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Biomedical subjects

I R Schwartz

Publications and source records attributed to I R Schwartz.

At least 19 recordsLinked to original sources

Selective retrograde transport of nipecotic acid, a GABA analog, labels a subpopulation of gerbil olivocochlear neurons.

Perfusion of the gerbil cochlea with micromolar quantities of 3H-gamma-aminobutyric acid (GABA) results in rapid, selective labeling of 50-60% of the olivocochlear (OC) efferent terminals on afferent dendrites beneath the inner hair cells, and all of the efferent terminals beneath the outer hair cells. In order to identify the neurons from which these GABA-accumulating terminals originate, the cell bodies were localized by using retrograde transport of 3H-nipecotic acid, a metabolically inert GABA analog. With survival times of 6-30 hours after cochlear injection, myelinated OC efferent fibers and cell bodies were well labeled, with the greatest number being labeled at 12-18 hours. All of the labeled neurons belonged to the medial OC system, and no lateral OC neurons were labeled. It is concluded that the GABA-accumulating endings in the gerbil cochlea arise from medial OC neurons, and therefore that medial OC efferent neurons in this species project to both inner and outer hair cell regions.

Animals

Neuronal populations in the gerbil PVCN: effects of age, hearing status and microcysts.

This study was designed to test the hypothesis that microcysts in the gerbil auditory system are formed from neuronal somata. Six neuronal types (octopus, multipolar, bushy, elongate, miscellaneous and small) were distinguished, counted and measured along with the microcysts in the posteroventral cochlear nuclei (PVCNs) of 3, 12 and 36 month old gerbils. No decrease was observed in the numbers of neurons in any neuronal class, or in the neuronal population as a whole, in the PVCN of the gerbil as a function of age. Neither was any change observed in the PVCN area occupied by non-neuronal, non-microcyst elements. Neuronal sizes were unchanged between 3 and 12 months, but multipolar and bushy cells, as well as the total neuronal population decreased significantly in size between 12 and 36 months. The number and size of microcysts increased significantly between 3 and 12 months of age and accounts for increases in PVCN volume. The number and size of microcysts decreased significantly between 12 and 36 months. Thus, the appearance of microcysts can not result from the selective loss of any single class of neurons. Hearing was assessed in five 36 month old animals with auditory brainstem responses (ABR) and number and size of microcysts were found to correlate with hearing status, being largest and most numerous in animals with the best hearing, and smallest and fewest in the deaf animal. It is concluded that microcysts cannot represent a neurodegenerative disease of neuronal somata. Microcyst formation appears to be a dynamic process related to the degree of auditory stimulation.

Aging

Collaterals from lateral and medial olivocochlear efferent neurons innervate different regions of the cochlear nucleus and adjacent brainstem.

Two populations of superior olivary neurons which project to different sensory cell regions in the cochlea also give off collateral projections to the ventral cochlear nucleus (VCN) and adjacent brainstem. To determine whether these VCN projections also have different targets they were characterized by selective retrograde amino acid transport. Retrograde transport of 3H-d-aspartate (D-ASP) selectively labeled the unmyelinated fibers and neurons of the lateral olivocochlear (OC) system including a dense collateral projection to the central VCN. Retrograde transport of 3H-nipecotic acid (NIP) labeled the myelinated fibers and neurons of the medial OC system, including collateral projections to the peripheral VCN, subpeduncular granule cells, and nucleus Y. Medial and lateral OC efferent collaterals thus innervate different regions of the CN. Lateral system collaterals overlap extensively with Type I spiral ganglion cell afferent input. They are well positioned to play a role in modulating afferent input to the central auditory system, as is the primary projection of these efferents to the cochlea. The medial system collaterals project near the recently described afferent projections of Type II spiral ganglion cells. The medial system collaterals may therefore be related to the function of outer hair cells, as the medial system primary axons appear to be in the cochlea.

Animals

Autoradiographic studies of selective amino acid uptake by neural and nonneural elements in the gerbil cochlea.

The cochlea is well suited for studies of the uptake properties of auditory neurons and nonneuronal supporting cells. Probe concentrations of radioisotopically labeled amino acids, including putative neurotransmitters and their precursors, breakdown products, and blockers, can be introduced via the natural, fluid-filled channels of the inner ear. Uptake patterns can be mapped at cellular and intracellular levels using light and electron microscopic autoradiographic methods. The procedures for introduction of label, fixation, plastic embedment, and light and electron microscopic autoradiography are described with special reference to the cochlea. Labeling patterns observed with over 20 amino acids are summarized for hair cells, spiral ganglion neurons, efferents, and nonneural elements of the stria vascularis, limbus, and modiolus. Limitations on the interpretation of results and their implications for the general usefulness of the methods are discussed.

Amino Acids

Safety of predeposit autologous blood donation in the third trimester of pregnancy.

The option of predeposit autologous blood donation (PABD) before elective surgery has been gaining popularity as a means of eliminating the transmission of the acquired immune deficiency syndrome and hepatitis. It also prevents potential antigen sensitization and transfusion reactions. The use of PABD in pregnant women has been described, but its safety for both mother and fetus, especially in the first and third trimester, has not been established. After studying 16 third-trimester pregnant women with antenatal surveillance techniques and continuous fetal monitoring, we concluded that PABD is a safe procedure for both mother and fetus.

Adult

Anatomic and physiological correlates in bullfrog vestibular nerve.

1. The correlations between anatomic and physiological characteristics of primary afferent neurons innervating the anterior semicircular canal in the bullfrog were investigated. These characteristics were examined separately in large groups of neurons, and the direct correlations between them were established in a subset of neurons by means of intraaxonal recording and labeling. 2. Anatomic features of the anterior canalicular nerve that were related with fiber diameter were studied. This nerve was composed of an average of 1,142 fibers (standard deviation of 171 in 5 samples), of which 42% were less than 2 microns in diameter and 8% were greater than 7 microns. The nerve branched into 6 clearly defined bundles, whose fiber diameter-dependent composition could be determined in 5 samples. In the 2 center bundles, 32% of the fibers had diameters greater than 7 microns. In contrast, these thick fibers comprised only 4% of the fiber population in the 2 lateralmost bundles, in which 44% of the fibers had diameters less than 2 microns. The projections of labeled afferent fibers were traced into the neuroepithelium, and it was demonstrated that all thick fibers, even those of the lateral bundles, turned toward more central regions of the crista. Consequently, in the bullfrog, there is a clear predominance of thick afferent fibers innervating the anterior crista's central region and thin fibers in the peripheral region. 3. The dendritic morphology of the broad classes of afferent fibers (i.e., thick and thin) was elucidated. Individually labeled thick afferents possessed dendrites forming short, thick, clawlike extensions to contact a few hair cells. The thinnest afferents were labeled through extracellular horseradish peroxidase (HRP) injections. In contrast to the thick fibers, thin afferents were characterized by an unbranched trajectory with serially located bouton-like structures that were apposed to successive hair cells. 4. The characteristics of spontaneous firing and the responses to rotational stimuli were determined for 138 anterior canalicular neurons. Spontaneous firing rates ranged from 0 to 95 spikes.s-1. The coefficient of variation (CV) of spontaneous firing ranged from 0.12 to 2.5. Response gains to high- (0.5 and 0.4 Hz) and medium- (0.05 Hz) frequency sinusoidal acceleration stimuli were positively correlated with CV (P less than 0.001) for neurons with a CV value less than or equal to 0.5. The gain of neurons characterized by more irregular spontaneous firing (CV values greater than 0.5) was uncorrelated with CV.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals

An improved flat embedding technique for immunoelectron microscopy.

Immunocytochemical staining has been widely used for localizing various hormonal antigens, protein markers and putative neurotransmitters in tissues. Immunostained sections can be examined light microscopically and specific areas selected for electron microscopic study.

Histological Techniques

Alteration in osteoblast activity and nutritional vitamin-D deficiency in non-hypercalcemic malignancy.

The biochemical parameters of bone mineral metabolism in patients with nonhypercalcemic malignancy have not been extensively investigated. Therefore, a group of 29 such patients with different types of malignancy was studied. Ten patients received corticosteroids. In the entire group, serum ionized calcium (Ca2+), bone gla protein (BGP), 25-hydroxyvitamin D (25OHD), and 1,25-dihydroxyvitamin D (1,25(OH)2D) were all lower than in age-matched controls, and carboxy-terminal parathyroid hormone (CPTH) was higher. Although both corticosteroid- and noncorticosteroid-treated patients had decreased BGP values, the corticosteroid-treated patients had lower BGP levels than those not on steroids (4.24 +/- 0.70 SE vs. 11.50 +/- 2.20 ng/ml; P less than 0.005). Patients on corticosteroids had lower 1,25(OH)2D values than controls (18.81 +/- 2.71 vs. 27.83 +/- 1.17 pg/ml; P less than 0.01), whereas those not on corticosteroids had normal 1,25(OH)2D values. These results suggest that patients with nonhypercalcemic malignancy have nutritional vitamin-D deficiency and secondary hyperparathyroidism with perhaps corticosteroid-induced suppression of serum 1,25(OH)2D and BGP. The decreased levels of serum BGP in the nonsteroid-treated patients suggest, in addition, a defect in osteoblast function.

Aged

Ultrastructural characterization of gerbil olivocochlear neurons based on differential uptake of 3H-D-aspartic acid and a wheatgerm agglutinin-horseradish peroxidase conjugate from the cochlea.

Two populations of olivocochlear (OC) neurons have been identified in the gerbil brain stem on the basis of differential labeling patterns of 3H-D-aspartic acid (D-ASP) and wheatgerm agglutinin-horseradish peroxidase conjugate (WGA/HRP) from the cochlear perilymph. While both populations are capable of uptake and retrograde uptake of WGA/HRP, one population accumulates and retrogradely transports D-ASP (D-ASP OC neurons) and the other does not (non-D-ASP OC neurons). D-ASP OC neurons are found in or near the lateral superior olive, are small in size, and receive very few synaptic contacts. The vast majority of these synapses contain small, mildly pleomorphic vesicles with scattered dense core vesicles. Synapses with distinctly larger pleomorphic vesicles have also been observed. These neurons possess all of the features common to neurons of the lateral olivocochlear system. Non-D-ASP OC neurons are found primarily in the ventral nucleus of the trapezoid body, as well as in the area between the medial superior olive and the medial nucleus of the trapezoid body. These neurons are larger and receive greater numbers and types of synaptic contacts than those found on D-ASP OC neurons. The 2 most common synapses found on non-D-ASP OC neurons are axosomatic ones containing small, mildly pleomorphic vesicles and scattered dense core vesicles similar to those seen on the D-ASP OC neurons, and axodendritic synapses containing large, round vesicles. Much less frequently observed are synapses containing small, round vesicles or ones containing predominantly flat vesicles. The ultrastructural features of the non-D-ASP OC neurons correspond to those described for neurons of the medial olivocochlear system.

Animals

Selective retrograde labeling of lateral olivocochlear neurons in the brainstem based on preferential uptake of 3H-D-aspartic acid in the cochlea.

We have previously shown that perfusion of the gerbil cochlea with probe concentrations of 3H-D-aspartic acid (D-ASP) results in immediate, selective labeling of 50-60% of the efferent terminals under the inner hair cells, presumably by high-affinity uptake. The present study was undertaken to determine the origin of these endings. Twenty-four hours after cochlear perfusion with D-ASP, labeled neurons were observed in the ipsilateral, and to a much lesser extent in the contralateral, lateral superior olivary nucleus (LSO). The cells were small, primarily fusiform, and showed fewer synaptic contacts than other LSO cells. Combined transport of D-ASP and horseradish peroxidase indicated that all olivocochlear neurons within the LSO that projected to the injected cochlea were labeled by D-ASP. Labeled fibers coursed dorsally from the LSO, joined contralateral fibers that had passed under the floor of the fourth ventricle, and entered the VIIIth nerve root at its ventromedial edge. Adjacent to the ventral cochlear nucleus (VCN), densely labeled collateral fibers crossed the nerve root to enter the VCN. Labeled fibers and terminals were prominent in the central VCN. Neither retrograde transport of D-ASP by medial olivocochlear and vestibular efferents nor anterograde transport by VIIIth nerve afferents was observed. The D-ASP-labeled cells and fibers are clearly lateral olivocochlear efferents. Retrograde transport of D-ASP thus allows the cells, axons, and collaterals of the lateral olivocochlear system to be studied, morphologically, in isolation from other cells that project to the cochlea. Since the olivocochlear neurons are almost certainly cholinergic, retrograde amino acid transport does not necessarily identify the primary neurotransmitter of a neuron. Rather, it indicates the presence of selective uptake by the processes of that neuron at the site of amino acid injection. Retrograde labeling appears to be markedly enhanced by the use of metabolically inert compounds such as d-isomer amino acids.

Animals

Morphological features of five neuronal classes in the gerbil lateral superior olive.

Five morphologically distinct classes of neurons can be identified within the neuropil of the gerbil lateral superior olivary nucleus (LSO) by using a variety of histological techniques and electron microscopy. The physical features of these five classes resemble those found in the cat LSO and are identified, by using criteria and nomenclature established for the cat, as principal neurons, multiplanar neurons, marginal neurons, small neurons, and class 5 neurons. Principal cells compose approximately 75% of the total LSO neuronal population. They possess a discoid dendritic organization and are oriented rostrocaudally, perpendicular to the transverse curvatures of the LSO. Roughly 8% of the LSO population is composed of multiplanar neurons, whose dendritic fields are not restricted to any single plane of section. Both principal and multiplanar neurons share similar cytoplasmic features, and greater than 65% of their perikaryal surface is in contact with synaptic terminals. Small neurons compose approximately 11% of the LSO neurons, have the lowest percentage of their somal surface contacted by synaptic terminals (approximately 8%), and are found mostly in the middle/medial portions of the LSO. Marginal neurons, which compose approximately 6% of the LSO population, appear similar to principal neurons at the light microscopic level except that they are found along the contours of the LSO, oriented orthogonal to principal neurons. Approximately 28% of the somal surface of marginal neurons is in contact with synaptic terminals. The class 5 neuronal somata receive a similar number of axosomatic synaptic contacts as marginal neurons (approximately 31%) but are found well within the matrix of the LSO, aligned parallel to principal neurons. Class 5 neurons share the same light microscopic features as principal neurons and can be identified electron microscopically based only on the reduced percentage of somal surface occupied by synaptic terminals.

Animals

Nipecotic acid: preferential accumulation in the cochlea by GABA uptake systems and selective retrograde transport to brainstem.

[3H]Nipecotic acid was shown to be preferentially accumulated by the same cochlear structures which selectively accumulate [3H]gamma-aminobutyric acid ([3H]-GABA), including the terminals of a subset of olivocochlear neurons. With both amino acids, olivocochlear fibers selectively transported label in a retrograde direction, from cochlea to brainstem. However, only [3H]nipecotic acid produced dense labeling, and labeling of cell bodies in the superior olive, presumably because it is metabolized very slowly. Nipecotic acid appears to provide a selective retrograde tracer, specific to neurons whose terminals exhibit preferential GABA uptake.

Animals

Amino acid labeling patterns in the efferent innervation of the cochlea: an electron microscopic autoradiographic study.

Light microscopic autoradiography and electron microscopic autoradiography were used to study the distribution of label in the cochlear efferents following in vivo incubation with tritiated amino acids. Two basic patterns of labeling were observed. These patterns correspond closely to the lateral and medial superior olivary complex (SOC) olivocochlear systems identified by Warr and Guinan ('79, Brain Res. 173:152-155). Our electron microscopic observations suggest that, at least in the gerbil, the complete separation of outer hair cell (OHC) versus inner hair cell (IHC) efferent innervation proposed by these investigators based upon light microscopic data does not occur. Rather, our data suggest that while the lateral SOC system supplies endings only to the region under the IHC, the medial SOC system may supply endings beneath both the IHCs and OHCs.

Amino Acids

Morphological evidence for the existence of multiple neuronal classes in the cat lateral superior olivary nucleus.

This study characterizes morphologically the neurons residing within the matrix of the cat lateral superior olive (LSO), excluding the hili and myelinated axon envelope. Several light microscopic techniques including Golgi impregnations, Nissl stains, and acetylcholinesterase histochemistry were used, as well as electron microscopy. Five distinct classes of neurons have been identified: principal neurons, multiplanar neurons, marginal neurons, small neurons, and class 5 neurons. These neuronal classes differ in regard to their size and shape, dendritic organization, perikaryal synaptic density, and their relative numbers. Principal neurons compose approximately three-quarters of the LSO neurons. They are multipolar and uniplanar in their dendritic arborization, radiating from the hili in rostrocaudal planes perpendicular to the curvatures of the LSO. In transverse sections the principal cell perikarya are fusiform and bipolar, with mean dimensions of 23 X 11 microns. More than 60% of the surface of these cells is contacted by synaptic terminals. Multiplanar neurons (averaging 23 X 19 microns) compose only 11% of the LSO neuronal population. Their dendritic arborization is not restricted to any particular plane, and their somal surface receives synaptic contacts similar, in number and type, to principal cells. Marginal neurons, although they are similar to principal neurons in shape and dendritic arborization, differ in that they are generally smaller (averaging 20 X 10.5 microns). They also possess fewer axosomatic synaptic contacts (approximately 33%), are oriented perpendicularly to principal neurons, are limited in distribution to the contours of the LSO immediately beneath the myelinated axon envelope, and constitute only 4% of the neuronal population. Small neurons (mean dimensions = 9 X 8 micron) compose 8% of the LSO neurons. They possess a multiplanar array of primary dendrites and have nuclei with multiple deep infoldings. Small neurons have the fewest axosomatic synaptic contacts of all classes of LSO neurons (approximately 10%). Additionally, there are neurons that are similar to principal neurons, but receive fewer axosomatic contacts (approximately 33%). These cells have been tentatively identified as class 5 neurons until more information on this type allows for the assignment of a more descriptive name. A number of acetylcholinesterase-positive neurons are also found within the LSO, whose relationship to the other classes of neurons is presently unresolved. Possible functions of the multiple neuronal types are discussed.

Acetylcholinesterase

Central projections of primary vestibular fibers in the bullfrog: I. The vestibular nuclei.

The central projections of the vestibular end organs in the bullfrog Rana calesbeiana were analyzed by using horseradish peroxidase labeling of the primary vestibular afferents. Separate extracellular injections were made of the anterior branch, the posterior branch, the ampullary nerve of each of the three semicircular canals, and the branch to the saccule. The anterior and posterior branches of the bullfrog eighth nerve, each containing both vestibular and auditory fibers, merge and enter the brain stem as a single nerve root. The thin caliber fibers of the anterior branch enter the brain stem on the ventral-posterior aspect of the nerve and immediately divide dichotomously into ascending (rostral) and descending (caudal) branches. The thick caliber fibers of the anterior branch enter the brain stem on the ventral-anterior aspect of the eighth nerve and traverse medially into the alar plate before dividing into ascending and descending branches. The primary afferent fibers of the vestibular nerve innervate an ipsilateral area of the brain stem which extends caudally from the rhombencephalon at the level of the twelfth nerve nucleus and rostrally up to and including the cerebellar nucleus and the cerebellum. The following vestibular nuclei can be identified by the fact that they receive primary vestibular afferents: the ventral vestibular nucleus, medial vestibular nucleus, descending vestibular nucleus, superior vestibular nucleus, and cerebellar nucleus. The dorsal (acoustic) nucleus, which receives primary auditory input, also receives afferents from the saccule. In addition to these nuclei, the cerebellum and the reticular formation receive significant primary input from the various vestibular receptors. The primary vestibulo-cerebellar fibers terminate mainly among the granular cells of the lobus auricularis and of the corpus cerebelli on the ipsilateral side. Each of the three semicircular canals projects into the cerebellum, while no such projection was observed in the saccular nerve preparations. Fibers from each of the three semicircular canals project to all of the vestibular nuclei. Heavily labeled large neurons, presumably vestibular efferents, are seen in the ipsilateral reticular formation, adjacent to the seventh motor nucleus.

Animals

Central projections of primary vestibular fibers in the bullfrog. II. Nerve branches from individual receptors.

The fibers from the nerves innervating each of the three semicircular canals and the saccule were labeled by injecting horseradish peroxidase extracellularly into these nerves. The projections into the various vestibular nuclei of each receptor were studied in transverse sections of the brain stem throughout the vestibular nuclear area. All five vestibular nuclei receive primary afferents throughout their areas. There are differences in the projection patterns of the canals. In the superior and ventral vestibular nuclei, the location of the projections depends on the crista injected. The anterior canal projects ventrally, the horizontal canal centrally, and the posterior canal more dorsally. Each canal, however, sends fibers to all areas, with overlap of fibers from the different cristae. The cerebellar nucleus receives uniform innervation from the three canals. The medial vestibular nucleus in the rostral and caudal areas receives only thin fibers from each canal, with considerable overlap. The descending nucleus in the rostral and caudal areas receives innervation from the cristae, also with considerable overlap, but with greater intensity in the ventral part of the caudal portion of the nucleus. Each crista sends fibers to the cerebellar granular layer and to the base of the cerebellar Purkinje cell layer. These fibers also innervate the reticular formation below the entry zone of the eighth nerve. The saccule innervates both the dorsal (acoustic) and the ventral nuclei, the latter in the most dorsal position. The innervation of the utricle could be ascertained only in the middle section of the descending and the medial nuclei, an area which does not receive significant innervation from the cristae. Primary afferent fibers course in the vestibular tract, forming a longitudinal bundle lateral to the vestibular nuclei. In the bundle the larger fibers are medially situated.

Afferent Pathways

Preferential glutamine uptake by cochlear hair cells: implications for the afferent cochlear transmitter.

The cochlear uptake of amino acids which are putative neurotransmitters, or closely-related compounds, was examined autoradiographically in the gerbil. Hair cells showed no preferential uptake of most compounds tested. However, preferential accumulation of glutamine by cochlear hair cells was striking. Vestibular hair cells showed no affinity for this amino acid. Glutamine uptake by cochlear hair cells may play an important role in afferent synaptic transmission, by providing transmitter precursor and/or by clearing the synaptic cleft.

Afferent Pathways

Experimental studies for correction of superior laryngeal paralysis by fusion of the thyroid to cricoid cartilages.

Contraction of the cricothyroideus muscles (CTMs), innervated by the superior laryngeal nerves (SLNs), modulates the voice by tilting the thyroid cartilage anteriorly onto the top of the cricoid and tensing the vocal cords. Either unilateral or bilateral paralysis of the SLNs is disabling for individuals with above-average voice demands. Some patients never compensate for this paralysis; there is no surgical procedure recognized to correct it. This study tested the hypothesis that surgical fusion of the thyroid and cricoid cartilages anteriorly can correct the problems of SLN injury by duplicating the mechanical tilt of the thyroid onto the cricoid cartilage normally produced by the CTMs. The SLNs were cut in 12 dogs. In six the cricoid and thyroid cartilages were fused anteriorly. Vocal cord and airway function was assessed preoperatively, immediately postoperatively, and 6 to 10 weeks after surgery. Following surgery there was no airway compromise and there appeared to be a more satisfactory compensation for the SLN paralysis in the fused larynges as compared with the unfused controls as determined by cinelaryngoscopic analysis.

Animals