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Biomedical subjects

N K Tyler

Publications and source records attributed to N K Tyler.

At least 19 recordsLinked to original sources
PubMed1992

Computer-assisted morphometry: point, intersection, and profile counting and three-dimensional reconstruction.

The use of computers in morphometry can involve 1) automated image analysis, semiautomated image analysis and point, intersection, intercept and profile counts of two-dimensional images on tissue sections with mathematical extrapolation to the third dimension, 2) direct measurement of volumes, surfaces, lengths, and curvature using x,y,z coordinates of serial sectioned images, or 3) stereologic techniques and serial sections which is a combination of 1 and 2 above. Automated and semiautomated image analysis are generally restricted to specimens that are characterized by differential contrast such as interalveolar septa in the lung or histochemically stained mucous granules in pulmonary epithelium. Point, intersection, and profile counts using hand-held, notebook PCs, portable PCs, or standard PCs and MS-DOS-based application programs are extremely efficient, precise, affordable, and convenient methods of quantitating average values of a population. When morphometric measurements of individual structures are required, computer-assisted three-dimensional reconstruction using x,y,z coordinates of the surface outline from serial sections is a tedious yet precise method. We describe a computer program that efficiently estimates mean caliper diameter, volume, and surface area with less than five percent error with five sections per structure. We also describe a program that does digital image subtraction on serial sections, superimposes digitally generated test systems on biological images, and accumulates point, intersection, and profile counts using a Macintosh II series computer.

Animals↗
PubMed1992

Management and monitoring of cancer-associated retinopathy.

Cancer-associated retinopathy is a rare paraneoplastic event that can involve allergic reactions and result in retinal degradation. A patient, who had a 35-year smoking history, complained of visual loss and was found to have serum antibodies that reacted with an extract of retina, including the previously described retinal cancer-associated retinopathy antigen. Prednisone treatment appeared to reduce the patient's antibody titers to normal levels. Visual fields stabilized, and the patient was able to maintain useful vision throughout the course of treatment until his death 1 year following initial diagnosis. To our knowledge, this is the first reported case in which monitoring of antibody responses to retinal antigens appeared to be useful in the decision whether to initiate prednisone therapy. Rising antibody titers to the cancer-associated retinopathy antigen probably occurs before progressive visual field loss and may be considered an indication for prompt steroid therapy.

Aged↗
PubMed1992

Circulating and localized immune complexes in experimental mycoplasma-induced arthritis-associated ocular inflammation.

Ocular deposits of immune complexes are believed to contribute to the anterior segment inflammations observed in association with the human arthritides. Arthritis-related ocular inflammations may be reproduced in animals by infection with certain species of mycoplasma. To evaluate the role of immune complexes in the production of ocular lesions, we studied their involvement in the rodent model of experimental arthritis-associated ocular inflammation induced by Mycoplasma arthritidis. Sprague-Dawley rats were infected with viable concentrates of M. arthritidis and monitored for the production of related circulating and intraocular immune complexes. Circulating immune complexes were monitored by antigen capture systems, and localized intraocular complexes were identified by indirect immunohistochemistry. Polyacrylamide gel immunoblot analysis of captured complexes confirmed the antigen(s) involved as proteins derived from M. arthritidis. Indirect immunofluorescence revealed localized complexes containing mycoplasma antigens within the ciliary-iris vasculature. Concentrations of the generated complexes diminished rapidly over a 30-day period. While complex deposits within ocular tissues could represent a contributing cause to the localized anterior segment inflammation reported in this rodent model, secondary challenge with viable M. arthritidis, which reproduced high concentrations of intraocular and circulating immune complexes, failed to elicit any ocular response.

Animals↗
PubMed1992

The cancer-associated retinopathy antigen is a recoverin-like protein.

Cancer-associated retinopathy (CAR) is a rare form of retinal degeneration that occurs in association with certain forms of cancer. CAR patients typically possess high titers of autoantibodies against a specific photoreceptor protein--the 23 kD retinal CAR antigen. The mechanisms involved in the vision loss experienced by CAR patients are not understood, but serologic studies indicate the process could include a series of autoimmune reactions directed at specific components of the retina. Because the retinal CAR antigen is the principal ocular autoantigen involved in the antibody response of CAR patients, characterizing it would contribute to the understanding of putative autoimmune involvement. Serum antibodies from CAR patients have been used to isolate the gene encoding the CAR antigen from a cDNA library of human retina. Nucleotide sequence analysis suggests that the CAR antigen shows approximately 90% homology to the published amino acid sequence of bovine recoverin.

Amino Acid Sequence↗
PubMed1991

Antibody indications of secondary and superimposed retinal hypersensitivity in retinitis pigmentosa.

Antibody reactions with recognized retinopathy-inducing retinal antigens may be interpreted to reflect ongoing autoimmune events responsible for some forms of vision loss. We sought evidence of secondary and superimposed retinal hypersensitivity indicated by such antibody reactivity in a random group of patients with retinitis pigmentosa. We identified patterns of immunologic reactivity within members of a group of 52 patients with retinitis pigmentosa, which suggests some patients with retinitis pigmentosa may experience consequential superimposed retinal hypersensitivity. Identifying subgroups of patients with retinitis pigmentosa who exhibit indications of retinal hypersensitivity to known uveitopathogenic retinal proteins may permit the reduction of their rate of retinal degradation by immunomodulation.

Adult↗
PubMed1991

Comparison of lectin reactivity in the vessel beds of the rat eye.

The capillary beds of the eye are lined by two types of endothelia, fenestrated in the choriocapillaris and ciliary body, and continuous in the retina and iris. In this study, we wished to find a marker for each of these types of vessel beds using lectin histochemistry. Sections of glutaraldehyde fixed rat eyes embedded in epoxy resin were extracted with sodium ethoxide and rehydrated. Binding of 15 different lectins was visualized using the avidin-biotin peroxidase technique. We found WGA, WGA-s, LFA and PHA-E to strongly bind retinal vessels. In addition to the above lectins, iris vessels bound GSL-I. Choriocapillaris reacted variably only with WGA and not at all with other lectins tested. Vessels of ciliary body processes did not react with any lectin studied. The less fenestrated vessels of the base of the ciliary process bound lectins similar to the retina. We speculate that the differential lectin staining of the various vessel beds of the eye may reflect the degree of fenestration of the endothelium. This reactivity may be influenced by variations in the surrounding milieu including cells and extracellular matrix.

Animals↗
PubMed1991

Alterations in glial cell morphology and glial fibrillary acidic protein expression in urethane-induced retinopathy.

Urethane injection in newborn rats causes a photoreceptor degeneration without initial damage to the retinal pigment epithelium, choriocapillaris, or inner retina. In later stages, retinal vessels become incorporated into the retinal pigment epithelium (RPE) and change from a continuous endothelial cell phenotype to a fenestrated phenotype. At the light-microscopic level, there do not appear to be morphologic changes in the inner retina up to 24 weeks of age. Ultrastructurally, however, there are alterations in Müller cell cytotopographic organization. In the normal retina, intermediate filaments are primarily found from the ganglion cell layer to the inner nuclear layer. These filaments do not show glial fibrillary acidic protein immunoreactivity (GFAP-IR) in the normal animal. In the urethane-treated animals, the compartmental organization of the Müller cell organelles is moved vitread. Intermediate filaments are found in the end-foot region, and in the inner plexiform layer, bundles of intermediate filaments become more prominent. All of these filaments are GFAP-IR positive. The new expression of GFAP in the Müller cell may be linked to the observed rearrangement of the cytoskeletal elements. In urethane-induced retinopathy, GFAP-IR is found associated with vessels in all layers of the remaining retina. However, it is not seen accompanying vessels into the RPE. Ultrastructurally, there is no glial investment of the RPE-associated vessels. This absence of glial investment may permit the change in phenotype observed in these vessels.

Animals↗
PubMed1990

Interactions of cultured rat synovial and ocular ciliary body cells with two strains of Mycoplasma arthritidis.

Strains of Mycoplasma arthritidis differ in their ability to cause joint and ocular inflammations. Although the reasons for this difference are not fully understood, pathogenic mycoplasmas commonly require close associations with the cells they damage. Using 3H-uridine labeled mycoplasma, we compared cellular interactions of in vitro cultivated rat synovial and ocular ciliary body epithelial cells with two American Type Culture Collection strains of M. arthriditis shown to differ in their virulence. Radiolabeling assays gave evidence of a stronger retention capability on cultured cells by the more pathogenic strain, 14152. Scanning electron microscopy demonstrated cellular associations with the two strains of mycoplasma, with more of the 14152 adhering to both cell types. Examination by transmission electron microscopy showed evidence of contact between the more virulent 14152 strain and both cell types, but no similar evidence with the comparatively less virulent strain, 19611. The pathogenicity of different strains of M. arthritidis may vary according to their ability to closely associate with specific target cells involved in the disease process.

Animals↗
PubMed1990

Selective neovascularization of the retinal pigment epithelium in rat photoreceptor degeneration in vivo.

Photoreceptor cell degeneration in rodents from a variety of causes results in neovascularization of the retinal pigment epithelium as a late stage phenomenon. Even though the vessels within the pigment epithelium arise from the retinal circulation, they can manifest the choroidal endothelial cell phenotype of fenestrated endothelial cells. In order to study the detailed cellular events which result in incorporation of retinal vessels within the retinal pigment epithelium, a morphological and morphometric analysis of the RPE and vasculature was performed in rats. Urethane, given subcutaneously to newborn rats, results in a photoreceptor degeneration but does not affect the RPE, choroid or inner retinal layers. Retinas were studied from rats of 8 to 24 weeks of age, the time period when vascularization of the RPE occurs. Loss of retinal vessels is first seen at 12 weeks, primarily in substantial dropout of vessel profiles in the outer plexiform layer (OPL) vessel bed. There is a gradient of loss from the OPL bed to the nerve fiber layer (NFL) bed and from the central to peripheral region. Total vessel density of the experimental retinas is greater than controls at 8 and 12 weeks. This occurs because there is marked loss of retinal thickness, due to photoreceptor degeneration, without a comparable loss of vessel profiles. The total retinal vessel density decreases from 8 to 20 weeks, and appears to stabilize at 20 and 24 weeks. Analysis of the separate vessel beds shows that this apparent stabilization is due to continued loss of vessels within the sensory retina, and increased presence of vascular profiles within the RPE. Total absence of the photoreceptor cell is necessary for incorporation of vessels within the RPE. Since new vessel profiles develop in the RPE but not the adjacent sensory retina, we speculate that the RPE may stimulate neovascularization of the RPE. A model of the cellular events leading to RPE neovascularization is proposed.

Animals↗
PubMed1990

Interglial cell gap junctions increase in urethane-induced photoreceptor degeneration in rats.

Gap junctions are found between astrocytes in the inner retina of normal rats, but they are rare between Müller cells or between astrocytes and Müller cells in the inner retina. After photoreceptor degeneration induced by urethane treatment of newborn animals, morphologic alterations of glial cells occur in the inner retina. The Müller cells withdraw from the inner limiting membrane, and the astrocytes hypertrophy and occupy the vitread surface of the inner limiting membrane. The frequency and size of the gap junctions between astrocytes increases with time in rats with urethane-induced photoreceptor degeneration, to a greater extent than expected from elaboration of additional astrocyte plasma membrane. The gap junction-profile length per glial cell membrane-contact length is 2.8 +/- 1.1 microns/1000 microns of membrane in 8-week-old normal animals; it increases to 18.9 +/- 9.4 microns/1000 microns of membrane at 56 weeks of age in urethane-treated animals. The average size of the gap junction-profile length doubles during this same period. To the authors' knowledge this is the first study demonstrating pathologic changes in gap junctions in central nervous system tissue. The authors speculate that this up-regulation of gap junctions occurs in response to an altered extracellular ionic composition in an attempt to increase the lateral spatial buffering of K+ by these cells. The relative location of glial cells in retina can determine, in part, the vulnerability of the retina to edema.

Animals↗
PubMed1989

Cytodifferentiation of two epithelial populations of the respiratory bronchiole during fetal lung development in the rhesus monkey.

This study describes the cytodifferentiation of the two populations of epithelial cells found in the respiratory bronchiole of the adult rhesus monkey. One population, pseudostratified and containing ciliated, nonciliated secretory, and basal cells, is found overlying the pulmonary artery (PA). The other population, not associated with the PA, contains nonciliated cuboidal cells between alveolar outpockets. In this study we used terminal conducting airways from the lungs of fetal (90 to 155 days gestational age [DGA]), postnatal, and adult rhesus monkeys. Ciliated cells were partially differentiated at 90 DGA (54% gestation) and completely differentiated by 134 DGA (80% gestation). Nonciliated secretory cells were partially differentiated at 95 DGA (57% gestation) but did not lose all glycogen until the postnatal period. Basal cells appeared by 134 DGA (80% gestation) and matured in the postnatal period. Small mucous granule cells appeared at 125 DGA (74% gestation) and did not change throughout fetal development. Neuroendocrine cells were present throughout the entire period studied. Nonciliated cuboidal bronchiolar cells of the nonciliated population of the respiratory bronchiole appeared at 105 DGA (62% gestation) and matured in the postnatal period. We conclude that 1) although most of the differentiation of the lower airway occurs before birth, most of the cell types are not completely differentiated at birth; 2) the sequence of differentiation for the cells of the ciliated pseudostratified epithelial population is ciliated, nonciliated secretory, and basal; 3) the sequence of differentiation for the nonciliated secretory cell is similar to that of the secretory cells in more proximal airways; and 4) basal, neuroendocrine, and small mucous granule cells are not a part of the differentiation sequence of the other cell types.

Animals↗
PubMed1988

Morphogenesis of the respiratory bronchiole in rhesus monkey lungs.

The epithelium of the respiratory bronchiole in the adult rhesus monkey consists of two populations: a pseudostratified epithelium with basal, mucous goblet, and ciliated cells located near the pulmonary artery (PA); and a simple cuboidal epithelium composed only of nonciliated bronchiolar epithelial (or Clara) cells in areas away from the PA. This study describes the pattern of differentiation of these two epithelial populations, and their relationship to the PA and to the time of appearance of alveoli in the respiratory bronchiole of the rhesus monkey during the period of 90-125 days gestational age (DGA). These events were related to changes in the adjacent parenchyma. Dissected airways of infusion-fixed, critical-point-dried lungs were evaluated by scanning microscopy followed by light microscopy of the same airways. At 54% of gestation (90 DGA), the distal airway was lined by a mixture of ciliated and nonciliated cells. By 67% of gestation (110 DGA), the ciliated cells were confined to the epithelium over the PA. The underlying connective tissue initially was cellular containing few fibers but was fibrous by 76% of gestation (125 DGA). Alveolarization began near the most distal cartilage at 57% of gestation (95 DGA), the same period at which secondary septation occurred in the distal acinus. Thus, alveolarization occurred simultaneously in two centers: 1) the proximal centriacinar region in the vicinity of the most distal cartilage and 2) the distal lung parenchyma. The duration of centriacinar alveolarization was short, approximately 5 days.

Animals↗
PubMed1988

Comparison of daily and seasonal exposures of young monkeys to ozone.

Oxidant air pollution tends to occur in both seasonal and daily cycles of polluted and clean air. To compare the effects of these 2 cycles, we exposed 2 groups of 7-month-old male monkeys to 0.25 ppm (0.49 mg/m3) of ozone (UV photometric standard) 8 h/day either daily or, in the seasonal model, days of alternate months during a total exposure period of 18 months. This is a longer ozone exposure period than any previously reported. A control group breathed only filtered air. Young monkeys were studied as their lungs are similar to those of man and their lungs, like those of man, grow over a period of several years. Monkeys from the seasonal exposure model, but not those exposed daily, had significantly increased total lung collagen content, chest wall compliance, and inspiratory capacity. All monkeys exposed to ozone had respiratory bronchiolitis with significant increases in related morphometric parameters. The only significant difference between seasonal and daily groups was in the volume fraction of macrophages. Even though the seasonally exposed monkeys were exposed to the same concentration of ozone for only half as many days, they had larger biochemical and physiological alterations and equivalent morphometric changes as those exposed daily. Lung growth was not completely normal in either exposed group. Long-term effects of oxidant air pollutants which have a seasonal occurrence may be more dependent upon the sequence of polluted and clean air than on the total number of days of pollution. Estimations of the risks of human exposure to seasonal air pollutants from effects observed in animals exposed daily may underestimate long-term pulmonary damage.

Air Pollutants↗
PubMed1988

Effect of murine gamma interferon on the cellular responses to bleomycin in mice.

Because in vitro studies have shown inhibition of fibroblast proliferation and collagen synthesis by interferon, we tested the hypothesis that murine gamma interferon inhibits bleomycin-induced pulmonary fibrosis in mice. Mice were divided into the following groups: saline plus vehicle (27), saline plus interferon (29), bleomycin plus vehicle (26), and bleomycin plus interferon (26). Bleomycin or saline were given intratracheally once at the beginning of the experiment and vehicle (phosphate-buffered saline) or interferon was given intramuscularly daily. Mice were killed at 14 or 21 days of the experiment. About half of the mice from each group were used for collagen biochemistry and half for bronchoalveolar lung lavage, transmission electron microscopy (TEM), and morphometry. Hydroxyproline content showed a significant reduction in bleomycin plus interferon compared to bleomycin plus vehicle mice at 21 days. The saline plus vehicle and saline plus interferon mice showed no difference in hydroxyproline content. Similarly, bronchoalveolar lavage showed no differences between saline plus vehicle and saline plus interferon mice; however, all mice treated with bleomycin showed significant increases in total cells as compared to saline treated mice. At 14 and 21 days in bronchoalveolar lavage there were significantly more lymphocytes in bleomycin plus interferon compared to bleomycin plus vehicle mice. In bronchoalveolar lavage, there were usually fewer neutrophils, monocytes and macrophages in bleomycin plus interferon compared to bleomycin plus vehicle mice. Morphometric estimates of the volume of lesion within lung showed no significant differences among the bleomycin treated groups. Stainable collagen fibers were less, but not significantly, in the bleomycin plus interferon compared to bleomycin plus vehicle mice. The number of fibroblasts per volume of lesion was significantly decreased at 14 and 21 days in bleomycin plus interferon compared to bleomycin plus vehicle mice. The total volume of lymphocytes in interstitial lesions was significantly greater at 14 and 21 days in bleomycin plus interferon mice compared to bleomycin plus vehicle mice. These results suggest an inhibitory action of gamma interferon on collagen accumulation and fibroblast proliferation associated with lymphocyte accumulation in the lungs of mice following bleomycin administration.

Animals↗
PubMed1988

Melanosome abnormalities of ocular pigmented epithelial cells in beagle dogs with hereditary tapetal degeneration.

Eyes of laboratory beagle dogs with an inherited tapetal degeneration were abnormally lightly pigmented. The development of pigmentation was followed morphologically from 7 days postnatal to 9 years of age. At all postnatal ages the iris pigmented epithelia contained no normal melanosomes, only organelles resembling secondary lysosomes or residual bodies. The ciliary body pigmented epithelium contained a variety of melanosome organelles at the earliest stages examined, but in fewer numbers than in normal animals. These included premelanosomes, partially melanized and some fully melanized pigment granules. However, the melanin deposition was usually patchy and irregular. With time, many of these granules appeared to condense into residual bodies. The retinal pigmented epithelium in peripheral and inferior posterior regions of affected animals never contained normal appearing melanin granules at any stage of postnatal development. The iris and choroidal stroma had melanosomes of normal size and shape, but many fewer than in normal animals. These results imply that there is local cellular control over melanosome production and regression, since the melanosome abnormalities do not follow the anterior to posterior development of pigment in ocular epithelia. It is proposed that a defect in synthesis of the matrix component of melanosomes could result in absent or abnormal deposition of melanin and initiate a process of autophagy of these organelles.

Animals↗
PubMed1987

Effects of ozone on lung and somatic growth. Pair fed rats after ozone exposure and recovery periods.

Minor differences in lung growth and development during childhood have been considered as a potential cause of rapid decline in pulmonary function in adulthood. Inhalation of ozone commonly causes changes in both body weight and lung volumes, which complicates interpretation of any changes in lung growth. The effects of ozone on lung growth were studied in rats which were pair fed. This technique permitted comparison of ozone-exposed and filtered-air control rats of the same body weight and body size as well as age and sex. Exposure was to filtered air or to 0.64 or 0.96 ppm ozone (UV standard) 8 h/night for 42 nights. A second control group was fed ad libitum and exposed to only filtered air. Half the rats were studied at the end of the 42-night exposures, the rest after a 42-day post-exposure period during which all rats were fed ab libitum and breathed filtered air. Rats examined at the end of the exposure period had larger saline and fixed lung volumes. These larger lungs had greater volumes of parenchyma, alveoli and respiratory bronchioles. Some of these changes persisted throughout a 42-day post-exposure period. Ozone inhalation by young rats alters lung growth and development in ways likely to be detrimental and those changes persist after ozone inhalation stops.

Animals↗
PubMed1987

Impairment in coupled beta-adrenergic receptor and adenylate cyclase system during bleomycin-induced lung fibrosis in hamsters.

The purpose of this study was to evaluate the coupled beta-adrenergic receptor (BAR) and adenylate cyclase (AC) system of the lung during the course of the bleomycin-(Bleo) induced pulmonary fibrosis in hamsters. The BAR population, dissociation constants (Kd), AC activity, and its sensitivity to various stimulators were studied at 2, 4, 7, 14, and 21 days after intratracheal administration of either 1 unit of Bleo or an equivalent volume of saline. The BAR population in the lungs of Bleo-treated animals did not differ from control at the early times, but it was significantly reduced to 5.9 X 10(3) fmol and 3.6 X 10(3) fmol from the control values of 1.1 X 10(4) fmol and 1.5 X 10(4) fmol per lung at 14 and 21 days after treatment, respectively. The Kd values for control hamster lung ranged from 2.5 X 10(-11) M to 3.7 X 10(-11) M, and for Bleo-treated hamster lung, from 2.7 X 10(-11) M to 4.8 X 10(-11) M. The Kd at the earliest time, 2 days after treatment, did not differ significantly from the Kd values at the subsequent times in control, while for Bleo-treated hamster lung, the Kd values at 7, 14, and 21 days were significantly higher than the Kd at 2 days after treatment. The Kd values for Bleo-treated hamster lung were also significantly higher than control at 14 and 21 days. The AC activity of the lung in Bleo-treated hamster was significantly reduced to 67%, 40%, 38%, and 50% of their respective controls in response to H2O (basal), GTP (10(-4) M), GTP + isoproterenol (10(-4) M each), and NaF (10 mM) at 21 days after treatment. The extent of AC stimulation in Bleo-treated hamster lung in response to various stimulators was generally less than that of saline control. Reductions in the BAR population and increased Kd values in Bleo-treated hamster lung were attributed to its fibrogenic ability and not to nutritional deficiency, which may partly be accountable for decreased AC activity of the lung in these animals. However, there were qualitative differences in the lung AC activity between Bleo-treated and nutritionally deprived hamsters, since the enzyme from the latter group was generally more responsive to stimulators than the enzyme from the former group. It was concluded from the findings of this study that an impairment in the coupled BAR and AC system of the lung may be partly responsible for the fibrogenic ability of bleomycin.

Adenylyl Cyclases↗