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C A Bates

Publications and source records attributed to C A Bates.

17 recordsLinked to original sources

Expression of polysialylated NCAM but not L1 or N-cadherin by regenerating adult mouse optic fibers in vitro.

This study asks if there might be irreversible maturational changes in adult neurons that limit their capacity to regenerate. Retina from adult and embryonic mouse were placed in culture on laminin substrates so that regenerating adult optic fibers could be compared to growing embryonic fibers. Several cell adhesion molecules (CAMs) known to mediate the growth of embryonic neurites on astrocytes were assayed by immunocytochemistry: L1, N-cadherin, and NCAM. Thy 1.2, a potential CAM with inhibitory activity, was also examined. As in vivo, embryonic fibers were found to express both L1 and N-cadherin. In contrast, regenerating adult fibers had no detectable amounts of either of these CAMs. N-Cadherin is normally down regulated during development so its absence in adult fibers suggests it can not be reexpressed during regeneration. L1 is normally found in the proximal regions of adult optic fibers so its absence indicates it is not expressed or transported in regenerating fibers. Adult regenerating fibers expressed high levels of Thy 1.2, which was undetectable in embryonic optic fibers. Thy 1.2 is normally found in mature fibers, indicating this phenotypic feature is preserved during regeneration. Both adult and embryonic fibers showed strong reactivity for NCAM, which in vivo is normally found in embryonic and at lower levels in adult fibers. Surprisingly, both embryonic and regenerating adult fibers expressed high levels of polysialic acid, which is normally absent in adult fibers. NCAM may be one of few CAMs available to adult optic fibers for regeneration on astrocytes.

Animals↗

The neurite-promoting effect of laminin is mediated by different mechanisms in embryonic and adult regenerating mouse optic axons in vitro.

Retinal explants from embryonic or adult mice were placed on laminin or merosin substrates and the outgrowth of optic fibers was assayed under serum-free conditions. Both substrates strongly promoted outgrowth. A blocking antibody to the beta1/beta3 integrin subunits completely blocked laminin-dependent growth of embryonic optic fibers but had no detectable effect on adult fibers. Similarly, a blocking antibody against the main neurite-promoting region within the globular domain of the E8 fragment of laminin inhibited growth of embryonic fibers but had no effect on adult optic fibers. The beta1 integrin subunit was identified immunohistochemically on both embryonic and adult fibers. These findings indicate that adult fibers have lost the beta1 function which dominates laminin-dependent growth in embryonic fibers but express a receptor for laminin-dependent growth that is not detectable in embryonic fibers. These findings suggest that there are intrinsic differences between embryonic and adult optic fibers that may have implications for regenerative failure in the central nervous system of adult mammals .

Age Factors↗

Antisperm antibodies and male subfertility.

The outcome of treatment for couples with male immunological infertility must be considered in conjunction with the risks, costs and time to success involved. Reversible factors should be treated. Steroid treatment is a good option but its failure in two-thirds of patients should add impetus to attempts to predict responders before or soon after starting treatment. The treatment options are not mutually exclusive [48]. The success of IUI may be enhanced further by new sperm preparation techniques. If severe immunological infertility exists or other infertility factors are present, IVF or ICSI may be considered from the outset.

Animals↗

Heterotrimeric G protein activation rapidly inhibits outgrowth of optic axons from adult and embryonic mouse, and goldfish retinal explants.

Axons in the adult mammalian CNS normally do not regenerate following axotomy even though they retain the capacity for growth under certain experimental conditions. Although this implies that the regeneration of adult axons is under regulative control, very little is known about the signaling pathways "responsible" for this regulation. This study examines the possibility that a G protein signaling system exists in adult mouse optic fibers and that it functions to regulate axonal outgrowth. To induce the growth of optic fibers, retinas from adult mouse were placed in organotypic culture under serum free conditions and allowed to regenerate onto a laminin substrate. Heterotrimeric G proteins were stimulated by adding mastoparan (MST) to the medium while monitoring growing fibers with time lapse microscopy. Mastoparan treatment produced rapid growth cone collapse and axonal retraction which persisted while MST was present. Prior addition of pertussis toxin (PTX), which irreversibly inactivates the G proteins, G(o) and G (i),completely blocked the effect of MST, confirming that MST was acting through the PTX sensitive G proteins. Selective activation of G proteins in the growth cone by local application of MST with a micropipet was equally effective. For comparison, equivalent experiments were performed on embryonic day 15 retinal explants and on retinal explants from adult goldfish, which normally regenerate in vivo. MST similarly inhibited these axons and this effect was blocked by PTX. However, embryonic fibers were less reliably affected compared to goldfish or adult mouse, suggesting a developmentally regulated sensitivity. The presence of G-proteins in the mouse axons was further tested immunohistochemically using antibodies against G(o)/G(i). Positive staining was detected in the growth cones and shaft of adult and embryonic mouse optic fibers. These findings demonstrate that G protein activation inhibits axonal outgrowth and suggest that there may be a G protein signaling pathway that normally regulates this outgrowth. However, since this pathway appears to exist in both axons that can regenerate and those that normally do not, the presence of PTX-sensitive G proteins alone cannot account for regenerative failure. Regenerative failure may instead be explained as the selective or increased activation of this pathway in the adult mammalian CNS.

Animals↗

Differential effect of serum on laminin-dependent outgrowth of embryonic and adult mouse optic axons in vitro.

Laminin is an extracellular matrix molecule which promotes neurite outgrowth from a variety of neurons in culture. However, the reported effectiveness of laminin on neurite outgrowth from retinal ganglion cells in rat and that from chick have been contradictory. In chick, embryonic retinal ganglion cells show strong laminin-dependent neurite outgrowth which is lost during development. In contrast, in rat, laminin promotes neurite outgrowth from adult, but not embryonic retinal ganglion cells. We have reexamined the response of adult and embryonic mouse retinal ganglion cells to laminin in culture. We found, first, that both adult and embryonic retinal neurites respond to laminin with neurite outgrowth in serum-free medium. Second, we found that the addition of serum to the medium greatly inhibits the outgrowth of neurites from embryonic, but not adult, retinal explants. This inhibition appears specific for neurite outgrowth involving laminin receptors, since embryonic explants showed extensive neurite outgrowth in the presence of serum when astrocytes were used as a substrate. These developmental differences in the effect of serum on laminin-dependent neurite outgrowth may indicate maturational changes in surface molecules on optic fibers related to regenerative failure in the adult CNS.

Aging↗

Distribution of microtubule-associated proteins (MAPs) in adult and embryonic mouse retinal explants: presence of the embryonic map, MAP5/1B, in regenerating adult retinal axons.

Microtubule-associated proteins (MAPs) are developmentally regulated proteins involved in microtubule polymerization and stabilization. We have asked whether MAPs in regenerating adult mouse retinal ganglion cell axons recapitulate the pattern of MAPs seen during development. Adult and Embryonic Day 15 (E15) mouse retinal segments were explanted onto laminin-coated coverslips and allowed to extend neurites in serum-free medium. Using a variety of monoclonal antibodies (Mabs), we stained adult and E15 explant cultures for early (MAP5) and late (MAP1, MAP2, MAP2a+b, tau) MAPs. Optic neurites growing from E15 explants were strongly immunoreactive for MAP5. Labeling was absent for MAP1 and MAP2a+b. Mabs to MAP2 and tau lightly stained axons and cell bodies, probably due to MAP2c and juvenile tau which are found in developing neurons. In adult explant cultures, both perikarya and axons were immunoreactive for MAP1. MAP2 and MAP2a+b labeled perikarya and fibers within the explant, and tau stained axons on the substrate. MAP5 immunoreactivity was intense in the adult explant cultures, labeling axons extending over the substrate and perikarya and dendrites in the explant in a pattern similar to that seen in E15 explants. In summary, adult retinal explants maintain their adult complement of MAPs, in showing high levels of MAP1, tau immunoreactivity restricted to neurites on the substrate, and MAP2 segregated into neurites and perikarya within the explant. The exception is MAP5 for which the pattern of immunoreactivity is similar in adult and E15 retinal explants.

Animals↗

The heavy neurofilament protein is expressed in regenerating adult but not embryonic mammalian optic fibers in vitro.

Axonal neurofilaments are composed of light (NF-L), medium (NF-M), and heavy (NF-H) subunits which are sequentially expressed during axonal development. In retina, NF-L and NF-M appear prenatally, followed postnatally by NF-H which occurs at about the time axons are reaching their target tissue. Phosphorylation of the NF-H protein occurs after it has first appeared in the axon. Phosphorylated NF-H is also downregulated in regenerating peripheral nerves. These observations lead to the hypothesis that NF-H stabilizes axons, thereby inhibiting their ability to grow. We have previously shown that adult mouse retinal ganglion cells (RGCs) can extend neurites in vitro and that these neurites reexpress the developmental protein GAP-43. Here we ask whether the expression of neurofilament proteins in the growing adult RGC axons involves the recapitulation of development. Adult mice which had a priming lesion of the optic nerve and Embryonic Day 15 mouse retinas were explanted onto laminin substrates and grown in culture. After 2-4 days the growing neurites were stained with a battery of monoclonal antibodies against differentially phosphorylated versions of the neurofilament subunits. Both adult and embryonic neurites were highly immunoreactive for NF-L and NF-M. Only the adult neurites stained with antibodies against phosphorylated NF-H. There was no immunoreactivity in the embryonic explants. This indicates that regrowing adult RGC axons maintain their adult cytoskeletal properties and can nevertheless regenerate.

Aging↗

Corticospinal tract plasticity and astroglial reactivity after cervical spinal injury in the postnatal rat.

We have investigated corticospinal (CS) axon growth around cervical spinal injury in the neonatal rat and related this growth to the astroglial reaction occurring at the lesion site. Rats received a high cervical overhemisection (left dorsal funiculotomy, right spinal hemisection) and a right cortical ablation on Postnatal Days (PNDs) 0, 3, 6, 12, and 21 to 24 (weanlings). In chronic operates the remaining CS projection from the left sensorimotor cortex was then assayed using wheat germ agglutinin-horseradish peroxidase as an anterograde tracer. In other operates the formation of the astroglial scar at the spinal lesion site was studied using a monoclonal antibody to glial fibrillary acidic protein. In PNDs 0-6 operates labeled axons extend through the intact left hemicord to bypass the lesion. The labeled axons travel to the edge of the lesion, cross the midline, and pass lateral to the lesion within the dorsal and intermediate gray and dorsal lateral white matter. Axons project bilaterally to normal areas of CS termination in PND 0 operates for a distance of 2.5 to 4 spinal segments caudal to the lesion which decreases to 1.5 to 2 segments in PND 6 operates. In PND 12 and weanling operates labeled fibers do not grow around the lesion but instead are retracted rostrally. There is an astrocytic reaction to injury at all ages by 3 days postoperatively (p.o.) that becomes greater with age and p.o. survival time. A more complicated cystic scar forms in 6-day and older operates. These data show that there is an age-related change in the ability of CS axons to grow around spinal injury which ends near the time CS elongation and gliogenesis is complete in the spinal cord.

Aging↗

Extension and regeneration of corticospinal axons after early spinal injury and the maintenance of corticospinal topography.

It has been established that neonatal corticospinal (CS) axons are able to grow around lesions of the spinal cord early in neonacy (Bernstein and Stelzner, J. Comp. Neurol. 221:382-400; Firkins, Bates, and Stelzner, Exp. Neurol., 120:1-15). To determine if these corticospinal axons include regenerating as well as late developing axons a double-labeling paradigm is used in which CS neurons are retrogradely labeled from the cervical spinal cord by injections of fast blue (FB) on Postnatal Day (PND) 2, 4, or 10. Two days later, the FB is aspirated along with the left dorsal funiculus and the right hemicord (CHR). As adults, the animals receive an injection of diamidino yellow (DY) or rhodamine into the spinal cord caudal to the lesion site. Thus, FB neurons are those that originally projected to the spinal cord before the lesion and which survived axotomy, DY neurons are those whose axons reached the spinal cord after the lesion, and double-labeled neurons (FB/DY) are cells which projected to the spinal cord prior to the lesion and regenerated a spinal axon postlesion. Animals FB injected on PND 2 have a widespread distribution of FB-labeled neurons in cortex, including areas outside of sensorimotor cortex. These animals also had both DY- and FB/DY-labeled cells within sensorimotor cortex, indicating that the population of axons growing caudal to neonatal spinal lesions consists of both late growing and regenerating axons. In animals FB injected on PND 10, the FB neurons were all located in sensorimotor cortex. Very few DY and no FB/DY neurons were present. We have also looked at the topography of the CS neurons which project caudal to early spinal lesions. Rat pups received a CHR on PND 0, 3, 6, or 12. As adults, horseradish peroxidase was injected into the cervical or lumbar enlargement of the spinal cord and the distribution of labeled cells in the cerebral cortex was plotted and compared to normal and lesioned adult controls. In all experimental animals, the distribution of retrogradely labeled cells was restricted to the area containing CS projection neurons in the normal animal. This is despite the fact that the number of CS projection neurons is greatly reduced from normal and the normal pathway for CS axonal outgrowth has been completely disrupted by the neonatal lesion.

Amidines↗

A new endoscopic method for treatment of malignant oesophagobronchial fistulas.

A short malignant oesophagobronchial fistula which could not be sealed using adhesive agents was successfully treated using a new endoscopic technique. The procedure provided good palliation and the results withstood the test of time in the patient. The method, which is described in detail, provides a useful modification to existing methods.

Aged↗

Tracheal lipoma.

A 50 year old man was found to have a tracheal lipoma two years after first noticing symptoms.

Asthma↗

Transganglionic transport of HRP from the circumvallate papilla of the rat.

To learn whether horseradish peroxidase (HRP) injections in gustatory papillae on the tongue can be used to study central topographical projections of taste buds and papillae, injections were made into the circumvallate papilla in rats. Labeled central projections after papilla injections were compared to projections after applying HRP to the cut glossopharyngeal nerve. Papilla injections result in HRP transport by afferent and efferent fibers of the glossopharyngeal nerve, and the pattern of central projections is similar to that after labeling the cut nerve. Projections include a separation in the brainstem of afferent, dorsally located fibers and efferent, ventrally located fibers. Afferent fibers project to the solitary nucleus and the trigeminal system. Efferent projections label muscle motorneurons in the nucleus ambiguus and the cells of origin of parasympathetic preganglionic fibers, which from the inferior salivatory nucleus. The parasympathetic neurons labeled after papilla projections are preganglionic fibers to Remak's ganglia in the tongue; post-ganglionic fibers of these ganglia are the secretomotor supply to the von Ebner's glands. In summary, injections of HRP into gustatory papillae reliably label central projections of the papilla and can be used for studies to discern topography in central projections of the taste system. Injections into the circumvallate papilla also have demonstrated that the parasympathetic neurons innervating von Ebner's glands are located in the inferior salivatory nucleus.

Animals↗

The organization of the neonatal rat's brainstem trigeminal complex and its role in the formation of central trigeminal patterns.

The present study delimits the relationship of primary trigeminal afferents to their targets, the brainstem trigeminal nuclei of the neonatal rat. Previously, the brainstem trigeminal complex of the rat has been subdivided on the basis of either cytoarchitectonics or patterns of succinic dehydrogenase activity into the principal sensory nucleus and the three subnuclei of the spinal trigeminal nucleus, oralis, interpolaris, and caudalis. In this paper, we demonstrate that each of these subdivisions can also be identified by its pattern of primary trigeminal afferents. In addition, we demonstrate that the terminations of these afferents are distributed in a punctate fashion which correlates with vibrissae-related patterns of histochemical staining. Further, vibrissae removal in the neonatal rat at any age studied results in a corresponding deafferentation of both the principal sensory nucleus and all subnuclei of the spinal trigeminal nucleus. This same procedure has a graded, age-dependent effect on the vibrissae-related pattern of cytochrome oxidase staining in somatosensory cortex. On this basis, we conclude that vibrissae-related pattern formation in the central trigeminal system can be best understood in terms of a single "sensitive" period for the entire system. We hypothesize that this is the period during which an interaction normally occurs between primary trigeminal afferents and target neurons of the principal sensory nucleus.

Afferent Pathways↗

The emergence of a discretely distributed pattern of corticospinal projection neurons.

The distribution of cortical neurons which project to the spinal cord was investigated in the developing and adult rat using the retrograde transport of horseradish peroxidase (HRP). Following injections of HRP into the cervical spinal cord of a postnatal day 4 rat, retrogradely labeled neurons are located in layer Vb throughout the neocortex. Gradually, over the first two postnatal weeks, labeled cells can no longer be found laterally or caudally in the neocortex. By the end of the second postnatal week, cortical neurons which project to the spinal cord are located in essentially their adult positions. These consist of: (1) a dorsomedial band of cells in layer V of frontal cortex, (2) a dorsomedial band in layer Vb of posterior frontal/anterior parietal cortex, and (3) a small group of cells located laterally in an area corresponding to SII. This change in the regional distribution of cortical neurons projecting to the spinal cord is interpreted as an economically adaptive way for the cortex to interconnect highly organized sensory and motor systems.

Animals↗

Central correlates of peripheral pattern alterations in the trigeminal system of the rat. III. Neurons of the principal sensory nucleus.

We provide evidence that the discrete clustered distribution of the trigeminothalamic projection neurons in the principal sensory nucleus of the trigeminal is dependent on the integrity of the trigeminal nerve during development. Nerve section at birth abolishes all evidence of cellular clustering in the principal sensory nucleus, while more discrete damage to specific rows of follicles results in changes in the cellular clustering pattern only in the portion of the nucleus related to the afflicted rows of vibrissae.

Afferent Pathways↗

Differential organization of thalamic projection cells in the brain stem trigeminal complex of the rat.

Following large injections of horseradish peroxidase into the thalamus of the adult rat, labeled neurons can be detected in the contralateral principal sensory nucleus and the subnucleus interpolaris of the spinal trigeminal nucleus. Thalamic projection neurons in the principal sensory nucleus are arranged in discrete aggregates which replicate the organization of the vibrissae and other parts of the face. This cellular organization corresponds very well with the pattern of vibrissae related afferent termination in this region of the nucleus as seen in SDH preparations. There is no such cellular organization in the subnucleus interpolaris.

Afferent Pathways↗