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Biomedical subjects

D L Felten

Publications and source records attributed to D L Felten.

At least 127 records · Page 7Linked to original sources

Effects of surgically induced instability on rat knee articular cartilage.

Degenerative lesions in the articular cartilage were present following transection of the anterior cruciate ligament in the rat. These lesions included surface disruptions, a reduction in matrix proteoglycans, and cellular changes and therefore were similar to lesions seen in dogs following transection of the anterior cruciate ligament as well as lesions seen in other mechanical derangement models. Lesions were more frequently encountered in animals that had been exercised on a treadmill. This suggests that the rat knee joint may be a useful small animal model in studying the effect of mechanical derangement on articular tissues.

Animals↗

Viscerotopic localization of preganglionic parasympathetic cell bodies of origin of the anterior and posterior subdiaphragmatic vagus nerves.

Utilizing the retrograde HRP transport method, fibers from anterior and posterior subdiaphragmatic branches of the vagus nerve in the rat were traced to their cells of origin in the brainstem. Efferents to the gut supplied by the subdiaphragmatic vagus nerves derive from cell bodies organized in a viscerotopic, spindle-shaped longitudinal cell column throughout the longitudinal extent of the classically described dorsal nucleus of the vagus (DNV) and in regions of nucleus commissuralis (NC), caudal to the DNV. This entire longitudinal group of cells is called the DNV cell column. In the caudal one third of the DNV cell column, the cell bodies were found in the midline and paramedian posterior portion of the NC, and in the anterior portion of the caudal DNV, in a horizontally oriented cluster of cells when viewed in cross section. In the middle one third of the DNV cell column, the cell bodies moved laterally, but still maintained their anterior position in the nucleus. In the rostral one third of the cell column, the cell bodies were located at the lateral margin of the DNV. A few scattered cell bodies extended caudally from the DNV cell column into the dorsal region of lamina X of spinal cord, and reached as far caudal as the C5-C6 segments. The anterior subdiaphragmatic branch of the vagus contained axons whose cell bodies were mainly but not exclusively located in the ipsilateral (left) side of the medulla, while the posterior subdiaphragmatic branch of the vagus contained axons whose cell bodies were found bilaterally in the medulla, with a majority (approx. 60%) located on the ipsilateral (right) side, and approximately 40% located on the contralateral (left) side.

Afferent Pathways↗

Sympathetic innervation of murine thymus and spleen: a comparative histofluorescence study.

Fluorescence microscopy of thymus and spleen from four strains of mice (C3H and ICR controls, AKR spontaneously leukemic and NZB autoimmune) revealed varicose noradrenergic (NE) fibers in perivascular and parenchymal regions of both organs. Thymic innervation was largely perivascular, but isolated islands and strings of free NE fibers were noted among thymic parenchymal cells. A morphological proximity between NE fibers in the thymus and mast cells was noted in all strains studied, but was exceptionally prominent in the NZB thymus. Perivascular plexuses within the splenic white pulp sent single NE fibers between the surrounding lymphocytes. Catecholamines and histamine have been shown to modulate lymphocyte development and activity in vitro. The present study provides morphological evidence that both NE and histamine are available to lymphocytes in thymus and spleen, and thus provides morphological evidence for neural modulation of immune activity in vivo.

Adrenergic Fibers↗

Ontogeny of caudal fourth ventricular tanycytes in the rabbit brain: a Golgi study.

A Golgi study of the floor of the caudal fourth ventricle in the developing and adult rabbit brain stem revealed the presence of several clusters of tanycytes. These tanycytes possessed ciliated apical surfaces and basal shafts extending into the substance of the medulla and pons where they intermingled with specific neuronal fields. These shafts ended in the serotonergic nuclei raphe obscurus and pallidus, and the noradrenergic locus coeruleus and nucleus intercalatus (group A2). The tanycyte shafts extended into the medullary midline early in ontogeny (day 18 of gestation), following which the neurons of the raphe began to sprout neurites. These shafts then formed the underlying structure for a large medullary dendrite bundle. These shafts developed extensive spines during early neonatal ontogeny, which then diminished in number through adulthood. the tanycyte shafts extending into locus coeruleus and nucleus intercalatus developed later in ontogeny than the midline shafts, just before birth. These shafts also persisted into adulthood in close relationship with the monoamine neurons. We suggest that the tanycytes on the floor of the fourth ventricle may take up substances from the CSF and transport them to the region of the monoamine nuclei where the shafts terminate, in a manner similar to median eminence tanycytes. The early development of shafts from fourth ventricular tanycytes suggests a possible regulatory role for these cells over the neuritic sprouting and maturation of the monoaminergic nuclei.

Animals↗

Aqueductal tanycytes in the rabbit brain: A Golgi study.

Utilizing Golgi-Cox impregnation, tanycytes were found in the ependyma of the cerebral aqueduct of the neonatal and adult rabbit. These tanycyte somas showed a variety of shapes, apical projections into the aqueduct, and basal processes (shafts) projecting into the mesencephalon, particularly into the periaqueductal gray (PAG). The shafts showed a variety of branching patterns, and sometimes abutted or terminated on capillaries or on specific neuronal elements. Other shafts coiled within the PAG or terminated within the neuropil of the mesencephalon. It is possible that these tanycytes provide a route for transport of cerebrospinal-fluid-borne substances from the aqueduct to the neuronal regions and vasculature of the mesencephalon. The presence of these tanycytes with complex branching patterns in proximity to neural and vascular structures suggests a permanent, active role for these specialized ependymal cells.

Aging↗

Distribution of choline acetyltransferase, acetylcholinesterase, muscarinic receptor binding, and choline uptake in discrete areas of the rat medulla oblongata.

Quantitative measurements were made of choline acetyltransferase (CAT) activity, acetylcholinesterase (AChE) activity and cholinergic muscarinic receptor binding ([3H]QNB) in eight areas of a cross-section of the rat medulla oblongata. A fourth cholinergic parameter, high-affinity choline uptake, was measured in three groups of these areas. CAT, AChE and [3H]QNB binding were found to be highest in the hypoglossal nucleus and the dorsal motor nucleus of the vagus; the lowest value was in the area which contains the inferior olive and the corticospinal tract. The distribution of AChE and CAT activities varied approximately 7- to 10-fold among the eight regions examined, whereas that of the muscarinic receptor varied only about 4-fold. The Na+-dependent high-affinity choline uptake varied approximately 20-fold from the region with the lowest activity (inferior olivary nucleus and corticospinal tract) to that with the highest activity (tissue areas containing the dorsal motor nucleus, hypoglossal nucleus of the solitary tract and nucleus cuneatus). The four cholinergic parameters are statistically correlated throughout all the areas of the medulla which were studied.

Acetylcholinesterase↗

Noradrenergic sympathetic innervation of lymphoid tissue in the rabbit appendix: further evidence for a link between the nervous and immune systems.

The rabbit appendix, a region of gut with well organized zones of lymphoid tissue, was examined with the glyoxylic acid histofluorescence technique for the localization of noradrenergic fibers, with high performance liquid chromatography with electrochemical detection (LCEC) for the quantitation of norepinephrine and serotonin, with Bielshowski and Giemsa stains for additional information about neural supply, and with acetylcholinesterase histochemistry for the localization of this hydrolytic enzyme. Fluorescent plexuses entered the serosal surface of the appendix associated with blood vessels, traveled longitudinally inside the muscularis interna, mainly in association with blood vessels but adjacent to enteric smooth muscle, and branched into long, linear, varicose plexuses that ran inward in a radial orientation towards the lumen in the internodular septa. As these fibers approached the interdomal regions near the epithelial surface, they passed through thymus-dependent cell zones, and arborized extensively throughout the interdomal region. A high density of varicosities was found in the subepithelial region where immunoglobulin-secreting plasma cells are found. These varicosities were sparse at 21 days of age, but were increased in number at 42 days of age. They were even further increased in number and density in adults. These fibers were further identified with a Bielshowski silver stain, and also demonstrated acetylcholinesterase activity. The noradrenergic varicosities in the interdomal regions of the adult rabbit appendix were closely associated with numerous yellow fluorescent cells of 25-40 microns diameter, which sometimes demonstrated fine varicose processes. The adult rabbit appendix contained a moderate concentration of norepinephrine (163.0 +/- 22.9 ng/g wet weight) and a very high concentration of serotonin (3981 +/- 283 ng/g wet weight). Levels in neonates were considerably lower, suggesting that the yellow fluorescent cells may contain serotonin. Acetylcholinesterase was associated with neural fibers and with non-neural regions of the lymph nodules and the domes, perhaps playing a protective role for these regions of the cellular immune system. The rabbit appendix is a well organized region of lymphoid tissue with specific zones of noradrenergic innervation and possible "paraneuronal" activity, with a readily accessible lumen for the isolation and collections of secretions. We propose this model as an excellent structure for further exploration of interactions between the nervous and immune systems.

Acetylcholinesterase↗

Ontogeny of medullary raphe nuclei in the rabbit brain stem: a Golgi study.

Nuclei raphe obscurus, pallidus, and magnus, found in the midline and paramedian regions of the medulla, were examined in rabbits between day 22 of gestation and adulthood. At day 22 of gestation (total gestation period of 32 days), the neurons were small with sparsely branched processes. Between day 26 of gestation and 6 days of age, the dendrites expanded, increased the number and length of their branches, and developed abundant spines. During this period, the cell bodies grew in size. From postnatal day 6 to adulthood, a mature pattern of dendritic branching was achieved, and the number of spines on the dendrites was reduced. Nuclei raphe obscurus, pallidus and magnus each possessed cells with unique morphological appearances early in ontogeny, but showed a similar pattern of enhanced dendritic branching with numerous spines through early neonatal development, followed by a reduction in the number and size of the spines. Despite the morphological heterogeneity of the medullary raphe nuclei, their general pattern of dendritic development is similar, suggesting that afferent connections to these nuclei may be formed during cellular maturation by a process similar to that described for the reticular formation and other central neurons.

Aging↗

Fourth ventricular tanycytes: a possible relationship with monoaminergic nuclei.

Tanycytes were found in discrete areas on the floor of the fourth ventricle of the developing and adult rabbit. The apical surfaces of the somas extended into the fourth ventricle and the shafts extended into the substance of the rhombencephalon. Shafts from midline tanycytes on the floor of the caudal fourth ventricle entered nuclei raphe obscurus and pallidus and shafts from midline tanycytes on the floor of the rostral fourth ventricle entered nuclei raphe dorsalis and centralis superior. These four raphe nuclei all contained serotonergic neurons and formed dendrite bundles in association with the tanycyte shafts. Shafts of tanycytes on the medial floor of the fourth ventricle entered nucleus intercalatus, and shafts of tanycytes on the lateral floor of the fourth ventricle entered locus coeruleus. Both of these nuclei contained noradrenergic cell bodies. The tanycyte shafts terminated only in these monoaminergic nuclei and did not extend to the pial surface of the ventral brain stem. We suggest that these tanycytes constitute a possible transport system for substances between the cerebrospinal fluid of the fourth ventricle and monoaminergic nuclei of the brain stem, in a role similar to that proposed for tanycytes of the median eminence.

Aging↗

Redefinition of the location of the dorsal (motor) nucleus of the vagus in the rat.

The rostrocaudal extent of the preganglionic parasympathetics of the vagus nerve (DNV, the dorsal nucleus of the vagus, also called the dorsal motor nucleus of the vagus) was traced using the retrograde horseradish peroxidase (HRP) transport method. Labeled cells were found within, and both rostral and caudal to, the classically-defined DNV. Cell bodies of origin of the preganglionic parasympathetics of the vagus formed a continuous longitudinal, spindle-shaped column extending from an area rostral to the rostralmost border of the inferior olivary nucleus caudally through the nucleus commissuralis (NC) of the lower medulla, and continuing in an attenuated fashion in the dorsal commissural gray (CG) of the cervical spinal cord. The rostral quarter of this cell column consisted of only a few cells lateral to the fourth ventricle in the mid-medulla. The middle one-half of the DNV cell column included the classically-defined dorsal nucleus of the vagus, located dorsolateral to the hypoglossal nucleus and lateral to the fourth ventricle rostrally, and located dorsolateral to the hypoglossal nucleus and the central canal caudally. In the caudal medulla, the caudal quarter of the cell column consisted of cell bodies in the NC. Scattered labeled cell bodies were found in the CG of the spinal cord, extending caudally to the C3--C6 level.

Animals↗

Sympathetic innervation of murine thymus and spleen: evidence for a functional link between the nervous and immune systems.

Sympathetic innervation was demonstrated in both perivascular and parenchymal regions of murine thymus and spleen. Catecholamine varicosities were associated with mast cells in these areas. The antibody response to sheep red blood cells of 7 week old mice that had been sympathectomized with six-hydroxydopamine (6OHDA) at birth was significantly elevated compared with saline treated controls. Alpha-methyl tyrosine (alpha-MT) and 6OHDA treatment of mice, producing a more complete sympathectomy, showed a significantly enhanced anti-SRBC response with respect to mice treated with alpha-MT or 6OHDA alone. Catecholamine levels in thymus, spleen, and adrenals of both experimental and control mice were measured using liquid chromatography with electrochemical detection (LCEC). The present study suggests that the sympathetic nervous system has a functional role in modulating the humoral immune response in vivo.

Adrenergic Fibers↗

Sympathetic noradrenergic innervation of guinea-pig liver: histofluorescence and pharmacological studies.

Norepinephrine concentration was higher in guinea-pig liver than in rat or mouse liver and evidence was obtained that the norepinephrine was present within nerves. In guinea pigs, norepinephrine in liver was depleted by reserpine, 6-hydroxydopamine and metaraminol. The depletion by 6-hydroxydopamine and metaraminol was antagonized by prior treatment with desipramine, an inhibitor of uptake into norepinephrine neurons. Guinea-pig liver concentrated metaraminol to a greater extent than did rat liver; the concentration of metaraminol was lowered by desipramine pretreatment and, within three tissues of the guinea pig (heart greater than liver greater than muscle), paralleled the concentration of endogenous norepinephrine. These findings constitute pharmacological evidence for noradrenergic innervation of guinea-pig liver to a greater extent than in other species. Histofluorescence studies confirmed the existence of norepinephrine-containing nerve terminals in guinea-pig liver. Norepinephrine-containing varicosities were seen adjacent to the hepatic artery, portal vein and bile duct in the portal spaces and adjacent to sinusoid capillaries and hepatocytes in the liver parenchyma. These findings strengthen the evidence for sympathetic innervation of liver and suggest the guinea pig as a useful species in exploring physiological roles of noradrenergic innervation of liver.

Animals↗

A quantitative comparison of motor and sensory conduction velocities in short- and long-term streptozotocin- and alloxan-diabetic rats.

Motor and sensory conduction velocities were measured in the sural and tibial nerves of streptozotocin (stz)-diabetic, alloxan-diabetic, and age-matched control rats. Conduction velocity (CV) determinations were made 2 weeks and 2, 4, 8, and 12 months following the induction of diabetes. CVs of control, stz-diabetic, and alloxan-diabetic rats were compared at each time period by one way analysis of variance and when appropriate by the Newman-Keuls multiple range test for multiple comparisons. Reductions of 10-20% in CV of diabetic rats were observed in several classes of sensory and motor nerve fibers. Larger reductions (31 and 38%) were seen in 2 classes of sensory nerve fibers in 12 month stz-diabetic rats. Sensory CV was slowed earlier and more frequently than motor CV. Differential involvement was also seen among the several classes of sensory nerve fibers examined. Slower conducting sensory fibers appeared to be affected earlier and more frequently than faster conducting sensory fibers. Comparing alloxan-diabetic with stz-diabetic rats revealed significant differences in CV 8 months after the induction of diabetes. Motor and sensory CVs of the tibial nerve were slower in stz-diabetic rats than in alloxan-diabetic rats. In general, the neuropathy appeared to be less severe and to develop later in the alloxan-diabetic rats. These data suggest that the neuropathy of stz- and alloxan-diabetes is primarily sensory in nature, and that the neuropathy in these 2 widely used models of diabetes may not be entirely equivalent.

Alloxan↗

Dendrite bundles in nuclei raphe dorsalis and centralis superior of the rabbit: a possible substrate for local control of serotonergic neurons.

A Golgi-Cox, cresyl violet, and histofluorescence study has revealed the presence of dendrite bundles in nuclei raphe dorsalis (NRD) and centralis superior (NCS) in the rabbit brain stem. In NRD, bundles were found in the midline, traversing the medial longitudinal fasciculus (MLF) and in a circumferential location around the MLF. In NCS, bundles were found oriented vertically in the midline. Serotonergic dendrites predominated in these bundles, but non-serotonergic dendrites from cells of the dorsal tegmental nucleus, adjacent reticular formation, and NCS also were present. Long descending shafts from tanycytes on the floor of the rostral fourth ventricle were also found in the dendrite bundles of both NRD and NCS. We suggest that the dendrite bundles constitute a local neuronal system for regulating the activity of these raphe neurons.

Animals↗

Effect of diabetes upon penile sympathetic nerves in impotent patients.

Samples of erectile tissue taken from the corpora cavernosa of 16 male diabetic patients suffering from impotence were studied. The content of norepinephrine, which reflects sympathetic nerve activity of that tissue, was significantly lower in insulin-dependent patients 104.2 +/- 24.8 (SE) pg/mg wet weight (P less than .001) and diet-controlled patients 483.7 +/- 103.7 (P less than .01) than the normal men (881.7 +/- 62.0). Myelinated and unmyelinated nerve fibers were observed intact and unaltered in each group of patients. The results indicated that normally a dense adrenergic innervation of human erectile tissue is present, but that a reduction occurs in norepinephrine content in diabetic patients with impotence. It appears, however, that the anatomic integrity of the sympathetic nerves is intact. The presence of intact nerve fibers along with a diminished content of neurotransmitter suggests the possibility of pharmacologic treatment of impotence.

Diabetes Complications↗

Alteration of the penile corpora in patients with erectile impotence.

We measured the content of the two principal neurotransmitters of the autonomic nervous system from the erectile tissue of four men with normal erection and 38 men impotent as a result of injury or disease. In the former the norepinephrine content was 812 +/- 82.6 (SE) pg per mg of wet weight; In the latter, statistically significant reductions of norepinephrine were found with the greatest decrease occurring with insulin-dependent diabetes mellitus. Neither choline acetyltransferase activity nor morphologic alterations of the nerve fibers of erectile tissue were observed in either group. Our findings suggest that the sympathetic nervous system is an integral component of human erection and that a functional alteration of the corporal nerve fibers occurs with several diseases associated with impotence.

Choline O-Acetyltransferase↗