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PubMed1992

Is there involvement of the central nervous system in hereditary sensory radicular neuropathy?

There is pathological evidence that hereditary sensory radicular neuropathy (HSN type I) is a disorder related to multi-system atrophy with marked cell loss in the cerebral cortex, thalamus, brain stem and cerebellum. We report here a clinical study of a case of HSN-I including audiometric testing, autonomic functions, electromyography, transcranial magnetic stimulation and magnetic resonance imaging of the brain. There were no signs of central nervous system involvement. It is stated that HSN-I remains a disorder of dorsal root ganglia and sensory nerves, leading to painless perforating ulceration and mutilation, within the course of the disease peripheral motor nerve involvement, but without involvement of central motor pathways.

Brain↗
PubMed1992

Priming of associative long-term depression in the dentate gyrus by theta frequency synaptic activity.

Associative long-term synaptic depression (LTD) was investigated utilizing negatively correlated activity patterns in the medial and lateral perforant path inputs to the dentate gyrus in anesthetized rats. Normally only nonassociative, or heterosynaptic, LTD is elicited in naive pathways. We report here, however, that associative LTD in the lateral path is readily induced after being "primed" by a brief period of lateral path synaptic activity at a theta rhythm frequency (5 Hz). Priming of associative LTD lasts at least 2 hr and is not seen following priming activity at non-theta frequencies (1 and 15 Hz). N-methyl-D-aspartate receptor activation is critical for establishing the priming effect, but not for the subsequent induction of the associative LTD. These data suggest that theta rhythm activity in the dentate gyrus may predispose the system to a specific form of synaptic plasticity, associative LTD.

Animals↗
PubMed1998

Lipid uptake in expanded polytetrafluoroethylene vascular grafts.

PURPOSE: The mechanisms of vascular prosthesis failure are reported to be associated, in part, with an atherosclerotic degenerative process that is related to an abnormal lipid infiltration. The lipid uptake in expanded polytetrafluoroethylene (ePTFE) vascular grafts was reproduced in vitro, and the effect of time on the permeability of these prostheses was studied. METHODS: Water permeability tests were carried out under dynamic flow conditions at various hydrostatic pressures. Lipid uptake was simulated by circulating a phosphatidylcholine suspension inside an expanded Teflon prosthesis under pulsatile or continuous transmural pressure ranging between 80 mm Hg and 180 mm Hg, at a flow rate of 500 mL/min and 2000 mL/min, for a duration ranging from 2 hours to 1 month. RESULTS: Water permeability tests indicated that under hydrostatic pressures of 180 mm Hg and 300 mm Hg, water percolated through the prosthesis wall after an exposure of 720 minutes and 75 minutes, respectively. After exposing the prostheses to the lipid dispersion under the various flow conditions, the fluid convection through the wall occurred. Preferential convection pathways with a constant periodicity were observed across the length of each prosthesis and were, therefore, associated with regularly spaced perforations depicted in the structure of the devices. Phospholipids gradually agglomerated within the prosthesis wall, allowing a restrictive molecular mobility. Infrared spectroscopy results indicated that the lipid uptake depended on the transmural pressure and time of exposure. CONCLUSION: The occurrence of the membrane permeability may be associated with the dilatation and plastic deformation of the prosthesis. Lipid uptake occurs in ePTFE grafts after an aggressive kinetic process.

Blood Vessel Prosthesis↗
PubMed2002

The sustained impact of an evidenced-based clinical pathway for acute appendicitis.

Appendicitis is a frequent pediatric surgical condition for which there is great variability among practitioners regarding diagnosis and postoperative management. With this in mind, the authors designed and implemented an evidence-based appendicitis clinical pathway at their institution. Establishment of the pathway resulted in decreased hospital cost, reduced hospital stay, and fewer unnecessary laboratory tests. The purpose of the current study was to determine the sustainability of the pathway beyond its initial implementation phase. The authors showed that several, but not all, favorable outcomes of the pathway were sustained. These data suggest that a clinical pathway for appendicitis at the authors' institution results in sustained beneficial effects in some but not all outcome parameters. Ongoing monitoring of pathway compliance, continued education of practitioners and nursing personnel, and identification of key pathway team member(s) responsible for the pathway system might result in a greater long-term impact of these guidelines.

Appendicitis↗
PubMed1997

Local spread of metastatic vertebral tumors. A histologic study.

STUDY DESIGN: Nineteen solitary metastatic vertebral tumors obtained by total en bloc spondylectomy were analyzed histologically. OBJECTIVES: To determine the mechanisms of local spread of vertebral tumors and identity barrier tissues to tumor progression in the vertebra. SUMMARY OF BACKGROUND DATA: Histologic studies of specimens resected at amputation or en bloc excision have determined the pattern of local spread of bone and soft tissue tumors in the extremities and identified barrier tissues to tumor spread. However, a similar assessment of vertebral malignancies is difficult. The development of total en bloc spondylectomy for primary vertebral malignancy and solitary has allowed the collection of tissue samples sufficient to analyze the pattern of local spread of tumors, using the concept of compartment and barrier. METHODS: Histologic sections of all vertebral elements were prepared from specimens collected after en bloc spondylectomy. Serial 5-mm sections in the sagittal plane were also prepared and examined. RESULTS: Analysis of tumor location showed that metastatic tumors reached the vertebral column by invading the bone marrow of the dorsal region of the vertebral body. The anterior longitudinal ligament, posterior longitudinal ligament, periosteum abutting the spinal canal, ligamentum flavum, periosteum of the lamina and spinous process, interspinous ligament, supraspinous ligament, cartilaginous endplate and the anulus fibrosus served as barriers to tumor progression. The posterior longitudinal ligament was the weakest barrier tissue and was gradually destroyed by the tumor at the point of perforating vessels. Even after destruction of the barrier tissue, tumor cells were covered with a thin, fibrous reactive membrane. Two pathways allowed tumor spread to the adjacent vertebrae: 1) from the edge of the vertebral body to the adjacent vertebral body beneath the longitudinal ligament, and 2) through the paravertebral muscles to the neighboring lamina. CONCLUSIONS: Each vertebra can be represented by a compartment surrounded by several barriers. The most common path for tumor spread is through the posterior longitudinal ligament to the epidural space.

Aged↗
PubMed1994

Transfer kindling between sites in the entorhinal cortex-perforant path-dentate gyrus system.

Repeated electrical stimulation of forebrain sites can lead to an enhanced epileptogenic response (the kindling phenomenon). When stimulation is subsequently applied to related sites, these developments occur more rapidly (the transfer effect). Axonal pathways do not support epileptiform discharge, so it is generally assumed that the kindling develops, when these pathways are stimulated, in the target structures of those pathways. Consequently, transfer kindling should be immediate, or at least very rapid. Primary and 'transfer' kindling effects were examined in the excitatory, monosynaptically coupled, entorhinal cortex-dentate gyrus system. Transfer kindling was begun following either a 24 h delay or a 4 week delay between the last primary site convulsion and the start of transfer kindling in the secondary site. A 4 week delay between kindling sites was chosen to minimize the effects of a previously reported transient suppression of transfer kindling and the increased inhibition that has been shown to develop in the dentate gyrus as a result of kindling the perforant path. Although there was a significant transfer to the dentate gyrus following perforant path stimulation, the dentate gyrus still required a mean of 18.5 (24 h delay) and 20.3 (4 week delay) stimulations to reach criterion. In the entorhinal cortex, there was a significant positive transfer following primary kindling of the perforant path only in the group in which transfer kindling was begun after a 4 week delay. When the perforant path itself was the transfer site, there was a significant savings in number of afterdischarges needed to reach criterion following dentate gyrus kindling but no savings following entorhinal cortex kindling.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed2003

Current controversies in the understanding of necrotizing enterocolitis. Part 1.

Necrotizing enterocolitis (NEC) has widespread implications for neonates. While mostly affecting preterm neonates, full-term neonates, especially those with congenital heart disease, are also at risk. Although the exact pathogenesis of NEC remains elusive, three major factors, a pathogenic organism, enteral feedings, and bowel compromise, coalesce in at-risk neonates to produce bowel injury. Initiation of the inflammatory cascade likely serves as a common pathway for the disorder. Clinical signs and symptoms range from mild feeding intolerance with abdominal distension to catastrophic disease with bowel perforation, peritonitis, and cardiovascular collapse. Vigilant assessment of at-risk neonates is crucial. When conservative medical management fails to halt injury, surgical intervention is often needed. Strategies to decrease the incidence and ultimately prevent NEC loom on the horizon, such as exclusive use of human breastmilk for enteral feedings and administration of probiotics.

Australia↗
PubMed2001

Gastropleural fistula originating from the lesser curve: a recognised complication, an uncommon pathway of communication.

Fistulous communications between the abdominal and the pleural cavity are rare; they implicate intra-abdominal sepsis. We present a rare case of subphrenic abscess following gastric perforation, which resulted in thoracic empyema. This report emphasises that gastropleural fistulas, although uncommon, should be considered in differential diagnoses of thoracic empyema, especially when there is a longstanding history of peptic ulceration.

Empyema, Pleural↗
PubMed1998

[The effect of NC-1900: its ameliorating effects on impairments of learning and memory in the CA1 neurons and its intracellular signal transduction pathways].

Effects of arginine vasopressin (AVP(1-9)) and its analogues on the glycine (Gly)-induced Cl- currents (IGly) were examined in acutely dissociated rat hippocampal CA1 neurons using nystatin perforated and conventional whole-cell patch recording modes under voltage-clamp conditions. The results suggest that the activation of V1 receptor induces IP3 production which release Ca2+ from IP3-sensitive Ca2+ storage sites. The Ca2+ binds to CaM, resulting in the activation of Ca2+/CaM-sensitive adenylate cyclases. Consequently, the activation of PKA inhibits IGly. The inhibitory actions of NC-1900 and its analogues on IGly might be involved in their ameliorating effects on impairments of learning and memory in the CA1 neurons.

Animals↗
PubMed1993

Possible role of both the alpha and beta gamma subunits of the heterotrimeric G protein, Gs, in transcytosis of the polymeric immunoglobulin receptor.

In endosomes the polymeric immunoglobulin receptor (pIgR) is sorted into transcytotic vesicles. Transcytosis of the pIgR in polarized Madin-Darby canine kidney (MDCK) cells is regulated both by phosphorylation of Ser664 and by binding of ligand, dimeric IgA (dIgA). Mutation of Ser664 to Ala (pIgR-Ala664) greatly reduces transcytosis of the pIgR without dIgA bound. Here we report that cholera toxin, which specifically activates the heterotrimeric G protein, Gs, stimulates transcytosis of pIgR-Ala664 when dIgA is not bound. However, transcytosis of the wild-type pIgR without dIgA bound was not stimulated by cholera toxin. To further analyze the involvement of Gs in transcytosis, we reconstituted part of the transcytotic pathway. Vesicles containing endocytosed ligand bound to the pIgR could be released from MDCK cells whose apical surface had been mechanically perforated. Release of these vesicles was controlled by phosphorylation of the pIgR and by binding of dIgA. The use of perforated cells allowed us to directly address the involvement of Gs. Our data suggest that both subunits of Gs, Gs alpha and beta gamma, function together to control vesicular release and may therefore be involved in transcytosis in vivo.

Alanine↗
PubMed2000

ATP and beta-adrenergic stimulation enhance voltage-gated K current inactivation in brown adipocytes.

Sympathetic activation of brown fat thermogenesis stimulates adrenergic and purinergic receptors. We examined the effects of extracellular ATP and beta-adrenergic agonists on voltage-activated K currents (IKv) in voltage-clamped rat brown adipocytes. ATP or the beta-adrenergic agonist isoproterenol increased the development of IKv inactivation during depolarizing voltage steps in perforated patch-clamped cells. The effects on inactivation developed slowly in the presence of agonist and continued to increase for long times following agonist washout. 8-bromo-cAMP or forskolin had similar effects on IKv inactivation. Development of IKv inactivation during depolarizations was consistently enhanced by ATP or beta-adrenergic stimulation in perforated-patch voltage-clamped cells but was not altered by these agents in whole cell recordings, suggesting that cytosolic factors are necessary for inactivation modulation. In either recording configuration, ATP or isoproterenol shifted the activation voltage dependence of IKv to more negative potentials, indicating the activation effect is mediated by a different pathway. Since both P2 purinergic and beta-adrenergic signaling pathways generate fatty acids, we tested whether fatty acids could reproduce these modulations of IKv. Linoleic or arachidonic acid applied in whole cell recordings had effects similar to those of ATP or isoproterenol in perforated-patch experiments. These results are consistent with the possibility that beta-adrenergic and P2 receptor stimulation modulate IKv through generation of fatty acids.

8-Bromo Cyclic Adenosine Monophosphate↗
PubMed1996

Bilateral organization of parallel and serial pathways in the dentate gyrus demonstrated by current-source density analysis in the rat.

1. Membrane currents evoked in the dentate gyrus (DG) by stimulation of afferent pathways from the entorhinal cortex (EC) and contralateral DG were examined by current-source density (CSD) analysis in urethan-anesthetized rats. Stimulation of each afferent pathway evoked membrane currents with distinct spatial and temporal organization in the DG. CSD and anatomic analysis revealed that afferent input from the EC activated the DG bilaterally through parallel and serial pathways. The analysis provided a detailed description of the location, timing, and relative amplitude of evoked monosynaptic and multisynaptic currents in the DG. 2. Orthodromic stimulation of the perforant path (PP) evoked a large ipsilateral excitatory postsynaptic current (iEPSC) at a latency of 2.5-4 ms in the middle and outer stratum moleculare (STM) of the DG, and a population spike that was generated by an excitatory inward current at a latency of 5-9 ms in the stratum granulosum. 3. A variable, low-amplitude ipsilateral inward current followed the population spike at a latency of 13-16 ms in the inner STM, which is the site of synaptic terminals of the associational and commissural pathways arising from neurons in the hilus of the DG. Orthodromic stimulation of the commissural pathway from the hilus of the contralateral DG also evoked an inward current in the inner STM at a latency of 2-6 ms, which was 40-60% of the amplitude of the monosynaptic iEPSC. 4. Orthodromic stimulation of the EC evoked a low-amplitude contralateral excitatory postsynaptic current (cEPSC) at a latency of 3-6 ms in the outer and middle STM of the contralateral DG, which was generated by monosynaptic transmission in the sparse crossed pathway from the EC. In contrast to the variable, low-amplitude inward current in the inner STM that followed the iEPSC, the cEPSC was consistently followed by a large inward current at a latency of 8-14 ms in the inner STM of the contralateral DG. 5. The large inward current in the inner STM of the contralateral DG was abolished by transection of the PP ipsilateral and rostral to the stimulating electrode, but was unaffected by transection of the PP at a similar location in the hemisphere contralateral to the stimulating electrode. These observations suggested that this current was most likely generated by a multisynaptic pathway involving the ipsilateral PP and the commissural pathway arising from the hilus of the DG. 6. In conclusion, efferents from the EC activated the DG bilaterally by parallel and serial pathways. Parallel monosynaptic pathways from the EC activated homologous distal segments of granule cell dendrites bilaterally, by a massive input to the ipsilateral DG and a sparse input to the contralateral DG. Sequential propagation from the EC through a multisynaptic pathway that included the commissural pathway from the hilus of the DG bilaterally activated the proximal segments of granule cell dendrites at longer latencies. The amplitude of the multisynaptic currents generated by serial pathways in the proximal dendrites varied inversely with the amplitudes of the monosynaptic currents evoked by parallel pathways in the distal dendrites. These observations may have implications for synaptic integration, associative properties, and information processing in the DG.

Afferent Pathways↗
PubMed1992

Autoradiographic localization of proline uptake in excitatory hippocampal pathways.

An autoradiographic method was developed to localize sites of high-affinity, Na(+)-dependent proline uptake in the rat hippocampal formation. Hippocampal slices were incubated with [3H]proline, fixed with a glutaraldehyde/carbodiimide mixture, and cut into frozen sections. The sections were coated with photographic emulsion and autoradiograms were prepared. Autoradiographic grain densities were highest over the inner and outer thirds of the dentate molecular layer, followed by stratum lacunosum-moleculare of area CA3. Stratum oriens and stratum radiatum of area CA1 and CA3 were fairly intensely labeled. The pyramidal and granule cell body layers, stratum lucidum of area CA3, and middle third of the dentate molecular layer were lightly labeled. Effects of surgical and kainic acid lesions suggested that the lateral perforant path, associational-commissural fibers in the fascia dentata, and Schaffer collateral-commissural-ipsilateral stratum oriens fibers have considerable proline uptake capacity. In contrast, the medial perforant path and the mossy fibers appear to accumulate little or no proline. These results suggest that high-affinity, Na(+)-dependent uptake of proline is expressed by a subset of hippocampal glutamate pathways. The relative capacities of glutamate terminal populations to transport glutamate and proline varies widely. Proline was previously shown to possess neuroexcitatory and excitotoxic properties in the rat hippocampal formation. Taken together, these findings argue that proline plays a role in excitatory transmission. In elucidating this role, comparisons between medial and lateral divisions of the perforant path may prove especially advantageous.

Animals↗
PubMed2001

Three dimensional configuration of the secretory pathway and segregation of secretion granules in the yeast Saccharomyces cerevisiae.

The structural elements of the secretory pathway in the budding yeast Saccharomyces cerevisiae were analyzed by 3D stereo-electron microscopy using relatively thick sections in which membranes were selectively impregnated. In a wild-type strain, tubular networks of various sizes and staining properties were distributed throughout the cytoplasm. As a rule, wide-meshed, lightly stained polygonal networks were connected to more or less fenestrated sheets of endoplasmic reticulum (ER). Some of these networks were continuous with more intensely stained networks and narrower meshes that displayed at their intersections nodular dilations that progressively increased in size and staining properties to reach those of secretion granules. Such networks presumably corresponded to Golgi elements. Indeed, stacked cisternae typical of the mammalian Golgi apparatus are rarely found in wild-type cells. However, if it is assumed that the Golgi apparatus plays a key role in the segregation and maturation of secretion granules, then tubular networks with nodular dilations should be equivalent to parts of this organelle. In correlation with the increase in size and density of the nodules there was a decrease in diameter and staining intensity of the interconnecting tubules. These results parallel observations on the formation of secretory granules in mammalian cells and suggest that the segregation of secretory material is concomitant with the progressive perforation and tubulization of previously unperforated sheets. When the sec21-3 thermosensitive mutant was examined at the nonpermissive temperature (37 degrees C), the secretory pathway was blocked at exit from the ER, which started to accumulate as clusters of narrow, anastomosed, unperforated ribbon-like elements. When the block was released by shifting down to permissive temperature (24 degrees C), tubular networks of various sizes and caliber, presumably Golgi in nature, formed as soon as 5 minutes after release of the block. At later time intervals, granules of various sizes and densities appeared to be released by rupture of these tubular networks or even to form at the edges of ER fenestrae. These observations support a dynamic maturation process in which the formation of secretion granules occurs by means of an oriented series of membrane transformations starting at the ER and culminating with the liberation of secretion granules from Golgi networks.

Biological Transport, Active↗
PubMed2006

ERK/MAPK pathway regulates GABAA receptors.

The GABAA receptor is a ligand-gated ion channel whose function and activity can be regulated by ligand binding or alternatively may be influenced indirectly through the phosphorylation of specific subunits that comprise the GABAA receptor pentamer. With respect to phosphorylation, most studies have focused on either beta or gamma subunits, whereas the role of the alpha subunit as a relevant target of signaling kinases is largely unknown. Interestingly, we found a putative phosphorylation site for extracellular-signal regulated kinase (ERK), a key effector of the MAPK pathway, in almost all known alpha subunits of the GABAA receptor, including the ubiquitously expressed alpha1 subunit. To determine whether this putative ERK phosphorylation site was functionally relevant, we evaluated if ERK inhibition (through pharmacological inhibition of its upstream kinase, MEK) altered GABA-gated currents. Using HEK293 cells stably transfected with the alpha1beta2gamma2 form of the GABAA receptor, we found that UO126 reduced basal ERK phosphorylation and resulted in an enhancement of GABA-induced peak current amplitudes. Further, the enhancement of GABA-gated currents required an intact intracellular environment as it was robust in perforated patch recordings (which preserves the intracellular milieu), but absent in conventional whole-cell recordings (which dialyzes the cytosolic contents), supporting the involvement of an intracellular signaling pathway. Finally, mutation of the ERK phosphorylation site (T375-->A) prevented the UO126-induced enhancement of GABA-gated currents. Collectively, our results implicate the MAPK pathway as a negative modulator of GABAA receptor function, whose influence on GABA-gated currents may be mediated by phosphorylation of the alpha subunit.

Animals↗
PubMed1996

[Changes of synaptic transmission efficiency in the MF-CA3 and PP-CA3 pathways of rat hippocampus during discrimination learning].

Electrophysiological and behavioral studies were performed in rat to investigate the changes of synaptic efficacy of the two inputs of hippocampal CA3 area [Mossy Fiber (MF) -CA3 and Perforant Path (PP) -CA3] during discrimination learning. The results showed that: (1) Amplitude of the population spike (PS) of both from MF-CA3 and PP-CA3 increased simultaneously with the establishment of conditioned response (CR) and both reached their maxima before CR reached the criterion of acquisition. (2) During natural extinction of CR, the amplitude of PS of both inputs decreased also simultaneously to their per-training level. These results indicated that the learning-dependent long-term potentiation (LTP) in both MF-CA3 and PP-CA3 inputs developed and extinguished synchronously, suggesting that the changes of synaptic efficacy of different inputs of hippocampal CA3 area coordinated during discrimination learning.

Animals↗
PubMed1984

Medial septal projections to the dentate gyrus of the rat: electrophysiological analysis of distribution and plasticity.

Previous electrophysiological experiments in rabbits have suggested that medial septal stimulation activates dentate granule cells and evokes an associated negative field response at the granule cell layer, without an associated "dendritic" response. Anatomical studies have suggested that septal input to the granule cells may be to stratum moleculare, or close to the cell layer, or may not exist at all. The present experiments confirmed in rats anaesthetised with urethane that medial septal stimulation elicits single action potentials from cells in the granule layer. The associated negative field potential was maximal in the granule cell layer and there was no sign of a separate dendritic potential. The fibres responsible for this potential travel to the dorsal hippocampus in the fornix superior rather than the fimbria, taking the same course as the fibres which contribute to the dense cholinesterase staining just above the granule cell layer. Stimulation at 100 Hz for 1 s of either medial septal, or perforant path, input to the dentate granule cell layer produced long term potentiation of the subsequent evoked field responses to the stimulated pathway. The responses to the non-stimulated pathway were unchanged. Paired pulse stimulation produced both homosynaptic and heterosynaptic potentiation. These data suggest that medial septal input synapses close to granule cell bodies and produces a negative field potential which is a combination of dendritic and population spike potentials. Medial septal input also appeared to produce direct activation of hilar neurones, some of which may be basket cells or other interneurones. The data also show that long term potentiation is specific to this input, perhaps dependent on presynaptic mechanisms. Paired pulse potentiation, at least in the heterosynaptic case appears to depend on postsynaptic mechanisms.

Animals↗
PubMed2004

Invasive cell behavior during Drosophila imaginal disc eversion is mediated by the JNK signaling cascade.

Drosophila imaginal discs are monolayered epithelial invaginations that grow during larval stages and evert at metamorphosis to assemble the adult exoskeleton. They consist of columnar cells, forming the imaginal epithelium, as well as squamous cells, which constitute the peripodial epithelium and stalk (PS). Here, we uncover a new morphogenetic/cellular mechanism for disc eversion. We show that imaginal discs evert by apposing their peripodial side to the larval epidermis and through the invasion of the larval epidermis by PS cells, which undergo a pseudo-epithelial-mesenchymal transition (PEMT). As a consequence, the PS/larval bilayer is perforated and the imaginal epithelia protrude, a process reminiscent of other developmental events, such as epithelial perforation in chordates. When eversion is completed, PS cells localize to the leading front, heading disc expansion. We found that the JNK pathway is necessary for PS/larval cells apposition, the PEMT, and the motile activity of leading front cells.

Animals↗