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At least 1,513 records · Page 84Linked to original sources
PubMed1989

Importance of aortic baroreflex in regulation of sympathetic responses during hypotension. Evidence from direct sympathetic nerve recordings in humans.

Arterial baroreceptors in the carotid sinus and aortic arch regions reflexly regulate heart rate and peripheral vascular responses during changes in arterial pressure. The relative influence of these two arterial baroreflex pathways on the control of these autonomic responses is debatable. Recent studies in our laboratory demonstrate that the aortic baroreflex produces substantial and sustained inhibition of efferent sympathetic nerve activity to muscle (MSNA) during increases in arterial pressure. The regulation of MSNA by these two baroreflexes in humans during hypotension, and particularly the role of the aortic baroreflex, remains undefined. We therefore performed a new series of studies to assess the relative influence of the aortic and carotid baroreflexes on MSNA responses during sustained decreases in arterial pressure. In eight normal male subjects, aged 23 +/- 1 years (mean +/- SEM), we directly measured mean arterial pressure, heart rate, central venous pressure, and MSNA (microneurography) during hypotension (combined aortic and carotid baroreceptor deactivation) produced by intravenous infusion of sodium nitroprusside and during nitroprusside infusion with superimposed application of external neck suction. Neck suction was applied at levels sufficient to maintain transmural carotid sinus pressure above control levels (carotid baroreceptor activation) while the aortic baroreflexes remained deactivated. Central venous pressure was maintained constant with volume infusion. We also studied responses of these same subjects to direct carotid baroreceptor deactivation with the application of external neck pressure. During neck pressure alone, there was a reflex increase in mean arterial pressure; thus, during this portion of the protocol, we achieved carotid baroreceptor deactivation with some aortic baroreceptor activation. Nitroprusside infusion (combined aortic and carotid deactivation) decreased mean arterial pressure from 90.8 +/- 3.1 to 77.8 +/- 1.1 mm Hg (p less than 0.01) with concomitant increases in heart rate from 62.6 +/- 3.0 to 89.7 +/- 6.1 beats/min (p less than 0.001) and in MSNA from 273.8 +/- 43.0 to 950.6 +/- 133.5 units (p less than 0.001). During continued nitroprusside infusion with superimposed neck suction (aortic baroreceptor deactivation and carotid baroreceptor activation), mean arterial pressure decreased to 70.3 +/- 1.9 mm Hg (p less than 0.001 vs. control), heart rate decreased to 82.5 +/- 6.5 beats/min (p less than 0.01 vs. control or vs. nitroprusside alone), but MSNA remained markedly increased at 889.7 +/- 105.1 units (p less than 0.001 vs. control; p = NS vs. nitroprusside alone).(ABSTRACT TRUNCATED AT 400 WORDS)

Adult↗
PubMed1993

Interconnection between thyroid hormone signalling pathways and parvovirus cytotoxic functions.

Nonstructural (NS) proteins of autonomous parvoviruses can repress expression driven by heterologous promoters, an activity which thus far has not been separated from their cytotoxic effects. It is shown here that, in transient transfection assays, the NS-1 protein of the parvovirus minute virus of mice (MVMp) activates the promoter of the human c-erbA1 gene, encoding the thyroid hormone (T3) receptor alpha. The endogenous c-erbA1 promoter is also a target for induction upon MVMp infection. Moreover, T3 was found to up-modulate the level of cell sensitivity to parvovirus attack. These data suggest an interconnection between T3 signalling and NS cytotoxic pathways.

Animals↗
PubMed1992

Expression of c-fos protein in lumbosacral spinal cord in response to vaginocervical stimulation in rats.

The pattern of vaginocervical stimulation-evoked expression of the proto-oncogene c-fos in lumbar 5-sacral 1 segments of the spinal cord of ovariectomized adult rats was mapped using immunocytochemistry. A calibrated force of mechanostimulation was applied to the vaginal cervix of experimental animals and to the perineum of control animals while they were gently restrained. The number of cells expressing c-fos was significantly greater in the experimental than the control animals in laminae I, IV, V-VI and X. The implications of the present findings for elucidating the spinal pathways mediating the various behavioral, neuroendocrine and autonomic effects of vaginocervical stimulation (VS) are discussed.

Animals↗
PubMed2002

Complexities in ETS-domain transcription factor function and regulation: lessons from the TCF (ternary complex factor) subfamily. The Colworth Medal Lecture.

The ETS-domain transcription factor family can be divided into a series of subfamilies. Elk-1 represents the founding member of the ternary complex factor (TCF) subfamily. By focusing on the TCF subfamily, we can demonstrate the complexities that exist in the function and regulation of ETS-domain transcription factors. This article focuses on Elk-1 in detail and summarizes the functions of other TCFs. The key themes covered include the domain structure of the TCFs, the mechanisms of complex formation with serum response factor, regulation of TCFs by mitogen-activated protein kinase cascades, and transcriptional regulatory properties of the TCFs. Finally, the emerging role of the TCFs in vivo is discussed. A picture is developing indicating that, while these proteins exhibit significant sequence and functional conservation, key differences in their structure and regulation are being identified which may relate to unique functions of these proteins in vivo.

Amino Acid Sequence↗
PubMed2002

Do sensory calcitonin gene-related peptide nerve fibres in the rat pelvic plexus supply autonomic neurons projecting to the uterus and cervix?

Sensory nerve fibres containing calcitonin gene-related peptide (CGRP) innervate neurons of the paracervical ganglion (PCG) in the female rat pelvic plexus. We have combined retrograde tracing with immunocytochemistry to investigate whether CGRP-immunoreactive (-IR) fibres supply neurons targeting the genital tract. Of the total neurons projecting to either the uterine horns or the cervix, 38 and 41% received CGRP-IR innervation, respectively. All these neurons displayed choline acetyltransferase-IR, thus are cholinergic. They were found throughout the PCG and other pelvic plexus ganglia, namely accessory ganglia (AG) and hypogastric plexus (HP). Pelvic nerve section showed that afferent fibres in these nerves provided most of the CGRP-IR fibres supplying uterine- or cervical-related neurons in the PCG/AG, none in HP. It is suggested that such sensory-motor network may provide a local pathway for reflex control of genital tract activity, acting through cholinergic nerve projections.

Animals↗
PubMed1984

Distribution of neurotensin-immunoreactivity within baroreceptive portions of the nucleus of the tractus solitarius and the dorsal vagal nucleus of the rat.

We have examined the distribution of neurotensin immunoreactivity within subnuclear regions of the nucleus of the tractus solitarius (NTS) and the dorsal motor nucleus of the vagus nerve (DVN) in the rat. In order to determine which regions of the NTS were involved in the regulation of baroreceptor reflexes, we mapped the central distribution of the aortic branch of the vagus nerve using transganglionic transport of horseradish peroxidase. Comparison of the pattern of aortic nerve innervation with that of the distribution of neurotensin-immunoreactive cells and fibers shows the dorsomedial nucleus of the NTS both to be the primary site of aortic baroreceptor termination and to contain the highest concentration of neurotensin-immunoreactive elements within the NTS. Neurotensin-immunoreactive fibers are also present in medial regions of the NTS adjacent to the area postrema where they may be involved in the modulation of vagal gastric afferents. Double-label experiments, in which, on the same tissue sections, neurotensin immunohistochemistry was combined with retrograde horseradish peroxidase labeling of DVN neurons, reveal a topographic innervation of vagal preganglionic motoneurons by neurotensin-immunoreactive fibers. The heaviest innervation is of lateral portions of the DVN and adjacent ventral portions of the NTS at the level of the obex, an area which may contain cardiac motoneurons. In this region neurotensin-immunoreactive fibers can be observed in close proximity to retrogradely labeled cells. The concentration of neurotensin elements in a region of the NTS which is involved in the control of baroreceptor reflexes provides a morphological basis for the cardiovascular effects produced by central administration of the peptide. Additional control may be exerted at the level of the motoneuron, as evidenced by apparent neurotensin fiber innervation of presumptive cardiac preganglionic neurons. Similarly, the distribution of neurotensin fibers suggests that the peptide may be acting in gastric regulatory areas of the NTS or on vagal secretomotor neurons to regulate gastric acid secretion.

Afferent Pathways↗
PubMed1989

Bed nucleus of the stria terminalis: cytoarchitecture, immunohistochemistry, and projection to the parabrachial nucleus in the rat.

The bed nucleus of the stria terminalis (BST) sends a dense projection to the parabrachial nucleus (PB) in the pons. The BST contains many different types of neuropeptidelike immunoreactive cells and fibers, each of which exhibits its own characteristic distribution within cytoarchitecturally distinct BST subnuclei. Corticotropin releasing factor (CRF)-, neurotensin (NT)-, somatostatin (SS)-, and enkephalin (ENK)-like immunoreactive (ir) neurons are particularly numerous within areas of the BST that project to the PB. In this study, we use the combined retrograde fluorescence-immunofluorescence method to determine whether neurons in the BST that project to the PB contain these immunoreactivities. After Fast Blue injections into PB, retrogradely labeled neurons were numerous throughout the lateral part of the BST, particularly in the dorsal lateral (DL) and posterior lateral subnuclei. Retrogradely labeled neurons were also present in the preoptic, ventral lateral, and supracapsular BST subnuclei and in the parastrial nucleus. Many of the CRF-ir, NT-ir, and SS-ir neurons in DL were retrogradely labeled. A few double-labeled cells of each type were also found in the posterior lateral, ventral lateral and supracapsular BST subnuclei ENK-ir neurons were never retrogradely labeled. Our results show that BST neurons that project to the PB stain for the same neuropeptides as those in the central nucleus of the amygdala (CeA) that project to the PB, demonstrating further the close anatomical relations between these two structures.

Afferent Pathways↗
PubMed2007

Lineage specification in neural crest cell pathfinding.

There are two principal models to explain neural crest patterning. One assumes that neural crest cells are multipotent precursors that migrate throughout the embryo and differentiate according to cues present in the local environment. A second proposes that the neural crest is a population of cells that becomes restricted to particular fates early in its existence and migrates along particular pathways dependent on unique cell-autonomous properties. Although it is now evident that the neural crest cell population, as a whole, is actually heterogenous (composed of both multipotent and restricted progenitors), evidence supporting the model of prespecification has increased over the past few years. This review will begin by telling the story of melanoblasts: a neural crest subpopulation that is biased toward a single fate and subsequently acquires intrinsic properties that guide cells of this lineage to their final destination. The remainder of this review will explore whether this model is exclusive to melanoblasts or if it can also be used to explain the patterning of other neural crest cells like those of the sensory, sympathoadrenal, and enteric lineages.

Animals↗
PubMed2003

Cytokine-stimulated inducible nitric oxide synthase expression in astroglia: role of Erk mitogen-activated protein kinase and NF-kappaB.

Expression of inducible nitric oxide synthase (iNOS), which leads to the production of nitric oxide (NO), is stimulated by proinflammatory cytokines such as interleukin-1beta (IL-1beta) and tumor necrosis factor-alpha (TNF-alpha). Here we report on the roles of nuclear factor-kappaB (NF-kappaB) and mitogen-activated protein (MAP) kinases in IL-1beta/TNF-alpha-induced iNOS expression in adult rat astroglia. Cytokine-induced increases in nitrite accumulation (an index of NO production) and iNOS expression were attenuated by inhibition of NF-kappaB with pyrrolidine dithiocarbamate (PDTC). Similar attenuation of these cytokine-induced responses was produced by inhibition of MAP kinase (MEK), the immediate upstream activator of Erk, using PD098,059. Combined treatment of astroglia with PDTC and PD098,059 completely abolished the cytokine-induced increases in iNOS expression and nitrite accumulation. By contrast, the selective p38 kinase inhibitor SB203,580 amplified the effects of IL-1beta/TNF-alpha on nitrite accumulation. In accordance with these findings, IL-1beta- and TNF-alpha-induced a time-dependent increase in Erk1/Erk2 activation. This cytokine action was completely abolished by PD098,059 but was not altered by PDTC. Finally, IL-1beta and TNF-alpha induced degradation of NF-kappaB's bound inhibitory protein, IkappaB-alpha, leading to translocation of NF-kappaB into the nucleus. IkappaB-alpha expression was not restored to control levels by inhibition of MEK. Furthermore, inhibition of MEK with PD098,059 did not alter IL-1beta- and TNF-alpha-induced expression of active NF-kappaB. The results demonstrate that autonomous Erk and NF-kappaB pathways mediate cytokine-induced increases in iNOS expression in astroglia.

Animals↗
PubMed1994

Altered growth and phenotype in clonal mycN transfectants of the SK-N-SH neuroblastoma cell line.

We have attempted to distinguish in human neuroblastoma between the effects of mycN on differentiation and its potential to promote malignant progression. Others have observed out-growth of autocrine cells with evidence of an advanced malignant phenotype in a mycN-transfected clonal cell line derived from the single-copy mycN neuroblastoma, SK-N-SH. We have now transfected the parental cell line with the same mycN expression vector and selected 5 clones characterized by unique and stable chromosomal integration sites and variable exogenous copy numbers. mycN gene expression was variable in the different clones and correlated roughly with the copy number of transfected mycN genes. Clones with minimal levels of mycN gene expression had a neuroblastic phenotype and low numbers of surface HLA class-I molecules. Clones with high levels of mycN expression had a Schwann/glial-like phenotype with higher surface HLA class-I display without imbalance of expression of specific loci and accelerated growth. Two such clones were capable of anchorage-independent growth in the absence of serum, and acquired tumorigenic properties. Our results show that exogenous mycN expression can be associated with a differentiation of neuroblastoma cells along the Schwann/glial pathway and can induce accelerated and autonomous growth.

Animals↗
PubMed1976

Peripheral sympathetic innervation of the deep pineal gland of the golden hamster.

Both the superficial and deep pineal components of the intact hamster contain a rich network of green to yellow-green fluorescent nerve fibres. After either superior cervical ganglionectomy or after transection of the nervi conarii the majority of the fluorescing fibres disappeared from both the superficial and deep pineal masses. Although the deep pineal remained intact after surgical removal of the superficial pineal, it was devoid of any green or yellow-green fluorescent fibres.

Animals↗
PubMed1995

Role of dorsal motor nucleus of vagus in gastric function and mucosal damage induced by ethanol in rats.

Experimental evidence indicates that the autonomic nervous system, especially the cholinergic pathway modulates the mucosal defensive mechanism and affects mucosal damage in the stomach. The present study investigated the role of the dorsal motor nucleus of vagus (DMV) in gastric function and its influences on ethanol-induced mucosal damage in pentobarbitone-anesthetized rats. Electrolytic lesion of the DMV as compared with sham operation and lesions of other brain areas, eg, nucleus reticular gigantocellularis and cuneate nucleus, reduced the basal gastric mucosal blood flow (GMBF) and also the blood flow after ethanol administration. The same operation did not affect the acid secretion either in the basal state or during the ethanol treatment period. Lesions at the caudal half of the DMV produced a bigger depression of GMBF when compared with lesion at the rostral half. In the sham-operated rats, ethanol induced severe hemorrhagic lesions in the gastric glandular mucosa, and this was significantly potentiated by lesions at the DMV, especially in the caudal half. The present findings indicate that acute DMV damage at the caudal half markedly affects the GMBF but not the acid secretion. The action on GMBF may contribute to the aggravation of ethanol-induced gastric damage in rats. These data reinforce the idea that the central vagal pathway, especially the caudal half of the DMV, plays a significant role in the modulation of GMBF, which in turn affects the integrity of gastric mucosal barrier.

Animals↗
PubMed1999

[Significance of esophagocardiac reflexes for inducing thoracic pain].

In the clinical setting the cardiologists' interest is focussed on the esophagus as a potential source of thoracic pain as a differential diagnosis of angina pectoris. However, visceral afferences originating in the mucosal wall of the esophagus activated by acid exposure may also influence cardiac function. The available data convincingly demonstrate a reduction of the exertional angina threshold and changes of the ECG (ST segment depression and arrhythmia). These effects are most likely due to a reduced coronary blood flow.

Afferent Pathways↗
PubMed2003

Fos-like immunoreactivity in auditory and nonauditory brain structures of hamsters previously exposed to intense sound.

Fos-like immunoreactivity (FLI) was evaluated in auditory and nonauditory brain structures in hamsters that had been exposed previously to intense sound and tested behaviorally for tinnitus. The immunocytochemical results demonstrated a significant increase in exposed animals of FLI in auditory brain structures such as the lateral lemniscus, central nucleus of inferior colliculus, and auditory cortex, as well as in some nonauditory brain structures such as the locus coeruleus, lateral parabrachial nucleus, certain subregions of the hypothalamus, and amygdala. The behavioral scores suggest that animals that had been exposed to intense sound developed tinnitus. This is consistent with the hypothesis that FLI induced by intense sound exposure might represent a neural correlate of tinnitus or of plasticity associated with tinnitus. The possibility and the mechanisms underlying the increased FLI are discussed.

Acoustic Stimulation↗
PubMed1991

Bombesin immunoreactive neurons in the hypothalamic paraventricular nucleus innervate the dorsal vagal complex in the rat.

Bombesin-like immunoreactivity has been localized within neuronal cell bodies of the hypothalamus and nerve terminals within the dorsal vagal complex. The possibility that the hypothalamus is a source for bombesin-like immunoreactive terminals within the dorsal vagal complex was examined using the combined retrograde tracing and immunohistochemical technique. After injections of retrograde tracer were made into the dorsal vagal complex, cells in the hypothalamus labeled with both retrograde tracer and bombesin immunoreactivity were localized in the parvocellular part of the paraventricular nucleus. In the paraventricular nucleus most of the vagal projecting bombesin immunoreactive neurons were located within the medial parvocellular subdivision. Approximately 30% of the bombesin immunoreactive neurons in this subnucleus projected to the dorsal vagal complex. The results suggest that the paraventricular hypothalamic nucleus is a major source of bombesin terminals within the dorsal vagal complex. This pathway may mediate some of the autonomic nervous system changes that are observed when bombesin is injected within the central nervous system. Additionally, this data adds to a growing amount of evidence supporting the role of bombesin as a peptide neurotransmitter.

Amidines↗