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Biomedical subjects

P A Raymond

Publications and source records attributed to P A Raymond.

At least 55 records · Page 3Linked to original sources
PubMed1992

Retinal regeneration.

The goal of research on neural regeneration is to restore brain function following injury. To many, this suggests regrowing damaged axons and re-establishing the interrupted pathways. A second, but little studied aspect of brain regeneration, is the replacement of lost neurons. For example, in some animals the neural retina is reconstituted by regenerative neurogenesis following its partial or total destruction. Two separate processes underlying retinal regeneration have been described: transdifferentiation of retinal pigmented epithelial cells into retinal neural progenitors (in adult urodeles, tadpoles, and embryonic chickens), and alteration in the fate of photoreceptor progenitors intrinsic to the retina (in adult fish).

Animals↗
PubMed1992

HLA genotyping of colorectal carcinoma in the Chinese population.

The HLA-DR genotypes of 61 primary colorectal carcinomas obtained from patients of Chinese origin were determined by using DNA-RFLP. No increase or decrease of a particular HLA genotype could be ascertained with the disease, although we detected an antigen frequency of 29.5% for the serologically ill-defined DR"X3" specificity. We identified and sequenced HLA-DRB1 and DRB3 genes from the DR"X3" haplotype. The DR"X3" DRB1 gene was found to be identical to DRB1*1201 (DR5[w12]). A unique observation is its unusual linkage with DRB3*0101 (DRw52a) or DRB3*0301 (DRw52c) instead of the usual linkage with DRB3*0201/2 (DRw52b). These associations are rare in whites and blacks.

Alleles↗
PubMed1992

Regeneration of dopaminergic neurons in goldfish retina.

The conditions necessary to trigger regeneration of dopaminergic neurons were investigated in the goldfish retina. Intraocular injection of 6-hydroxydopamine (6-OHDA) was used to destroy dopaminergic neurons, and neuronal regeneration was monitored by injections of the thymidine analog bromodeoxyuridine (BUdR). Regenerated dopaminergic neurons, (identified by double-labeling with anti-tyrosine hydroxylase and anti-BUdR antibodies) were found within 3 weeks after 2 injections of 0.6 mg/ml 6-OHDA (estimated intraocular concentration), but not after injection of lower doses. All retinas with regenerated dopaminergic neurons also contained other types of regenerated neurons, including cones and ganglion cells, consistent with nuclear counts which revealed non-selective cell loss (34-36%) in both the outer and inner nuclear layers after exposure to the high dose, but not lower doses of 6-OHDA. Regenerated neurons were produced by clusters of dividing neuroepithelial cells probably derived from rod precursors in the outer nuclear layer. These results demonstrate that dopaminergic neurons will not regenerate after they are selectively ablated but only as part of a developmental process that involves generation of multiple cell types.

Animals↗
PubMed1991

Retinal regeneration in teleost fish.

The neural retina in teleost fish can regenerate after surgical or neurotoxic destruction. Whereas in amphibians the retina regenerates by transdifferentiation of pigmented retinal epithelial cells, in goldfish (Carassius auratus) the source of regenerated retinal cells is a population of scattered proliferating cells located in the outer nuclear layer within the differentiated retina. These proliferating cells are modified neuroepithelial cells termed 'rod precursors' because in the intact retina they produce only rod photoreceptor cells and do so continuously, inserting new rods into the growing adult retina. Although rod precursors normally exhibit a restricted developmental fate they appear not to be committed to the rod lineage. When retinal neurons are destroyed, rod precursors cease producing rods and give rise to clusters of primitive neuroepithelial cells which divide vigorously and reconstitute the retina in an orderly temporal pattern that mimics the process of normal development. Only after production of cones and other retinal neurons has ceased do rod precursors again appear and resume the generation of rods. We conclude that rod precursors respond to local cues in their environment that regulate the differentiation and choice of cell fate by their progeny.

Animals↗
PubMed1991

Müller glial cells of the goldfish retina are phagocytic in vitro but not in vivo.

The role of Müller glial cells in the process of degeneration and regeneration of the goldfish retina is poorly understood. One potential role is phagocytosis of neuronal debris in degenerating retinas. We investigated the phagocytic capacity of Müller glial cells of the goldfish retina both in vitro and in vivo. Müller glial cells from primary or first passage cultures were incubated with latex beads to assess their phagocytic ability, and acridine orange staining was used to identify phagolysosomes in living Müller glial cells. These experiments showed that Müller glial cells are phagocytic in culture. Cell identity was verified with an antibody raised against glial fibrillary acidic protein (GFAP). For the in vivo experiments fluorescent latex beads alone or in combination with the metabolic poison ouabain were injected into the posterior chamber. At various intervals (4 days to 8 weeks) after injection the retinas were prepared for immunocytochemistry. Polyclonal anti-GFAP and NN-1, a monoclonal antibody which recognizes macrophages and microglia within the goldfish retina, were used to identify the phagocytic cells. When the beads were injected into the eye, they were phagocytosed by macrophages/microglia cells but not by Müller cells.

Animals↗
PubMed1990

Horizontal cell axon terminals in growing goldfish.

In the retina of teleost fish, cone horizontal cell axons penetrate the inner nuclear layer, where they enlarge into fusiform terminal swellings. The present study shows that horizontal cell axon terminals enlarge disproportionately during postembryonic growth of the retina in juvenile and adult goldfish: the relative volume of axon terminals increases almost 20-fold, while the volume of the entire retina increases only about fourfold during a 2-3-yr period. The enlarging axon terminals fill in the gaps created as the numerical density of nuclei in the inner nuclear layer falls. Horizontal cell axon terminals are thought to participate in cone-dominated visual pathways, although their precise role is unclear. The results of this study suggest that a comparison of horizontal cell function in small and large fish might help to resolve this issue.

Animals↗
PubMed1990

Improved method for obtaining 3-microns cryosections for immunocytochemistry.

The following describes a modified technique for obtaining 3-microns sections for light microscopic level immunocytochemistry. By combining 20% sucrose with Tissue-Tek OCT embedding compound in a ratio of 2:1, we produced a block that was suitable for cutting 3-microns sections on a conventional cryostat. The 3-microns sections were dramatically improved compared with 10-microns sections cut from tissue embedded in OCT alone, when viewed with both differential interference contrast microscopy (Nomarski optics) and indirect immunofluorescence. The method is simple, uses materials already available, and does not require training in a new technique.

Cryopreservation↗
PubMed1990

Time course of opsin expression in developing rod photoreceptors.

We have investigated the time course of rod photoreceptor determination in the goldfish retina. Rod precursor cells located in the outer nuclear layer of the mature retina continuously generate rod photoreceptors. In this study, we asked when rod precursor cells begin to express opsin, which would signal their commitment to the rod pathway of differentiation. There are three possibilities: a rod precursor could express opsin while still mitotic, at or shortly after the terminal mitosis but before differentiation, or during differentiation. We used immunocytochemistry with antibodies against bromodeoxyuridine, BrdU (a thymidine analogue) and against opsin to determine when during the mitotic history of a cell the expression of opsin first occurred, taking a double labelled cell to be evidence of commitment to the rod cell fate. We found that the first double labelled cells appeared at 4 days after BrdU injection. The number of double labelled cells increased to peak at 10 days, and then fell. These results support the hypothesis that dividing rod precursor cells are probably multipotent stem cells not committed to the rod cell fate.

Animals↗
PubMed1989

Specific localization of thallium 201 in human high-grade astrocytoma by microautoradiography.

The ability to accurately distinguish remaining or recurrent high-grade astrocytoma from necrosis or edema following treatment is essential to optimal patient management. Thallium 201 planar gamma-camera imaging has been shown to be helpful in detecting recurrent high-grade astrocytoma; however, due to tissue heterogeneity adjacent to and within tumor, the cellular specificity and quantification of 201Tl uptake are largely unknown. In order to determine which tissues are responsible for the radioisotope uptake, microautoradiographic techniques were used to examine multiple tissue sections from five patients with high-grade astrocytoma. Each patient received 5 mCi of 201Tl i.v. 1 h prior to tumor removal. Additionally, all patients received computerized tomographic and 201Tl planar gamma-camera scans prior to surgery. Following surgery, the excised tissue specimens were tentatively classified by gross pathological examination and then immediately processed for dry mount autoradiography; grain density was determined over regions containing tumor, adjacent and uninvolved brain tissue, necrotic tissue, and background. Highly significant differences were found in grain densities (201Tl uptake) between tumor and uninvolved brain tissue, as well as between uninvolved brain tissue and necrotic tissue; there was no significant difference between background grain density and that in necrotic tissue. Mean grain densities (grains/cm2 +/- 1 SD) across patients were: tumor, 102 +/- 23; adjacent, uninvolved brain tissue, 29 +/- 11; necrotic tissue, 6.2 +/- 1.1; and background, 7.0 +/- 4.1. We conclude that the ability of 201Tl to selectively image high-grade astrocytoma is due to its preferential uptake into tumor cells.

Adult↗
PubMed1989

Developing retinotectal projection in larval goldfish.

The retinotectal projection in larval goldfish was studied with the aid of anterograde filling of optic fibers with HRP applied to the retina. The results show that optic fibers have already reached the tectum and begun to form terminal arbors in newly hatched fish. The projection is topographic in that fibers from local regions of the retina project to discrete patches of tectum, with the smallest patch covering 3.5% of the total surface area of tectal neuropil. Many fibers in young larvae have numerous short side branches along their length and only some of them show evidence of terminal sprouting. The arbors are approximately elliptical in shape and average about 1,500 microns 2. Growth cones are seen frequently. In older larvae, terminal arbors are larger and more highly branched, and they have begun to resemble those in adult fish. Fibers terminate in two strata; those in the upper layer are smaller (1,800 microns 2 on average) than those in the deeper stratum (4,000 microns 2 on average). The fraction of tectal surface area covered by individual arbors (the "tectal coverage") ranges from 1.5% to 3% of the total surface area of the tectal neuropil. In contrast, the tectal coverage of individual arbors in young adult goldfish is much smaller, ranging from 0.02% to 0.42% of tectal surface area (Stuermer, '84, and unpublished). This apparent increase in precision of the map in older animals is not due to retraction of arbors, which are slightly larger in adults, but is accounted for by overall tectal growth: the tectal neuropil in goldfish increases in area by about 250-fold during this period (Raymond, '86).

Animals↗
PubMed1989

Development of lymphocytotoxic and platelet reactive antibodies: a prospective study in patients with acute leukaemia.

Lymphocytotoxic (LCT) and platelet reactive (PR) antibody (Ab) responses were serially determined in 49 patients with acute leukaemia. LCTAb were found in 20 patients and occurred in 13 patients with acute myeloid leukaemia and 7 patients with acute lymphoblastic leukaemia. Four differing patterns of LCTAb responses could be defined. Thirteen of 22 subjects showed marked reduction or loss of LCTAb. Indirect platelet immunofluorescence, measured by flow cytometry, provided the most convenient means of detecting PRAb which were found in 11 subjects and generally showed moderate or weak reactivity.

Adolescent↗
PubMed1988

Axons added to the regenerated visual pathway of goldfish establish a normal fiber topography along the age-axis.

Throughout a goldfish's life, new generations of ganglion cells are added on the retinal margin and their axons extend centrally to occupy predictable positions in the retinotectal pathway, adjacent to their predecessors and subjacent to the pia. The stacking of successive generations of axons defines the age-axis of the pathway. This study examined whether an ordered array of predecessor axons is a prerequisite for the patterned growth of new axons. One optic nerve was crushed intraorbitally and the fish was injected with 3H-thymidine to label the proliferating cells on the retinal margin. The ring of 3H-thymidine-labeled cells separated retina that was present at the time of nerve crush (inside the ring) from new retina added afterward (outside). After a period of 14-16 months postcrush, both tectal lobes received two punctate applications of horseradish peroxidase (HRP), one in the central and the other in peripheral tectum, to retrogradely label contralateral retinal ganglion cell bodies and their axons. The pattern of HRP labeling from the control tectum confirmed earlier work: axons on the central tectum had somata in the central retina, and axons on the peripheral tectum had somata in the peripheral retina. The labeled cells and axons were both in predictable patterns. The somata that were backfilled from applications to the center of the experimental tectum lay inside the radioactive ring and had therefore regenerated their axons. The patterns of their labeled axons in the optic pathway and of their somata in the retina were typical of the regenerated condition as described in earlier studies. The somata backfilled from the periphery of the experimental tectum were outside the radioactive ring and had been added after the optic nerve crush. The patterns of their labeled axons and somata were comparable to the normal pattern. These observations indicate that new axons do not depend on an ordered array of predecessors to reestablish normal order along the age-axis of the pathway.

Aging↗
PubMed1988

Neuronal cell proliferation and ocular enlargement in Black Moor goldfish.

The mechanisms that control cell proliferation in the developing nervous system are not well understood. In larval and adult goldfish addition of new retinal neurons continues as the eye grows, but the factors that modulate the rate of cell proliferation are unknown. The eyes of Black Moors grow excessively during postembryonic life, probably as a direct result of abnormally elevated intraocular pressure. Ocular growth must be partly autonomous in Black Moors because in some individuals the two eyes are very different in size. To determine whether cell proliferation and neuronal cell number in the retina were correlated with size of the eye, we counted dividing neuronal progenitor cells (rod precursors) and mature retinal neurons (ganglion cells) in the retinas of ocularly asymmetric fish. Rod precursors, which are scattered across the retina in the outer nuclear layer, were labeled with 3H-thymidine and counted on histological sections processed for autoradiography. Ganglion cells were counted in retinal whole mounts. We found that the total population of dividing rod precursors and the total number of ganglion cells were systematically greater in the large eye compared to the small eye of individual fish. We conclude that control of the rate of neuronal proliferation in the teleost retina is intrinsic to the eye and is probably regulated by the same factors that control ocular growth.

Animals↗
PubMed1988

Regeneration of goldfish retina: rod precursors are a likely source of regenerated cells.

This study describes regeneration of the neural retina in juvenile goldfish. The retina was destroyed with an intraocular injection of ouabain, a technique introduced by Wolburg and colleagues (Maier and Wolburg, 1979; Kurz-Isler and Wolburg, 1982). We confirmed their observation that the level of damage produced by the toxin was graded, in that neurons in the inner retinal layers were preferentially destroyed, and only in the more severely affected retinas were cells in the outer nuclear layer (i.e., photoreceptor cells) damaged. Evidence of retinal regeneration could be seen beginning about 2 weeks after the injection of ouabain. In contrast to previous studies (Maier and Wolburg, 1979), we found that regeneration took place only in those retinas in which photoreceptors had been destroyed. In cases in which the outer nuclear layer was spared, no regeneration of inner layers occurred, even after 6 months. Thymidine autoradiography was used to document the regeneration of new retinal neurons and to show that rod precursors, like other dividing cells, were not destroyed by the ouabain, but in contrast showed an increased mitotic activity. Regeneration did not proceed uniformly, but was initiated at neurogenic foci scattered across the retina. These foci consisted of clusters of dividing neuroepithelial-like cells. The evidence is consistent with the proposal that these cells were derived from rod precursors. These results imply that rod precursors are capable of a wider range of developmental fates than they normally express.

Animals↗
PubMed1988

Visual detection by the rod system in goldfish of different sizes.

New rods are continually generated and inserted across the entire differentiated retina in juvenile and adult goldfish; no other retinal cells share this characteristic. How does the preferential addition of rods affect visual function? To examine the relation between continued rod addition and visual sensitivity, we measured absolute threshold in fish of different sizes. Twenty-nine fish were trained in a classical conditioning paradigm, and psychometric functions were obtained for each of them for detection of a 532 nm light 5 sec in duration, 140 deg in angular subtense, presented while the fish was fully dark adapted. We found that absolute threshold (expressed in terms of retinal photon density) was lower in larger fish, but by a very small amount; on average, large fish (15.4 +/- 0.5 cm standard body length) were 1.45 times more sensitive than small fish (4.3 +/- 0.3 cm). Morphometric analysis showed that the planimetric density of rods in goldfish retina increases at a similar rate between small and large fish, while the density of retinal ganglion cells declines between small and large fish (by a factor of 3.8). The ratio of rods to ganglion cells (a possible indicator of neural convergence) increased, but by a factor that is too large to reconcile with the psychophysical results (5.3 x). The results suggest that absolute visual threshold in the goldfish is closely related to the density of rods in the retina.

Animals↗
PubMed1988

Post-lumbar puncture headache. Etiology and management.

Headache following a lumbar puncture is a common and often debilitating syndrome. Continued leakage of cerebrospinal fluid from a puncture site decreases intracranial pressure, which leads to traction on pain-sensitive intracranial structures. The headache is characteristically postural, often associated with nausea and optic, vestibular, or otic symptoms. Although usually self-limited after a few days, severe postural pain can incapacitate the patient. Management is mainly symptomatic, but definitive treatment with the epidural blood patching technique is safe and effective when done by an expert operator.

Adult↗
PubMed1988

Lighting conditions and retinal development in goldfish: photoreceptor number and structure.

The retinas of 63 goldfish were examined after varying durations of exposure to one of three environmental lighting conditions beginning before hatching: constant light (340 lux), cyclic light (12 hr 320 lux, 12 hr dark) and constant dark. Up to 8 months, no effects of constant light or dark on photoreceptor numbers or structure were apparent. Densities of rod and cone nuclei were normal and all retinal layers appeared normal by light microscopy. Exposure to constant light for 12 months or longer resulted in a reduction in rod density by 37%. Cone numbers were unaffected by constant light, even with exposures of 3 yr, and rod and cone outer segments were normal in length at 11-20 months under all environmental conditions. Due to poor survival, only one animal was available for quantitative examination from the group reared in constant dark 12 months or longer. Photoreceptor size and number in this retina were similar to those in the constant light condition. The results suggest that the formation and maturation of rods and cones in goldfish retina is unaffected by rearing in constant light. However, long-term exposure (greater than or equal to 12 months) may disrupt maintenance of differentiated rods.

Aging↗