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Biomedical subjects

R S Swenson

Publications and source records attributed to R S Swenson.

At least 19 recordsLinked to original sources

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↗

Organization of cerebral cortico-olivary projections in the rat.

Injection of wheatgerm agglutinin-conjugated horseradish peroxidase into electrophysiologically identified portions of the rodent sensorimotor and medial frontal cortex revealed anterograde-labeled projections to the inferior olivary complex. Forelimb motor cortical and supplementary motor cortical regions were found to project predominantly to the principal olive while forelimb sensory cortex fibers distributed mainly within the dorsal accessory olive. Forelimb cortical fibers (both sensory and motor) terminated more rostrally and medially in the medial and dorsal accessory olives than did hindlimb projections. Medial frontal cortex projected to the beta subnucleus, the rostral medial accessory olive (especially the ventral aspect), and to the ventrolateral outgrowth of the dorsal cap. These findings indicate a more extensive origin for cortico-olivary projections than previously described for rats or cats and they demonstrate a rather precise topography for olivary projections from various cortical regions.

Animals↗

Effects of a substance P analogue with antagonist properties ([D-Arg1, D-Trp7,9, Leu11]substance P) on spontaneous activity of the adrenal sympathetic nerve and its evoked reflex discharges in response to somatic afferent stimulation.

The present study was designed to test the effect of a substance P (SP) antagonist, [D-Arg1, D-Trp7,9, Leu11]substance P (Spantide), on spontaneous efferent activity of adrenal sympathetic nerve and the two A- and C-sympathetic reflex components evoked in adrenal sympathetic nerve by stimulation of myelinated A- and unmyelinated C-afferent nerve fibers of a hindlimb nerve, respectively, in anesthetized rats. The spontaneous adrenal nerve activity and both of the A- and C-sympathetic reflex components were proportionally reduced by intrathecal application of the SP antagonist (0.038-0.76 nmol), although the same doses did not affect A- and C-somatic reflex components. These data suggest that the SP antagonist has a greater effect on SP-containing neurons related to the generation of spontaneous activity of sympathetic neurons and somato-sympathetic reflex pathways than on SP-containing primary somatic afferent nerves and somato-somatic reflex pathways.

Action Potentials↗

The effects of morphine administered intrathecally on the somatosympathetic reflex discharges in anesthetized cats.

The effect of intrathecally applied morphine or naloxone on the sympathetic A and C reflexes evoked by stimulation of somatic myelinated A and unmyelinated C afferent nerves was investigated in anesthetized cats. Intrathecal application of morphine in the lumbar spinal region depressed the C reflex elicited by stimulation of a hindlimb nerve (superficial peroneal, SP) without affecting the C reflex elicited by stimulation of a forelimb nerve (radial, RA). Also, intrathecal application of naloxone in the lumbar spinal region was found to reverse the intravenous morphine-induced depression of the C reflex elicited by stimulation of the SP nerve. The present results suggest that selective depression of morphine on the somatosympathetic C reflex is mediated at the spinal cord level.

Animals↗

Sympatho-adrenal medullary functions in response to intracerebroventricularly injected corticotropin-releasing factor in anesthetized rats.

Effects of intracerebroventricular (i.c.v.) administration of corticotropin-releasing factor (CRF) on adrenal sympathetic efferent nerve activity, adrenal catecholamine secretion rate and cardiovascular function (i.e. blood pressure, heart rate and renal nerve activity) were investigated in halothane-anesthetized rats. Administration (i.c.v.) of CRF resulted in a dose-dependent increase (to 140% of control, for a 6.4 nmol dose) in adrenal sympathetic nerve activity which began several minutes after injection and reached maximum values approximately 30-60 min later. This increase was significant, when tested against vehicle injected controls, for doses of 6.4 nmol and 640 pmol; however, a 64 pmol dosage did not produce significant effects. Acute hypophysectomy did not influence the response of adrenal nerve activity to i.c.v. injection of CRF. Intravenous administration of CRF (6.4 nmol) did not produce any significant increases in ongoing activity of the adrenal nerve. Following i.c.v. administration of CRF (640 pmol), epinephrine and norepinephrine secretion, as measured from adrenal venous blood samples, showed a similar response pattern to that of the adrenal nerve. Significant increases (maximum increases, from 13.2 to 31.5 ng/kg/min and from 4.1 to 8.6 ng/kg/min for epinephrine and norepinephrine secretion rates, respectively) were observed over the 90 min blood sampling period. The present study demonstrates by direct recording of adrenal sympathetic nerve activity and measurement of adrenal catecholamine secretion rate, that i.c.v. administered CRF can increase adrenal sympathetic efferent nerve activity resulting in increases in catecholamine secretion. In addition, renal nerve activity also showed dose-dependent increases after CRF i.c.v. administration (to 160% of control, for a 6.4 nmol dose) as did heart rate (increases of 35 beats/min for a 6.4 nmol dose).(ABSTRACT TRUNCATED AT 250 WORDS)

Adrenal Medulla↗

Disruption of corticospinal plasticity by 6-hydroxydopamine as measured by intracortical microstimulation in rats.

Intracortical microstimulation in normal, adult rats evoked low-threshold contralateral and high-threshold ipsilateral forelimb movements. In comparison, stimulation of the intact cortex in adult rats that sustained unilateral cortical lesions at birth evoked ipsilateral movements at abnormally low-threshold levels in addition to normal contralateral movements. Depletion of cortical and spinal cord noradrenaline levels by treatment with 6-hydroxydopamine prior to the placement of neonatal cortical lesions eliminated the low-threshold ipsilateral movements when tested at maturity. These findings suggest that the noradrenergic system may influence corticospinal plasticity.

Animals↗

The effects of vertebral artery injections of an enkephalin analogue, (D-Met2,Pro5)-enkephalinamide, on somatosympathetic reflexes.

The present study was initiated to test the effects of intravertebral arterial injection of an enkephalin analogue (D-Met2,Pro5)-enkephalinamide on somatosympathetic responses to myelinated A afferent and to unmyelinated C afferent stimulation (A- and C-reflex, respectively). In anesthetized cats, 0.5 mg/kg administered directly into the vertebral artery, the artery supplying most of the cat brain stem and upper cervical spinal cord, depressed both the A- and C-reflex (to 66 and 64% of control, respectively) while intravenous or carotid arterial injections did not have any effect on these reflexes. It is suggested that intravertebral arterial administration may be a useful method of restricting the effective sites of delivery of biologically active compounds to areas of the brain supplied by this artery.

Analgesics↗

Acquired cystic disease of the end-stage kidney.

The development of multiple cysts in the previously noncystic chronically diseased kidneys of patients undergoing long-term dialysis appears to be associated with spontaneous renal bleeding and benign and malignant renal tumors. Two cases of acquired cystic disease with renal hemorrhage and adenocarcinoma are presented; metastases occurred in one patient and the other had bilateral carcinoma requiring bilateral nephrectomy. Combined data from 13 studies indicate acquired cystic disease occurs in one third of patients undergoing maintenance hemodialysis and is associated with adenocarcinoma in 4 percent of cases. Four cases of metastases and five deaths linked to acquired cystic disease have been reported. Eight of 24 patients with acquired cystic disease and clinical manifestations of renal bleeding had renal adenocarcinoma. Autopsy series indicate tumors associated with acquired cystic disease are usually benign but commonly bilateral and multiple. Cystic transformation of the end-stage kidney is more frequent after several years of hemodialysis. It is suggested that patients receiving dialysis treatments for more than three years have a baseline radiologic examination of the kidneys so that subsequent problems can be more easily identified and evaluated.

Aged↗

Reflex responses evoked in the adrenal sympathetic nerve to electrical stimulation of somatic afferent nerves in the rat.

The present study was initiated to determine the role of somatic A (myelinated) and C (unmyelinated) afferent fibers in both responses of increases and decreases in adrenal sympathetic nerve activities during repetitive mechanical pinching and brushing stimulations of the skin in anesthetized rats with central nervous system (CNS) intact. Accordingly, changes in adrenal sympathetic nerve activity resulting from repetitive and single shock electrical stimulation of various spinal afferent nerves, especially the 13th thoracic (Th13) spinal nerve and the sural nerve, were examined in urethane/chloralose-anesthetized rats. Repetitive electrical stimulation of A afferent fibers in Th13 spinal or sural nerve decreased the adrenal nerve activity similarly as brushing stimulation of skin of the lower chest or hindlimb did, while repetitive stimulation of A plus C afferent fibers of those nerves increased the adrenal nerve activity as pinching stimulation of those skins did. Single shock stimulation of spinal afferent nerves evoked various reflex components in the adrenal nerve: an initial depression of spontaneous activity (the early depression); the following reflex discharge due to activation of A afferent fibers (the A-reflex); a subsequent reflex discharge due to activation of C afferent fibers (the C-reflex); and following post-excitatory depressions. These reflexes seem to be mediated mainly via supraspinal pathways since they were abolished by spinal transection at the C1-2 level. Although the supraspinal A- and C-reflexes could be elicited from stimulation of a wide variety of spinal segmental afferent levels, the early depression was more prominent when afferents at spinal segments closer to the level of adrenal nerve outflow were excited. It is suggested that the decreased responses of the adrenal nerve during repetitive electrical stimulation of A afferent nerve fibers are attributable to summation of both the early depression and post-excitatory depression evoked by single shock stimulation, while the increased responses during repetitive stimulation of A plus C afferent fibers are attributable to summation of the C-reflex after single shock stimulation. In spinalized rats, repetitive stimulation of Th13 always increased the adrenal nerve activities regardless of whether A fibers alone or A plus C fibers were stimulated, just as brushing and pinching of the lower chest skin always increased them. The increased responses in spinal animals seem to be related to the fact that single electrical stimuli of Th13 produced A- and C-reflexes of spinal origin without clear depressions.

Adrenal Glands↗

Topography of spinal, dorsal column nuclear, and spinal trigeminal projections to the pontine gray in rats.

Several studies using a variety of animals have reported conflicting evidence concerning the distribution, laterally, and indeed the presence of ascending projections to the pontine nuclei. In an attempt to clarify this issue, projections to the pontine nuclei from the spinal cord, dorsal column nuclei, and spinal trigeminal nucleus were investigated with anterograde methods, i.e., the Fink-Heimer technique and/or autoradiography, in Long-Evans black-hooded rats. Results revealed that dorsal column nuclear projections to the contralateral pontine gray terminate predominantly in two regions--one in the caudal aspect of the medial pontine subdivision and another overlapping the ventral and lateral subdivisions. Within the medial and ventral lateral nuclear regions, fibers from nucleus cuneatus primarily terminated more rostrally to afferents from the nucleus gracilis. Spinal trigeminal projections terminated most heavily within the contralateral pontine gray at midpontine levels. Similar to the dorsal column nuclear projections, trigeminal afferents were observed in the medial and ventrolateral subdivisions, although these terminations were rostral and dorsal to areas receiving cuneatus input. Additional projections from the spinal trigeminal nuclei to the contralateral ventral peduncular nucleus were also observed. In comparison to the above-mentioned pontine afferents, both high cervical and midthoracic spinal cord lesions produced a similar pattern of axonal degeneration in the ipsilateral pontine gray which overlapped substantially with gracilis inputs. The observed topographic distribution pattern of ascending afferents to pontine gray confirm and extend previous findings which in general have only briefly described these pathways.

Afferent Pathways↗

Acquired renal cystic disease and renal neoplasms in hemodialysis patients.

Noninvasive imaging studies were performed on 26 patients undergoing chronic hemodialysis. We found cysts in 46% of patients and neoplasms in 7.7%. The cysts were relatively easy to detect. However, the neoplasms were very difficult to detect; this problem has been described before in the literature. The natural history of acquired cystic disease and neoplasms in hemodialysis patients is largely unknown. A review of the problems associated with the imaging and management of these patients is included.

Adenocarcinoma↗

Convergence of noxious and non-noxious cutaneous afferents and baroreceptor afferents onto single adrenal sympathetic neurons in anesthetized rats.

Single units of the adrenal sympathetic nerve (n = 46) were dissected and characterized with respect to tonic discharge and response to cutaneous and baroreceptor stimulation. The frequency of tonic discharge averaged 1.6 Hz and cardiovascular rhythmic modulation was observed in 53% of the units. The stimuli employed in the present study included phenylephrine-induced increases in blood pressure and pinching or brushing of lower chest skin. Mean unit activity increased 27% on lower chest pinching stimulation, decreased 12% on lower chest brushing stimulation and decreased 62% on phenylephrine-induced baroreceptor stimulation. Although there was a tendency for units with higher tonic firing frequency to have a greater response to stimulation, this relationship was not significant for pinching or brushing of lower chest skin. The close correlation between tonic activity and response to phenylephrine was explicable on the basis of a near total depression of many units, which resulted in a larger decrease in firing frequency for units with initially high spontaneous discharge rates. As might be expected, units with cardiovascular rhythmicity manifested greater responses to baroreceptor activation. This correlation was independent of tonic rate of discharge since rhythmic and non-rhythmic units did not significantly differ in tonic activity. While a majority of units responded in a typical fashion to all three stimuli (i.e. with increases to pinching and decreases to brushing and phenylephrine administration), there was little correlation between the response magnitude of individual units to any two of the stimuli employed. We conclude, therefore, that most adrenal sympathetic units receive convergent reflex input from cutaneous noxious and non-noxious afferents as well as from baroreceptor afferents, although for any individual unit the quantitative significance of each input varies.

Adrenal Medulla↗

Sympathetic nervous system response to mechanical stress of the spinal column in rats.

The effects of mechanical stimulation of the spine on blood pressure, heart rate and the activity of selected sympathetic nerves (renal and adrenal) were examined in alpha-chloralose/urethane anesthetized rats. Spinal segments from T10 to T13 or from L4 to L7 were isolated from surrounding muscle and the upper and lower segments of the four segment units were fixed by means of spinal clamps. Forces from 0.5 to 3.0 kg were applied to the lateral aspect of the two mobile segments. Stimulations of the thoracic or the lumbar region produced large decreases in blood pressure (-29.8 +/- 3.1 mmHg) along with small decreases in heart rate (6.1 +/- 1.6 beats/min). Additionally, large and immediate decreases were observed in renal nerve activity. While responses attenuated during the course of stimulation, they generally outlasted the stimulus. The adrenal nerve, after an initial decline in activity, showed subsequent increases which were attributed to baroreceptor effects, since bilateral lesion of the vagi and carotid sinus nerves abolished them. After baroreceptor denervations only initial decreases in activity were observed by mechanical stimulation of the spine. The observed responses were found not to be due to spinal cord compression, but rather were ascribed to afferent fiber mediated reflexes. Cutting dorsal (sensory) roots T10 to L2, bilaterally, abolished the response to lower lumbar stimulation. Additionally, in recording from the peripheral end of the severed dorsal roots, large increases in afferent activity were observed by spine stimulation. The present study has demonstrated potent somatovisceral reflexes from mechanical stimulation of the spinal column. These results are discussed in relation to other studies of somatovisceral responses and with regard to various clinical reports.

Adrenal Glands↗

The long-term clinical course of systemic lupus erythematosus in end-stage renal disease.

In an attempt to define the long-term clinical course of systemic lupus erythematosus followed by end-stage renal disease, we studied 28 patients with lupus nephritis at Stanford University between January 1969 and December 1980. The clinical and serologic manifestations of both renal and nonrenal disease improved with long-term hemodialysis despite the withdrawal of immunosuppressive drugs in almost all the patients. Rehabilitation was excellent, and a return to normal physical activity was generally the rule. The mortality rate was low (6 of the 28 patients died), but death occurred primarily in patients receiving high doses of prednisone. Recovery from renal failure and discontinuation of dialysis were not rare (eight patients recovered) despite the reduction in immunosuppressive drugs. Renal transplantation was also well tolerated. We found the long-term clinical course of these patients to be comparable to that of patients with end-stage renal disease associated with disorders other than systemic lupus erythematosus.

Adolescent↗

Metabolic alkalosis during immobilization in monkeys (M. nemestrina).

We studied the systemic and renal acid-base response of monkeys during ten weeks of immobilization. By three weeks of immobilization, arterial pH and bicarbonate concentrations were elevated (chronic metabolic alkalosis). Net urinary acid excretion increased in immobilized animals. Urinary bicarbonate excretion decreased during the first three weeks of immobilization, and then returned to control levels. Sustained increases in urinary ammonium excretion were seen throughout the time duration of immobilization. Neither potassium depletion nor hypokalemia was observed. Most parameters returned promptly to the normal range during the first week of recovery. Factors tentatively associated with changes in acid-base status of monkeys include contraction of extracellular fluid volume, retention of bicarbonate, increased acid excretion, and possible participation of extrarenal buffers.

Acid-Base Equilibrium↗