PubMed Health⌕ Search

Biomedical subjects

M Norval

Publications and source records attributed to M Norval.

At least 91 records · Page 5Linked to original sources
PubMed1992

The effect of ultraviolet B irradiation and urocanic acid isomers on dendritic cell migration.

Irradiation with ultraviolet-B light (UV-B) suppresses some cell-mediated immune responses to a variety of antigens, including contact sensitizers. Following UV irradiation there is modulation of Langerhans' cells' markers and keratinocytes are induced to synthesize and secrete tumour necrosis factor-alpha (TNF-alpha). Cis-urocanic acid (cis-UCA) has been suggested as a photoreceptor for UV and has been demonstrated to suppress immune responses in several experimental systems. UCA is found naturally in the stratum corneum as the trans-isomer and converts to the cis-isomer on irradiation. In the present study the migration of dendritic cells (DC) to lymph nodes following UV-B irradiation or epicutaneous application of UCA isomers was examined in unsensitized mice and mice sensitized with fluorescein isothiocyanate (FITC). It was found that UV-B irradiation alone induced DC migration to draining lymph nodes (DLN) and that UV-B irradiation prior to skin sensitization at the same site enhanced DC migration. A maximum number of DC was present in DLN 48 hr following irradiation. In sensitized mice, the percentage of DC bearing FITC and the quantity of FITC per DC was unaltered by prior UV exposure. In contrast, neither isomer of UCA had any significant effect on DC numbers in sensitized or unsensitized mice. It was concluded that UV-B irradiation induced the migration of DC from the epidermis to draining lymph nodes, an effect possibly mediated by TNF-alpha release, while UCA may act by a different mechanism, perhaps via histamine-like receptors in the epidermis.

Animals↗
PubMed1991

Response of efferent lymph and popliteal lymph node to epidermal infection of sheep with orf virus.

Functional and phenotypic changes in the cell populations were monitored in the popliteal efferent lymph of sheep following experimental epidermal infection with orf virus. In another group of sheep, cells from the popliteal lymph node draining the site of infection were similarly monitored and compared with the cells from contralateral popliteal and mesenteric lymph nodes. All sheep showed serological evidence of previous exposure to orf virus. Following infection, anti-orf antibody titres rose and efferent lymphocyte and blast cell output increased. Interferon-like activity was detected in efferent lymph early after orf virus but not mock infection. Lymphocytes from the draining popliteal lymph node showed antigen-specific lymphoproliferation on Days 3-7 while cells in the efferent lymph demonstrated proliferative activity on Days 4-6. The requirement for exogenous antigen-presenting cells in the culture of efferent lymphocytes varied between individual sheep. The culture supernatant from proliferating lymph node cells contained interferon-like activity but no anti-orf antibodies, the reverse of that from cultured efferent lymphocytes, perhaps indicating a different reactive T cell population. During the course of the experiment there was an increase in the percentage of efferent lymphocytes expressing MHC Class II antigens and surface immunoglobulins, the latter being recorded as a double peak. The short-term nature of the local T cell response may in part explain the incompleteness of immunity to orf virus in sheep.

Animals↗
PubMed1991

Seminal polyamines as agents of cervical carcinoma: production of aneuploidy in squamous epithelium.

The effects of several polyamines found in seminal fluid on the cell cycle and ploidy of three cervical cell lines and of primary epithelial cells cultured from cervical biopsy specimens were monitored by fluorescent flow cytometry. The rate of cell growth did not change but there were indications of either hypodiploidy or hyperdiploidy in some cultures at certain concentrations of spermine and spermidine. An interaction of exogenous polyamines with the DNA of cervical cells was shown to occur, leading to changes in ploidy with, perhaps, the potential to induce or promote dysplasia.

Adult↗
PubMed1990

Antigen presentation in patients with recrudescent orofacial herpes simplex virus infections.

Recovery from epidermal herpes simplex virus (HSV) infection depends primarily on development of an effective cell-mediated immune response, possibly generated following antigen (Ag) presentation by epidermal cells (EC). The ability of EC to present HSV Ag was investigated in 12 subjects with occasional recrudescent facial HSV infections. All had circulating HSV specific antibodies and cell-mediated immunity to the virus. Peripheral blood mononuclear cell suspensions, depleted of antigen presenting cells (APC) by glass adherence and then enriched for T cells by adsorption on nylon wool columns, did not proliferate in response to HSV Ag. Both EC suspensions, prepared from suction blister roofs, and glass-adherent peripheral blood mononuclear cells (AC) preincubated with ultraviolet-inactivated HSV, reconstituted the T-cell proliferative response to HSV. EC were more efficient than AC at presenting HSV Ag to T cells. Depletion of CD1+ cells from EC suspensions by cell sorting reduced their ability to present HSV Ag and augmentation of CD1+ cell numbers supplemented it. Preincubation of EC or AC with monoclonal antibodies to major histocompatibility complex class II antigens DP, DQ or DR, blocked the lymphoproliferative response to HSV Ag. Evidence was obtained that cells co-ordinately expressing products of the DP, DQ and DR loci are involved in presentation of HSV Ag by both EC and AC.

Adult↗
PubMed1990

The use of tissue culture for the detection of mycotoxins.

After incubation with 20 different mycotoxin standards and extracts from fungi and feed stuffs, fluorescent flow cytometry was used to measure viability of NS-1 cells and compared to microscopic assessment of cytotoxicity on stained HEp-11 monolayers. Both methods gave essentially the same results but the cytometric analysis offered a more quantitative approach and was particularly appropriate in the screening of extracts containing fats. The potential uses of a cytotoxic test in the analysis of feed stuffs and fungal extracts for the presence of mycotoxins are discussed.

Animals↗
PubMed1990

Lymphoproliferative responses in recrudescent orofacial herpetic infections.

The relationship between antibody (Ab) and lympho-proliferative responses to herpes simplex virus (HSV) and recrudescent orofacial HSV lesions were investigated in 65 patients. All had HSV-specific Ab and cell mediated immune responses (CMIR) demonstrated by ELISA and in vitro lymphoproliferation respectively. Thirteen control subjects were negative in both tests. Thirty-three patients were repeatedly investigated for 6-38 months during which time they suffered 1-8 recrudescences. HSV-induced lymphoproliferation was depressed during recrudescences, rose to a peak several weeks later, and declined slowly to a background level. However, ELISA titres and lymphoproliferative responses to Concanavalin A (Con A) were high throughout and circulating peripheral blood mononuclear cell (PBMC) subsets did not change. Depressed lymphoproliferative responses to HSV antigen (Ag) during recrudescences were enhanced by removal of CD8+ cells from PBMC using either a panning technique or cell sorting; reconstitution of CD8+ cells suppressed the HSV-specific lymphoproliferative response. CD8+ cell depletion affected neither HSV-induced lymphoproliferation recrudescence, nor lymphoproliferative responses to another Ag (PPD) during recrudescence. Depressed HSV-induced lymphoproliferation during recrudescences might thus be due to CD8+ suppressor T cell (Ts) function rather than low numbers of circulating lymphocytes. Suppression or delay of normal CMIR to asymptomatic recurrent epidermal HSV infection by Ts might allow development of recrudescent HSV lesions.

Adolescent↗
PubMed1990

The effect of histamine receptor antagonists on immunosuppression induced by the cis-isomer of urocanic acid.

Urocanic acid (UCA) is found in the stratum corneum predominantly as the trans-isomer; on ultraviolet B (UVB) irradiation, isomerization to the cis-isomer occurs. Cis-UCA has been shown to mimic the consequences of UVB irradiation in generating transient suppression of contact and delayed hypersensitivity (DH) responses. In an attempt to elucidate the mechanisms of action of UCA, the effects of 2 histamine receptor antagonists, cimetidine and terfenadine, were examined. One day after skin painting murine ears with cis-UCA, the number of ATPase- cells was reduced from 1068 to 408 mm-2. However, if cimetidine or terfenadine was applied at the same time as cis-UCA, the number of ATPase- cells was reduced only slightly from the control value, to 1028 and 892 respectively. Cis-UCA given subcutaneously or epidermally 5 h before infection of mice with herpes simplex virus suppressed the DH response on subsequent challenge with the virus. If cimetidine or terfenadine was added at the same time as cis-UCA, little suppression of the DH response to the virus occurred. Thus 2 effects of cis-UCA, on the number of ATPase+ epidermal cells and on DH response, were reduced or abrogated by histamine receptor antagonists, which may indicate that cis-UCA acts through histamine-like receptors in the skin.

Adenosine Triphosphatases↗
PubMed1989

Immune response of lambs to experimental infection with Orf virus.

A group of six specific pathogen free (SPF) lambs were infected epidermally with Orf virus. Seven weeks later they were reinfected. For a period of 4 weeks after each inoculation they were observed clinically and blood was collected for analysis of virus specific antibody measured by ELISA and peripheral blood lymphocyte (PBL) proliferative response to various viral antigens. After the primary infection all animals showed clinical signs of Orf, namely vesicle formation which became pustular followed by scabbing; this steadily became heavier prior to shedding and the resolution of the infection by about 4 weeks. The severity of infection varied within the group. Little lymphoproliferative activity was recorded during the primary infection, although five/six test animals had positive lymphoproliferative responses to an sodium dodecyl sulphate (SDS) solubilised scab purified Orf virus preparation at some point between days 7 and 14 after inoculation. All animals seroconverted to Orf virus, lymphoproliferative activity always preceding specific antibody detection. Resolution of the secondary infection was very rapid. Vesicles were visible by day 2 after inoculation which became pustular followed by scab formation and resolution in the majority of animals by day 8. All animals showed a significant (greater than four-fold) rise in specific antibody titre following secondary inoculation. The proliferative activity of PBL's was much greater than that recorded for the primary infection although the magnitude of this response varied greatly between individuals.

Animals↗
PubMed1989

Identification of ovine interferons: differential activities derived from fibroblast and lymphoid cells.

A bioassay has been developed to detect interferon (IFN) activity in supernatant fluids of cultured sheep cells by measuring their ability to inhibit the cytopathic effect of Semliki Forest Virus on an immortalised ovine fibroblastic cell line. IFN produced by spleen or lymph node cells stimulated with mitogen was labile at pH 2 as was a similar activity produced by CD4 lymphocytes stimulated with mitogen or specific antigen. In contrast, the IFN produced by fibroblasts stimulated with synthetic double-stranded RNA was stable at that pH. These results demonstrate the existence of an ovine IFN with properties similar to those described for IFN-gamma in mouse and man.

Animals↗
PubMed1989

Lymphoproliferative response to fusion proteins of human papillomaviruses in patients with cervical intraepithelial neoplasia.

The cell-mediated immune response (CMI) to E6 and E4 fusion proteins of human papillomavirus type 16 (HPV-16), E6 fusion protein of HPV-18, and to control proteins similarly produced, was analysed in 29 patients with cervical intraepithelial neoplasia (CIN) and in 15 age-matched laboratory personnel using a lymphocyte proliferation assay (LPA). Compared to controls without any added proteins, a positive response (stimulation index greater than 2.0) to the highly purified E6 control protein was found in only one patient. Positive responses to the E4 control protein which contained beta-galactosidase were noted in three patients and two controls. With control proteins as baseline, the lymphocytes from nine patients (28%) and three laboratory personnel (20%) responded to at least on HPV fusion protein after 7 days in culture. Stimulation indices were low in both groups with a range of 2.06-4.69 and the difference in incidence of positive responses between the groups is not significant. Proliferative responses to HPV-1 and HPV-2 virion antigens were noted in 6/23 (26%) of the patients and 2/15 (18%) of the other group. No correlation between responsiveness and degree of dysplasia or presence of koilocytes was found in the patient group. The relevance of the low proliferative responses is discussed.

Adult↗
PubMed1989

Cervical intraepithelial neoplasia in lymphoma patients: a cytological and colposcopic study.

Twenty-seven patients with Hodgkin's (n = 19) and non-Hodgkin's (n = 8) lymphomas underwent cytological and colposcopic screening of the uterine cervix. Colposcopically directed cervical punch biopsies were taken from all patients in whom a colposcopic abnormality was detected. Lymphoma patients were compared with 79 controls with normal cervical cytology and no known haematological abnormality. Colposcopically directed punch biopsies were taken from the cervical transformation zone of all controls. Significantly more lymphoma patients (19%) than controls (3%) had CIN II or III (P less than 0.01) and cervical human papillomavirus infection, as judged by the presence of koilocytes (52% of lymphoma patients; 27% of controls; P less than 0.02). All six lymphoma patients with CIN had Hodgkin's disease (HD), and five had received combination chemotherapy. Half of the cases of CIN in lymphoma patients and all the cases of CIN in control patients were not detected by cervical cytology. This study suggests that female patients with HD are at increased risk of CIN, and that cervical cytology alone may be an inadequate form of screening for these patients.

Adult↗
PubMed1989

Lymphoproliferative and serological responses to herpes simplex virus during primary infection, recrudescence, and re-infection in a murine model.

Mice were infected epidermally with herpes simplex virus type 1 (HSV-1) after mild tape stripping. Some were re-infected by the same route several weeks later; recrudescences were induced in others by UV-irradiation before the primary infection followed by re-irradiation and tape stripping at a later date. Clinical symptoms were noted; serological responses to HSV and lymphoproliferative and phenotypic analysis of local lymph node cells were measured throughout. Experience of a primary lesion did not prevent lesions developing again on re-infection although morbidity and mortality were decreased. Recrudescent lesions were less severe than primary or secondary lesions, never zosteriform and healed rapidly. Antibodies to HSV were not found to play a major role in preventing development of lesions. The lymphoproliferative response on primary infection was maximal just after the lesions were most severe and then waned. There was a second, although not accelerated, lymphoproliferative response on re-infection with a persisting high level for at least one month. On recrudescence, limiting dilution culture analysis of lymphoproliferation demonstrated a recruitment within two days of HSV-1 specific lymphocytes to lymph nodes draining sites of lesions, which may limit their severity and duration.

Animals↗
PubMed1989

Urocanic acid and immunosuppression.

Urocanic acid, a molecule found at high concentration in the stratum corneum, acts as a photoreceptor for UV-light, isomerizing from the naturally occurring trans-form to the cis-form. It has been proposed that cis-urocanic acid may mediate the transient alteration in immune surveillance resulting in immunosuppression induced after UV-irradiation, by interacting with immune cells locally and/or systemically to generate T cells with suppressor function. The evidence to support this hypothesis is summarized, and possible interactions of urocanic acid with immune cells and their outcome are discussed.

Animals↗
PubMed1989

Urocanic acid analogues and the suppression of the delayed type hypersensitivity response to Herpes simplex virus.

Ultraviolet irradiated urocanic acid (4-imidazoleacrylic acid) containing a mixture of cis- and trans-isomers has been shown previously to induce suppression of the delayed type hypersensitivity (DTH) response to Herpes simplex virus type 1 (HSV-1) in a murine model of infection. The cis-isomer of urocanic acid was prepared and the cis- and trans-isomers of 2-methylurocanic acid. 2-pyrroleacrylic acid, 2-furanacrylic acid, 2-thiopheneacrylic acid, 3-thiopheneacrylic acid as well as dihydrourocanic acid and histamine. Each was applied at concentrations of 1 and 50 micrograms per mouse to the shaved dorsal skin and the mice were infected subcutaneously with HSV 5 h later. After 8-10 days the DTH response to the virus was measured by an ear swelling test. It was found that cis-urocanic acid was effective in suppressing the DTH response at levels of 1 microgram per mouse or less. The cis- and trans-isomers of 2-furanacrylic acid, 2-pyrroleacrylic acid and 2-thiopheneacrylic acid were also effective, with the cis- form generally being more active than trans, and 2-pyrroleacrylic acid being particularly potent. Cis- and trans-3-thiopheneacrylic acid, on the other hand, were only marginally immunosuppressive while neither isomer of 2-methylurocanic acid had any suppressive ability. Dihydrourocanic acid and histamine were also shown to suppress the DTH response. Thus the structural features necessary for urocanic acid and its analogues to act as mediators of UV-induced immunosuppression could be deduced and implications for their mechanism of action discussed.

Chemical Phenomena↗
PubMed1989

Papillomavirus and c-myc antigen expression in normal and neoplastic cervical epithelium.

Cervical punch biopsy specimens or brushings were collected from 33 patients with cervical human papilloma virus (HPV) infection, cervical intraepithelial neoplasia (CIN), or invasive cervical carcinoma, and from eight control patients with recent normal cervical cytology. Prostatic chippings obtained from six men with benign prostatic hypertrophy were used as further controls. Biopsy specimens and brushings were assayed by flow cytometry for c-myc oncogene antigen and papillomavirus antigen expression and rate of cell division (by measuring DNA content). Results obtained from analysis of specimens and brushings were similar in terms of c-myc antigen and total DNA content, but when the percentages of nuclei from biopsy and brush specimens staining positively with antibody to papilloma viral antigens were compared, brush specimens gave consistently higher percentages than biopsy specimens. More specimens from normal epithelium were c-myc antigen positive (five of eight, (63%) than specimens from CIN II or III (two of 10, 20%), or invasive carcinoma (0%). No association was found between c-myc antigen expression and cell division. HPV antigen positive specimens were found to contain more dividing cells than negative specimens.

Antigens, Viral, Tumor↗
PubMed1989

Detection of human papilloma viruses in paraffin wax sections with biotinylated synthetic oligonucleotide probes and immunogold staining.

Human papilloma virus was detected by in situ hybridisation in routinely processed paraffin wax sections using a synthetically produced oligonucleotide probe, end-labelled with biotin, and amplified with anti-biotin-immunogold silver staining (anti-biotin-IGSS). This system proved more sensitive than amplification with streptavidin-biotinylated alkaline phosphatase for detecting human papilloma virus type 16 in cervical tissues. The method was successfully combined with antigen staining for papilloma virus common antigens in skin and genital warts. This simple and quick method, using non-radioactively labelled synthetic probes, may be useful for the detection of other viruses in stored material and may be suitable for other double staining procedures.

DNA Probes↗