PubMed Health⌕ Search

Biomedical subjects

C Newton

Publications and source records attributed to C Newton.

At least 109 records · Page 6Linked to original sources
PubMed1988

Topically applied cyclosporine in azone prolongs corneal allograft survival.

The purpose of this study was to develop and test a topical ocular delivery system for the immunosuppressive drug cyclosporine. To this end, cyclosporine was dissolved in the penetration enhancer, Azone, and applied topically to allografted rabbit eyes. The concentration of cyclosporine in the cornea, the aqueous humor, and blood of the treated rabbits was determined by radioimmunoassay. The effect of the cyclosporine-Azone preparation on the survival of corneal allografts was assessed by clinical evaluation of the grafts and by histopathologic and immunohistologic evaluation of the cellular infiltrate in the grafts. Clinically significant concentrations of cyclosporine were measured in the treated corneas but little or no drug was found in the aqueous humor or blood of the treated animals. Cyclosporine in Azone resulted in suppression in the severity and incidence of graft rejection. The suppression of graft rejection was borne out by the immunohistologic observations. Cyclosporine-treated grafts contained significantly fewer infiltrating T lymphocytes than did the drug/solvent-treated allografts, indicating that the topical application of cyclosporine actively inhibited the entry of T cells into the grafts. This study, for the first time, presents a solvent that is apparently not toxic but is effective in delivering immunologically active concentrations of cyclosporine following topical application to the cornea.

Administration, Topical↗
PubMed1987

Corneal biopsy in chronic keratitis.

Failure to identify the causative agent makes the treatment of chronic keratitis difficult. Inability to obtain a definitive diagnosis may be related to the depth of the pathogen within the cornea, partial or inappropriate treatment that interferes with diagnostic cultures, or fastidious growth characteristics of the organism in culture. Biopsy by lamellar keratectomy provides sufficient tissue for culture and for histopathologic evaluation by histochemistry, immunohistopathology, and, if necessary, electron microscopy. Consultation with an ophthalmic pathologist before biopsy can prevent inappropriate handling of the specimen, which may preclude essential diagnostic procedures. Many studies can be done within 24 hours of biopsy, often permitting rapid identification of the pathogen and prompt institution of appropriate therapy.

Biopsy↗
PubMed1987

Age-associated differences in cannabinoid-induced suppression of murine spleen, lymph node and thymus cell blastogenic responses.

The effects of delta 9-tetrahydrocannabinol (THC) and 11-OH THC on the proliferative responses of murine thymus, spleen and lymph node cells were examined. Specifically, weanling and adult mouse lymphocytes were stimulated in vitro with the T-cell mitogens concanavalin A and phytohemagglutinin. Thymus cells were suppressed at lower cannabinoid concentrations than cells from either spleen or lymph nodes. However, splenic cells from weanling mice were much more readily suppressed than were those from adult animals. Lymphoid cell numbers were varied from 1 x 10(6) to 8 x 10(6) cells/ml/culture and treated with a constant dose of THC or 11-OH THC. The smallest number of cells from the spleen or lymph nodes resulted in the greatest suppression. Thymus cells, however, were more readily suppressed than spleen or lymph node cells, regardless of the number of cells in culture. Furthermore, 11-OH THC suppressed the responses of the thymus cells to phytohemagglutinin more than to concanavalin A. The proliferative responses of spleen and lymph node cells from weanling mice to concanavalin A and phytohemagglutinin were much more readily suppressed than were cells from adult mice. This age-related difference was seen in the dose-response studies as well as in the studies with varying cell numbers in culture. In all cases, spleen and lymph node cells from younger mice were more readily suppressed to concanavalin A and phytohemagglutinin than those from older mice when treated with the cannabinoid preparations.

Age Factors↗
PubMed1987

Differential effects of marijuana components on proliferation of spleen, lymph node and thymus cells in vitro.

The effects of delta 9 THC and 11-OH THC on the proliferative response of murine spleen cells stimulated in vitro with the T cell mitogens Con A or PHA were compared with the effects of these drugs on the mitogen-induced proliferation of murine thymus and lymph node cells. Thymus cells were found to be suppressed at lower cannabinoid concentration than either spleen or lymph node cells. However, splenic cells were more easily suppressed than were the lymph node cells. Lymphoid cell numbers were varied from 1 X 10(6) to 8 X 10(6) cells and treated with a constant dose of either THC or 11-OH THC. When suppression was noted with spleen and lymph node cells, the smallest number of cells in the assay resulted in the greatest level of suppression of cell proliferation. No significant suppression to PHA induced proliferation was found for lymph node cells at any cell number tested. Thymus cells were always more readily suppressed than spleen or lymph node cells regardless of the number of cells in culture. Furthermore, 11-OH THC suppressed the responsiveness of the thymus cells to PHA more than to Con A under the experimental conditions used. Thus, the ability of cannabinoids to induce suppression of the proliferative response of lymphoid cells to mitogens depends on the organ source of the cells, nature of the cannabinoid (THC or 11-OH THC), dose of the cannabinoid, mitogen used (PHA or Con A), and number of cells in culture.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1987

Inhibition of natural killer cell function by marijuana components.

The extent of modulation of host resistance mechanisms by marijuana components is not fully understood. Natural killer (NK) cells are a subpopulation of lymphoid cells and are important in host resistance mechanisms against malignant cells, virus-infected cells, and possibly pathogenic bacteria and fungi. We report that the marijuana component delta-9-tetrahydrocannabinol (THC) injected into mice results in a suppression of splenic NK activity. Furthermore, THC and the hydroxylated metabolite 11-hydroxy-delta-9-tetrahydrocannabinol (11-hydroxy-THC) suppress the NK activity of cultured murine splenocytes in a dose-dependent manner (range 1 X 10(-5) to 3.2 X 10(-5) M) without diminishing NK cell viability. The hydroxylated derivative appears to possess a more potent suppressive effect, in that it suppresses at lower concentrations than THC does and requires a shorter incubation time with the effector cells for its suppressive action. Purification of NK cells by Percoll density-gradient centrifugation suggests that both cannabinoids act directly on the natural killer cell population, resulting in suppression. Studies involving target binding analysis and calcium ionophore experiments suggest that cannabinoids do not suppress NK cell killing by the inhibition of effector/target binding or by disruption of calcium ion flux. These results suggest that two principal psychoactive cannabinoids can suppress natural killer cell function by interacting directly with the killer cells and disrupting cellular events postbinding and during the programming for lysis. Furthermore, the data suggest different modes of action for THC and the hydroxylated metabolite.

Animals↗
PubMed1987

Interferon induction by endotoxin-derived nontoxic polysaccharides.

Polysaccharide-rich preparations from Serratia marcescens-derived endotoxin and components thereof, including Lipid A, were studied in terms of their ability to induce interferon (IFN) activity in murine spleen cell cultures in vitro. Although the polysaccharide-rich derivatives, similar to intact endotoxin, were only weak stimulators for IFN induction, pretreatment of splenocyte cultures with recombinant interleukin-2 (IL-2) significantly increased IFN-inducing activity. Both an endotoxin-derived polysaccharide and a "White type" polysaccharide prepared from intact Serratia had similar ability to induce IFN in vitro, but only when spleen cells were first treated with IL-2. The polysaccharide preparations were nontoxic as compared with the high degree of toxicity of the intact endotoxin, yet induced similar IFN levels as whole endotoxin. Much of the IFN induced by these preparations was of the gamma type, since activity was either not neutralized or only incompletely neutralized by treatment with anti-alpha/beta interferon antibody.

Animals↗
PubMed1987

Immunogenicity and adjuvanticity of lipopolysaccharide from Legionella pneumophila.

Lipopolysaccharide isolated from Legionella pneumophila was found to be a potent antigen and inducer of antibody with strong adjuvant activity for related and unrelated antigens such as sheep erythrocytes by in vivo and in vitro systems. The LPS was also a potent stimulator of blastogenic responses by spleen cells from normal mice as well as from mice immunized with inactivated whole cells of Legionella. It strongly stimulated production of interferon and interleukin 1. These results indicate that the LPS of Legionella may be an important immune regulator in the host response.

Adjuvants, Immunologic↗
PubMed1987

Enhanced suppression of blastogenic responses by weanling mouse lymphoid cells treated with tetrahydrocannabinol in vitro.

The suppressive effects of delta 9-tetrahydrocannabinol (THC) on the proliferation of lymphocytes from the spleen, lymph node, and thymus of weanling animals vs adult animals to the T-cell mitogen PHA were examined. THC had a suppressive effect on thymus cells from animals of both younger and older mice. THC suppressed spleen and lymph node cells responses to phytohemagglutinin (PHA) more readily when the cells were obtained from young mice rather than older animals. Suppression by THC in the adult mice was greater in an organ containing fewer mature T lymphocytes such as the thymus in comparison to lymphocytes in secondary organs such as the spleen and lymph nodes which contain more mature lymphocytes.

Age Factors↗
PubMed1987

Suppressed in vitro blastogenic responsiveness of rat spleen cells after continuous infusion of endotoxin by an implanted osmotic pump.

Continuous infusion of a gram-negative bacterial endotoxin in relatively small doses into rats by means of an implanted osmotic pump was studied. The model system was designed to examine the effects of endotoxin on the blastogenic response of spleen cells to the endotoxin itself and to a nonspecific T-cell mitogen, concanavalin A (Con A). Rats were implanted with an osmotic pump which delivered saline for the first 42 hr to provide postsurgical recovery before the onset of endotoxin infusion. Previous studies had shown that during the first 1-4 days after administration of endotoxin marked alterations of metabolism and some changes in physiologic parameters such as blood pressure and in vitro myocardial performance occurred. In the present study the blastogenic responsiveness of spleen cells to endotoxin itself as well as to the nonspecific T-cell mitogen Con A was markedly decreased after several days of continuous administration of endotoxin. Control animals receiving only saline for the same period of time showed a similar depression of blastogenic responsiveness to the lipopolysaccharide (LPS), as well as to Con A, however, with a delay of 2-4 days before comparable levels of suppression became evident. These results indicate that marked alterations of immune competence as measured by blastogenesis of spleen cells to Escherichia coli LPS and to a mitogen such as Con A may occur after implantation of an osmotic pump, with or without continuous infusion of endotoxin. Further studies seem warranted to determine the role of the foreign body reaction to the osmotic pump as well as to the endotoxin administered by the pump.

Animals↗
PubMed1987

Distinctive immunomodulatory effects of endotoxin and nontoxic lipopolysaccharide derivatives in lymphoid cell cultures.

Endotoxin derived from Serratia marcescens, as well as a hydrolyzed polysaccharide-rich derivative from the bacteria similar to the White-type polysaccharide (WPS), and hydrolyzed split products of endotoxin, including Lipid A and the nontoxic polysaccharide (PS), were studied in terms of their ability to induce mitogenic proliferation of murine spleen cells in vitro and enhancement of antibody formation to sheep erythrocytes. The intact endotoxin and the Lipid A component induced marked proliferative activity of normal lymphoid cells, but the PS components obtained after a 30 min or longer mild hydrolysis of the endotoxin had much less mitogenic activity. The WPS preparation retained mitogenic activity after 30 min but lost it during continued hydrolysis. Nevertheless, all of the components were marked adjuvants for murine spleen cells in vitro in terms of enhancing the antibody response to sheep red cells. Both the intact endotoxin as well as the Lipid A component induced interleukin-1 and interferons, including alpha/beta and gamma, following stimulation of spleen cell cultures for 24 h in vitro. Although only the endotoxin and Lipid A, but not the PS components, were mitogenic for murine splenocytes, all of these preparations had immune adjuvant effects and induced spleen cells to produce or release interferons. However, the PS-rich derivative did not induce tumor necrosis factor. These distinct properties of components of endotoxin indicate that the nontoxic PS-rich derivative, as compared to the toxic endotoxin or Lipid A, has some immunostimulatory activities but lacks others.

Adjuvants, Immunologic↗
PubMed1987

Acanthamoeba keratitis. A growing problem in soft and hard contact lens wearers.

Eleven contact lens-wearing patients presented with Acanthamoeba keratitis. Eight cases were culture- and/or stain-positive for Acanthamoeba and three were presumed to have Acanthamoeba keratitis based on history and clinical findings. Six wore daily wear soft contact lenses, two wore extended-wear soft contact lenses, one wore a polymethylmethacrylate hard contact lens, one wore a gas-permeable hard contact lens, and one wore a Saturn lens (combined hard and soft lens). Four patients used distilled water and salt tablet saline, three used tap water and salt tablet saline, two used tap water rinse, two used well water rinse or storage, and one used intravenous (IV) saline. It is apparent that all contact lens wearers are at some risk for Acanthamoeba keratitis developing if proper contact lens care is not maintained. Of great concern is the inability of most current chemical sterilization methods to kill the organism if the lens becomes contaminated. Heat disinfection will kill Acanthamoeba trophozoites and cysts but the lens must not be placed into contaminated solutions afterward. Prevention is very important because medical and surgical treatment failures are frequent. Eye care practitioners who fit contact lenses are advised to use heat disinfection for low-water content stock soft contact lenses, and to use hydrogen peroxide without a catalyst for a minimum of 6 hours for all other stock lens fitting sets, to specifically inquire about contact lens care habits used by their patients, and to discourage the use of homemade saline solutions.

Acanthamoeba↗
PubMed1986

Chronic keratitis caused by Mycobacterium gordonae.

We treated a patient with chronic keratitis caused by Mycobacterium gordonae, a slow-growing, atypical mycobacterium not previously reported as a cause of corneal infection. The patient was a 34-year-old man who was hit in the eye with some vegetable matter while gardening. Initially, the patient was treated for a presumptive diagnosis of herpes simplex keratitis. Because of progression of the keratitis, a lamellar corneal biopsy was performed 3 1/2 years later and the definitive diagnosis was made. Subsequently, a penetrating keratoplasty was performed and the patient's condition then remained stable. The diagnosis of atypical mycobacterium should be considered in a patient with an indolent corneal ulcer. Lamellar corneal biopsy may disclose the pathogen when the infection is deep, chronic, or partially treated.

Adult↗
PubMed1986

Marijuana effects on immunity: suppression of human natural killer cell activity of delta-9-tetrahydrocannabinol.

Delta-9-tetrahydrocannabinol (THC), the major psychoactive component of marijuana, was tested for its ability to modulate human natural killer (NK) cell function. THC was toxic for peripheral blood lymphocytes at 20 micrograms/ml but not at 10 micrograms/ml or less. This component of marijuana also was inhibitory for NK activity against K562, a human tumor cell line at concentrations down to 5 micrograms/ml when pre-incubated with the effector cells. Suppression of NK function was dependent upon the concentration of THC and the length of time of pre-incubation but was independent of the ratio of effector to target cells. Prostaglandins were not involved in suppression of NK activity.

Cannabis↗
PubMed1986

In vitro and in vivo suppressive effects of delta-9-tetrahydrocannabinol on interferon production by murine spleen cells.

Delta-9-tetrahydrocannabinol (THC), the major psychoactive component in marijuana, has been reported to be suppressive on some immune functions. Since interferons (IFNs) are important immunomodulatory proteins, the effect of in vivo or in vitro administration of THC on induction of IFN by various mitogens was examined. Splenocytes from normal mice in the presence of THC produced significantly less IFN when stimulated by phytohemagglutinin (PHA), concanavalin A (Con A), or Escherichia coli lipopolysaccharide (LPS). Induction of IFN by a bacterial antigen, Legionella pneumophila bacterial cells, was also suppressed by THC. Also, splenocytes which were incubated up to 24 h in the presence of THC partially recovered responses to mitogens when cells were washed before stimulation. This suggested that THC must be present in order to mitigate IFN induction. Splenocyte cultures from mice which were chronically injected with THC for 6-8 weeks were also less responsive to induction of IFN by the various mitogens. These results suggest that at least part of the immunosuppressive effects of THC may be related to depressed IFN production by stimulated lymphocytes. Since Con A and PHA are T cell mitogens and LPS is considered to be a macrophage and B cell stimulator, suppression of IFN production by these classes of cells indicate a wide range of effects of THC.

Animals↗
PubMed1985

Acanthamoeba keratitis associated with soft contact lenses.

Three patients (a 13-year-old girl, a 25-year-old man, and a 22-year-old woman) who used daily-wear soft contact lenses, sterilized with saline made from distilled water and salt tablets, developed Acanthamoeba keratitis. Acanthamoeba was cultured from the contact lens solution of one patient. This patient, in whom the diagnosis was made by corneal biopsy early in the clinical course, was successfully treated with topical neomycin-polymyxin, miconazole, and propamidine isethionate. The other two patients underwent penetrating keratoplasty. One of these patients, who received a graft early in the clinical course, developed a recurrence of disease in the graft, whereas the other, who received the graft 18 months after the initial symptoms, has maintained a clear corneal transplant with useful vision.

Adolescent↗
PubMed1985

A respiratory epithelial choristomatous cyst of the orbit.

A 23-year-old woman presented with a 19-year history of unilateral, intermittently painful, slowly progressive proptosis. Clinical examination disclosed decreased orbital resiliency and choroidal folds in the posterior pole. Orbital echography revealed an acoustically empty cystic lesion superotemporally. Computerized tomography demonstrated bony molding of the adjacent lateral orbital wall. At operation, a discrete, well-encapsulated mass was found adherent to the periorbita behind the lacrimal gland and extending into the muscle cone. There was no connection with the bony orbit. Histological examination disclosed the well-encapsulated cyst to be lined by pseudostratified ciliated columnar epithelium with goblet cells and filled with mucoid debris. We postulate that the cyst arose from respiratory epithelium sequestered during the intrauterine development of the paranasal sinuses.

Adult↗
PubMed1981

Calcium- and magnesium-induced fusion of mixed phosphatidylserine/phosphatidylcholine vesicles: effect of ion binding.

The aggregation, leakage, and fusion of pure PS (phosphatidylserine) and mixed PS/PC (phosphatidylcholine) sonicated vesicles were studied by light scattering, the release of encapsulated carboxyfluorescein, and a new fusion assay which monitors the mixing of the internal compartments of fusing vesicles. On a time scale of 1 min the extent of fusion was considerably greater than leakage. The Ca2+ and Mg2+ concentrations required to induce fusion increased when the PS content of the vesicles was decreased, and/or when the NaCl concentration was increased. Calculations employing a modified Gouy-Chapman equation and experimentally determined intrinsic binding constants of Na+ and Ca2+ to PS were shown to predict correctly the amount of Ca2+ bound in mixed PS/PC vesicles. For vesicles composed of either pure PS or of mixtures with PC in 100 mM NaCl (4:1 and 2:1 PS/PC); the induction of fusion (on a time scale of minutes) occurred when the amount of Ca or Mg bound/PS molecule exceeded 0.35-0.39. The induction of fusion for both pure PS and PS/PC mixed vesicles (with PS exceeding 50%) can be explained by assuming that destabilization of these vesicles requires a critical binding ratio of divalent cations to PS.

Binding Sites↗