PubMed Health⌕ Search

Biomedical subjects

M Norval

Publications and source records attributed to M Norval.

At least 127 records · Page 7Linked to original sources

Two phenotypically distinct T cells are involved in ultraviolet-irradiated urocanic acid-induced suppression of the efferent delayed-type hypersensitivity response to herpes simplex virus, type 1 in vivo.

When UVB-irradiated urocanic acid, the putative photoreceptor/mediator for UVB suppression, is administered to mice it induces a dose-dependent suppression of the delayed-type hypersensitivity response to herpes simplex virus, type 1 (HSV-1), of similar magnitude to that induced by UV irradiation of mice. In this study, the efferent suppression of delayed-type hypersensitivity by UV-irradiated urocanic acid is demonstrated to be due to 2 phenotypically distinct T cells, (Thy1+, L3T4-, Ly2+) and (Thy1+, L3T4+, Ly2-). The suppression is specific for HSV-1. This situation parallels the generation of 2 distinct T-suppressor cells for HSV-1 by UV irradiation of mice and provides further evidence for the involvement of urocanic acid in the generation of UVB suppression.

Animals↗

In vivo modulation of antigen presentation generates Ts rather than TDH in HSV-1 infection.

The role of suppressor cells in control of persistent infections may be of profound importance. Whether a positive immune response or suppression of immunity is generated at the time of initial exposure to pathogens causing such infections may in part be due to the nature of the initial antigen presentation to the specific cells of the immune system. We have shown that in vivo modulation of epidermal APCs by an environmentally encountered stimulus (UV-B light exposure) and subsequent transfer of these APCs together with live HSV-1 to naive syngeneic recipients is sufficient to generate suppression of DH rather than DH to HSV-1. This suppression is T-cell mediated and specific for HSV-1. The phenotype of the Ts cell induced by epidermal cell transfer is Thy1+ L3T4+ Ly2-.

Animals↗

Interactions between herpes simplex virus and murine bone marrow macrophages.

Macrophages from murine bone marrow (strain C3Hf Bu/Kam) were cultured in vitro in L-cell conditioned medium. After 0, 2, 4, 6, 8 and 10 days, they were infected with a clinical strain of herpes simplex virus type 1 and the outcome followed morphologically, by phagocytic index, infectious virus yields, immunofluorescence, expression of Fc receptors and major histocompatibility complex (MHC) Class II antigens. At a multiplicity of infection of 1-5, little morphological difference was apparent between infected and uninfected cultures at early stages in vitro but marked changes occurred later with reduction in cell numbers in the infected cultures. Indirect immunofluorescence failed to detect cells expressing early viral antigens, and yields of infectious virus indicated that permissive infection was not taking place. While phagocytic index and Fc receptor expression did not change 24 hours post-infection, MHC Class II antigen expression was increased. Thus, although the bone marrow macrophages seem predominantly resistant to infection with HSV-1, they may be modified by the presence of the virus. Since macrophages may act as antigen presenting cells for the immune system, this type of mechanism may be important in the generation of local immune responses.

Animals↗

Effect of concanavalin A and succinyl concanavalin A on cytomegalovirus replication in fibroblasts.

In order to investigate inhibition of viral replication, human embryonic fibroblasts infected with cytomegalovirus (CMV) were treated with 0 to 25 micrograms/ml concanavalin A (Con A) and 0 to 150 micrograms/ml succinylated Con A (S-Con A). Alterations in cellular morphology occurred by day 2 post infection (p.i.) in cultures treated with 10 micrograms/ml Con A and 25 micrograms/ml S-Con A. With increasing concentrations of Con A and S-Con A there was decreased virus production from day 4 p.i. to day 10 p.i. Increasing levels of Con A and S-Con A also reduced the number of cells in culture. When virus titres were corrected to take cell number into account, decreased CMV titres in Con A and S-Con A treated cells appeared mainly to reflect decreased cell numbers. In support of this finding, in comparison with untreated CMV-infected fibroblasts, viral DNA synthesis was reduced and acid phosphatase levels were increased in CMV-infected cells treated with Con A or S-Con A.

Acid Phosphatase↗

Exposure to low-dose ultraviolet radiation suppresses delayed-type hypersensitivity to herpes simplex virus in mice.

Ultraviolet B (UVB) radiation is reported to induce a defect in epidermal antigen presentation which leads to specific suppression of the delayed-type hypersensitivity (DTH) response to trinitrochlorobenzene. We have used a similar system to examine the murine DTH response to herpes simplex virus type 1 (HSV-1). Mice irradiated with 96 mJ/cm2 UVB on shaved dorsal skin 3 days before s.c. injection of live HSV-1 in the flank showed 54-92% suppressed DTH responses to challenge with inactivated virus compared with nonirradiated control animals. If irradiation took place 7 days before inoculation with virus, some suppression of DTH occurred; if 14 days before, no suppression was found. The transient nature of the UVB response is further illustrated by the observation that irradiation with the same dose of UVB 5 h before, or 3 days after, inoculation with virus had no effect on DTH. Once induced, some degree of UVB suppression was found to persist for at least 3 months after irradiation.

Animals↗

Ultraviolet-irradiated urocanic acid suppresses delayed-type hypersensitivity to herpes simplex virus in mice.

Ultraviolet radiation is known to induce a transient defect in epidermal antigen presentation which leads to the generation of antigen-specific suppression of the delayed-type hypersensitivity (DTH) response. The putative receptor in skin for the primary event in UV-suppression is urocanic acid (UCA) which may then interact locally, or systemically, with antigen presenting cells or initiate a cascade of events resulting in suppression. We present the first direct evidence that UCA, when irradiated with a dose (96 mJ/cm2) of UVB radiation known to suppress the DTH response to herpes simplex virus, type 1 (HSV-1) in mice, can induce suppression following epidermal application or s.c. injection of the irradiated substance. This suppression is transferable with nylon wool-passed spleen cells.

Animals↗

Copper and zinc levels in serum from patients with abnormalities of the uterine cervix.

Serum copper and zinc levels were determined by atomic absorption spectroscopy in 110 women with varying degrees of cervical dysplasia up to carcinoma-in-situ and in 9 women with invasive carcinoma of the cervix, and compared with levels in 21 women with no evidence of cervical dysplasia. The average serum copper and zinc levels in the control group were 1.25 mg/l and 1.02 mg/l (respectively). The mean serum copper level increased with dysplasia to 1.4 mg/l and with invasive carcinoma to 1.47 mg/l. The mean serum zinc levels were decreased in cervical intra-epithelial neoplasia (CIN) grade 1 to 0.81 mg/l and in invasive carcinoma to 0.73 mg/l. The copper:zinc ratios varied significantly between controls, patients with cervical dysplasia and patients with invasive carcinoma (p less than 0.01). Measurement of serum ceruloplasmin revealed no significant differences among the control group and the groups of patients.

Adult↗

Alterations in epidermal handling of HSV-1 antigens in vitro induced by in vivo exposure to UV-B light.

In order to investigate the cellular interactions involved in the immune response to herpes simplex virus type 1 (HSV-1) in a murine model, an in vitro antibody induction system was developed. This comprised HSV-1-primed T cells from infected mice, trinitrophenol (TNP)-primed B cells from mice primed with TNP-coupled calf erythrocytes, and TNP-HSV-1 as antigen. When antigen-presenting cells (APC) were removed from the assay system, the induced antibody response disappeared but could be reconstituted by the addition of APC derived from the peritoneal cavity or skin of normal mice. Since HSV-1 is an epidermal pathogen, it was decided to investigate the role of skin APC in HSV-1 immunity. Skin APC from mice irradiated 3 days previously with a suberythemal dose of ultraviolet (UV)-B were found to have a decreased capacity to present HSV-1 antigen in vitro. However, the APC capacity of their peritoneal cells was unaffected. The reduction in APC capacity is not only a local effect at the irradiated site, as APC from mice exposed to UV-B with one ear protected by black electrical tape were equally affected in both ears.

Animals↗

Two phenotypically distinct T cells (Ly1+2- and Ly1-2+) are involved in ultraviolet-B light-induced suppression of the efferent DTH response to HSV-1 in vivo.

We have previously demonstrated that the delayed-type hypersensitivity (DTH) response to herpes simplex virus type 1 induced by subcutaneous injection with live virus was suppressed by irradiating mice with a low dose (96 mJ/cm2) of ultraviolet-B (UV-B) light 3 days before sensitization. In order to determine the nature of the suppression, cells from mice irradiated with UV-B before immunization with live virus were transferred to syngeneic animals that had been sensitized with live virus without prior UV-B exposure. Efferent suppression of DTH to HSV-1 was shown to be due to T lymphocytes, and two phenotypically distinct T cells were involved: an Ly1+2- subset and an Ly1-2+ subset.

Animals↗

The effect of UV-irradiation on viral infections of the skin.

The effect on the skin of exposure to relatively small doses of ultraviolet light has long been thought beneficial and socially desirable, leading to a 'healthy tan'. However it is less well known that similar (if not smaller) doses of UV-B radiation can have transient but profound depressive effects on the immune response to antigens or pathogens encountered by the skin. The result of this on the immunopathology of both primary and recurrent episodes of persistent viral infections of the epidermis is discussed.

Animals↗

Nucleic acid probes in diagnosis of viral diseases of man. Brief review.

With the recent, rapid advances in recombinant DNA technology, it has become possible to consider the use of nucleic acid probes in diagnosis of human viral diseases. Several examples are discussed which employ techniques of dot blot hybridization, sandwich hybridization and in situ hybridization. Typing of viral strains using restriction endonuclease digestion as an epidemiological tool is considered. Finally, the present limitations of molecular hybridization are discussed, and future developments including the production of non-radioactively labeled probes, are assessed.

Cytomegalovirus↗

Rumen papillomas in sheep.

Out of a sample of 200 rumens from sheep slaughtered in Edinburgh, papillomas were found in 25. They occurred as fibro-papillomas, mostly along the pillar of muscle between the dorsal and ventral rumen, and were often multiple. No inclusion bodies were seen in the lesions or papilloma virus particles on electron microscopy. Homogenisation of papillomatous tissue followed by various methods of purification did not yield identifiable virus particles, and viral DNA was not detected. Immunoperoxidase staining showed a very small number of positive cells at or on the surface of 6 out of 10 lesions examined. Thus, it seems probable that virus particles are not found in large numbers in the rumen papillomas of sheep, unlike the situation in ovine skin warts, but are present in a few epithelial cells which are rapidly shed from the surface of the mucous membrane.

Animals↗

Elution of cytomegalovirus antibodies from adenocarcinoma of the colon.

Eluates were prepared by high salt extraction from normal colonic mucosa and adenocarcinomatous tissue from 28 patients, eight more from unmatched colonic tissue and five from patients with other gastrointestinal disease. Immunoglobulins were detected by ELISA: IgG was present in 24% eluates from normal colon and 21% from carcinomas; IgA in 55% eluates from normal colon and 39% from carcinomas; IgM in 55% from normal colon and 37% from carcinomas. Cytomegalovirus-specific antibody was found in 15% eluates from normal colon and in 18% carcinomas. Out of the 28 matched specimens, cytomegalovirus-specific IgG was detected in one normal and four tumour eluates, specific IgA in two normal and four tumour eluates, and specific IgM in two normal and two tumour eluates. In two instances cytomegalovirus-specific antibody was present in the eluates prepared from the normal and tumour tissue of the same patient. Of those eluates which contained cytomegalovirus-specific antibodies by ELISA, two were positive by anti-complement immunofluorescence of human embryo fibroblasts infected with cytomegalovirus strain AD-169. It seems possible, therefore, that cytomegalovirus antigens on colonic cells may be masked by complexing with anti-cytomegalovirus antibodies, and may not therefore be detected by techniques such as immunofluorescence.

Adenocarcinoma↗

Cell-mediated immune responses to cytomegalovirus in patients with dysplasia of the uterine cervix.

Peripheral blood lymphocytes from 172 women with various degrees of cervical dysplasia were assayed for responsiveness to cytomegalovirus-induced early and late antigens using lymphocyte stimulation tests. No evidence was found to suggest that any group of patients was specifically sensitized to either of the antigens tested. Neither was there any difference between the patient groups in respect of mitogen-induced stimulation. The concept that cytomegalovirus might be involved in cervical cell transformation leading to carcinoma has therefore not been strengthened as a result of this study.

Antibodies, Viral↗

Characteristics of a feline mammary carcinoma cell line.

The establishment of an epithelial cell line, JM, from a feline mammary adenocarcinoma is described. In vitro, the morphological and cultural properties of these cells, their surface features such as lectin binding and their response to hormones were ascertained. In vivo, they are tumorigenic in athymic nude mice inducing tumour nodules composed of epithelia-like cells.

Adenocarcinoma↗

Studies of three canine mammary carcinoma cell lines--I. In vitro properties.

Three cells lines, REM 134, 111 and 367, have been derived from canine mammary carcinomas and their morphological characteristics in vitro are described. They are tumorigenic in athymic nude mice, have no demonstrable fibronectin on their cell surfaces and exhibit a varied pattern of lectin binding. They can be cloned in semi-solid agar. One line, REM 134, responds to oestrogen and luteotropic hormone in vitro, although none of the three had demonstrable oestrogen receptors.

Animals↗

Studies of three canine mammary cell lines--II. In vivo properties.

Three cell lines, REM 134, 111 and 367, derived from canine mammary carcinomas have been used to induce tumours in athymic nude mice after subcutaneous injection. The histopathology of the tumours was compared and each was found to resemble closely the original tumour. This did not change after serial in vivo passage. Metastasis never occurred. Injection of REM 134 cells intracranially resulted in a fast-growing tumour which also did not metastasize; injection intrapleurally resulted in growths most commonly on the mediastinum with confinement to the chest cavity. Fibronectin was present in the subcutaneous tumours. Two of the cell lines were cloned in semi-solid agar. When tested, these clones induced tumours identical histologically to the uncloned ones. Finally, male and female mice were injected subcutaneously with the same number of cells from each of the three lines but the rate of tumour growth did not differ significantly between the two sexes.

Animals↗