Biomedical subjects

C H Price

Publications and source records attributed to C H Price.

At least 19 recordsLinked to original sources

PubMed1993

The envelope glycoprotein of HIV-1 alters NMDA receptor function.

Human immunodeficiency virus (HIV-1) infection often results in central nervous system (CNS) dysfunction, yet the mechanism(s) of action for HIV-1 in the CNS are not fully understood. In the present study gp120, the HIV-1 envelope glycoprotein, was shown to selectively inhibit N-methyl-D-aspartate (NMDA) receptor function. In addition to inhibiting radioligand binding to rat NMDA receptors, gp120 inhibited NMDA-induced currents in Xenopus oocytes, attenuated NMDA-stimulated calcium flux and cytotoxicity in cultured cerebellar granule cells, and provided partial protection against NMDA-induced lethality in vivo. These findings suggest that NMDA receptor complex is a possible site of action of HIV-1 within the CNS.

Animals↗

PubMed1993

The role of receptor binding in drug discovery.

Radioligand receptor binding has been used extensively to identify and characterize a host of receptors and enzymes targeting virtually every therapeutic area. Many drug discovery programs have been based on the utilization of radioligand receptor binding technology to identify lead compounds which interact with receptors likely to be important in neuronal, immunological, gastrointestinal, and cardiovascular function/dysfunction. There are several obvious advantages to using in vitro receptor binding as a first level screen when compared to in vivo pharmacometric screens. Scientifically, the structure activity data generated in binding assays is a direct reflection of the ligand/receptor interaction minus the complications which result from secondary events, bioavailability, and pharmacodynamic issues. Technically, the binding studies require only a small amount of test compound (< or = 1 mg), while whole animal studies routinely need gram quantities. Similarly, only a small amount of tissue is required, compared with the cost of purchase and maintenance of live animals for in vivo screening. Supply and labor costs are drastically reduced due to the limited volume and test tube based technology of receptor binding. For these reasons receptor binding assays have been utilized with considerable success to discover site specific lead compounds in virtually every therapeutic area.

Animals↗

PubMed1986

Anatomical and electrophysiological study of multitransmitter neuron R14 of Aplysia.

This study provides detailed information on the Aplysia neuron R14, including its endogenous electrical activity and extensive axonal projections to a variety of vascular and vascular-related tissues. With the aid of intracellular recording techniques, R14 was found to display in vitro variable spontaneous patterns of silent, beating, or bursting activity. Electrophysiological tracing and intracellular cobalt staining revealed the peripheral processes and target tissues of R14. The white-colored axons of R14 exit the parietovisceral ganglion in the genito-pericardial, spermathecal, branchial, and vulvar nerves. These processes extended 20 mm or more into peripheral tissues: the pericardial wall and lumen, digestive gland sheath, aortae, arteries, and veins. R14 axons also project to the right bag cell cluster. Its extensive axonal projections to tissues associated with the cardiovascular system verify physiological studies that show that R14 plays a role in cardiovascular regulation. This neuron appears to have a wide influence over several aspects of circulation in contrast to individual neurons of the R3-13 group, each of which projects to limited numbers of vascular and vascular-related tissues. R14 also uniquely innervates digestive tissues, thus suggesting that it may act as a nexus between influences on digestive and renal physiology such as ion/water regulation, in addition to modulating cardiovascular homeostasis.

Action Potentials↗

PubMed1986

Electrophysiological and anatomical identification of the peripheral axons and target tissues of Aplysia neurons R3-14 and their status as multifunctional, multimessenger neurons.

The giant neurons R3-14 in the parietovisceral ganglion of Aplysia, originally proposed to be a homogeneous group of neuroendocrine cells, are likely candidates for a multifunctional and multiple messenger status. The studies reported here suggest that individual R3-14 giant neurons not only innervate specific target tissues but appear to operate more autonomously than previously thought. Identified members of the group were traced into peripheral tissues by electrophysiological, autoradiographic, and intracellular cobalt staining techniques. Five neurons (numbered R6, R7, R8, R11, and R14) were identified on the basis of their unique patterns of axonal projections. R6 innervates the ganglionic artery and pericardial area; R7 and R8, the heart; R11, the kidney; and R14, a large number of vascular tissues. The wide distribution of R3-14 terminals innervating a variety of vascular tissues indicates that several general and local aspects of circulatory physiology are likely to be regulated by these neurons. R3-14 contain the free amino acid glycine, a putative neuromodulator that potentiates cardiac and vascular smooth muscle contraction and several small peptides of unknown, but probably neurohormonal, function. A model is proposed in which R3-14 release glycine to modulate local (e.g., hemolymph pressure and distribution) cardiovascular performance and, indirectly, metabolic homeostasis as well.

Animals↗

PubMed1985

Peripheral axons of the parabolic burster neuron R15.

In a combined electrophysiological and anatomical study, the parabolic burster neuron R15 was found to project axons through the genito-pericardial nerve onto the pericardial wall and digestive gland sheath and, more variably, into the heart and pericardial coelom. Projection into these tissues is consistent with the hypothesis that R15 is neurosecretory and may play a role in circulation and/or ion-water regulation in Aplysia.

Animals↗

PubMed1984

Anatomy and innervation of the anterior aorta of Aplysia and the ultrastructure of specialized neuromuscular junctions on vascular smooth muscle.

The fine structure of the cellular layers and innervation of smooth muscle in the anterior aorta of Aplysia were examined. The inner layer of circular muscle is not innervated but its fibers may be electrically coupled. In contrast, longitudinal fibers in the outer layer are well separated and richly innervated by highly specialized neuromuscular junctions (NMJ). Three distinct types of NMJ are present on this smooth muscle, each identifiable by a set of quantitatively described morphological features including size, degree of contact with sarcolemma, density of active zones, number of mitochondria and vesicular content. The three types of NMJ are likely to arise from the identified serotonergic (RDAAE), cholinergic (RDAAI), and glycinergic (R14) neurons that provide the major known excitatory, inhibitory, and modulatory inputs to this vessel. Each longitudinal muscle fiber is separately innervated by one or more NMJ of each type. Since there are no intercellular junctions between longitudinal fibers, coordination of contractility is clearly a function of the pattern of neural activity. This report further characterizes the rapid and fine control of the vasculature in Aplysia and demonstrates the utility of this preparation for cellular-level studies on the neural control of smooth muscle and neurochemical messengers mediating its activity.

Animals↗

PubMed1984

Selective retrograde axonal transport of free glycine in identified neurons of Aplysia.

The specific retrograde axonal transport of free glycine within the identified neurons R3-14 of Aplysia californica was studied. The soma of the R3-14 neurons are located in the parietovisceral ganglion and their axons project down the branchial nerve to end in a large peripheral field. Using a double-chambered apparatus, the peripheral tissue was incubated in medium containing a 3H-amino acid for 4-48 hr, while the nerve and ganglion were isolated and perfused with plain or chemically altered medium. The nerve and ganglion were then either rapidly frozen for scintillation counting or fixed for autoradiography. When 3H-glycine was used, radioactivity entered the nerve rapidly, reached the ganglion in 3 hr, and was transported largely (greater than 80%) in the free amino acid form [trichloroacetic acid (TCA) soluble]. The right parietovisceral hemiganglion accumulated up to nine times more radioactivity than the left hemiganglion, reflecting the presence of the R3-14 axons and soma. Two phases of radioactivity were observed, a fast component moving at about 3 mm/hr and a slower (but larger) component moving at about 0.4 mm/hr. Light microscope autoradiography on nerves containing 3H-glycine revealed that the R3-14 axons accounted for more than 30% of the total label in the nerve but occupied less than 7% of the total cross-sectional area of the axonal core. Electron microscope autoradiography showed a close association of silver grains and dense core vesicles in the R3-14 axons. Retrograde axonal transport of free glycine was inhibited by (in decreasing order of effectiveness) mercuric chloride, vinblastine, colchicine, Nocodazole, and 2,4-dinitrophenol (2,4-DNP). Comparative studies of other amino acids [3H-leucine, 3H-serine, 3H-glutamic acid, 3H-gamma-aminobutyric acid (3H-GABA), and 3H-alanine] showed that 3H-glycine is the only amino acid that is rapidly axonally transported in large quantities within the R3-14 axons. This work demonstrates, for the first time, that a free amino acid, glycine, is transported in the retrograde direction within a select group of axons. The significance of this transport of glycine is discussed in relation to its use as a neural messenger by neurons R3-14.

2,4-Dinitrophenol↗

PubMed1984

Influences of glycine and neuron R14 on contraction of the anterior aorta of Aplysia.

Firing neuron R14 in the Aplysia parietovisceral ganglion enhances the force of stimulated contractions and causes rhythmic contractions rather than individual contractions in response to a single stimulation of the anterior aorta of Aplysia. Bath application of 1.0 mM glycine to the artery causes a small depolarization, rhythmic contractions and enhances the force of individual, neurally induced contractions of the anterior aorta. These observations suggest that the physiological role of the innervation of the anterior aorta by R14 is to convert the mode of contraction of the anterior aorta from direct neural control to a myogenic mode. R14 activity does not produce classical junction potentials and inotophoretically applied glycine does not produce detectable potential changes in the anterior aorta muscle fibers. Glycine increases the force and frequency of Aplysia heart beat, and blood pressure. Glycine causes release of preloaded Ca2+ from the ventricle of the Aplysia heart, implying that glycine causes intracellular release of Ca2+. The similarity of the actions of glycine and electrical activity in R14 extend previous evidence that R14 may utilize glycine to modulate the contractility of Aplysia circulatory muscle.

Animals↗

PubMed1981

Localization of axonally transported [3H]glycine in vesicles of identified neurons.

A specific association of axonally transported, free [3H]glycine with vesicles in the identified neurons R3-R15 of Aplysia is demonstrated by high resolution autoradiography. The association of glycine with vesicles, the first such finding in any animal for a neuroactive amino acid, adds to evidence that glycine may be utilized as a neuro-chemical messenger by R3-R14.

Animals↗

PubMed1981

Modulation of arterial muscle contraction in Aplysia by glycine and neuron R14.

Glycine and electrical activity in neuron R14 both enhance the contractility of the anterior aorta of the gastropod Aplysia californica. Glycine and R14 do not seem to cause contraction directly, change membrane permeabilities or alter junctional potentials occurring in the muscle fibers, yet they increase the force of contractions induced by other means. Modulation of muscle contraction is a new function for glycine.

Animals↗

PubMed1981

A light and electron microscopic investigation of the neurosecretory bag cells of Aplysia.

The two bilateral clusters of neurosecretory bag cells of Aplysia were studied with both light and electron microscopy. Autoradiography revealed that the bag cells rapidly accumulate 3H-labelled amino acids and that after 1-2 h, heavy concentrations of silver grains appear over Golgi complexes and in the proximal axons. Intrasomatic injections of CoCl2 or lucifer yellow showed clear branch points and numerous varicosities along individual axons. Many of the bag cells are multipolar. Electron-microscopic observations confirmed that individual fibres branch and showed that the varicosities are packed with dense-cored vesicles similar in size (180 nm diameter) and electron density to those found in the somata. The axons of several cells are usually associated into bundles that travel (within the connective tissue sheath) either rostrally up the pleurovisceral connective or toward the contralateral bag cell cluster. Bundled in groups of tens to hundreds, a total of many thousands of axons fill the sheath around each cell cluster and around the proximal 2-5 mm of the pleurovisceral connective; the number of axon bundles in the sheath decreases rapidly with distance from the cluster. Individual axons reaching the outer edges of bundles from neurosecretory endings near blood sinuses in the sheath, creating an extensive neurohemal release area. Dense-cored vesicles are packed into the endings, often in very close apposition to the plasma membrane. Possible release profiles (omega-shaped) and smaller clear vesicles (85 nm diameter) were observed in the axon endings. A number of axons also enter and travel among the conventional (non-neurosecretory) axons in the core of the pleurovisceral connective nerve. These 'core' bag cell axons project for several millimetres beyond the terminations of the bundled axons of the sheath. The findings support the hypothesis proposed in physiological studies that the distribution and branching of the axonal tree are the basis for the extracellularly recorded wave forms and of the potentiation of electrical signals during bag-cell activity. Additional evidence indicates that exocytosis is the means by which bag-cell hormone is released during afterdischarges.

Animals↗

PubMed1979

Anatomy and ultrastructure of the axons and terminals of neurons R3-R14 in Aplysia.

Using light and electron microscopy and autoradiography, we have traced the axons of neurons R3-R14 in the parietovisceral ganglion (PVG) of Aplysia to terminal fields associated with vascular tissue. The axons are identified by their large size (15-30 micrometer diameter), extensive glial infolding, characteristic dense core vesicles (DCV; approximately 180 nm diameter), and specific, rapid uptake of 3H-glycine. Each neuron in this homogeneous group sends an axon via the branchial nerve to the pericardial region surrounding the junction of the efferent gill vein and the heart. R14 also sends axons to major arteries near the PVG. The R3-R14 axons branch extensively; we estimate that there are at least several hundred per cell. Branches along axons in the branchial nerve exit the nerve, subdivide, and end blindly in the sheath which is bathed by hemolymph. Similar blind endings from R3R14 occur in the sheath of the PVG (Coggeshall, '67). Axonal branches in the pericardial region and the special R14 axons in the arterial walls form both varicose endings near and terminals in contact with vasvular smooth muscle. All R3-R14 endings are free of glia, packed with DCV, show occasional omega-shaped profiles and rapidly take up 3H-glycine. R3-R14 manufacture specific low molecular weight peptides (Gainer and Wollberg, '74), and both the cell bodies (Iliffe et al., '77) and the germinals contain unusually high concentrations of glycine. The presence of peptides as putative neurohormones and sheath endings (neurohormonal release areas) are consistent with R3-R14 being neurosecretory (Coggeshall et al., '66). While glycine could not be a circulating hormone due to its high circulating levels (Iliffe et al., '77), glycine could act as a local chemical messenger between R3-R14 and smooth muscle. The terminal morphology of R3-R14 is consistent with these neurons having both synaptic-type and neurosecretory-type functions.

Animals↗

PubMed1979

Bidirectional axonal transport of free glycine in identified neurons R3--R14 of Aplysia.

The axonal transport of 3H-amino acids was studied in the axons of identified neurons R3--R14 in the parietovisceral ganglion (PVG) of the mollusc Aplysia. The PVG was incubated (3--24 hr) in media containing physiological concentrations of single 3H-amino acids while the isolated nerve was superfused with plain or chemically altered media. The nerve was then sliced into sequential segments for biochemical analyses or fixed for autoradiography. 3H-glucine was transported at 70 mm/day in 6X greater quantities than other amino acids which were transported at less than 40 mm/day. In the 3H-glycine experiments, greater than 80% of the label transported into the nerve remained as free glycine, comigrating with glycine in thin-layer chromatographs. In autoradiographs of sections 4 mm from the ganglion-nerve barrier, greater than 50% of the silver grains were over R3--R14 axons which occupy less than 10% of the nerve cross-sectional area. EM autoradiographs confirmed that grains were within R3--R14 and not in surrounding glia. The selective transport of glycine was inhibited by Hg2+, by vinblastine and Nocodazole, and by low Ca2+ media. Autoradiographs of vinblastine-treated nerves showed a drastic reduction in label over R3--R14 and other axons. Label was also transported retrogradely; this transport rate was similar to the orthograde rate, but 5--10 times less label moved retrogradely. Autoradiographs showed that the retrograde label was localized to R3--R14 axons. This report clearly demonstrates the rapid, selective, and bidirectional transport of a free amino acid and provides further evidence that glycine may be used as a neurochemical messenter by neurons R3--R14.

Amino Acids↗

PubMed1978

Specific glycine uptake by identified neurons of Aplysia californica. I. Autoradiography.

The identified giant neurons R3-R14 in the Aplysia parietovisceral ganglion (PVG) have a rapid, Na+-dependent and Hg2+-sensitive uptake system for glycine not found in neighboring neurons. In autoradiographs of PVG incubated in [3H]glycine (glutaraldehyde fix), the cytoplasms of R3-R14 have 3--4 times more silver grains (No./100 sq.micrometer) than other neurons. The glycine uptake system in R3-R14 is selective (alanine, serine, leucine, and proline are taken up equally by all neurons) and is unaffected by reserpine and anisomycin. Neurons R3-R14 contain 2 times less label when ganglia are fixed in formaldehyde than when glutaraldehyde is used as a fixative. Because formaldehyde fixes free amino acids poorly, much of the glycine taken up by R3-R14 is, therefore, not incorporated into protein. In autoradiographs of PVG incubated in [3H]glycine, silver grains are distributed randomly throughout the cytoplasm and nucleus of R3-R14; no association of the grains with the dense core granules characteristic of these neurons7 or other cellular components was found. In contrast, grains in the neurosecretory "bag cells" of the PVG were clustered in numerous discrete areas of the cytoplasm (Golgi complex areas) and the nucleus was only sparsely labeled. The existence of a rapid and selective glycine uptake system in R3-R14, together with their high endogenous glycine concentrations17, suggests that glycine may be a neurotransmitter in these neurons.

Animals↗

PubMed1978

Specific glycine uptake by identified neurons of Aplysia californica. II. Biochemistry.

Glycine is taken up twice as rapidly by neurons R3-R14 as by other identified neurons in the Aplysia parietovisceral ganglion. Earlier studies had shown that R3-R14 have much higher glycine concentrations than other Aplysia neurons. Most of the glycine taken up by R3-R14 was biochemically untransformed for at least 1 h following its uptake. Glycine is actively transported into into R3-R14 and other Aplysia neurons by carrier-mediated processes. Glycine uptake by R3-R14 was markedly reduced in the absence of Na+ and in the presence of Hg2+, while these treatments had little effect on glycine uptake by other Aplysia neurons. There appears to be a special glycine uptake system present in R3-R14 and a general glycine uptake system common to all Aplysia neurons. The elevated glycine concentrations and special glycine uptake associated with R3-R14 may indicate that glycine is utilized as a neurotransmitter by those neurons.

Alanine↗

PubMed1977

Regeneration in the central nervous system of a pulmonate mollusc, Melampus.

The left cerebral ganglion was ablated from 72 anesthetized, adult Melampus bidentatus (Mollusca: Pulmonata). Skin incisions were well healed and normal feeding and locomotion observed four days after surgery. Dissections of animals sacrificed weekly showed that most nerves and connectives regrew within 30 days, attaching to the swollen end of the major labial nerve. The enlarged end of this nerve later developed into a distinctive bud; some of these buds contained cell bodies as soon as 42 days after surgery. As the first known report of central nervous tissue regeneration in molluscs, this study points to the need for controls in experiments involving section or ablation of nervous tissue in molluscs.

Animals↗

PubMed1977

Incidence of bone sarcoma in SW England, 1946-74, in relation to age, sex, tumour site and histology.

A study is presented of all cases of primary sarcoma of bone registered during the period 1946 to 1974 for a specified population resident in south-western England. Ninety-six per cent of the 365 cases were histologically and radiologically verified and are separated into 8 categories of sarcoma. The number of tumours presenting during each hemi-decade did not markedly diverge from the 5-year mean for the period, nor was any significant change found in tumour incidence during the last 20 years of the survey. The age, sex and site distributions correspond with those reported elsewhere. Age-specific incidence rates are compared with those published for Sweden. For osteosarcoma and Ewing's tumour, both commoner in young people, the two series agree closely up to age 55 years, after which the Swedish incidence rates rise and are not exceeded when, for the present cases, Paget's osteosarcomas are included. Whilst Paget's disease may change the age incidence of some types of bone sarcoma, it is uncertain whether it increases the total number which occur. Differences in tumour incidence between males and females, whether for a specific type or for all bone sarcomas, are seldom statistically significant, but the patterns appear to be consistent.

Adolescent↗

PubMed1977

Chondrosarcoma of the bones of the hand.

Nineteen chondrosarcomas are reported arising in proximal phalanges or metacarpal bones of the hand mainly in elderly patients, predominantly women. The usual clinical presentation was of a progressively painful large tumour, often arising in a dormant lesion near the metacarpo-phalangeal joint. Radiologically most showed some bone expansion with a poorly defined area of destruction and a considerable soft-tissue swelling. Histologically, malignancy was usually obvious, but confusion might arise from the inclusion of bland areas of chondromatous tissue that probably represented the original lesion. Four tumours, initially curetted and grafted, recurred locally and necessitated amputation of the digit or ray. Amputation was the primary treatment for fourteen other tumours and was curative except in one patient who eventually needed amputation through the forearm for a large second recurrence. One tumour was satisfactorily controlled by excision of the affected phalanx. None of these nineteen tumours is known to have metastasised. Correct treatment implies a carefully considered balance between conservation of function and complete removal of all tumour tissue.

Adult↗