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Biomedical subjects

J A McNulty

Publications and source records attributed to J A McNulty.

At least 19 recordsLinked to original sources

Pinealocyte synaptic ribbons and neuroendocrine function.

A comparative study of pinealocyte synaptic ribbons (SR) revealed two predominant populations exhibiting either a rod/ribbon shape (SRr) or a spherical/punctate shape (SRsp). Species-specific differences were found in the abundance of SR, the ratio of SRr/SRsp, and the occurrence of SR in ribbon fields. The close topographical relationship of SR to the plasma membrane and the numerical changes that occurred with changes in metabolism of the pinealocytes suggest that SR have important vesicle-mediated interactions with the cell membrane. Experiments designed to clarify the relationship between SR and pineal neuroendocrine function revealed a positive correlation between SR numbers and indole intermediates during pineal development in the rat, and increased SR frequency after denervation of the rat pineal gland or administration of the beta-adrenergic agonist, isoproterenol. These data are consistent with the hypothesis that SR function is linked to receptor mechanisms regulating indoleamine production in the pineal gland.

Animals

Immunocytochemical and circadian biochemical analysis of neuroactive amino acids in the pineal gland of the rat: effect of superior cervical ganglionectomy.

Semiquantitative immunocytochemistry by immuno-gold techniques revealed differences in the spatial distribution of glutamate, glutamine, and taurine within the pineal gland, with greatest labeling over pinealocytes, glia, and endothelia, respectively. At the subcellular level, glutamate labeling tended to be highest over pinealocyte synaptic ribbons and mitochondria, and lowest over lipid inclusions. Pineal levels of glutamate, glutamine and taurine, as measured by high performance liquid chromatography, did not vary over a light: dark cycle. Superior cervical sympathetic denervation, which abolishes pineal melatonin synthesis, resulted in a nearly 50% reduction in pineal glutamate levels, but had no effect on levels of glutamine and taurine. Other amino acids (alanine, arginine, aspartate, serine) were reduced by 23%-33% following sympathectomy. These data suggest an important role for glutamate in pinealocyte function(s) possibly related to the noradrenergic innervation of the gland.

Alanine

Sympathetic denervation and chronic serotonin uptake blockade by fluoxetine do not affect pineal gland 5-hydroxyindole acetic acid: evidence that oxidative deamination of pineal serotonin is a property of the pinealocyte.

This investigation tested the hypothesis that oxidative deamination of 5HT in the pineal gland occurs primarily in cellular compartments other than the pinealocyte (i.e., noradrenergic nerve terminals and glia). Following sympathetic denervation of the pineal gland by bilateral superior cervical sympathectomy, pineal levels of 5HT and its oxidative metabolite, 5HIAA, were measured by HPLC from samples collected at six time points over the 24 h photoperiod. The role of glia in 5HT deamination was further examined by chronic treatment with the 5HT uptake blocker, fluoxetine (10 mg/kg). Sympathectomy abolished the circadian rhythms of both 5HT and 5HIAA, but had no statistically significant effect on the ratio of 5HIAA/5HT compared to sham-operated and intact controls over the 24 h period. Pineal daytime levels of both 5HT and 5HIAA were unaffected by fluoxetine treatment. These findings indicate that the pinealocyte is an important cellular compartment for 5HT oxidative metabolism.

Animals

Chronic histologic changes after vascular clamping are not associated with altered vascular mechanics.

The mechanical properties of arteries, along with the histologic and scanning electron microscopy characteristics of the nonatherosclerotic canine arteries, were investigated six months after vascular clamping. Different vessel clamps were applied to 73 sites on the carotid and femoral arteries in five anesthetized dogs. Each clamp was applied for 30 minutes with (a) sufficient force to just occlude blood flow or (b) as tightly as the clamp could be placed. After six months the vessels were excised, filled with barium sulfate suspension, and pressurized in 25 mmHg steps up to 150 mmHg. High resolution contact radiographs were taken at each pressure. These were magnified 35x and measured. Scanning electron microscopy and conventional histology disclosed that the clamped sites exhibited serrated clamp "tracks" in the intima, intimal hyperplasia, and, in a few cases, fractured elastic lamellae. These histologic changes were seen more frequently in the femoral artery than in the carotid artery (p less than .01). The mechanical properties, as determined from radiographic measurements, demonstrated that, for all types of clamps, the luminal diameter, pressure-diameter relationship, and compliance of the clamped vessels were not significantly different from nonclamped control regions (ANOVA). These studies demonstrate that careful application of clamps to nonatherosclerotic arteries produces persistent morphologic changes, but these are not associated with altered mechanical properties of the vessel wall.

Animals

Pineal gland transplants into the cerebral hemisphere of newborn rats: a study of the blood brain barrier and innervation.

Pineal glands from neonatal (0-1 day) Long-Evans black-hooded rats were transplanted into the cerebral hemispheres of litter mates for periods of 1 to 5.5 months. Grafts exhibited differentiated pinealocytes that were intensely immunoreactive for serotonin. Transplant vasculature was permeable to endogenous IgG, comprised fenestrated endothelia with wide pericapillary spaces typical of in situ glands, and had a volume density intermediate to that of surrounding cortex and in situ pineals. Along the periphery, transplant capillaries tended to have continuous endothelia similar to those of host cortex. This peripheral zone was impermeable to endogenous IgG and appeared to increase in size in older grafts. The presence of noradrenergic-like fibers within the perivascular compartment suggested that transplants were innervated by peripheral sympathetic neurons from the superior cervical ganglia. In animals which had been superior cervical ganglionectomized, noradrenergic-like fibers were absent or degenerating. Neural regulation of transplant metabolic activity was suggested by the increased frequency of pinealocyte synaptic ribbons in denervated grafts. These findings are consistent with the hypothesis that factors from both graft and host influence vasculature physiology and differentiation in neural transplants. Furthermore, grafts appeared to receive appropriate neural input from the peripheral sympathetic system.

Animals

Quantification of tartrate resistant acid phosphatase activity using a computerized image analysis system.

Tartrate resistant acid phosphatase (TRAP) has been accepted as a marker for identification of osteoclasts. A method is reported here for quantitating TRAP using an image analysis system. The amount of the enzyme specific to osteoclasts can be used to differentiate osteoclasts from other cells capable of TRAP expression. TRAP expression characteristic of the osteoclast was compared with that of multi-nucleated giant cells (MNGC)s recruited to the site of subcutaneously implanted mineralized bone matrix. Two weeks post-implantation, the pellets were removed and processed for the demonstration of TRAP along with rat proximal tibiae. A large amount of TRAP was consistently expressed by the in situ osteoclasts. The MNGCs associated with the mineralized bone implants expressed little if any TRAP reaction product. Using this system, the amount of TRAP reaction product or any other enzyme reaction product expressed can be objectively and reproducibly quantitated.

Acid Phosphatase

A circannual cycle in pinealocyte synaptic ribbons in the hibernating and seasonally reproductive 13-lined ground squirrel (Spermophilus tridecemlineatus).

Pinealocyte synaptic ribbons (SR) in the 13-lined ground squirrel were quantified at monthly intervals over a one-year period spanning the hibernating and reproductive cycles of these animals. SR numbers were high (70-90/20,000 microns2) during periods of activity and reproductive quiescence (May-October). With the onset of hibernation (November-December) there was a rapid 6 to 7-fold reduction in SR frequency. During arousal (January-February) and sexual maturation (March-April) there was a gradual increase in SR frequency. The winter decline in SR frequency is consistent with the decline in pineal melatonin during hibernation and supports the hypothesis that pinealocyte SR play an important role in the neurotransduction of melatonin biosynthesis.

Animals

Magnetic resonance imaging (MRI) effects on rat pineal neuroendocrine function.

This study investigated the effects of MRI on receptor-mediated activation of pineal gland indole biosynthesis. Exposure of rats to MRI reduced the effects of isoproterenol on pineal serotonin and N-acetylserotonin levels suggesting that strong magnetic fields and/or radio-frequency pulsing used in MRI inhibited beta-adrenergic activation of the gland. There was no effect of MRI on saline controls.

Animals

Ultrastructure and organization of circumventricular organs and endolymphatic tubules in the treefrog, Hyla versicolor.

The morphology and anatomical relationship of the paraphysis, anterior choroid plexus, and endolymphatic tubules of Hyla versicolor suggest that these structures may act as a functional unit to regulate composition of the cerebrospinal fluid (CSF). Ependymal cells of both the paraphysis and the choroid plexus exhibit ultrastructural features (an extensive microvillar border, large intercellular spaces containing an amorphous material, and apically located mitochondria) which indicate active exchange between the blood and CSF. Mast cells (which may play a role in regulating vascular permeability) also occur on the brush border. The tubules of the endolymphatic sacs were found to lie in close relation with the dorsal portion of the paraphysis. The endolymphatic organ is known to play a role in systemic buffering during respiratory acidosis and may influence Na/K fluxes via calcium release. The association of the paraphysis with the endolymphatic tubules may therefore represent an important mechanism for ion regulation in the CSF of amphibians. The ultrastructure of the pineal organ agrees with descriptions for other species. No pineal stalk was present. Photoreceptor inner and outer segments project into a central lumen continuous with the third ventricle. Outer segments show signs of disorganization. Photoreceptor/neural dendrite contacts involve synaptic ribbons and conventional synapses.

Animals

Circadian analysis of mononuclear cells in the rat following pinealectomy and superior cervical ganglionectomy.

The role of the pineal gland and adrenocorticosteroids in circadian rhythmicity of immune function was investigated in Sprague-Dawley rats that either had been pinealectomized (PX) or had undergone superior cervical ganglionectomy (SCGX), which functionally denervates the pineal. For both experiments, conducted between August and October, rats were entrained to a 10-h light:14-h dark cycle and fed ad libitum. The circadian rhythm in monocytes (ANOVA, p less than .01 for Control + Sham + PX samples) tended to parallel that of plasma corticosteroid levels (ANOVA, p less than .01) with the peak during early dark and the nadir at early light. In comparison, suppressor/cytotoxic T cells and B cells tended to be more frequent during early light with minimum levels during early dark (ANOVA, p less than .05 and .01, respectively, for Control + Sham + PX samples). Natural killer (NK) activity in control animals varied significantly (ANOVA, p less than .05) over the light:dark cycle with peak activity during early dark in the SCGX experiment, but was only slightly elevated during late dark in the PX experiment. PX animals exhibited increased frequency of NK cells, but only in samples collected during the day (t test, p less than .05). This effect was not observed in sham-operated PX controls and in SCGX animals. Neither PX nor SCGX had a significant (ANOVA) effect on plasma corticosterone levels. These observations in the rat are consistent with findings in mice and humans that corticosteroids play an important general role in circadian rhythmicity of immune functions. In contrast, the present study suggests that pineal gland influence of immune function(s) is more specific and that pineal gland interaction with NK cells has a circadian component.

Animals

Pineal gland free amino acids and indoles during postnatal development of the rat: correlations in individual glands.

Free amino acids and indoles were measured by HPLC in single pineal glands of 5-, 10- and 20-day-old rats sacrificed during mid-light and mid-dark at each age. Melatonin was detectable in neonates (5-day-old), but day vs night differences in indole constituents did not occur until 10 days of age. Free amino acid steady state levels were high in neonates and there was a tendency for reversal of day vs night differences coinciding with the onset of circadian rhythmicity in indole biosynthesis. High correlations (r greater than 0.85) existed for taurine vs. glutamate in individual glands regardless of age and time of sacrifice. These findings suggest that taurine and glutamate are biochemically interrelated and that developmental changes in amino acid metabolic pools reflect functional innervation of the gland.

Amino Acids

Day-night differences in the vesicle populations of nerve terminals in the rat and chick pineal gland.

Day-night differences in the ultrastructure of pineal neuronal elements were quantitated in the rat and the chick--two species that exhibit important differences in adrenergic control of melatonin synthesis. Area densities of small clear vesicles (40-60 nm) and small dense-cored vesicles (40-60 nm) in nerve terminals were significantly reduced during the night in the rat. In the chick, there were no day-night differences in the frequency of clear vesicles, but the number of small dense-cored vesicles tended to be greater at night. There was no effect of day-night sampling on area densities of large dense-cored vesicles (80-120 nm) in either species. These findings are consistent with biochemical evidence for day-night species differences in the adrenergic control of pineal function.

Animals

A comparative light and electron microscopic study of the pineal complex in the deep-sea fishes, Cyclothone signata and C. acclinidens.

The pineal complexes of the two closely related deep-sea fished Cyclothone signata and C. acclinidens were compared both qualitatively and quantitatively. Photoreceptor and supportive cells were identified in both species. The deeper-dwelling species, C. acclinidens, had a significantly greater number of photoreceptor-cell outer segment saccules and a higher ratio of receptor cells to nerve fibers in the pineal stalk. It was suggested that these indicate increased photosensitivity of the pineal. Supportive cells were sometimes seen to contain arrays of undulating tubules. The functional significance of these tubules is not understood. A prominent dorsal sac is closely associated with the pineal end-vesicle. Both structures appear to have a common vascular supply suggesting that they are functionally related. Dorsal sac cells contained abundant mitochondria, glycogen, and large filament-like inclusions.

Animals

Fine structure of the pineal organ in the troglobytic fish, Typhlichthyes subterraneous (Pisces: Amblyopsidae).

The pineal organ of the blind, cave-dwelling fish, Typhlichythyes subterraneous, was examined with both light and electron microscopes. Like the eyes, the pineal in this troglobytic species was found to be regressed. Two cell types, photoreceptor and supportive cells, were described in the pineal epithelium. Although ganglion cells were not identified, small, unmyelinated nerve fibers were present. The photoreceptor cells had degenerated outer segments. Accordingly, it was suggested that the pineal in this species is not likely to function in photoreception. However, the presence of well developed Golgi bodies, clear and dense-cored vesicles, variable amounts of rough endoplasmic reticulum and glycogen particles indicated that both cell types are metabolically active and may play a role in secretion.

Animals

Failure of medial forebrain bundle or raphe ablation to alter the daily temperature rhythm of the rat.

The data presented in the present study suggest that neither the ascending noradrenergic fibres confined to the MFB nor the serotonergic fibres originating in or passing through the mesencephalic raphe are essential for periodicity in body temperature. Both control and experimental groups, i.e., rats subjected to medial forebrain bundle or raphe ablation presented circadian periodicity in body temperature and neither the phase, amplitude or overall mean of experimentals differed significantly from controls.

Animals

A light and electron microscopic study of the pineal in the blind goby, Typhlogobius californiensis (Pisces: Gobiidae).

The pineal of the burrow-inhabiting, blind goby, Typhlogobius californiensis, was studied by light and electron microscopy. The two predominant cell types were photoreceptor and supportive cells. Ganglion cells could not be positively identified. The majority of photoreceptor cells had well developed outer segments and made apparent synaptic contact with nerve processes of unknown origin. Similar unmyelinated nerve fibers containing dense-cored vesicles were seen descending the pineal stalk. The cytoplasm of supportive cells contained several Golgi zones, occasional dense aggregations of smooth endoplasmic reticulum, abundant quantities of glycogen, some dense-cored vesicles and unusual rod crystalline inclusions measuring approximately 0.5 micrometer in width and 4-5 micrometer in length. These observations suggest that the pineal in this light-deprived species has retained its photoreceptive function and is a metabolically active organ which may also function in secretion.

Animals

The pineal of the troglophilic fish, Chologaster agassizi: an ultrastructural study.

The pineal of the facultative, cave-dwelling fish, Chologaster agassizi, was examined electron microscopically. Two cell types, photoreceptor and supportive cells, were identified in the pineal epithelium. The photoreceptor cells had well developed outer segments and contained Golgi bodies which were surrounded by both clear and dense-cored vesicles. Vesicle-crowned rods were frequently seen in various regions of the cell. The supportive cells also contained Golgi bodies from which both clear and dense-cored vesicles appeared to originate. In addition, these cells were characterized by peculiar arrangements of the smooth endoplasmic reticulum and the presence of pigment granules. Large quantities of glycogen were observed in both cell types. Small, unmyelinated nerve fibers were seen coursing throughout the pineal epithelium. Terminals filled with pleomorphic, clear vesicles and dense-cored vesicles were present in the vicinity of these nerve fibers. Similar vesicle-filled terminals were observed in close association with the supportive cells. The results of this study indicate that the pineal in this light-deprived species is a metabolically active organ capable of photoreception. Specializations of the organelles in the pineal cells were similar to those observed in other vertebrates living in environments of low light levels.

Animals

Morphology of the pineal complex in seven species of lanternfishes (Pisces: Myctophidae).

The morphology of the pineal complex was compared in seven species of lanternfishes (family Myctophidae) using both light and electron microscopes. On the basis of compactness of the pineal end-vesicle and presence or absence of a dorsal sac, the species in this study were divided into two groups. This grouping seems to correlate well with current views on the phylogenetic relationships among these fishes. Receptor cells and supportive cells are described in the pineals of all species examined. The deepest-dwelling of the forms studied, Parvilux ingens, showed a significant increase in the mean number of lamellar membranes in the outer segments of the receptor cells and a higher convergence ratio of receptor cells to ganglion cells as compared to the shallow-dwelling form Tarletonbeania crenularis. Accordingly it is suggested that the pineal of P. ingens is more photosensitive. Additional differences among species were found in the ultrastructure of the supportive cells. Dorsal sacs were absent in the three shallowest-occurring myctophids studied. In those species with a dorsal sac, its close association with the pineal-end-vesicle suggests a functional relationship between the two structures.

Animals