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J Stone

Publications and source records attributed to J Stone.

At least 235 records · Page 13Linked to original sources

Distribution of catecholaminergic cells in the retina of the rat, guinea pig, cat, and rabbit: independence from ganglion cell distribution.

By using an antibody against tyrosine hydroxylase (TH), the rate-limiting enzyme in the production of catecholamines, we have examined the morphology and distribution of catecholaminergic cells in the retinas of the rat, guinea pig, cat, and rabbit. In the albino rat, as reported by others, most TH-immunoreactive (TH-IR) cells were amacrine cells, and formed two morphological classes. Cells of one class (class 1) are stellate amacrine cells, the somata of most being in the inner part of the inner nuclear layer (INL). Cells of the second class (class 2) were seen only as small somata, also in the inner part of the INL. Cells of both classes were found in all areas of the retina, with a distinct but broad concentration around the superior-temporal margin of the retina. A small number of TH-IR interplexiform cells was seen. In the pigmented rat, only class 1 cells were recognized, also concentrating at the superior-temporal margin. In the guinea pig, cat, and rabbit, TH-IR cells also seemed to form one morphological class of amacrine cells, which resembled the class 1 cells of the albino rat. In the guinea pig and cat, their distribution resembled that seen in the rat, with the cells concentrating at the superior-temporal margin of the retina. In the rabbit, TH-IR cells concentrated weakly in the visual streak, but at both ends of the streak the concentration of TH-IR cells extended farther peripherally than the concentration of ganglion cells. Overall, the distribution of TH-IR cells seems largely or (in the rabbit) partially independent of the distribution of ganglion cells. This independence raises questions of the development and function of this group of amacrine cells.

Animals↗

The periphery effect in cat retinal ganglion cells: variation with functional class and eccentricity.

We have studied the responses of ganglion cells of the cat retina to visual stimulation remote from the center of their receptive field. Following previous work, this response is termed the periphery effect (PE). Cells were identified as Y-, X- or W-class from the latency of their response to optic chiasm stimulation and from their receptive field properties. The strength of the PE elicited by a rotating windmill or counterphased grating stimulus was measured for ganglion cells of all major classes. The PE was consistently stronger in Y- than in X-cells, and the strength of the effect in both X- and Y-cells increased significantly with retinal eccentricity. A PE was elicited from about 47% of W-cells studied. In some (36%) the effect was excitatory, as for X- and Y-cells; in others (11%) it was inhibitory. Despite this heterogeneity, the PE in W-cells increased significantly with eccentricity. These variations of the PE with eccentricity and cell class have implications for the circuitry of the inner plexiform layer.

Animals↗

Müller cell endfeet at the inner surface of the retina: light microscopy.

Using fractions of the protein spectrum of the cat retina as immunogens, we have generated antibodies with substantial specificity for the Müller cells of the retina of cat, rabbit, guinea pig, and rat. The antibodies appear to bind to the filamentous components of the Müller cells and allow demonstration of the pattern of Müller cell endfeet at the inner surface of the retina, best seen in wholemount preparations. In sections and at the edge of wholemount preparations the somas and processes of the cells can be observed. Müller cells are more evenly distributed over the retina than ganglion cells, indicating that their proliferation continues during the differential growth of retina which continues into postnatal life. The morphology and distribution of the endfeet varies with the structures present at the inner surface of the retina. Where the axon bundles are thick, the endfeet are relatively small and are confined to narrow rows between bundles. Müller cell endfeet are also separated widely by large blood vessels. In both situations, it seems likely that Müller cells and astrocytes both contribute, perhaps competitively, to form the glia limitans of the inner surface of the retina. Where the somas of neurones are densely packed in the ganglion cell layer, the endfeet are small and numerous, forming rings around the somas. Where axon bundles, vessels, and somas are sparse, the endfeet appear largest and form a regular array.

Animals↗

Distribution of cholinergic amacrine cells in the retinas of normally pigmented and hypopigmented strains of rat and cat.

We have examined the soma size, number, and distribution of cholinergic amacrine cells in the retinas of albino and pigmented rats and of Siamese and common cats, using an antibody against choline acetyl transferase (ChAT). In the pigmented strains of rat and cat, ChAT-immunoreactive (ChAT-IR) somata were located in both the inner part of the inner nuclear layer (INL) and ganglion cell layer (GCL), and their processes spread in distinct strata of the inner plexiform layer (IPL). The diameters of the somata in the INL and GCL did not differ significantly at any retinal location. Furthermore, soma diameter did not vary with eccentricity, except at the area centralis of the common cat, where ChAT-IR somata in both layers were relatively smaller. In both species, ChAT-IR somata in the GCL outnumbered those in the INL at all retinal locations. Both populations of cells tended to concentrate at the area of peak ganglion cell density and along the visual streak. Additionally, areas of relatively high density extended superiorly from the area of peak density. The same features of morphology and distribution were identifiable in the hypopigmented strains of rat and cat, but the numbers of ChAT-IR cells were consistently higher.

Animals↗

Does cyclosporin A adversely affect Pneumocystis carinii infection?

Fourteen immunosuppressed patients with Pneumocystis carinii infection presented in two clusters that were separated by 2 years. The diagnosis in all cases was made early by alveolar lavage with cytology. The first group of seven patients was immunosuppressed with cyclophosphamide or azathioprine and prednisolone. All recovered with high dose co-trimoxazole. The second group of seven patients was on prednisolone and cyclosporin A. Despite identical treatment three patients died and a further two who survived lost their grafts from rejection. Our data suggest that cyclosporin A adversely affects the prognosis from Pneumocystis carinii infection and raises the question of prophylactic co-trimoxazole in these patients. The clustering of Pneumocystis carinii infection suggests the possibility of nosocomial transmission although in this study we were unable to implicate person-to-person spread of infection.

Adult↗

Head injury and hemorrhagic shock: studies of the blood brain barrier and intracranial pressure after resuscitation with normal saline solution, 3% saline solution, and dextran-40.

The effect of fluid resuscitation from hemorrhagic shock on cerebral edema, intracranial pressure (ICP), and blood brain barrier function was investigated in the presence of a simulated head injury. Beagle dogs were anesthetized and ICP was measured via a right subarachnoid bolt while a contralateral epidural balloon was inflated in the left hemicranium to mimic a closed head injury. Forty percent of the dogs' blood was shed and the shock state was maintained for 1 hour. Resuscitation was initiated with shed blood and a volume of either normal saline solution (NS, n = 5), 10% dextran-40 (D-40, n = 6), or hypertonic (3%) saline solution (HS, n = 6) equal to the amount of shed blood. Evans blue solution was infused intravenously, and intravascular volume was then maintained with normal saline solution. Control (n = 5) dogs did not undergo shock, but received equivalent volumes of normal saline solution and Evans blue solution. The dogs were killed after 2 hours of resuscitation, and the brains were removed, weighed, and fixed in formalin. The average intracranial pressure value after epidural balloon inflation was 18.6 +/- 0.80 mm Hg and decreased equally in all groups during the shock period, averaging 10.8 +/- 1.24 mm Hg at the end of the shock period. Fluid resuscitation markedly elevated ICP in the NS and D-40 groups, reaching maximal values of 46.6 +/- 12.11 mm Hg and 45.3 +/- 28.95 mm Hg, respectively. Maximal ICP values in control and HS groups measured 21.8 +/- 1.36 mm Hg and 15.8 +/- 2.04 mm Hg, respectively (p less than 0.25 for HS versus NS control). Wet brain weights were significantly less in the HS group compared with either NS or D-40 groups (p less than 0.05). Coronal sections of fixed HS brains showed deep cortical Evans blue staining on the side of balloon injury. Therefore, in the presence of an intracranial mass lesion, resuscitation with hypertonic (3%) saline solution is accompanied by lower ICP values and less cerebral edema than is isotonic saline or colloid resuscitation. Blood brain barrier function is not restored by hypertonic saline solution resuscitation.

Animals↗

The wolf inside.

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Adult↗

Relationship between astrocytes, ganglion cells and vasculature of the retina.

We have studied the distribution of astrocytes in the ganglion cell and nerve fibre layers of the retina in cat, rat, rabbit, and possum using anti-serum and a monoclonal antibody against glial fibrillary acidic protein (GFAP) and our own monoclonal antibody against glial filaments. The distribution of retinal astrocytes appears to be strongly determined by the vasculature of the retina; astrocytes are absent from almost all the retina of the possum and from the avascular regions of the rabbit retina. In the cat and rabbit, retinal astrocytes also show a strong affinity for the bundles of ganglion cell axons found at the inner surface of the retina. Retinal astrocytes do not invest the somas of ganglion cells, and even in areas of retina in which they are numerous, they are sharply confined to the layer of ganglion cell axons. It is suggested that retinal astrocytes are "immigrant" fibrous astrocytes that enter the retina with its vasculature.

Animals↗

Age-dependent antibody response in mice and humans following oral influenza immunization.

In order to compare the antibody response in serum and secretions from healthy young subjects and the elderly (greater than 60 years), volunteers were immunized with the commercial inactivated influenza virus vaccine, by the usual (parenteral) route or orally. Also, young and old mice (mean age, 20 months) were orally immunized with live influenza virus. The older mice responded with a very slight rise in their serum and respiratory tract antibody levels compared with the young mice but showed no diminution in protection against lethal viral challenge. Elderly volunteers showed only slight serum antibody responses after parenteral immunization compared with the young. Neither group demonstrated a rise in serum antibody following oral immunization. With respect to the secretory IgA (SIgA) antibody response, certain differences were noted between the young and the elderly: the preimmunization levels of antibody to influenza virus were significantly greater in nasal secretions and saliva in the elderly as compared to the young volunteers, and the salivary antibody response was diminished in the elderly. This lack of a salivary antibody response in the elderly was explicable by the inverse relationship between the preimmunization SIgA antibody titers and the response to immunization. Oral immunization led to no more side effects than observed in the placebo control group.

Administration, Oral↗

Definition of regions in human c-myc that are involved in transformation and nuclear localization.

To study the relationship between the primary structure of the c-myc protein and some of its functional properties, we made in-frame insertion and deletion mutants of the normal human c-myc coding domain that was expressed from a retroviral promoter-enhancer. We assessed the effects of these mutations on the ability of c-myc protein to cotransform normal rat embryo cells with a mutant ras gene, induce foci in a Rat-1-derived cell line (Rat-1a), and localize in nuclei. Using the cotransformation assay, we found two regions of the protein (amino acids 105 to 143 and 321 to 439) where integrity was critical: one region (amino acids 1 to 104) that tolerated insertion and small deletion mutations, but not large deletions, and another region (amino acids 144) to 320) that was largely dispensable. Comparison with regions that were important for transformation of Rat-1a cells revealed that some are essential for both activities, but others are important for only one or the other, suggesting that the two assays require different properties of the c-myc protein. Deletion of each of three regions of the c-myc protein (amino acids 106 to 143, 320 to 368, and 370 to 412) resulted in partial cytoplasmic localization, as determined by immunofluorescence or immunoprecipitation following subcellular fractionation. Some abnormally located proteins retained transforming activity; most proteins lacking transforming activity appeared to be normally located.

Animals↗

Stages in the structural differentiation of retinal ganglion cells.

Using a cultured wholemount technique we have studied the morphological differentiation of ganglion cells in the retina of the rat and cat, during normal development. In both species the differentiation of ganglion cells begins in embryonic life, before embryonic day (E) 17 in the rat and E36 in the cat. It is useful to describe the morphological differentiation of ganglion cells as occurring in three stages. In the first stage, each germinal cell becoming a ganglion cell extends an axon into the fibre layer of the retina and towards the optic disc, and the soma of the cell moves towards the ganglion cell layer. As the soma approaches the ganglion cell layer, the processes that attach its poles to the inner and outer surfaces of the retina are withdrawn. When the soma reaches the ganglion cell layer, a stage of active dendritic growth begins, which lasts until shortly before birth in the cat and until several days after birth in the rat. The cell extends stem dendrites that branch profusely and are commonly tipped by growth cones. The major morphological classes of ganglion cell become distinct in the latter part of stage 2, as do the centroperipheral gradients in ganglion cell size apparent in the cat. During the third stage, the dendritic trees of ganglion cells no longer branch or extend by means of active growth cones. Very considerable growth of all parameters of the cell (soma size, dendrite calibre and length, axon calibre) occurs nevertheless, presumably by interstitial addition of membrane throughout the cell.

Age Factors↗

Synaptogenesis in the retina of the cat.

We have studied the development of synapses in the retina of the cat from E(embryonic day)21 to adulthood. The inner plexiform layer (IPL) could be distinguished by E36, but at this age no synapses had formed, although compact processes had formed in the IPL and membrane specialisations had developed in adjacent processes. Conventional synapses form in the IPL from E45 and become increasingly numerous and differentiated over subsequent weeks. Extracellular space and cellular debris were prominent during the formation of these synapses. The conventional synapses appear to form principally between amacrine cells until E56, when ganglion cell dendrites could be identified as postsynaptic processes. Ribbon synapses characteristic of bipolar cells were identified around birth, suggesting that bipolar cells do not form synapses until that age. The outer plexiform layer (OPL) could be distinguished in central retina at E56. Extracellular space, debris of degenerating cells and mounds of agranular vesicles were prominent at this age but synapses were not observed until E59, when cone pedicles formed ribbon synapses onto horizontal cell processes. The first synapses clearly formed by spherules, also onto horizontal cells, were seen at E62. The central process of the postsynaptic triad, considered to be the dendrite of a bipolar cell, was first observed in both cone pedicles and rod spherules around birth, again suggesting that bipolar cells do not enter into synaptic arrangements until that age. Synaptogenesis in the OPL shows a strong centro-peripheral gradient; its initial stages were observed centrally in the late E50's but synapse formation was not complete in the retinal periphery until P(postnatal day)7 or later. We could not detect a centro-peripheral gradient in the formation of conventional synapses in the IPL, but the formation of ribbon synapses in this layer began centrally at birth and in the mid-periphery at P5. In summary, the first synapses to form in the retina are those which spread information laterally within the plexiform layers, between amacrine cells and from receptor to horizontal cells. The cells which carry information centrally, in particular bipolar cells, enter into synaptic arrangements considerably later. Further, retinal cells seem to form synapses in a distinct sequence: first amacrines, then receptors and lastly bipolar cells.

Animals↗

René Laënnec.

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Cardiology↗

Secretory antibody following oral influenza immunization.

Secretory IgA antibody may be important in protection against respiratory viral infections, and the concept of a common mucosal immune system offers the theoretical basis for the convenient stimulation of this antibody. Therefore, the oral route was compared with intramuscular injection in a double-blind, placebo-controlled study in young healthy volunteers. A killed influenza vaccine, given in enteric-coated capsules (total of 98 ug hemagglutinin of A/Bangkok) led to significant salivary and nasal IgA antibody rises in a 4-week period. The preimmunization titers in secretions were inversely correlated with the antibody rise after immunization. The orally administered vaccine was associated with no more side effects than placebo, in contradistinction to reactions following the intramuscular route. The latter route also was without significant effect in regard to a stimulation of secretory antibodies. The observed simultaneous induction of antibodies in saliva and nasal secretions following oral administration of killed vaccine gives further evidence of a common mucosal immune system and its possible clinical use.

Administration, Oral↗