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Biomedical subjects

S M Altschuler

Publications and source records attributed to S M Altschuler.

At least 37 records · Page 2Linked to original sources
PubMed1994

Cystic fibrosis transmembrane conductance regulator protein expression in brain.

The cystic fibrosis transmembrane conductance regulator protein (CFTR) has been identified in bovine brain clathrin-coated vesicles, rat brain and a human neuroblastoma cell line using affinity-purified polyclonal peptide antibodies against CFTR. Immunocytochemical staining of multiple dendrites and soma of neurons of the diencephalon, midbrain, pons and medulla oblongata, has also been demonstrated. Whole cell lysates and membranes derived from rat brain, neuroblastoma cells and bovine brain clathrin-coated vesicles express the mature 150-165 kDa and 130 kDa unglycosylated forms of CFTR. The localization of CFTR to brain regions controlling homeostasis and energy expenditure may relate to the pathogenesis of non-pulmonary manifestations of cystic fibrosis. CFTR expression in neurons and coated vesicles suggests a possible effect on neuropeptide vesicle trafficking by mutant CFTR.

Amino Acid Sequence↗
PubMed1994

Dendritic architecture of hypoglossal motoneurons projecting to extrinsic tongue musculature in the rat.

The tracer, cholera toxin-horseradish peroxidase, was used to determine the dendritic architecture and organization of hypoglossal motoneurons in the rat. In 22 animals, the tracer was injected unilaterally into either the geniohyoid, genioglossus, hyoglossus, or styloglossus muscle. Within the hypoglossal nucleus, motoneurons innervating the extrinsic tongue muscles were functionally organized. Geniohyoid and genioglossus motoneurons were located within the ventrolateral and ventromedial subnuclei, respectively, while hyoglossus and styloglossus motoneurons were located within the dorsal subnucleus. Motoneurons located in all subnuclear divisions were found to have extensive dendrites that extended laterally into the adjacent reticular formation and medially to the ependyma. Less extensive extranuclear dendritic projections were found in the dorsal vagal complex and median raphe. Prominent rostrocaudal and mediolateral dendritic bundling was evident within the ventral subnuclei and dorsal subnucleus, respectively. Dendritic projections were also found extending inter- and intrasubnuclearly with a distinct pattern for each muscle. These data suggest that the varied and extensive dendritic arborizations of hypoglossal motoneurons provide the potential for a wide range of afferent contacts for, and interactions among, motoneurons that could contribute to the modulation of their activity. Specifically, the prominent dendritic bundling may provide an anatomic substrate whereby motoneurons innervating a specific muscle receive and integrate similar afferent input and are thus modulated as a functional unit. In contrast, the extensive intermingling of both inter- and intrasubnuclear dendrites within the hypoglossal nucleus may provide a mechanism for the coordination of different muscles, acting synergistically or antagonistically to produce a tongue movement.

Animals↗
PubMed1994

Brain stem localization of rodent esophageal premotor neurons revealed by transneuronal passage of pseudorabies virus.

BACKGROUND/AIMS: Brain stem premotor neurons control swallowing through contacts with both afferent neurons and motoneurons. The location and connectivity of premotor neurons innervating the esophagus was determined using pseudorabies virus. METHODS: In 30 rats, viral injections were made into either the cervical or subdiaphragmatic esophagus, cricothyroid muscle, or stomach. After a 48-62-hour survival, brain sections were processed immunocytochemically for the virus. RESULTS: Neuronal labeling was limited to the compact formation of the nucleus ambiguus for survivals of 48-54 hours. At 57-62-hour survivals, virus-labeled second-order neurons (premotor neurons) were localized to the central subnucleus of nucleus of the solitary tract. Injections in the cricothyroid muscle and stomach resulted in distinct patterns of motoneuronal labeling in the nucleus ambiguus and dorsal motor nucleus and premotor neuronal labeling in the nucleus of the solitary tract. CONCLUSIONS: Virus-labeled premotor neurons in the nucleus of the solitary tract occurred as a result of retrograde transport of the virus from the nucleus ambiguus because no viral antigen was present in the tractus solitarius. The esophagus is controlled by a central circuit whereby esophageal vagal afferents terminate on premotor neurons in the central subnucleus that in turn innervate esophageal motoneurons in the nucleus ambiguus.

Animals↗
PubMed1994

NMDAR1 mRNA expression in the brainstem circuit controlling esophageal peristalsis.

We investigated the expression of NMDA receptors within the brainstem circuit controlling esophageal swallowing using transneuronal viral labeling and in situ hybridization. Neurons of the central subnucleus of the nucleus solitary tract (NTScen) are interneurons linking vagal afferents with esophageal motoneurons in the compact formation of the nucleus ambiguus (NAc). Following injections of Pseudorabies virus (PRV) into rat esophagus and incubation with NMDAR1 cRNA, neurons infected with PRV localized to the NAc and NTScen expressed NMDAR1 mRNA.

Animals↗
PubMed1994

Oral-oesophageal inoculation of mice with herpes simplex virus type 1 causes latent infection of the vagal sensory ganglia (nodose ganglia).

Herpes simplex virus type 1 (HSV-1) gingivostomatitis during childhood is known to result in a latent infection of the trigeminal ganglion neurons, which innervate the oral mucosa. During latency the viral genome is maintained in a non-infectious state. However, stimuli such as stress, fever or localized trauma can cause HSV-1 to reactivate in neurons and produce recrudescent disease in the peripheral tissues. Recently, HSV-1 proteins and nucleic acids have been detected in biopsies from human duodenal and gastric ulcers, raising the possibility that HSV-1 latency within the enteric nervous system is involved in this chronic recurrent gastrointestinal disorder. The studies in mice described here were done to determine whether HSV-1 latency could be established in neurons that innervate the murine gut. We found that after either intraperitoneal or oral-oesophageal inoculation of mice, HSV-1 establishes a latent infection in nodose ganglia of the vagus nerve, whose sensory neurons project to the gastrointestinal tract. This animal model of HSV-1 latency in the vagal sensory ganglia will be useful to examine the possible relationship between HSV-1 and recurrent gastrointestinal disease.

Animals↗
PubMed1993

The central organization of the vagus nerve innervating the colon of the rat.

BACKGROUND: The extent to which the vagus nerve innervates the colon remains controversial. METHODS: In 29 rats the tracer cholera toxin-horseradish peroxidase was injected into the cecum, the ascending, transverse, or descending colon or the rectum. For comparison, control injections were made into the stomach. RESULTS: For all areas of colon except the rectum, brainstem motoneuronal labeling was limited to the lateral third of the dorsal motor nucleus of the vagus nerve bilaterally. In contrast, gastric injections resulted in motoneuronal labeling limited to the medial portions of the nucleus. The number of labeled motoneurons was greatest following injection of the cecum, and it significantly decreased for the more distal areas of the colon. Colonic motoneuron dendrites projected into the nucleus of the solitary tract and within the dorsal motor nucleus of the vagus nerve. Sensory afferent terminal labeling was limited to the commissural and medial subnuclei of the nucleus of the solitary tract. For the rectum, sensory and motor labeling was limited to the spinal cord. CONCLUSIONS: The distribution of labeling within the vagal complex indicates that all regions of the colon, except the rectum, are innervated by the celiac and accessory celiac branches of the vagus nerve.

Afferent Pathways↗
PubMed1992

Calcitonin gene-related peptide in nucleus ambiguus motoneurons in rat: viscerotopic organization.

Calcitonin gene-related peptide has been reported in the rat nucleus ambiguus. This nucleus comprises a dorsal division that is the source of special visceral efferents innervating the striated muscle of the upper alimentary tract and a ventral division supplying general visceral efferents primarily to the heart. The distribution of calcitonin gene-related peptide immunoreactive neurons in the two divisions was determined by using a combination of immunocytochemical techniques and fluorescent retrograde tracing. In 22 rats, injections of Fluoro-Gold were made into either the supranodosal vagus nerve, palatopharynx, larynx, esophagus, or heart. Following colchicine injection, medullary sections were processed immunocytochemically for calcitonin gene-related peptide. Injection of Fluoro-Gold into the supranodosal vagus resulted in prominent labeling of neurons in the dorsal and ventral divisions of the nucleus ambiguus. The majority of fluorescent labeled neurons in the dorsal division were found to be immunoreactive for calcitonin gene-related peptide, while those labeled neurons in the ventral division were unreactive for the peptide. With esophageal, and palatopharyngeal and cricothyroid injections, many fluorescent labeled neurons that were immunoreactive for calcitonin gene-related peptide were found respectively in the compact and semicompact formations of the dorsal division. In contrast, injections of the heart resulted in fluorescent labeled neurons, which were unreactive for calcitonin gene-related peptide, localized to the external formation. The results demonstrate that calcitonin gene-related peptide immunoreactive neurons are localized entirely to the dorsal division of the nucleus ambiguus and that all striated muscular areas of the alimentary tract are innervated by calcitonin gene-related peptide containing motoneurons. The localization of calcitonin gene-related peptide to vagal motoneurons also known to contain acetylcholine and the increase in acetylcholine receptor synthesis caused by this peptide suggest that calcitonin gene-related peptide acts as a cotransmitter with acetylcholine in special visceral efferent vagal motoneurons.

Animals↗
PubMed1992

Pseudo-obstruction in children.

Pseudo-obstruction of the gastrointestinal tract is a rare disorder of impaired gastrointestinal motility. The more common symptoms of pseudo-obstruction in the infant or child include dysphagia, nausea, vomiting, abdominal distention, abdominal pain, and constipation. The majority of children have symptoms within the first year of life. Chronic cases of pseudo-obstruction are associated with neuropathic or myopathic changes in other parts of the body. Bladder dysfunction and neurological problems have been reported. The diagnosis of pseudo-obstruction is based on history, physical examination, radiographic studies and motility studies. Advances in medical technology have facilitated the identification of abnormal motility patterns in children. Therapy for pseudo-obstruction is primarily supportive. The use of motility agents has been unsuccessful in treating pseudo-obstruction. Nutritional and antibiotic therapy are the mainstays of treatment. Nursing interventions, patient/family education and advances in home care technology have improved the quality of life for children with pseudo-obstruction. Small bowel transplantation offers hope for the future.

Child, Preschool↗
PubMed1991

Dendritic architecture of nucleus ambiguus motoneurons projecting to the upper alimentary tract in the rat.

The motor innervation for palatal, pharyngeal, laryngeal, and esophageal muscles originates within the nucleus ambiguus. Although the viscerotopic organization of the upper alimentary tract in the nucleus ambiguus has been extensively studied, little information concerning the dendritic arborization of nucleus ambiguus motoneurons is available. The neural tracer cholera toxin-horseradish peroxidase, which is particularly effective at revealing dendrites of retrogradely labeled neurons, was used to determine the dendritic architecture and organization of nucleus ambiguus motoneurons. In 72 rats, cholera toxin-horseradish peroxidase in volumes of 1.0-18 microliters was directly applied under pressure to the musculature of various sites along the upper alimentary tract. Motoneurons innervating the soft palate, pharynx, cricothyroid muscle, and cervical esophagus were all found to have extensive dendrites that extended into the adjacent reticular formation with a distinct pattern for each muscle group. In contrast, the dendrites of motoneurons innervating the thoracic and subdiaphragmatic esophagus were confined to the compact formation of the nucleus ambiguus. Dendritic bundling within the confines of the nucleus ambiguus was prominent following injection of tracer into the soft palate, pharynx, and esophagus. The bundles were primarily oriented in a rostrocaudal direction. These data suggest that the extensive extranuclear dendritic arborization of motoneurons innervating the soft palate, pharynx, larynx, and cervical esophagus provide a wide ranging target for multiple central afferents that may be involved in the differential control of muscles that participate in multiple complex motor functions. The lack of extensive extranuclear dendrites of motoneurons innervating the distal esophagus suggest that they receive focused central afferents. The prominent bundling of dendrites within the nucleus ambiguus may provide for synchronization of motoneurons innervating a specific muscle and perhaps for synchronization of motoneurons innervating different muscles acting in sequence.

Animals↗
PubMed1991

Representation of the cecum in the lateral dorsal motor nucleus of the vagus nerve and commissural subnucleus of the nucleus tractus solitarii in rat.

Motor fibers of the accessory celiac and celiac vagal branches are derived from the lateral columns of the dorsal motor nucleus of the vagus nerve. These branches also contain sensory fibers that terminate within the nucleus of the tractus solitarii. This study traces the innervation of the intestines by using the tracer cholera toxin-horseradish peroxidase. In 53 rats, the tracer was injected into either the stomach, duodenum, jejunum, terminal ileum, cecum, or ascending colon. With all cecal injections, prominent retrograde labeling of cell bodies occurred bilaterally in the lateral columns of the dorsal motor nucleus of the vagus nerve above, at, and below the level of the area postrema. Dendrites of laterally positioned neurons projected medially and rostrocaudally within the dorsal motor nucleus of the vagus nerve and dorsomedially into both the medial subnucleus and parts of the commissural subnucleus of the nucleus of the tractus solitarii. Sensory terminal labeling occurred in the dorsolateral commissural subnucleus at the level of the rostral area postrema and the medial commissural subnucleus caudal to the area postrema. Additionally, there was sensory terminal labeling within a small confined area of the dorsomedial zone of the nucleus of the tractus solitarii immediately adjacent to the fourth ventricle at a level just anterior to the area postrema. Stomach injections labeled motoneurons of the medial column of the entire rostrocaudal extent of the dorsal motor nucleus of the vagus nerve and a sensory terminal field primarily in the subnucleus gelatinosus, with less intense labeling extending caudally into the medial and ventral commissural subnuclei. Dendrites of gastric motoneurons project rostrocaudally and mediolaterally within the dorsal motor nucleus of the vagus nerve and dorsolaterally within the nucleus of the tractus solitarii. They are most pronounced at the level of the rostral area postrema where many dendrites course dorsolaterally terminating primarily within the subnucleus gelatinosus. Injections of the duodenum labeled a small number of the cells within the medial aspects of the dorsal motor nucleus of the vagus nerve. Jejunal, ileal, and ascending colon injections labeled cells sparsely within the lateral aspects of the dorsal motor nucleus of the vagus nerve bilaterally. No afferent terminal labeling was evident after injection of these areas of the bowel.(ABSTRACT TRUNCATED AT 400 WORDS)

Afferent Pathways↗
PubMed1990

The newborn piglet: a model of neonatal gastrointestinal motility.

Small intestinal myoelectric activity has been studied extensively in adult humans and in many animal models. However, little is known about gut myoelectrical activity in newborns, a population susceptible to primary and secondary motility disorders. We report the development of a chronic neonatal piglet model for assessment of gastric and small intestinal myoelectric activity. Six piglets aged 12 to 27 days and weighing 2.3 to 4 kg underwent laparotomy and implantation of four to six bipolar serosal electrodes along the small intestine; and selectively on the gastric antrum. Myoelectric records were obtained daily after operation in awake animals using low (0.16 Hz) and high (30 Hz) frequency filters. Electrical control activity (ECA) was observed in the stomach (4 to 5 cycles per minute) and in the duodenum (14 to 15 cycles per minute) on postoperative day 1; along with random bursts of spiking activity. The migrating myoelectric complex (MMC) appeared on postoperative day 2 or 3. In piglets followed for a week or more, the MMC cycle duration and phase III duration (period of maximal spiking activity) were longer in the proximal small intestine than at the terminal ileum (80 +/- 5 versus 47 +/- 3 minutes and 5.1 +/- 0.3 versus 3.7 +/- 0.1 minutes, respectively; mean +/- SEM, P less than .005), suggesting that some MMCs arise spontaneously in the distal small bowel without traversing the upper intestine. The antral and duodenal ECA frequencies are similar to values reported in human adults; the MMC cycle duration is slightly shorter.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1989

Viscerotopic representation of the upper alimentary tract in the rat: sensory ganglia and nuclei of the solitary and spinal trigeminal tracts.

The aim of this study was to map the viscerotopic representation of the upper alimentary tract in the sensory ganglia of the IXth and Xth cranial nerves and in the subnuclei of the solitary and spinal trigeminal tracts. Therefore, in 172 rats 0.5-65 microliters of horseradish peroxidase (HRP), wheat germ agglutinin-HRP, or cholera toxin-HRP were injected into the trunks and major branches of the IXth and Xth cranial nerves as well as into the musculature and mucosa of different levels of the upper alimentary and respiratory tracts. The results demonstrate that the sensory ganglia of the IXth and Xth nerves form a fused ganglionic mass with continuous bridges of cells connecting the proximal and distal portions of the ganglionic complex. Ganglionic perikarya were labeled in crude, overlapping topographical patterns after injections of tracers into nerves and different parts of the upper alimentary tract. After injections into the soft palate, pharynx, esophagus, and stomach, anterograde labeling was differentially distributed in distinct subnuclei in the nucleus of the tractus solitarius (NTS). Palatal and pharyngeal injections resulted primarily in labeling of the interstitial and intermediate subnuclei of the NTS and in the paratrigeminal islands (PTI) and spinal trigeminal complex. Esophageal and stomach wall injections resulted in labeling primarily of the subnucleus centralis and subnucleus gelatinosus, respectively. The distribution of upper alimentary tract vagal-glossopharyngeal afferents in the medulla oblongata has two primary groups of components, i.e., a viscerotopic distribution in the NTS involved in ingestive and respiratory reflexes and a distribution coextensive with fluoride-resistant acid-phosphatase-positive regions of the PTI and spinal trigeminal nucleus presumably involved in visceral reflexes mediated by nociceptive or chemosensitive C fibers.

Animals↗
PubMed1987

Role of medullary inspiratory neurones in the control of the diaphragm during oesophageal stimulation in cats.

1. The effect of oesophageal distension and swallowing on the activity of medullary respiratory neurones was recorded in decerebrate, spontaneously breathing cats. The distension, produced by inflating a balloon in the thoracic portion of the oesophagus, was of sufficient magnitude to induce inhibition of the peri-oesophageal part of the crural diaphragm, with little effect on the respiratory function of the diaphragm as measured by the activity in the C5 branch of the phrenic nerve. 2. 424 neurones were tested. They were located bilaterally, in the region of the nucleus tractus solitarius (dorsal respiratory group) or the ambiguous complex (ventral respiratory group). No cell exhibited a change in activity during periods of strong inhibition of crural electrical activity induced by distension or swallowing. The activity of all cells paralleled that of the C5 phrenic neurogram, which was unaffected by the tests. 3. We conclude that the reflex inhibition of the crural diaphragm during oesophageal distension does not result from an inhibition of medullary premotor inspiratory neurones of the dorsal and ventral groups. Additional central pathways must exist that inhibit motoneurones to the crural diaphragm during gastrointestinal reflexes.

Action Potentials↗
PubMed1987

Responses of feline gastroesophageal junction to changes in abdominal pressure.

The responses of the lower esophageal sphincter (LES), stomach, and diaphragm and their contribution to changes in the high-pressure zone (HPZ) at the gastroesophageal junction were determined during extrinsic abdominal compression or intragastric balloon distension in anesthetized cats. Abdominal compression consistently induced an increase in intraluminal end-expiratory LES and gastric pressure (P less than 0.01). Changes in LES pressure significantly exceeded the changes in gastric pressure (P less than 0.01). In contrast, the LES response during gastric distension was variable in the group of animals despite a consistent volume-dependent increase in gastric pressure. Mean LES pressure for the group was unchanged, although 33% of individual animals exhibited a decrease in LES pressure during gastric distension. Both abdominal stimuli induced sustained inhibition of crural (P less than 0.01), but not costal, diaphragmatic electromyographic activity. Vagotomy affected the LES but not the gastric or diaphragmatic responses to both stimuli. In the group of animals, the combined effect of the changes in the three measured variables on the HPZ resulted in maintenance of the antireflux barrier during abdominal compression but a significant decrease in the barrier during gastric distension.

Abdomen↗
PubMed1985

Role of the diaphragm in the genesis of lower esophageal sphincter pressure in the cat.

To determine the role of the diaphragm in the genesis of the high-pressure zone at the lower esophageal sphincter (LES) we studied the effect of diaphragmatic contraction on lower esophageal sphincter pressure in 10 anesthetized adult cats. Despite anchoring the pressure recording assembly within the LES to prevent axial movement of the sphincter during respiration relative to the pressure recording ports, there was an average oscillation in LES pressure of 17.4 +/- 5.5 mmHg, the frequency of which was the same as the respiratory rate. Peak LES pressure occurred at end-inspiration corresponding with peak diaphragmatic electromyogram. During periods of central apnea induced by manual hyperventilation there was absence of both diaphragmatic electromyogram and the oscillations in LES pressure. Lower esophageal sphincter pressure during apnea was equal to end-expiratory pressure during spontaneous respiration. Following complete neuromuscular blockade with pancuronium, artificial respiration with increasing tidal volumes resulted in increasing oscillations in pressure. However, the magnitude of the pressure oscillation even at tidal volumes four times normal was always significantly below that observed during spontaneous eupnic respiration. Furthermore, progressive augmentation of diaphragmatic electromyogram activity by breathing 5% CO2 in air revealed a linear correlation between the magnitude of the respiratory-induced pressure oscillations of the LES and peak integrated diaphragmatic electromyogram in individual animals. It is concluded, therefore, that (a) intrinsic LES tone is best approximated by end-expiratory pressure during spontaneous respiration, (b) the respiratory-induced oscillations in LES pressure are primarily the result of active diaphragmatic contraction, and (c) the level of diaphragmatic electrical activity directly influences the magnitude of the pressure oscillation.

Analysis of Variance↗
PubMed1985

Simultaneous reflex inhibition of lower esophageal sphincter and crural diaphragm in cats.

We have previously suggested that both the lower esophageal sphincter and diaphragm contribute to the high-pressure zone (HPZ) at the gastroesophageal junction. The purpose of this study in anesthetized cats was to compare changes in diaphragmatic electrical activity with changes in the intraluminal pressure profile in the HPZ following either balloon distension of the esophagus or swallowing evoked by pharyngeal stimulation. Intraluminal pressure was continuously recorded by a perfused manometric assembly anchored to the gastric fundus through an abdominal surgical approach. Integrated EMG was simultaneously measured in the costal and crural parts of the diaphragm. Our results indicate that simultaneous relaxation of the lower esophageal sphincter (LES) and crural diaphragm follows both swallowing and balloon distension of the esophagus; during swallowing both inhibitory reflexes depend on the initiation of esophageal peristalsis; crural relaxation abolishes respiratory-induced pressure oscillations in the HPZ during LES relaxation; ventilation is maintained during relaxation of the HPZ in part by continued contraction of the costal diaphragm; and different neural pathways control LES relaxation and crural relaxation. The data support the view that the crural diaphragm augments the intrinsic smooth muscle sphincter mechanism at the gastroesophageal junction and that crural relaxation may be an important factor in mouth-to-gastric transit.

Animals↗