, Jonathan E; Rybak, Ilya A

2016-01-01

This study focuses on computational and theoretical investigations of neuronal activity arising in the pre-Bötzinger complex (pre-BötC), a medullary region generating the inspiratory phase of breathing in mammals. A progressive increase of neuronal excitability in medullary slices containing the pre-BötC produces mixed-mode oscillations (MMOs) characterized by large amplitude population bursts alternating with a series of small amplitude bursts. Using two different computational models, we demonstrate that MMOs emerge within a heterogeneous excitatory neural network because of progressive neuronal recruitment and synchronization. The MMO pattern depends on the distributed neuronal excitability, the density and weights of network interconnections, and the cellular properties underlying endogenous bursting. Critically, the latter should provide a reduction of spiking frequency within neuronal bursts with increasing burst frequency and a dependence of the after-burst recovery period on burst amplitude. Our study highlights a novel mechanism by which heterogeneity naturally leads to complex dynamics in rhythmic neuronal populations. DOI: http://dx.doi.org/10.7554/eLife.13403.001 PMID:26974345

Lack of Association of the Serotonin Transporter Polymorphism With the Sudden Infant Death Syndrome in the San Diego Dataset

PubMed Central

Paterson, David S.; Rivera, Keith D.; Broadbelt, Kevin G.; Trachtenberg, Felicia L.; Belliveau, Richard A.; Holm, Ingrid A.; Haas, Elisabeth A.; Stanley, Christina; Krous, Henry F.; Kinney, Hannah C.; Markianos, Kyriacos

2011-01-01

Dysfunction of medullary serotonin (5-HT)-mediated respiratory and autonomic function is postulated to underlie the pathogenesis of the majority of sudden infant death syndrome (SIDS) cases. Several studies have reported an increased frequency of the LL genotype and L allele of the 5-HT transporter (5-HTT) gene promoter polymorphism (5-HTTLPR), which is associated with increased transcriptional activity and 5-HT transport in vitro, in SIDS cases compared with controls. These findings raise the possibility that this polymorphism contributes to or exacerbates existing medullary 5-HT dysfunction in SIDS. In this study, we tested the hypothesis that the frequency of LL genotype and L allele are higher in 179 SIDS cases compared with 139 controls of multiple ethnicities in the San Diego SIDS Dataset. We observed no significant association of genotype or allele with SIDS cases either in the total cohort or on stratification for ethnicity. These observations do not support previous findings that the L allele and/or LL genotype of the 5-HTTLPR are associated with SIDS. PMID:20661167

Positive and Negative Regulatory Mechanisms for Fine-Tuning Cellularity and Functions of Medullary Thymic Epithelial Cells.

PubMed

Akiyama, Taishin; Tateishi, Ryosuke; Akiyama, Nobuko; Yoshinaga, Riko; Kobayashi, Tetsuya J

2015-01-01

Self-tolerant T cells and regulatory T cells develop in the thymus. A wide variety of cell-cell interactions in the thymus is required for the differentiation, proliferation, and repertoire selection of T cells. Various secreted and cell surface molecules expressed in thymic epithelial cells (TECs) mediate these processes. Moreover, cytokines expressed by cells of hematopoietic origin regulate the cellularity of TECs. Tumor necrosis factor (TNF) family RANK ligand, lymphotoxin, and CD40 ligand, expressed in T cells and innate lymphoid cells (ILCs), promote the differentiation and proliferation of medullary TECs (mTECs) that play critical roles in the induction of immune tolerance. A recent study suggests that interleukin-22 (IL-22) produced by ILCs promotes regeneration of TECs after irradiation. Intriguingly, tumor growth factor-β and osteoprotegerin limit cellularity of mTECs, thereby attenuating regulatory T cell generation. We will review recent insights into the molecular basis for cell-cell interactions regulating differentiation and proliferation of mTECs and also discuss about a perspective on use of mathematical models for understanding this complicated system.

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

PubMed

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.

Fluorescent tagging of rhythmically active respiratory neurons within the pre-Bötzinger complex of rat medullary slice preparations.

PubMed

Pagliardini, Silvia; Adachi, Tadafumi; Ren, Jun; Funk, Gregory D; Greer, John J

2005-03-09

Elucidation of the neuronal mechanisms underlying respiratory rhythmogenesis is a major focal point in respiratory physiology. An area of the ventrolateral medulla, the pre-Bötzinger complex (preBotC), is a critical site. Attention is now focused on understanding the cellular and network properties within the preBotC that underlie this critical function. The inability to clearly identify key "rhythm-generating" neurons within the heterogeneous population of preBotC neurons has been a significant limitation. Here we report an advancement allowing precise targeting of neurons expressing neurokinin-1 receptors (NK1Rs), which are hypothesized to be essential for respiratory rhythmogenesis. The internalization of tetramethylrhodamine conjugated substance P in rhythmically active medullary slice preparations provided clear visualization of NK1R-expressing neurons for subsequent whole-cell patch-clamp recordings. Among labeled neurons, 82% were inspiratory modulated, and 25% had pacemaker properties. We propose that this approach can be used to greatly expedite progress toward understanding the neuronal processes underlying the control of breathing.

Characterization of the central neural projections to brown, white, and beige adipose tissue.

PubMed

Wiedmann, Nicole M; Stefanidis, Aneta; Oldfield, Brian J

2017-11-01

The functional recruitment of classic brown adipose tissue (BAT) and inducible brown-like or beige fat is, to a large extent, dependent on intact sympathetic neural input. Whereas the central neural circuits directed specifically to BAT or white adipose tissue (WAT) are well established, there is only a developing insight into the nature of neural inputs common to both fat types. Moreover, there is no clear view of the specific central and peripheral innervation of the browned component of WAT: beige fat. The objective of the present study is to examine the neural input to both BAT and WAT in the same animal and, by exposing different cohorts of rats to either thermoneutral or cold conditions, define changes in central neural organization that will ensure that beige fat is appropriately recruited and modulated after browning of inguinal WAT (iWAT). At thermoneutrality, injection of the neurotropic (pseudorabies) viruses into BAT and WAT demonstrates that there are dedicated axonal projections, as well as collateral axonal branches of command neurons projecting to both types of fat. After cold exposure, central neural circuits directed to iWAT showed evidence of reorganization with a greater representation of command neurons projecting to both brown and beiged WAT in hypothalamic (paraventricular nucleus and lateral hypothalamus) and brainstem (raphe pallidus and locus coeruleus) sites. This shift was driven by a greater number of supraspinal neurons projecting to iWAT under cold conditions. These data provide evidence for a reorganization of the nervous system at the level of neural connectivity following browning of WAT.-Wiedmann, N. M., Stefanidis, A., Oldfield, B. J. Characterization of the central neural projections to brown, white, and beige adipose tissue. © FASEB.

Network, system, and status software enhancements for the autonomously managed electrical power system breadboard. Volume 3: Commands specification

NASA Technical Reports Server (NTRS)

Mckee, James W.

1990-01-01

This volume (3 of 4) contains the specification for the command language for the AMPS system. The volume contains a requirements specification for the operating system and commands and a design specification for the operating system and command. The operating system and commands sits on top of the protocol. The commands are an extension of the present set of AMPS commands in that the commands are more compact, allow multiple sub-commands to be bundled into one command, and have provisions for identifying the sender and the intended receiver. The commands make no change to the actual software that implement the commands.

Exercise-induced neuronal plasticity in central autonomic networks: role in cardiovascular control.

PubMed

Michelini, Lisete C; Stern, Javier E

2009-09-01

It is now well established that brain plasticity is an inherent property not only of the developing but also of the adult brain. Numerous beneficial effects of exercise, including improved memory, cognitive function and neuroprotection, have been shown to involve an important neuroplastic component. However, whether major adaptive cardiovascular adjustments during exercise, needed to ensure proper blood perfusion of peripheral tissues, also require brain neuroplasticity, is presently unknown. This review will critically evaluate current knowledge on proposed mechanisms that are likely to underlie the continuous resetting of baroreflex control of heart rate during/after exercise and following exercise training. Accumulating evidence indicates that not only somatosensory afferents (conveyed by skeletal muscle receptors, baroreceptors and/or cardiopulmonary receptors) but also projections arising from central command neurons (in particular, peptidergic hypothalamic pre-autonomic neurons) converge into the nucleus tractus solitarii (NTS) in the dorsal brainstem, to co-ordinate complex cardiovascular adaptations during dynamic exercise. This review focuses in particular on a reciprocally interconnected network between the NTS and the hypothalamic paraventricular nucleus (PVN), which is proposed to act as a pivotal anatomical and functional substrate underlying integrative feedforward and feedback cardiovascular adjustments during exercise. Recent findings supporting neuroplastic adaptive changes within the NTS-PVN reciprocal network (e.g. remodelling of afferent inputs, structural and functional neuronal plasticity and changes in neurotransmitter content) will be discussed within the context of their role as important underlying cellular mechanisms supporting the tonic activation and improved efficacy of these central pathways in response to circulatory demand at rest and during exercise, both in sedentary and in trained individuals. We hope this review will stimulate more comprehensive studies aimed at understanding cellular and molecular mechanisms within CNS neuronal networks that contribute to exercise-induced neuroplasticity and cardiovascular adjustments.

Joint Chiefs of Staff > Media > Photos

Science.gov Websites

U.S. Army Gen. Curtis M. Scaparrotti, left, Commander of U.S. European Command and Supreme Allied , Commander of U.S. European Command and Supreme Allied Commander, Europe; speaks after receiving the . U.S. Army Gen. Curtis M. Scaparrotti, Commander of U.S. European Command and Supreme Allied Commander

A Physiological Neural Network for Saccadic Eye Movement Control

DTIC Science & Technology

1994-04-01

cerebellum, substantia nigra, nucleus reticularis tegmenti pontis, the thalamus, the deep layers of the superior colliculus and the oculomotor plant...and pause cells), the vestibular nucleus , abducens nucleus , oculomotor nucleus , cerebellum, substantia nigra, nucleus reticularis tegmenti pontis, the...vestibular nucleus , abducens nucleus , oculomotor nucleus , cerebellum, substantia nigra, nucleus reticularis tegmenti pontis (NRTP), the thalamus, the

[Changes of blood vessels in glucocorticoid-induced avascular necrosis of femoral head in rabbits].

PubMed

Zhou, Q; Li, Q; Yang, L; Liu, F

2000-03-01

To evaluate the effects of fatty tamponade in medullary cavity (serious intramedullary fatty infiltration) on the changes of blood vessels in femoral heads during the pathological process of glucocorticoid (GC)-induced avascular necrosis (AVM) of the femoral heads. The animal model of AVN was established with injection of dexamethasone (DEX) at a high dose of 2.5 mg x kg(-1) x d(-1) in rabbits. Histopathological and morphological changes of blood vessels in the femoral heads were investigated during GC-treatment and after the cessation scanning electron microscope, light microscope, and image analysis. At the 2nd week of DEX-treatment, the fatty tamponade in the medullary cavity appeared in the femoral heads. Intramedullary vascular sinusoids were pressed by an excess of lipocytes and became narrow. The impressions of lipocytes on the surface of vascular sinusoids were definitely displayed on the vascular casts and ink-perfused slides of the femoral heads. These changes were pronounced with the prolongation of the treatment and the vascular sinusoids gradually lost their characteristics. Image analysis showed that the vascular area in the femoral heads continuously decreased. At the 8th week, the effects of fatty tamponade were the most marked. Intramedullary vessels became very sparse and the vascular area decreased to 1/4 of the controls. At the 6th week after the GC-treatment cessation, intramedullary fatty infiltration still existed. The blood vessels were fine and sparse, and the structural features of vascular sinusoids disappeared in the load-bearing regions of the femoral heads. At the 4th week, typical osteonecrosis focuses appeared in the femoral heads. The focuses became larger and the degree of osteonecrosis was increasing with the time of experiment. The fatty tamponade in the medullary cavity is one of the important pathological factors causing ischemic damage to the femoral heads, and plays an important role in the early stage of GC-induced AVN.

Minimum urine flow rate during water deprivation: importance of the nonurea versus total osmolality in the inner medulla.

PubMed

Soroka, S D; Chayaraks, S; Cheema-Dhadli, S; Myers, J A; Rubin, S; Sonnenberg, H; Halperin, M L

1997-06-01

Antidiuretic hormone leads to an increase in the permeability for water and urea in the inner medullary collecting duct. Hence, urea may not be an "effective" osmole in the inner medulla during maximal renal water conservation. Accordingly, the purpose of this study was to evaluate whether differences in the rate of urea excretion would influence maximum renal water conservation in humans. In water-deprived rats, the concentration of urea and total osmolality were somewhat higher in the urine exiting the inner medullary collecting duct than in interstitial fluid obtained from the entire papillary tip. Nevertheless, the "nonurea" (total osmolality minus urea in millimolar terms) osmolality was virtually identical in both locations. Chronically fasted human subjects that were water-deprived for 16 h had a lower rate of urea excretion (71 +/- 7 versus 225 +/- 14 mumol/min) and a somewhat lower urine osmolality (745 +/- 53 versus 918 +/- 20 mosmol/kg H2O). Nevertheless, they had identical urine flow rates (0.5 +/- 0.01 and 0.5 +/- 0.02 ml/min, respectively), and their nonurea osmolality also was similar (587 +/- 25 and 475 +/- 14 mosmol/kg H2O, respectively) to the water-deprived normal subjects. The composition of their urine differed in that the principal nonurea osmoles became NH4+ and beta-hydroxybutyrate rather than Na and C1. During water deprivation in normal subjects, the ingestion of urea caused a twofold rise in urine flow rate, a fall in the nonurea osmolality, and a rise in the rate of excretion of nonurea osmoles. The nonurea osmolality of the urine, and presumably the medullary interstitial fluid as well, was inversely related to the urea excretion rate. In chronic fasting, the nature, but not the quantity, of nonurea osmoles changed. The similar minimum urine volume was predictable from an analysis based on nonurea osmole considerations.

Predicted consequences of diabetes and SGLT inhibition on transport and oxygen consumption along a rat nephron

PubMed Central

Vallon, Volker; Edwards, Aurélie

2016-01-01

Diabetes increases the reabsorption of Na+ (TNa) and glucose via the sodium-glucose cotransporter SGLT2 in the early proximal tubule (S1-S2 segments) of the renal cortex. SGLT2 inhibitors enhance glucose excretion and lower hyperglycemia in diabetes. We aimed to investigate how diabetes and SGLT2 inhibition affect TNa and sodium transport-dependent oxygen consumption QO2active along the whole nephron. To do so, we developed a mathematical model of water and solute transport from the Bowman space to the papillary tip of a superficial nephron of the rat kidney. Model simulations indicate that, in the nondiabetic kidney, acute and chronic SGLT2 inhibition enhances active TNa in all nephron segments, thereby raising QO2active by 5–12% in the cortex and medulla. Diabetes increases overall TNa and QO2active by ∼50 and 100%, mainly because it enhances glomerular filtration rate (GFR) and transport load. In diabetes, acute and chronic SGLT2 inhibition lowers QO2active in the cortex by ∼30%, due to GFR reduction that lowers proximal tubule active TNa, but raises QO2active in the medulla by ∼7%. In the medulla specifically, chronic SGLT2 inhibition is predicted to increase QO2active by 26% in late proximal tubules (S3 segments), by 2% in medullary thick ascending limbs (mTAL), and by 9 and 21% in outer and inner medullary collecting ducts (OMCD and IMCD), respectively. Additional blockade of SGLT1 in S3 segments enhances glucose excretion, reduces QO2active by 33% in S3 segments, and raises QO2active by <1% in mTAL, OMCD, and IMCD. In summary, the model predicts that SGLT2 blockade in diabetes lowers cortical QO2active and raises medullary QO2active, particularly in S3 segments. PMID:26764207

Carbon based secondary compounds do not provide protection against heavy metal road pollutants in epiphytic macrolichens.

PubMed

Gauslaa, Yngvar; Yemets, Olena A; Asplund, Johan; Solhaug, Knut Asbjørn

2016-01-15

Lichens are useful monitoring organisms for heavy metal pollution. They are high in carbon based secondary compounds (CBSCs) among which some may chelate heavy metals and thus increase metal accumulation. This study quantifies CBSCs in four epiphytic lichens transplanted for 6months on stands along transects from a highway in southern Norway to search for relationships between concentrations of heavy metals and CBSCs along a gradient in heavy metal pollutants. Viability parameters and concentrations of 21 elements including nutrients and heavy metals in these lichen samples were reported in a separate paper. Medullary CBSCs in fruticose lichens (Ramalina farinacea, Usnea dasypoga) were reduced in the most polluted sites, but not in foliose ones (Parmelia sulcata, Lobaria pulmonaria), whereas cortical CBSC did not change with distance from the road in any species. Strong positive correlations only occurred between the major medullary compound stictic acid present in L. pulmonaria and most heavy metals, consistent with a chelating role of stictic acid, but not of other studied CBSCs or in other species. However, heavy metal chelating did not protect L. pulmonaria against damage because this species experienced the strongest reduction in viability in the polluted sites. CBSCs with an accumulation potential for heavy metals should be quantified in lichen biomonitoring studies of heavy metals because they, like stictic acid, could overshadow pollutant inputs in some species rendering biomonitoring data less useful. In the two fruticose lichen species, CBSCs decreased with increasing heavy metal concentration, probably because heavy metal exposure impaired secondary metabolism. Thus, we found no support for a heavy metal protection role of any CBSCs in studied epiphytic lichens. No intraspecific relationships occurred between CBSCs versus N or C/N-ratio. Interspecifically, medullary CBSCs decreased and cortical CBSCs increased with increasing C/N-ratio. Copyright © 2015 Elsevier B.V. All rights reserved.

Lipid Peroxidation and Antioxidant Status in Patients with Medullary Thyroid Carcinoma: A Case-Control Study.

PubMed

Hosseini-Zijoud, Seyed-Mostafa; Ebadi, Seyed Alireza; Goodarzi, Mohammad Taghi; Hedayati, Mehdi; Abbasalipourkabir, Roghayeh; Mahjoob, Mohammad Parsa; Poorolajal, Jalal; Zicker, Fabio; Sheikh, Nasrin

2016-02-01

Oxidative stress or oxidant/antioxidant imbalance has a crucial role in the pathogenesis of some diseases like cancer. Medullary thyroid carcinoma (MTC) originates in the thyroid parafollicular cells and includes 3-4% of the malignant neoplasms that have an effect on this gland. The aetiology of MTC has not been clarified. However, oxidative stress may be one of the factors involved. The aim of the current study was to evaluate the antioxidant enzyme activity of catalase (CAT), Glutathione (GSH), total antioxidant capacity (TAC) and the levels of the lipid peroxidation product malondialdehyde (MDA) in blood samples of MTC patients as compared to healthy controls. A case-control study was designed enrolling patients with confirmed MTC diagnosis and age-and sex group matched healthy volunteers referred to the clinic of the Research Institute for Endocrine Sciences, Tehran, Iran from April 2013 to July 2015. Fasting blood samples were taken for study. Catalase, GSH, MDA and TAC levels were measured by colorimetry using commercial kits (ZellBio GmbH, Germany). Data were analysed using SPSS 17 software, comparing mean±SD through t-test and difference between proportions through chi-square. No statistical difference was observed in the demographic characteristic between cases and controls. The final MTC group included 40 males and 45 females with a mean age of 30±12.9 year, and the control group 40 males and 47 females, with a mean age of 31.2±12.3 year. Anthropometric parameters, dietary and thyroid hormones levels (T3, T4 and TSH) were similar. Serum TAC (p=0.015), GSH (p=0.029) and CAT (p<0.001) levels were found to be significantly lower in the MTC patients, while serum MDA levels were significantly higher in MTC patients than controls (p<0.001). These preliminary findings suggest that oxidant/antioxidant imbalance may be associated with or possibly indicate an increased risk to medullary thyroid carcinoma. Further studies are needed to explore these findings.

Redescription of Testudotaenia testudo (Magath, 1924) (Eucestoda: Proteocephalidea), a parasite of Apalone spinifera (Le Sueur) (Reptilia: Trionychidae) and Amia calva L. (Pisces: Amiidae) in North America and erection of the Testudotaeniinae n. subfam.

PubMed

de Chambrier, Alain; Coquille, Sandrine C; Mariaux, Jean; Tkach, Vasyl

2009-05-01

Testudotaenia testudo (Magath, 1924) is redescribed from the intestine of the softshell turtle Apalone spinifera (Le Sueur) (Trionychidae) and the bowfin Amia calva Linnaeus (Amiidae) from Reelfoot Lake, Tennessee, United States. A new subfamily, the Testudotaeniinae, is erected. The new taxon differs from all proteocephalidean subfamilies in the position of the genital organs in relation to the longitudinal internal musculature, i.e. the testes are cortical, rarely medullary; the ovary is partly medullary, with cortical lobes; the vitelline follicles are mainly medullary, with some follicles in the cortex; and the uterus is cortical. A key to the subfamilies of the order Proteocephalidea Mola, 1928 is provided. The most characteristic features of T. testudo are the precocious uterine aperture, the presence of internal uterine pores (as previously described for Proteocephalus paraguayensis (Rudin, 1917)), the eggs laid unripe, the very long strobila (up to 970 mm), and the presence of an anterior circular musculature in the suckers, which is considered as a good differential character. Three other species were found in Amia calva: Proteocephalus perplexus La Rue, 1911, P. ambloplitis (Leidy, 1887) and a new, undescribed form. Sequences of the partial nuclear 28S rRNA gene of specimens of T. testudo from Apalone spinulifera and Amia calva confirm the conspecificity of samples from these two very distinct hosts, which may represent a capture phenomenon. As the subfamily Adenobrechmoinae Bursey, Goldberg & Kraus, 2006 and the genus Adenobrechmos Bursey, Goldberg & Kraus, 2006 are based on the presence of an apical organ, a character which reflects a rather common convergence, we consider the Adenobrechmoinae to be a junior synonym of the Proteocephalinae La Rue, 1911 and Adenobrechmos a junior synonym of Ophiotaenia La Rue, 1911. Adenobrechmos greeri Bursey, Goldberg & Kraus, 2006 thus becomes Ophiotaenia greeri (Bursey, Goldberg & Kraus, 2006) n. comb.

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

PubMed

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 < 0.05) and decreased after L-NMMA injection to 1.57 ± 0.17 ml·g tissue(-1)·min(-1) (P < 0.05). Cortical 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 < 0.05]. PET/CT scanning allows identification of a 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.

Radiographic study of the fifth metatarsal for optimal intramedullary screw fixation of Jones fracture.

PubMed

Ochenjele, George; Ho, Bryant; Switaj, Paul J; Fuchs, Daniel; Goyal, Nitin; Kadakia, Anish R

2015-03-01

Jones fractures occur in the relatively avascular metadiaphyseal junction of the fifth metatarsal (MT), which predisposes these fractures to delayed union and nonunion. Operative treatment with intramedullary (IM) screw fixation is recommended in certain cases. Incorrect screw selection can lead to refractures, nonunion, and cortical blowout fractures. A better understanding of the anatomy of the fifth MT could aid in preoperative planning, guide screw size selection, and minimize complications. We retrospectively identified foot computed tomographic (CT) scans of 119 patients that met inclusion criteria. Using interactive 3-dimensional (3-D) models, the following measurements were calculated: MT length, "straight segment length" (distance from the base of the MT to the shaft curvature), and canal diameter. The diaphysis had a lateroplantar curvature where the medullary canal began to taper. The average straight segment length was 52 mm, and corresponded to 68% of the overall length of the MT from its proximal end. The medullary canal cross-section was elliptical rather than circular, with widest width in the sagittal plane and narrowest in coronal plane. The average coronal canal diameter at the isthmus was 5.0 mm. A coronal diameter greater than 4.5 mm at the isthmus was present in 81% of males and 74% of females. To our knowledge, this is the first anatomic description of the fifth metatarsal based on 3-D imaging. Excessive screw length could be avoided by keeping screw length less than 68% of the length of the fifth metatarsal. A greater than 4.5 mm diameter screw might be needed to provide adequate fixation for most study patients since the isthmus of the medullary canal for most were greater than 4.5 mm. Our results provide an improved understanding of the fifth metatarsal anatomy to guide screw diameter and length selection to maximize screw fixation and minimize complications. © The Author(s) 2014.

Steroid hormone receptors ERalpha and PR characterised by immunohistochemistry in the mare adrenal gland.

PubMed

Alm, Ylva Hedberg; Sukjumlong, Sayamon; Kindahl, Hans; Dalin, Anne-Marie

2009-07-22

Sex steroid hormone receptors have been identified in the adrenal gland of rat, sheep and rhesus monkey, indicating a direct effect of sex steroids on adrenal gland function. In the present study, immunohistochemistry using two different mouse monoclonal antibodies was employed to determine the presence of oestrogen receptor alpha (ERalpha) and progesterone receptor (PR) in the mare adrenal gland. Adrenal glands from intact (n = 5) and ovariectomised (OVX) (n = 5) mares, as well as uterine tissue (n = 9), were collected after euthanasia. Three of the OVX mares were treated with a single intramuscular injection of oestradiol benzoate (2.5 mg) 18-22 hours prior to euthanasia and tissue collection (OVX+Oe). Uterine tissue was used as a positive control and showed positive staining for both ERalpha and PR. ERalpha staining was detected in the adrenal zona glomerulosa, fasciculata and reticularis of all mare groups. Ovariectomy increased cortical ERalpha staining intensity. In OVX mares and one intact mare, positive ERalpha staining was also detected in adrenal medullary cells. PR staining of weak intensity was present in a low proportion of cells in the zona fasciculata and reticularis of all mare groups. Weak PR staining was also found in a high proportion of adrenal medullary cells. In contrast to staining in the adrenal cortex, which was always located within the cell nuclei, medullary staining for both ERalpha and PR was observed only in the cell cytoplasm. The present results show the presence of ERalpha in the adrenal cortex, indicating oestradiol may have a direct effect on mare adrenal function. However, further studies are needed to confirm the presence of PR as staining in the present study was only weak and/or minor. Also, any possible effect of oestradiol treatment on the levels of steroid receptors cannot be determined by the present study, as treatment time was of a too short duration.

The Wnt signaling antagonist Kremen1 is required for development of thymic architecture.

PubMed

Osada, Masako; Ito, Emi; Fermin, Hector A; Vazquez-Cintron, Edwin; Venkatesh, Tadmiri; Friedel, Roland H; Pezzano, Mark

2006-01-01

Wnt signaling has been reported to regulate thymocyte proliferation and selection at several stages during T cell ontogeny, as well as the expression of FoxN1 in thymic epithelial cells (TECs). Kremen1 (Krm1) is a negative regulator of the canonical Wnt signaling pathway, and functions together with the secreted Wnt inhibitor Dickkopf (Dkk) by competing for the lipoprotein receptor-related protein (LRP)-6 co-receptor for Wnts. Here krm1 knockout mice were used to examine krm1 expression in the thymus and its function in thymocyte and TEC development. Krm1 expression was detected in both cortical and medullary TEC subsets, as well as in immature thymocyte subsets, beginning at the CD25+CD44+ (DN2) stage and continuing until the CD4+CD8+(DP) stage. Neonatal mice show elevated expression of krm1 in all TEC subsets. krm1(-/-) mice exhibit a severe defect in thymic cortical architecture, including large epithelial free regions. Much of the epithelial component remains at an immature Keratin 5+ (K5) Keratin 8(+)(K8) stage, with a loss of defined cortical and medullary regions. A TOPFlash assay revealed a 2-fold increase in canonical Wnt signaling in TEC lines derived from krm1(-/-) mice, when compared with krm1(+/+) derived TEC lines. Fluorescence activated cell sorting (FACS) analysis of dissociated thymus revealed a reduced frequency of both cortical (BP1(+)EpCAM(+)) and medullary (UEA-1(+) EpCAM(hi)) epithelial subsets, within the krm1(-/-) thymus. Surprisingly, no change in thymus size, total thymocyte number or the frequency of thymocyte subsets was detected in krm1(-/-) mice. However, our data suggest that a loss of Krm1 leads to a severe defect in thymic architecture. Taken together, this study revealed a new role for Krm1 in proper development of thymic epithelium.

Expression of vesicular glutamate transporters, VGluT1 and VGluT2, in axon terminals of nociceptive primary afferent fibers in the superficial layers of the medullary and spinal dorsal horns of the rat.

PubMed

Li, Jin-Lian; Fujiyama, Fumino; Kaneko, Takeshi; Mizuno, Noboru

2003-03-10

We examined immunohistochemically whether the vesicular glutamate transporters (VGluTs), VGluT1 and VGluT2, might be expressed in synaptic terminals of nociceptive primary afferent fibers within laminae I and II of the medullary and spinal dorsal horns of the rat. VGluT1 immunoreactivity (IR) was intense in the inner part of lamina II but weak in lamina I and the outer part of lamina II. VGluT2-IR was most intense in lamina I and the outer part of lamina II. Expression of VGluTs in synaptic terminals was confirmed by dual immunofluorescence histochemistry for VGluTs and synaptophysin. Expression of VGluTs in axon terminals of primary afferent fibers terminating in laminae I and II was also confirmed immunohistochemically after unilateral dorsal rhizotomy. The dual immunofluorescence histochemistry indicated expression of VGluTs in substance P (SP)-containing axon terminals in lamina I and the outer part of lamina II. Electron microscopy confirmed the coexpression of VGluTs and SP in axon terminals within laminae I and II; VGluTs was associated with round synaptic vesicles at the asymmetric synapses. It was further observed that isolectin IB4, a marker for unmyelinated axons, often bound with VGluT2-immunopositive structures but rarely with VGluT1-immunopositive structures in lamina II. Thus, the results indicated in laminae I and II of the medullary and spinal dorsal horns that both VGluT1 and VGluT2 were expressed in axon terminals of primary afferent fibers, including SP-containing nociceptive fibers and that VGluT in unmyelinated primary afferent fibers terminating in lamina II was primarily VGluT2. Copyright 2003 Wiley-Liss, Inc.

Dorsomedial pontine neurons with descending projections to the medullary reticular formation express orexin-1 and adrenergic α2A receptor mRNA

PubMed Central

Volgin, Denys V.; Malinowska, Monika; Kubin, Leszek

2009-01-01

Neurons located in the dorsomedial pontine rapid eye movement (REM) sleep-triggering region send axons to the medial medullary reticular formation (mMRF). This pathway is believed to be important for the generation of REM sleep motor atonia, but other than that they are glutamatergic little is known about neurochemical signatures of these pontine neurons important for REM sleep. We used single-cell reverse transcription and polymerase chain reaction (RT-PCR) to determine whether dorsomedial pontine cells with projections to the mMRF express mRNA for selected membrane receptors that mediate modulatory influences on REM sleep. Fluorescein (FITC)-labeled latex microspheres were microinjected into the mMRF of 26–34 day-old rats under pentobarbital anesthesia. After 5–6 days, rats were sacrificed, pontine slices were obtained and neurons were dissociated from 400–600 μm micropunches extracted from dorsomedial pontine reticular formation. We found that 32 out of 51 FITC-labeled cells tested (63%±7(SE)) contained the orexin type 1 receptor (ORX1r) mRNA, 27 out of 73 (37%±6) contained the adrenergic α2A receptor (α2Ar) RNA, and 6 out of 31 (19%±7) contained both mRNAs. The percentage of cells positive for the ORX1r mRNA was significantly lower (p<0.04) for the dorsomedial pontine cells that were not retrogradely labeled from the mMRF (32%±11), whereas α2Ar mRNA was present in a similar percentage of FITC-labeled and unlabeled neurons. Our data suggest that ORX and adrenergic pathways converge on a subpopulation of cells of the pontine REM sleep-triggering region that have descending projections to the medullary region important for the motor control during REM sleep. PMID:19427365

Use of Monoclonal Antibodies to Study the Structural Basis of the Function of Nicotinic Acetylcholine Receptors on Electric Organ and Muscle and to Determine the Structure of Nicotinic Acetylcholine Receptors on Neurons

DTIC Science & Technology

1989-03-16

nucleus robustus archistriatalis 1 1 1 nucleus reticularis gigantocellularis 1 3 3 nucleus reticularis lateralis 1 3 3 nucleus ... reticularis pontis caudalis 1 1 3 nucleus reticularis parvocellularis 1 1 2 nucleus rotundus 1 1 1 nucleus tractus solitarii 1 3 3 nucleus semilunaris...Structure a-bungarotoxin mAb 35 inAb 270 nucleus accumbens 1 1 1 nucleus basalis 1 1 1 nucleus cerebelli intermedium 2 3 3

32 CFR 700.1053 - Commander of a task force.

Code of Federal Regulations, 2010 CFR

2010-07-01

... 32 National Defense 5 2010-07-01 2010-07-01 false Commander of a task force. 700.1053 Section 700... Command Detail to Duty § 700.1053 Commander of a task force. (a) A geographic fleet commander, and any other naval commander, may detail in command of a task force, or other task command, any eligible...

The C3-System User. Volume II. Workshop Notes

DTIC Science & Technology

1977-02-01

system that provides the means for operational direction and technical administrative support involved in the function of command and control of U.S...information systems of the Headquarters of the Military Depart- ments; the command and control systems of the Headquarters of the Service Component Commands...the Service Component Commands - Military Airlift Command - Military Sealift Command - Military Traffic Management Command - 3.2.5 Command and

32 CFR 700.703 - To announce assumption of command.

Code of Federal Regulations, 2010 CFR

2010-07-01

... 32 National Defense 5 2010-07-01 2010-07-01 false To announce assumption of command. 700.703... Chief and Other Commanders Titles and Duties of Commanders § 700.703 To announce assumption of command. (a) Upon assuming command, commanders shall so advise appropriate superiors, and the units of their...

32 CFR 700.703 - To announce assumption of command.

Code of Federal Regulations, 2012 CFR

2012-07-01

... 32 National Defense 5 2012-07-01 2012-07-01 false To announce assumption of command. 700.703... Chief and Other Commanders Titles and Duties of Commanders § 700.703 To announce assumption of command. (a) Upon assuming command, commanders shall so advise appropriate superiors, and the units of their...

32 CFR 536.8 - Responsibilities and operations of command claims services.

Code of Federal Regulations, 2010 CFR

2010-07-01

... 32 National Defense 3 2010-07-01 2010-07-01 true Responsibilities and operations of command claims... operations of command claims services. (a) Chiefs of command claims services. Chiefs of command claims... Commander USARCS, and assigned an office code. However, the chief of a command claims service may...

32 CFR 700.703 - To announce assumption of command.

Code of Federal Regulations, 2014 CFR

2014-07-01

... 32 National Defense 5 2014-07-01 2014-07-01 false To announce assumption of command. 700.703... Chief and Other Commanders Titles and Duties of Commanders § 700.703 To announce assumption of command. (a) Upon assuming command, commanders shall so advise appropriate superiors, and the units of their...

32 CFR 700.703 - To announce assumption of command.

Code of Federal Regulations, 2013 CFR

2013-07-01

... 32 National Defense 5 2013-07-01 2013-07-01 false To announce assumption of command. 700.703... Chief and Other Commanders Titles and Duties of Commanders § 700.703 To announce assumption of command. (a) Upon assuming command, commanders shall so advise appropriate superiors, and the units of their...

32 CFR 700.703 - To announce assumption of command.

Code of Federal Regulations, 2011 CFR

2011-07-01

... 32 National Defense 5 2011-07-01 2011-07-01 false To announce assumption of command. 700.703... Chief and Other Commanders Titles and Duties of Commanders § 700.703 To announce assumption of command. (a) Upon assuming command, commanders shall so advise appropriate superiors, and the units of their...

32 CFR 536.8 - Responsibilities and operations of command claims services.

Code of Federal Regulations, 2011 CFR

2011-07-01

... 32 National Defense 3 2011-07-01 2009-07-01 true Responsibilities and operations of command claims... operations of command claims services. (a) Chiefs of command claims services. Chiefs of command claims... Commander USARCS, and assigned an office code. However, the chief of a command claims service may...

32 CFR 536.8 - Responsibilities and operations of command claims services.

Code of Federal Regulations, 2012 CFR

2012-07-01

... 32 National Defense 3 2012-07-01 2009-07-01 true Responsibilities and operations of command claims... operations of command claims services. (a) Chiefs of command claims services. Chiefs of command claims... Commander USARCS, and assigned an office code. However, the chief of a command claims service may...

The United States Navy Arctic Roadmap for 2014 to 2030

DTIC Science & Technology

2014-02-01

of the Oceanographer of the Navy; the Chief of Naval Research; Commander, Naval Meteorology and Oceanography Command; Commander, Office of Naval...Q3, FY14 Q3, FY15 FY15-18 FY18 2.3.4: Improve traditional meteorological forecast capability in the polar regions through the...CNE Commander Naval Forces Europe CNIC Commander Navy Installations Command CNMOC Commander Naval Meteorology and Oceanography Command CNO Chief

Use of GDNF-Releasing Nanofiber Nerve Guide Conduits for the Repair of Conus Medullaris/Cauda Equina Injury in the Nonhuman Primate

DTIC Science & Technology

2013-10-01

Electromyography (EMG) recordings of the external anal sphincter were obtained pre- operatively as baseline records. The external anal sphincter muscle was chosen...Lee U, Chang HH, Christe KL, Havton LA. Evoked voiding contractions and corresponding urethral sphincter electromyography in non-human primates differ

[Inflammatory spondylodiscitis as a unique radiological manifestation of the SAPHO syndrome].

PubMed

Cabay, J E; Marcelis, S; Dondelinger, R F

1998-04-01

We describe two cases of SAPHO with an exclusive spinal involvement. Diagnosis was established by sterno-clavicular arthralgias, palmar and plantar pustulosis and by radiological signs of inflammatory spondylodiscitis and vertebral osteitis. Spondylodiscitis and medullary edema resolved as shown by MRI after administration of steroids in one case and methotrexate in the other.

32 CFR 536.12 - Commanding General, U.S. Army Medical Command.

Code of Federal Regulations, 2011 CFR

2011-07-01

... 32 National Defense 3 2011-07-01 2009-07-01 true Commanding General, U.S. Army Medical Command... AND ACCOUNTS CLAIMS AGAINST THE UNITED STATES The Army Claims System § 536.12 Commanding General, U.S. Army Medical Command. (a) After consulting with the Commander USARCS on the selection of medical claims...

32 CFR 536.14 - Commanders of major Army commands.

Code of Federal Regulations, 2012 CFR

2012-07-01

... 32 National Defense 3 2012-07-01 2009-07-01 true Commanders of major Army commands. 536.14 Section... CLAIMS AGAINST THE UNITED STATES The Army Claims System § 536.14 Commanders of major Army commands... respective commands for compliance with the responsibilities assigned in §§ 536.9 and 536.10. (b) Assist...

32 CFR 536.12 - Commanding General, U.S. Army Medical Command.

Code of Federal Regulations, 2012 CFR

2012-07-01

... 32 National Defense 3 2012-07-01 2009-07-01 true Commanding General, U.S. Army Medical Command... AND ACCOUNTS CLAIMS AGAINST THE UNITED STATES The Army Claims System § 536.12 Commanding General, U.S. Army Medical Command. (a) After consulting with the Commander USARCS on the selection of medical claims...

32 CFR 536.14 - Commanders of major Army commands.

Code of Federal Regulations, 2010 CFR

2010-07-01

... 32 National Defense 3 2010-07-01 2010-07-01 true Commanders of major Army commands. 536.14 Section... CLAIMS AGAINST THE UNITED STATES The Army Claims System § 536.14 Commanders of major Army commands... respective commands for compliance with the responsibilities assigned in §§ 536.9 and 536.10. (b) Assist...

32 CFR 536.14 - Commanders of major Army commands.

Code of Federal Regulations, 2013 CFR

2013-07-01

... 32 National Defense 3 2013-07-01 2013-07-01 false Commanders of major Army commands. 536.14... ACCOUNTS CLAIMS AGAINST THE UNITED STATES The Army Claims System § 536.14 Commanders of major Army commands... respective commands for compliance with the responsibilities assigned in §§ 536.9 and 536.10. (b) Assist...

32 CFR 536.14 - Commanders of major Army commands.

Code of Federal Regulations, 2011 CFR

2011-07-01

... 32 National Defense 3 2011-07-01 2009-07-01 true Commanders of major Army commands. 536.14 Section... CLAIMS AGAINST THE UNITED STATES The Army Claims System § 536.14 Commanders of major Army commands... respective commands for compliance with the responsibilities assigned in §§ 536.9 and 536.10. (b) Assist...

32 CFR 536.12 - Commanding General, U.S. Army Medical Command.

Code of Federal Regulations, 2014 CFR

2014-07-01

... 32 National Defense 3 2014-07-01 2014-07-01 false Commanding General, U.S. Army Medical Command... AND ACCOUNTS CLAIMS AGAINST THE UNITED STATES The Army Claims System § 536.12 Commanding General, U.S. Army Medical Command. (a) After consulting with the Commander USARCS on the selection of medical claims...

32 CFR 536.12 - Commanding General, U.S. Army Medical Command.

Code of Federal Regulations, 2010 CFR

2010-07-01

... 32 National Defense 3 2010-07-01 2010-07-01 true Commanding General, U.S. Army Medical Command... AND ACCOUNTS CLAIMS AGAINST THE UNITED STATES The Army Claims System § 536.12 Commanding General, U.S. Army Medical Command. (a) After consulting with the Commander USARCS on the selection of medical claims...

32 CFR 536.14 - Commanders of major Army commands.

Code of Federal Regulations, 2014 CFR

2014-07-01

... 32 National Defense 3 2014-07-01 2014-07-01 false Commanders of major Army commands. 536.14... ACCOUNTS CLAIMS AGAINST THE UNITED STATES The Army Claims System § 536.14 Commanders of major Army commands... respective commands for compliance with the responsibilities assigned in §§ 536.9 and 536.10. (b) Assist...

32 CFR 536.12 - Commanding General, U.S. Army Medical Command.

Code of Federal Regulations, 2013 CFR

2013-07-01

... 32 National Defense 3 2013-07-01 2013-07-01 false Commanding General, U.S. Army Medical Command... AND ACCOUNTS CLAIMS AGAINST THE UNITED STATES The Army Claims System § 536.12 Commanding General, U.S. Army Medical Command. (a) After consulting with the Commander USARCS on the selection of medical claims...

The SAS-3 delayed command system

NASA Technical Reports Server (NTRS)

Hoffman, E. J.

1975-01-01

To meet the requirements arising from the increased complexity of the power, attitude control and telemetry systems, a full redundant high-performance control section with delayed command capability was designed for the Small Astronomy Satellite-3 (SAS-3). The relay command system of SAS-3 is characterized by 56 bystate relay commands, with capability for handling up to 64 commands in future versions. The 'short' data command service of SAS-1 and SAS-2 consisting of shifting 24-bit words to two users was expanded to five users and augmented with a 'long load' data command service (up to 4080 bits) used to program the telemetry system and the delayed command subsystem. The inclusion of a delayed command service ensures a program of up to 30 relay or short data commands to be loaded for execution at designated times. The design and system operation of the SAS-3 command section are analyzed, with special attention given to the delayed command subsystem.

Hepatitis C Virus Infection Activates a Novel Innate Pathway Involving IKKα in Lipogenesis and Viral Assembly

PubMed Central

Li, Qisheng; Pène, Véronique; Krishnamurthy, Siddharth; Cha, Helen; Liang, T. Jake

2013-01-01

Hepatitis C virus interacts extensively with host factors not only to establish productive infection but also to trigger unique pathological processes. Our recent genome-wide siRNA screen demonstrated that IKKα is a critical host factor for HCV. Here we describe a novel NF-κB-independent and kinase-mediated nuclear function of IKKα in HCV assembly. HCV infection, through its 3’-untranslated region, interacts with DDX3X to activate IKKα, which translocates to the nucleus and induces a CBP/p300-mediated transcriptional program involving SREBPs. This novel innate pathway induces lipogenic genes and enhances core-associated lipid droplet formation to facilitate viral assembly. Chemical inhibitors of IKKα suppress HCV infection and IKKα-induced lipogenesis, offering a proof-of-concept approach for novel HCV therapeutic development. Our results show that HCV commands a novel mechanism to its advantage by exploiting intrinsic innate response and hijacking lipid metabolism, which likely contributes to a high chronicity rate and the pathological hallmark of steatosis in HCV infection. PMID:23708292

14 CFR 91.1031 - Pilot in command or second in command: Designation required.

Code of Federal Regulations, 2011 CFR

2011-01-01

... 14 Aeronautics and Space 2 2011-01-01 2011-01-01 false Pilot in command or second in command... RULES Fractional Ownership Operations Program Management § 91.1031 Pilot in command or second in command: Designation required. (a) Each program manager must designate a— (1) Pilot in command for each program flight...

32 CFR 724.405 - Commandant of the Marine Corps or the Commander, Naval Military Personnel Command.

Code of Federal Regulations, 2014 CFR

2014-07-01

... 32 National Defense 5 2014-07-01 2014-07-01 false Commandant of the Marine Corps or the Commander, Naval Military Personnel Command. 724.405 Section 724.405 National Defense Department of Defense... Personnel Command. Personnel managers of the Marine Corps and the Navy; responsible for providing limited...

32 CFR 700.1058 - Command of a submarine.

Code of Federal Regulations, 2011 CFR

2011-07-01

... 32 National Defense 5 2011-07-01 2011-07-01 false Command of a submarine. 700.1058 Section 700... Command Detail to Duty § 700.1058 Command of a submarine. The officer detailed to command a submarine shall be an officer of the line in the Navy, eligible for command at sea and qualified for command of...

14 CFR 135.109 - Pilot in command or second in command: Designation required.

Code of Federal Regulations, 2011 CFR

2011-01-01

... 14 Aeronautics and Space 3 2011-01-01 2011-01-01 false Pilot in command or second in command... ON BOARD SUCH AIRCRAFT Flight Operations § 135.109 Pilot in command or second in command: Designation required. (a) Each certificate holder shall designate a— (1) Pilot in command for each flight; and (2...

32 CFR 724.405 - Commandant of the Marine Corps or the Commander, Naval Military Personnel Command.

Code of Federal Regulations, 2010 CFR

2010-07-01

... 32 National Defense 5 2010-07-01 2010-07-01 false Commandant of the Marine Corps or the Commander, Naval Military Personnel Command. 724.405 Section 724.405 National Defense Department of Defense... Personnel Command. Personnel managers of the Marine Corps and the Navy; responsible for providing limited...

14 CFR 1214.703 - Chain of command.

Code of Federal Regulations, 2010 CFR

2010-01-01

... 14 Aeronautics and Space 5 2010-01-01 2010-01-01 false Chain of command. 1214.703 Section 1214.703... Shuttle Commander § 1214.703 Chain of command. (a) The Commander is a career NASA astronaut who has been... particular flight and is second in command of the flight. If the commander is unable to carry out the...

14 CFR 135.109 - Pilot in command or second in command: Designation required.

Code of Federal Regulations, 2013 CFR

2013-01-01

... 14 Aeronautics and Space 3 2013-01-01 2013-01-01 false Pilot in command or second in command... ON BOARD SUCH AIRCRAFT Flight Operations § 135.109 Pilot in command or second in command: Designation required. (a) Each certificate holder shall designate a— (1) Pilot in command for each flight; and (2...

32 CFR 724.405 - Commandant of the Marine Corps or the Commander, Naval Military Personnel Command.

Code of Federal Regulations, 2011 CFR

2011-07-01

... 32 National Defense 5 2011-07-01 2011-07-01 false Commandant of the Marine Corps or the Commander, Naval Military Personnel Command. 724.405 Section 724.405 National Defense Department of Defense... Personnel Command. Personnel managers of the Marine Corps and the Navy; responsible for providing limited...

32 CFR 724.405 - Commandant of the Marine Corps or the Commander, Naval Military Personnel Command.

Code of Federal Regulations, 2013 CFR

2013-07-01

... 32 National Defense 5 2013-07-01 2013-07-01 false Commandant of the Marine Corps or the Commander, Naval Military Personnel Command. 724.405 Section 724.405 National Defense Department of Defense... Personnel Command. Personnel managers of the Marine Corps and the Navy; responsible for providing limited...

14 CFR 91.1031 - Pilot in command or second in command: Designation required.

Code of Federal Regulations, 2012 CFR

2012-01-01

... 14 Aeronautics and Space 2 2012-01-01 2012-01-01 false Pilot in command or second in command... RULES Fractional Ownership Operations Program Management § 91.1031 Pilot in command or second in command: Designation required. (a) Each program manager must designate a— (1) Pilot in command for each program flight...

32 CFR 700.1058 - Command of a submarine.

Code of Federal Regulations, 2010 CFR

2010-07-01

... 32 National Defense 5 2010-07-01 2010-07-01 false Command of a submarine. 700.1058 Section 700... Command Detail to Duty § 700.1058 Command of a submarine. The officer detailed to command a submarine shall be an officer of the line in the Navy, eligible for command at sea and qualified for command of...

14 CFR 1214.703 - Chain of command.

Code of Federal Regulations, 2013 CFR

2013-01-01

... 14 Aeronautics and Space 5 2013-01-01 2013-01-01 false Chain of command. 1214.703 Section 1214.703... Shuttle Commander § 1214.703 Chain of command. (a) The Commander is a career NASA astronaut who has been... particular flight and is second in command of the flight. If the commander is unable to carry out the...

14 CFR 91.1031 - Pilot in command or second in command: Designation required.

Code of Federal Regulations, 2010 CFR

2010-01-01

... 14 Aeronautics and Space 2 2010-01-01 2010-01-01 false Pilot in command or second in command... RULES Fractional Ownership Operations Program Management § 91.1031 Pilot in command or second in command: Designation required. (a) Each program manager must designate a— (1) Pilot in command for each program flight...

32 CFR 700.1058 - Command of a submarine.

Code of Federal Regulations, 2012 CFR

2012-07-01

... 32 National Defense 5 2012-07-01 2012-07-01 false Command of a submarine. 700.1058 Section 700... Command Detail to Duty § 700.1058 Command of a submarine. The officer detailed to command a submarine shall be an officer of the line in the Navy, eligible for command at sea and qualified for command of...

32 CFR 700.1058 - Command of a submarine.

Code of Federal Regulations, 2014 CFR

2014-07-01

... 32 National Defense 5 2014-07-01 2014-07-01 false Command of a submarine. 700.1058 Section 700... Command Detail to Duty § 700.1058 Command of a submarine. The officer detailed to command a submarine shall be an officer of the line in the Navy, eligible for command at sea and qualified for command of...

14 CFR 135.109 - Pilot in command or second in command: Designation required.

Code of Federal Regulations, 2014 CFR

2014-01-01

... 14 Aeronautics and Space 3 2014-01-01 2014-01-01 false Pilot in command or second in command... ON BOARD SUCH AIRCRAFT Flight Operations § 135.109 Pilot in command or second in command: Designation required. (a) Each certificate holder shall designate a— (1) Pilot in command for each flight; and (2...

14 CFR 135.109 - Pilot in command or second in command: Designation required.

Code of Federal Regulations, 2012 CFR

2012-01-01

... 14 Aeronautics and Space 3 2012-01-01 2012-01-01 false Pilot in command or second in command... ON BOARD SUCH AIRCRAFT Flight Operations § 135.109 Pilot in command or second in command: Designation required. (a) Each certificate holder shall designate a— (1) Pilot in command for each flight; and (2...

32 CFR 700.1058 - Command of a submarine.

Code of Federal Regulations, 2013 CFR

2013-07-01

... 32 National Defense 5 2013-07-01 2013-07-01 false Command of a submarine. 700.1058 Section 700... Command Detail to Duty § 700.1058 Command of a submarine. The officer detailed to command a submarine shall be an officer of the line in the Navy, eligible for command at sea and qualified for command of...

32 CFR 724.405 - Commandant of the Marine Corps or the Commander, Naval Military Personnel Command.

Code of Federal Regulations, 2012 CFR

2012-07-01

... 32 National Defense 5 2012-07-01 2012-07-01 false Commandant of the Marine Corps or the Commander, Naval Military Personnel Command. 724.405 Section 724.405 National Defense Department of Defense... Personnel Command. Personnel managers of the Marine Corps and the Navy; responsible for providing limited...

14 CFR 1214.703 - Chain of command.

Code of Federal Regulations, 2012 CFR

2012-01-01

... 14 Aeronautics and Space 5 2012-01-01 2012-01-01 false Chain of command. 1214.703 Section 1214.703... Shuttle Commander § 1214.703 Chain of command. (a) The Commander is a career NASA astronaut who has been... particular flight and is second in command of the flight. If the commander is unable to carry out the...

14 CFR 1214.703 - Chain of command.

Code of Federal Regulations, 2011 CFR

2011-01-01

... 14 Aeronautics and Space 5 2011-01-01 2010-01-01 true Chain of command. 1214.703 Section 1214.703... Shuttle Commander § 1214.703 Chain of command. (a) The Commander is a career NASA astronaut who has been... particular flight and is second in command of the flight. If the commander is unable to carry out the...

14 CFR 135.109 - Pilot in command or second in command: Designation required.

Code of Federal Regulations, 2010 CFR

2010-01-01

... 14 Aeronautics and Space 3 2010-01-01 2010-01-01 false Pilot in command or second in command... ON BOARD SUCH AIRCRAFT Flight Operations § 135.109 Pilot in command or second in command: Designation required. (a) Each certificate holder shall designate a— (1) Pilot in command for each flight; and (2...

14 CFR 91.1031 - Pilot in command or second in command: Designation required.

Code of Federal Regulations, 2014 CFR

2014-01-01

... 14 Aeronautics and Space 2 2014-01-01 2014-01-01 false Pilot in command or second in command... RULES Fractional Ownership Operations Program Management § 91.1031 Pilot in command or second in command: Designation required. (a) Each program manager must designate a— (1) Pilot in command for each program flight...

14 CFR 91.1031 - Pilot in command or second in command: Designation required.

Code of Federal Regulations, 2013 CFR

2013-01-01

... 14 Aeronautics and Space 2 2013-01-01 2013-01-01 false Pilot in command or second in command... RULES Fractional Ownership Operations Program Management § 91.1031 Pilot in command or second in command: Designation required. (a) Each program manager must designate a— (1) Pilot in command for each program flight...

Re-engineering the Multimission Command System at the Jet Propulsion Laboratory

NASA Technical Reports Server (NTRS)

Alexander, Scott; Biesiadecki, Jeff; Cox, Nagin; Murphy, Susan C.; Reeve, Tim

1994-01-01

The Operations Engineering Lab (OEL) at JPL has developed the multimission command system as part of JPL's Advanced Multimission Operations System. The command system provides an advanced multimission environment for secure, concurrent commanding of multiple spacecraft. The command functions include real-time command generation, command translation and radiation, status reporting, some remote control of Deep Space Network antenna functions, and command file management. The mission-independent architecture has allowed easy adaptation to new flight projects and the system currently supports all JPL planetary missions (Voyager, Galileo, Magellan, Ulysses, Mars Pathfinder, and CASSINI). This paper will discuss the design and implementation of the command software, especially trade-offs and lessons learned from practical operational use. The lessons learned have resulted in a re-engineering of the command system, especially in its user interface and new automation capabilities. The redesign has allowed streamlining of command operations with significant improvements in productivity and ease of use. In addition, the new system has provided a command capability that works equally well for real-time operations and within a spacecraft testbed. This paper will also discuss new development work including a multimission command database toolkit, a universal command translator for sequencing and real-time commands, and incorporation of telecommand capabilities for new missions.

14 CFR § 1214.703 - Chain of command.

Code of Federal Regulations, 2014 CFR

2014-01-01

... 14 Aeronautics and Space 5 2014-01-01 2014-01-01 false Chain of command. § 1214.703 Section Â... of the Space Shuttle Commander § 1214.703 Chain of command. (a) The Commander is a career NASA... the pilot on a particular flight and is second in command of the flight. If the commander is unable to...

Distribution of methionine-enkephalin in the minipig brainstem.

PubMed

Sánchez, Manuel Lisardo; Vecino, Elena; Coveñas, Rafael

2013-05-01

We have studied the distribution of immunoreactive cell bodies and axons are containing methionine-enkephalin in the minipig brainstem. Immunoreactive axons were widely distributed, whereas the distribution of perikarya was less widespread. A high or moderate density of axons containing methionine-enkephalin were found from rostral to caudal levels in the substantia nigra, nucleus interpeduncularis, nucleus reticularis tegmenti pontis, nucleus dorsalis raphae, nucleus centralis raphae, nuclei dorsalis and ventralis tegmenti of Gudden, locus ceruleus, nucleus sensorius principalis nervi trigemini, nucleus cuneatus externalis, nucleus tractus solitarius, nuclei vestibularis inferior and medialis, nucleus ambiguus, nucleus olivaris inferior and in the nucleus tractus spinalis nervi trigemini. Immunoreactive perikarya were observed in the nuclei centralis and dorsalis raphae, nucleus motorius nervi trigemini, nucleus centralis superior, nucleus nervi facialis, nuclei parabrachialis medialis and lateralis, nucleus ventralis raphae, nucleus reticularis lateralis and in the formatio reticularis. We have also described the presence of perikarya containing methionine-enkephalin in the nuclei nervi abducens, ruber, nervi oculomotorius and nervi trochlearis. These results suggest that in the minipig the pentapeptide may be involved in many physiological functions (for example, proprioceptive and nociceptive information; motor, respiratory and cardiovascular mechanisms). Copyright © 2013 Elsevier B.V. All rights reserved.