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Biomedical subjects

L M Fox

Publications and source records attributed to L M Fox.

At least 19 recordsLinked to original sources
PubMed1992

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↗
PubMed1992

An inhibitor of Ca2+/calmodulin-dependent protein kinase II, KN-62, inhibits cholinergic-stimulated parietal cell secretion.

Cholinergic stimulation of parietal cell secretion is mediated by an increase in intracellular calcium. KN-62, a selective inhibitor of Ca2+/calmodulin-dependent protein kinase II (CaMK II), has recently been synthesized (Tokomitsu et al. J. Biol. Chem. 265: 4315-4320, 1990). To define the role of CaMK II in parietal cell secretion, we determined the effects of KN-62 on secretagogue-stimulated acid secretion in isolated rabbit parietal cells. Pretreatment of parietal cells with KN-62 resulted in the inhibition of carbachol-stimulated [14C]aminopyrine uptake over a concentration range of 3 to 60 microM (IC50 of 20 microM). KN-62 (60 microM) reduced carbachol-stimulated aminopyrine uptake to unstimulated levels. KN-62 did not alter carbachol-stimulated increases in cytoplasmic free Ca2+ concentration. High concentrations of KN-62 (60 microM) elicited a small decrease in aminopyrine uptake stimulated by forskolin, but did not significantly inhibit histamine stimulation. A potent CaMK II activity was identified in total membrane from parietal cells. These results suggest that CaMK II may mediate cholinergic-stimulated parietal cell secretion.

1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine↗
PubMed1992

The major calmodulin-binding protein in rabbit parietal cells is Ca2+/calmodulin-dependent protein kinase II.

Parietal cell secretion can be stimulated by both histaminergic and cholinergic agonists. We have recently found that inhibition of calmodulin-dependent protein kinase II (CaMK II) activity can abolish cholinergic but not histaminergic stimulation of parietal cell secretion (Am. J. Physiol. 262:G118-122). We have investigated the presence of calmodulin-binding proteins and CaMK II in isolated rabbit parietal cells. Calmodulin-binding proteins with apparent molecular masses of 50, 60, 85, 100, and 240 kDa were observed. The major calmodulin-binding species was a 50 kDa band which was enriched in 50,000 g. microsomal membranes. The 50 kDa calmodulin binding comigrated with immunoreactivity for CaMK II. Partial purification of the microsomal CaMK II demonstrated a 250 kDa oligomer. The results demonstrate that CaMK II is the major calmodulin-binding protein in parietal cells and is associated primarily with light microsomal membranes.

Animals↗
PubMed1991

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↗
PubMed1991

Cardiac manifestations of Weber-Christian disease: report and review of the literature.

A patient with chronic systemic Weber-Christian disease who was treated with hydroxychloroquine developed cardiac dilatation with congestive heart failure. Endomyocardial biopsy demonstrated myocyte degeneration and interstitial fibrosis, but no typical features of chloroquine induced cardiomyopathy. Clinical symptoms of congestive heart failure also were recognized in 7 of the 11 reported autopsy cases of Weber-Christian disease having cardiac involvement. This involvement can affect the pericardium and the myocardium.

Adult↗
PubMed1990

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↗
PubMed1990

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↗
PubMed1990

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↗
PubMed1990

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↗
PubMed1989

Effects of isoproterenol on synaptic ribbons in pinealocytes of the rat and C57BL/6J mouse.

Synaptic ribbons (SR) in melatonin-deficient pinealocytes of the C57BL/6J mouse were quantitatively compared to SR in pinealocytes of the rat after beta-adrenergic receptor activation by isoproterenol. Two populations of SR comprising synaptic spherules (SRsp) and synaptic rods (SRr) were described in both the mouse and the rat, but species differences existed in the ratio of SRr to SRsp. Isoproterenol caused a significant increase in frequency of SR of the rat but had little or no effect on SR populations in the mouse. It is unlikely that beta-adrenergic receptors are absent on mouse pinealocytes or were not activated since isoproterenol elevated plasma renin concentrations indicating activation of beta-adrenergic receptors. Furthermore the pineal of both species receives heavy sympathetic input. These findings indicate that the role and regulation of pinealocyte SR are complex and are functionally linked to beta-adrenergic receptors as well as other mechanisms related to the production of melatonin.

Animals↗
PubMed1989

Delayed redistribution in thallium 201 SPECT myocardial perfusion studies.

Stress 201Tl myocardial perfusion studies are useful in differentiating viable, reversibly ischemic from infarcted myocardium. A perfusion defect that shows redistribution 2 to 4 h after 201Tl injection is diagnostic of ischemia, while a fixed defect suggests infarction. However, occasional patients with a fixed defect at 4 h have redistribution at 24 h. This study evaluates the frequency and significance of this delayed redistribution with SPECT 201Tl. Patients with either no or incomplete redistribution at 4 h had repeat imaging 18 to 48 h later. Delayed redistribution was seen in 8/26 (31 percent). Four had incomplete and four had no redistribution at 4 h. Delayed redistribution with SPECT 201Tl is more common than generally appreciated, and we recommend delayed images in patients with fixed perfusion defects or incomplete redistribution at 4-h imaging, particularly in patients with previous infarctions for whom a revascularization procedure is being considered.

Adult↗
PubMed1989

Quantification of plasma cortisol levels in ascorbic acid studies using guinea pigs implanted with ACTH pellets.

A method is described that permits multiple blood collections from unanesthetized, unrestrained guinea pigs with minimal disruption to the animal, as verified by plasma cortisol (PC) levels. Blood (100-200 microliters) was collected from the lateral metatarsal vein using a vacuum-assisted method. Using this method, the effect of subcutaneously-implanted slow-releasing ACTH versus placebo pellets on PC levels was determined. A small, but significant, increase in PC concentration occurred in the control group, reflecting the stress of handling and the implant procedure. In contrast, the peak concentration of PC after implantation of a pellet containing ACTH was 20 times the starting level and occurred within 4 hr. However, the PC level was not correlated with the content of ACTH in the pellet because a similar level was achieved with 0.125 or 8 mg/pellet. A decline in Pc to pre-treatment levels occurred within 24 to 48 hr. The results indicate that administration of ACTH by pellet, although intended to achieve a sustained elevation in PC level, is not suitable for maintaining elevated PC levels.

Adrenocorticotropic Hormone↗
PubMed1989

The influence of anesthesia and surgery on plasma cortisol and tissue ascorbic acid levels in the guinea pig.

The influence of methoxyflurane anesthesia alone compared to anesthesia and laparotomy surgery on plasma cortisol (PC) levels and tissue ascorbic acid (AA) levels was examined in adult male albino guinea pigs (485 +/- 7 g) consuming 500 mg AA/kg diet. Anesthesia resulted in a 60% decrease in food intake on day 1 after treatment, while surgery resulted in a 71% decrease. By day 4, food intake for both groups was equal to that of control animals. Body weight decreased 5-7% on day 1 after both treatments; recovery of body weight to pre-treatment levels was slowest in the animals exposed to surgery. After anesthesia alone, PC levels were twice that of controls by 1 hr and the five-fold higher peak PC level was observed at 9 hr. Surgery induced a more immediate five-fold rise in PC level that plateaued at 1 hr. PC levels decreased to levels similar to the control animals after 72 hr after both treatments. Weight, percent water, and AA levels of tissues examined at seven days after treatment were similar among groups. The results indicate that the adrenal cortical response to surgery is of the same magnitude as for anesthesia alone, although the peak PC level is more quickly achieved. Tissue AA levels are similar seven days after surgery or anesthesia alone even though elevated PC levels sustained for several days.

Abdomen↗
PubMed1979

Effects of antihypertensive therapy on cardiovascular response to exercise.

The effects of alpha methyldopa and hydrochlorothiazide therapy on exercise induced changes in arterial pressure, heart rate, rate-pressure product and total duration of exercise were evaluated with graded treadmill exercise. Although both agents were equally effective in reducing resting arterial pressure, alpha methyldopa appeared to provide slower build-up, a lower ceiling and more rapid recovery of arterial pressure in response to exercise stress than did hydrochlorothizide. Alpha methyldopa significantly reduced the degree of rise of the rate-pressure product (an index of myocardial oxygen consumption) during the exercise and recovery phases, whereas hydrochlorothiazide failed to do so. The total duration of exercise (an index of work capacity) was unchanged with either hydrochlorothiazide or alpha methyldopa. Therapy with alpha methyldopa presumably reduced myocardial oxygen demand without reducing work capacity.

Adult↗