Towards structured sharing of raw and derived neuroimaging data across existing resources.

Data sharing efforts increasingly contribute to the acceleration of scientific discovery. Neuroimaging data is accumulating in distributed domain-specific databases and there is currently no integrated access mechanism nor an accepted format for the critically important meta-data that is necessary for making use of the combined, available neuroimaging data. In this manuscript, we present work from the Derived Data Working Group, an open-access group sponsored by the Biomedical Informatics Research Network (BIRN) and the International Neuroimaging Coordinating Facility (INCF) focused on practical tools for distributed access to neuroimaging data. The working group develops models and tools facilitating the structured interchange of neuroimaging meta-data and is making progress towards a unified set of tools for such data and meta-data exchange. We report on the key components required for integrated access to raw and derived neuroimaging data as well as associated meta-data and provenance across neuroimaging resources. The components include (1) a structured terminology that provides semantic context to data, (2) a formal data model for neuroimaging with robust tracking of data provenance, (3) a web service-based application programming interface (API) that provides a consistent mechanism to access and query the data model, and (4) a provenance library that can be used for the extraction of provenance data by image analysts and imaging software developers. We believe that the framework and set of tools outlined in this manuscript have great potential for solving many of the issues the neuroimaging community faces when sharing raw and derived neuroimaging data across the various existing database systems for the purpose of accelerating scientific discovery.

Capsaicin-induced neuronal death and proliferation of the primary sensory neurons located in the nodose ganglia of adult rats.

To evaluate the potential for neuronal replacement following destruction of vagal afferent neurons, we examined nodose ganglia following i.p. capsaicin treatment of adult rats. Rats received capsaicin or vehicle followed by a regimen of 5'-bromo-2'-deoxyuridine injections (BrdU) to reveal DNA replication. Nodose ganglia were harvested at various times post-treatment and processed for 4',6-diamidino-2-phenylindole (DAPI) nuclear staining and immunofluorescence to estimate neuronal numbers and to determine vanilloid receptor, cleaved caspase 3, TUNEL, BrdU, the neuron-selective marker protein gene product (PGP) -9.5 and neurofilament-M-immunoreactivity. Twenty-four hours after capsaicin approximately 40% of nodose ganglion neurons expressed cleaved caspase 3-immunoreactivity and 16% revealed TUNEL staining, indicating that primary sensory neurons are killed by the capsaicin treatment of adult rats. The occurrence of neuronal death was confirmed by counts of DAPI-stained neuronal nuclei, which revealed >or=50% reduction of nodose neuron number by 30 days post-capsaicin. However, by 60 days post-capsaicin, the total numbers of neuronal nuclei in nodose ganglia from capsaicin-treated rats were not different from controls, suggesting that new neurons had been added to the nodose ganglia. Neuronal proliferation was confirmed by significant BrdU incorporation in nuclei of nodose ganglion cells immunoreactive for the neuron-specific antigen PGP-9.5 revealed 30 and 60 days post-capsaicin. Collectively, these observations suggest that in adult rats massive scale neurogenesis occurs in nodose ganglia following capsaicin-induced neuronal destruction. The adult nodose ganglion, therefore, provides a novel system for studying neural plasticity and adult neurogenesis after peripheral injury of primary sensory neurons.

Analysis of connectivity: neural systems in the cerebral cortex.

The mammalian cerebral cortex is composed of many distinct areas, which are very richly interconnected. The very large number of connections between cortical areas require analysis to be undertaken before reliable conclusions about the organization of neural systems in the cortex can be drawn. We review the methodology and results of two means of analysing central nervous connectivity, hierarchical analysis and optimization analysis. We conclude that these methods are reliable methods for analysing neural connectivity data, and that their results concur. The analyses indicate that all major cortical sensory systems are organized hierarchically, some central sensory systems are divided structurally into several "streams" of processing, the cortical motor system is embedded in the cortical somatosensory system, the frontal and limbic structures are connectionally associated, and that these frontal and limbic areas are invariably associated with the least peripheral sensory processing regions, and are therefore connectionally central. Finally, we discuss the differences on this common plan between the organizations of the cat and primate that these analyses reveal.

Sump syndrome complicating Roux-en-Y hepaticojejunostomy: case report and review of the literature.

Sump syndrome is a rare complication of biliary-enteric anastomosis. Classically, the distal bile duct becomes obstructed by gastrointestinal debris after choledochoduodenostomy, resulting in cholangitis or, less commonly pancreatitis. Obstruction of the biliary tree by gastrointestinal contents after Roux-en-Y choledochojejunostomy or hepaticojejunostomy has not been described in the English-language literature. This report details the diagnostic and operative management of the first patient with sump syndrome after hepaticojejunostomy. The presumed pathophysiology was reflux of vegetable matter up the efferent limb, resulting in hepatic duct obstruction and cholangitis. The patient ultimately required complex choledochoscopic drainage of the intrahepatic biliary tree and revision of the previous Roux-en-Y hepaticojejunostomy.

Transiently catecholaminergic cells in the fetal rat express mRNA for the glutamate NMDAR1 receptor.

The N-methyl-D-aspartate (NMDA) subtype of the glutamate receptor has been shown to be vital to the development of the central nervous system. The purpose of this study was to determine if the neural crost-derived precursors which migrate to the primitive gut contain mRNA encoding for the NMDA receptor. Many of these enteric precursors briefly elaborate tyrosine hydroxylase (TH) and have been termed transiently catecholaminergic (TC) cells. TH-like immunoreactivity (TH-ir) serves as a marker for them. Immunocytochemistry combined with NMDAR1 in situ hybridization revealed that TH-ir cells in Day 14 rat embryos do express mRNA coding for the NMDAR1 receptor. However, the TC cells did not contain detectable levels of immunoreactivity for the NMDAR1 receptor peptide. The absence of detectable NMDAR1-like immunoreactivity might reflect some form of transcriptional or translational regulation, such that the onset of functional receptor activity is delayed until differentiation and/or synaptogenesis commence. Whether TC cell migration is glutamate-mediated remains unclear, since some of them successfully reached the gut without expressing NMDAR1 message. Characterizing TC cell NMDA receptor activity and determining exactly when it ensues will be of paramount importance to defining the role(s) of this receptor in ENS development. In conclusion, the expression of NMDAR1 mRNA by TH-ir cells suggests a possible developmental role for this receptor.

Lesions of the dorsal vagal complex abolish increases in meal size induced by NMDA receptor blockade.

Rats increase meal size and duration after intraperitoneal injection of MK-801, a non-competitive N-methyl-D-aspartate (NMDA) receptor antagonist. This effect depends upon intact vagal fibers, since the antagonist does not increase intake when visceral afferent and efferent pathways have been interrupted by bilateral subdiaphragmatic vagotomy. NMDA receptors have been demonstrated on vagal afferent fibers and on second-order neurons in the medial subnucleus of the solitary tract (NTS), the area postrema (AP), and the dorsal motor nucleus of the vagus. To determine whether neurons in these structures are crucial for NMDA receptor effects on feeding, we examined the effect of MK-801 on intake of 15% sucrose in rats with aspiration lesions of the AP and adjacent NTS. MK-801 (100 microg/kg, i.p.) significantly increased sucrose intake in these lesioned rats compared to sham-lesioned rats (32.3+/-0.1 ml versus 23.3+/-0.1 ml, P<0.001). However, when the AP/NTS aspiration lesions were combined with bilateral electrolytic destruction of the medial NTS and the DMV, lesioned rats consumed nearly the same amount of sucrose after either saline or MK-801 (25.9+/-2.4 ml versus 24.3+/-3. 0 ml; P=0.687). By contrast, sham-lesioned controls ingested significantly more sucrose following MK-801 compared to saline (19. 8+/-1.0 ml versus 13.1+/-0.8 ml, P<0.001). These results suggest that an intact caudomedial NTS and/or DMV are necessary for increases in intake induced by NMDA receptor blockade. While the AP might participate in MK-801-induced enhancement of intake, it is not essential for this effect.

Delay in meal termination follows blockade of N-methyl-D-aspartate receptors in the dorsal hindbrain.

We have reported that rats increased their intake of food, but not water, following an intraperitoneal injection of MK-801, a non-competitive antagonist of N-methyl-d-aspartate (NMDA)-activated ion channels. The antagonist appears to specifically interfere with signals that participate in meal termination (satiety), thereby prolonging the meal and increasing its size. The anatomical site at which MK-801 acts to increase food intake is not known. However, vagal sensory neurons are known to participate in satiation for food. Furthermore, NMDA receptor immunoreactivity is present in the caudal nucleus of the solitary tract (NTS) where vagal sensory fibers terminate. Therefore, we hypothesized that MK-801 might increase food intake by blocking NMDA receptors in the NTS. To test this hypothesis, we microinjected MK-801 directly into the hindbrain, immediately prior to a deprivation-induced meal of 15% sucrose. We found that sucrose intake was significantly increased following injection of MK-801 (2 microgram/3 microliter) into the fourth ventricle. When MK-801 was injected directly into the caudomedial NTS, intake was increased significantly by doses as small as 198 ng/30 nl, while equivalent injections into other hindbrain areas or the fourth ventricle did not increase food intake. These data are consistent with control of food intake by endogenous glutamate and NMDA-type glutamate receptors located in the caudomedial NTS.

Expression of mRNA for the N-methyl-D-aspartate (NMDAR1) receptor by the enteric neurons of the rat.

In this study, in situ hybridization techniques were employed to map the distribution of enteric neurons which express mRNA for the glutamate N-methyl-D-aspartate receptor 1 (NMDAR1). We hybridized tissue sections from the stomach, duodenum, ileum and descending colon of adult rats with a 1.43-kB riboprobe cleaved from a clone of the NMDA receptor. Enteric neurons expressing the mRNA were found in both myenteric and submucosal ganglia at each of the sampling sites. Possible functions of NMDA receptors on enteric neurons are discussed.

Visceral afferent participation in delayed satiation following NMDA receptor blockade.

We previously reported that rats increase their food intake, but not water intake, following intraperitoneal (i.p.) injection of MK-801, a noncompetitive antagonist of N-methyl-D-aspartate (NMDA)-activated ion channels. The drug appears to specifically interfere with signals that participate in satiation, thereby prolonging the meal and increasing its size. The mechanism by which delayed satiation occurs is not known. However, some well-studied satiety signals are carried by visceral sensory fibers that innervate the abdominal viscera. We hypothesized that MK-801 might increase food intake by interfering with satiety signals transmitted by visceral afferent neurons. To test this hypothesis, we examined MK-801's effect on food intake in rats systemically treated with capsaicin, a neurotoxin that destroys small unmyelinated visceral afferent neurons. Capsaicin treatment significantly attenuated increased sucrose intake following MK-801. We also investigated whether the effects of MK-801 on food intake would persist in rats treated with total subdiaphragmatic vagotomies. MK-801 increased the intake of 15% sucrose by sham-vagotomized rats, while vagotomized rats did not increase their intake following MK-801. Taken together, these results support the hypothesis that capsaicin-sensitive visceral sensory neurons are involved in increased food intake following systemic NMDA receptor blockade. This, in turn, suggests that NMDA receptor activation may be an important component of the neural circuitry involved in satiation.

The non-competitive NMDA antagonist MK-801 increases food intake in rats.

A role for excitatory amino acids in the control of feeding behavior has not been extensively investigated. Nevertheless, there is direct and circumstantial evidence to indicate that some circuits involved with feeding behavior include glutamatergic elements. To test the hypothesis that endogenous glutamate participates in the control of food intake, we performed experiments to determine whether MK-801, a non-competitive N-methyl-D-aspartate (NMDA) ion channel antagonist, is capable of altering intake of liquid and solid foods in hungry or satiated rats. Following a 16 h fast, intake of 15% sucrose was significantly enhanced by systemic treatment with MK-801. Water intake was not altered by the NMDA antagonist. Rats did not ingest more rat chow after MK-801, unless they had been fasted. When a more palatable food (cookies) was offered, MK-801 did increase intake. Thus MK-801 enhanced food intake only when feeding was initiated by food-deprivation or increased palatability. In conclusion, our results support the hypothesis that endogenous glutamate plays a role in the control of food intake. Blockade of NMDA receptor function by MK-801 may diminish or delay satiety signals, rather than initiate feeding behavior per se.

Abdominal compartment syndrome in patients with burns.

Abdominal compartment syndrome (ACS) is a well-recognized perioperative complication that occurs in patients who undergo intra-abdominal operations and who require extensive fluid resuscitation. The classic presentation of this syndrome includes high peak airway pressures; oliguria, despite adequate filling pressures; and intra-abdominal pressures of more than 25 mm Hg. A decompressive laparotomy performed at the bedside can alleviate ACS. If left untreated, sustained intra-abdominal hypertension is often fatal. In the literature, ACS has been described in pediatric patients with burns but not in adult patients with burns. This article describes 3 adults who sustained burns of more than 70% of their body surface areas, who required more than 20 L of crystalloid resuscitation, and who developed ACS during their resuscitation after the burn injury. The mortality rate among these patients was 100%, which confirms the grave consequences of this syndrome. In our institution, intra-abdominal pressure is now routinely measured as part of the burn resuscitation process in an attempt to diagnose and treat this syndrome earlier and more efficaciously. It is recommended that the possibility of ACS be considered when diagnosing any patient with burns who develops high airway pressures, oliguria, or both.

Clinical evaluation of Scotchbond: three-year results.

In a previous paper, the one-year retention of composite resin in non-undercut Class V abrasion lesions mediated by self-cure Scotchbond dentine bonding agent without enamel etching was reported. The present paper reports the three-year results. Initially, a total of 310 restorations was placed using Silux, Silar, Ketac-Fil and Fuji II. The percentage cumulative loss of the restorations at two and three years, respectively, was: Silux 27, 30; Silar 58, 58; Ketac-Fil 0, 0; Fuji II 4, 14. Over the total study period, there was a high loss rate of composite restorations in the first six months, and a tendency to increased loss over one to three years. There was a significant increase in marginal discoloration, assessed photographically, over the three-year period, and caries was present around some restorations.

NMDA NR2 receptors participate in CCK-induced reduction of food intake and hindbrain neuronal activation.

Previous work has shown that blockade of NMDAR by non-competitive (MK-801) and competitive (AP5) antagonists increase food intake by acting in the dorsal hindbrain. NMDAR are heteromeric complexes composed of NR1, NR2 and NR3 subunits. Competitive NR2B antagonists potently increase feeding when injected into the hindbrain. NR2 immunoreactivity is present in the hindbrain, vagal afferents and enteric neurons. NMDA receptors expressed on peripheral vagal afferent processes in the GI tract modulate responsiveness to GI stimuli. Therefore, it is possible that peripheral as well as central vagal NMDA receptors participate in control of food intake. To examine this possibility, we recorded intake of rodent chow, a palatable liquid food (15% sucrose), and non-nutrient (0.2% saccharin) solutions following intraperitoneal (i.p.) administration of D-CPPene, a competitive NMDA receptor antagonist that is selective for binding to the NR2B/A channel subunit. To assess participation of peripheral NMDA receptors in postoral satiation signals, we examined the ability of D-CPPene to attenuate reduction of feeding and hindbrain Fos expression following IP CCK administration. IP D-CPPene (2, 3 mg/kg) produced a significant increase in sucrose and chow intake but not saccharin. Pretreatment with D-CPPene (2 mg/kg) reversed CCK (2 microg/kg)-induced inhibition of sucrose intake, and attenuated CCK-induced Fos-Li in the dorsal hindbrain. These results confirm that antagonism of hindbrain NMDA receptors increases food intake. In addition our results suggest that NMDA receptors outside the hindbrain, perhaps in the periphery, participate in vagally mediated, CCK-induced reduction of food intake and NTS neuron activation.

Hindbrain administration of NMDA receptor antagonist AP-5 increases food intake in the rat.

Hindbrain administration of MK-801, a noncompetitive N-methyl-D-aspartate (NMDA) channel blocker, increases meal size, suggesting NMDA receptors in this location participate in control of food intake. However, dizocilpine (MK-801) reportedly antagonizes some non-NMDA ion channels. Therefore, to further assess hindbrain NMDA receptor participation in food intake control, we measured deprivation-induced intakes of 15% sucrose solution or rat chow after intraperitoneal injection of either saline vehicle or D(-)-2-amino-5-phosphonopentanoic acid (AP5), a competitive NMDA receptor antagonist, to the fourth ventricular, or nucleus of the solitary tract (NTS). Intraperitoneal injection of AP5 (0.05, 0.1, 1.0, 3.0, and 5.0 mg/kg) did not alter 30-min sucrose intake at any dose (10.7 +/- 0.4 ml, saline control) (11.0 +/- 0.8, 11.2 +/- 1.0, 11.2 +/- 1.0, 13.1 +/- 2.2, and 11.0 +/- 1.9 ml, AP5 doses, respectively). Fourth ventricular administration of both 0.2 mug (16.7 +/- 0.6 ml) and 0.4 mug (14.9 +/- 0.5 ml) but not 0.1 and 0.6 mug of AP5 significantly increased 60-min sucrose intake compared with saline (11.2 +/- 0.4 ml). Twenty-four hour chow intake also was increased compared with saline (AP5: 31.5 +/- 0.1 g vs. saline: 27.1 +/- 0.6 g). Furthermore, rats did not increase intake of 0.2% saccharin after fourth ventricular AP5 administration (AP5: 9.8 +/- 0.7 ml, vs. saline: 10.5 +/- 0.5 ml). Finally, NTS AP5 (20 ng/30 nl) significantly increased 30- (AP5: 17.2 +/- 0.7 ml vs. saline: 14.6 +/- 1.7 ml), and 60-min (AP5: 19.4 +/- 0.6 ml vs. saline: 15.5 +/- 1.4 ml) sucrose intake, as well as 24-h chow intake (AP5: 31.6 +/- 0.3 g vs. saline: 26.1 +/- 1.2 g). These results support the hypothesis that hindbrain NMDA receptors participate in control of food intake and suggest that this participation also may contribute to control of body weight over a 24-h period.

NMDA channels control meal size via central vagal afferent terminals.

The N-methyl-D-aspartate (NMDA) ion channel blocker MK-801 administered systemically or as a nanoliter injection into the nucleus of the solitary tract (NTS), increases meal size. Furthermore, we have observed that ablation of the NTS abolishes increased meal size following systemic injection of dizocilpine (MK-801) and that MK-801-induced increases in intake are attenuated in rats pretreated with capsaicin to destroy small, unmyelinated, primary afferent neurons. These findings led us to hypothesize that NMDA receptors on central vagal afferent terminals or on higher-order NTS neurons innervated by these vagal afferents might mediate increased food intake. To evaluate this hypothesis, we examined 15% sucrose intake after 50-nl MK-801 injections ipsilateral or contralateral to unilateral nodose ganglion removal (ganglionectomy). On the side contralateral to ganglionectomy, vagal afferent terminals would be intact and functional, whereas ipsilateral to ganglionectomy vagal afferent terminals would be absent. Three additional control preparations also were included: 1) sham ganglionectomy and 2) subnodose vagotomy either contralateral or ipsilateral to NTS cannula placement. We found that rats with subnodose vagotomies increased their sucrose intake after injections of MK-801 compared with saline, regardless of whether injections were made contralateral (12.6 +/- 0.2 vs. 9.6 +/- 0.3 ml) or ipsilateral (14.2 +/- 0.6 vs. 9.7 +/- 0.4 ml) to vagotomy. Rats with NTS cannula placements contralateral to nodose ganglionectomy also increased their intake after MK-801 (12.2 +/- 0.9 and 9.2 +/- 1.1 ml for MK-801 and saline, respectively). However, rats with placements ipsilateral to ganglionectomy did not respond to MK-801 (8.0 +/- 0.5 ml) compared with saline (8.3 +/- 0.4 ml). We conclude that central vagal afferent terminals are necessary for increased food intake in response to NMDA ion channel blockade. The function of central vagal afferent processes or the activity of higher-order NTS neurons driven by vagal afferents may be modulated by NMDA receptors to control meal size.

The teniae of the equine intestinal tract.

At several locations along the equine cecum and colon, the outer longitudinal portion of the tunica muscularis is gathered into discrete bands of smooth muscle and connective tissue called "teniae". In this study, the disposition of the teniae ceci and coli was traced along the equine intestinal tract. It was discovered that, in several instances, arrays of teniae converge toward the valves and sphincters which separate the various intestinal compartments. The teniae may also provide support for and directionality to, peristaltic contraction waves. The tissue proportions of the teniae vary in different locations. The tenia libera lateralis of the ventral colon is rich in elastic connective tissue, while that of the right dorsal colon is primarily composed of smooth muscle. This may reflect the different responsibilities of these two compartments. The teniae are innervated and their smooth muscle cells are joined by many gap junctions. The connective tissue constituents afford intestinal support while yielding to intestinal distension. The smooth muscle and neural elements may foster active tenial participation in peristalsis. This premise must be tested by electrophysiological experimentation. Further experimentation is also necessary to ascertain whether injury to the teniae might predispose a horse to colic.

Knowledge management of the neuroscientific literature: the data model and underlying strategy of the NeuroScholar system.

This paper describes the underlying strategy and system's design of a knowledge management system for the neuroscientific literature called 'NeuroScholar'. The problem that the system is designed to address is to delineate fully the neural circuitry involved in a specific behaviour. The use of this system provides experimental neuroscientists with a new method of building computational models ('knowledge models') of the contents of the published literature. These models may provide input for analysis (conceptual or computational), or be used as constraint sets for conventional neural modelling work. The underlying problems inherent in this approach, the general framework for the proposed solution, the practical issues concerning usage of the system and a detailed, technical account of the system are described. The author uses a widely used software specification language (the Universal Modelling Language) to describe the design of the system and present examples from published work concerned with classical eyeblink conditioning in the rabbit.

Neuropeptide distributions in the colon, cecum, and jejunum of the horse.

The pelvic flexure portion of the equine large colon is the proposed location of a pacemaker mechanism. This study was conducted to ascertain whether the distribution of certain putative neurotransmitters differs at the pelvic flexure compared to other sampling sites. Tissue samples were collected from the intestinal tracts of six horses. Serial sections from these samples were reacted with primary antisera specific for substance P, vasoactive intestinal polypeptide (VIP), methionine-Enkephalin, and calcitonin gene-related peptide (CGRP). The regional distribution of immunoreactive neuronal elements was uniform for each of the neuropeptides except VIP. Although neurons exhibiting VIP-like immunoreactivity were abundant throughout the colon, they were somewhat more plentiful near the apex of the pelvic flexure and the left dorsal colon. These neurons may participate in the initiation and propagation of the propulsive/retropulsive contraction waves, which emanate from this location and are believed to lend a sphincter-like capacity to the pelvic flexure. The submucosal plexus was replete with neurons with intense substance P and VIP-like reactivity. Reactive fibers left submucosal ganglia to project to the intestinal mucosa, reflecting a possible secretogogic role for these neurons. This role may be especially important for the horse as a hindgut fermenter. There were abundant methionine-Enkephalin and substance P-like reactive varicosities throughout the myenteric plexus, many of which established a pericellular plexus of varicose fibers. The abundance of these varicosities, which may correlate with a high degree of neuronal integration, did not vary regionally. These data may enhance our understanding of both normal colonic peristalsis and motility disorders caused by a depletion of these neuropeptides.

Equine myenteric plexus with special reference to the pelvic flexure pacemaker.

Sellers et al. (1979, Am. J. Phys., 237: E457-E464) proposed a pelvic flexure pacemaker mechanism to account for the bidirectional contraction waves needed to both retain ingesta within the right ventral colon for cellulose digestion and terminal fermentation and to transport the digesta distad once the process has been completed. To corroborate the presence of a pelvic flexure pacemaker, we prepared whole mount samples of the tunica muscularis from 23 horses at ten sites along the large colon, cecum and jejunum. Following smooth muscle enzymatic digestion, somata of the myenteric plexus were stained with an RNA-specific agent, Cuprolinic blue. These somata were quantified at each site to establish any regional variations in neuronal density. Results indicated an increased neuronal density at the level of the pelvic flexure, especially in the region of the left dorsal colon. The increased neuronal density at the left dorsal colon compared to the other sampling sites was statistically significant (Wilcoxon signed rank test, P less than .01 at each sampling site). There was remarkable size variation (from 10-60 microns) among neurons at the individual sampling sites. However, no statistically significant size discrepancy existed between sampling sites (Friedman's rank test, P = .10). The 23 horses ranged from 6 months to 15 years of age. No age-related differences in neuronal density was discovered (Kruskal-Wallis ANOVA test, P greater than .05). Neuronal densities did not vary on the basis of sex (Wilcoxon signed pairs test, P greater than .05).(ABSTRACT TRUNCATED AT 250 WORDS)