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Biomedical subjects

M Norval

Publications and source records attributed to M Norval.

At least 109 records · Page 6Linked to original sources
PubMed1989

Herpes simplex virus infections: new concepts in an old disease.

This paper reviews recent clinical and laboratory investigations on herpes simplex viruses (HSV). New findings add to our knowledge about factors influencing HSV infection such as site of infection, virus type and they also point to the importance of the immune system for the outcome of infection. It appears that circumstances at the time of primary infection can modify the type of immune response generated and affect the likelihood of later recrudescence. One of these factors is UV light which seems to act via a photoisomer [cis(Z-)urocanic acid] on the immune system.

Herpes Simplex↗
PubMed1989

Nuclear DNA analysis of prostate tissues: correlation with stage and grade of tumour.

Flow cytometry was used to analyse the DNA content of 20 unfixed prostatic specimens obtained from patients with cancer of the prostate. The tumours were of different stages and grades of differentiation and the numbers of cells in each phase of the cell cycle were compared to those obtained from 26 patients with benign prostatic hyperplasia. It was noted that, as the cancer progressed from a well to a poorly differentiated state, there was a distinct shift in the distribution of cells in the G0/G1 phase towards the S and G2+M phases. This was particularly marked in cases with a summed Gleason score of 7-10, and was independent of the stage and bulk of the tumour. Furthermore, all tumours with a Gleason score of 7 or more exhibited a tetraploid histogram, whereas only 2 of 14 patients with a well or moderately well differentiated cancer had tetraploid histograms. Two patients were found to have tumours with aneuploid DNA content, and both died within 2 years from the time of diagnosis. Although it is too early to speculate on the place flow cytometry in the clinical management of patients with cancer of the prostate, the results generated from this present study suggest that flow cytometry may be capable of providing prognostic information not supplied from histopathological analysis.

Aged↗
PubMed1989

Severe eczema herpeticum is associated with prolonged depression of cell-mediated immunity to herpes simplex virus.

Nine patients with eczema herpeticum (EH) and 2 with atopic eczema and recurrent cold sores were investigated for cell-mediated immunity (CMI) and antibodies (Ab) to herpes simplex virus (HSV). All patients had Ab to HSV and a high lymphoproliferation response to concanavalin A and all but 3 showed lymphoproliferation to HSV antigens. These 3 patients had very severe EH and absent CMI to HSV for many months after clinical recovery despite normal Ab and concanavalin A responses. In 2 of them, depletion of CD8+ T cells by panning restored the lymphoproliferative response to HSV. Thus their absent CMI may be due to suppressor cell function rather than lack of responsive cells.

Dermatitis, Atopic↗
PubMed1989

Variation in lymphoproliferative responses during recrudescent orofacial herpes simplex virus infections.

Sixty-five patients with recrudescent orofacial herpes simplex virus (HSV) infections all had circulating HSV-specific antibody measured by ELISA and cell-mediated immunity (CMI) to HSV by in vitro lymphoproliferation. Thirteen control subjects with no history of HSV were negative for both tests. Thirty-three patients, repeatedly investigated during 6 to 38 months, had between 1 and 8 recrudescences each. Lymphoproliferative responses to HSV were low during recrudescence, rose to a peak a few weeks later and then declined to a positive background level. However, ELISA titres and lymphoproliferative responses to concanavalin A were high throughout, and peripheral blood mononuclear cell (PBMC) subset numbers measured by fluorescent flow cytometry remained within normal limits. During HSV lesions, depressed lymphoproliferation to HSV was abrogated by removal of CD8+ T cells from PBMC either by using a panning technique (nine patients) or by cell sorting (three patients). Reconstitution of the CD8-depleted population suppressed the lymphoproliferative response to HSV. Depletion of CD8+ T cells did not affect lymphoproliferation to HSV outwith recrudescence (four patients), nor lymphoproliferative responses to another antigen (PPD; five patients) during recrudescence. Thus, reduced lymphoproliferation to HSV during recrudescence may be due to HSV-specific CD8+ suppressor T lymphocyte function, rather than lack of HSV-responsive lymphocytes. This may result in depression of normal CMI responses to the virus during an asymptomatic recurrence allowing recrudescent lesions to develop.

Adolescent↗
PubMed1988

Humoral and cellular immunity to papillomavirus in patients with cervical dysplasia.

The cell-mediated and humoral immune responses to human papillomavirus (HPV) were tested in groups of patients with various degrees of cervical intraepithelial neoplasia (CIN) using a lymphocyte proliferation assay (LPA) as a measure of circulating sensitised T-cells and an enzyme-linked immunosorbent assay (ELISA) for antibodies. Twenty-three of 92 patients (25%) gave stimulation indices (S.I.) greater than two to at least one of the several antigen preparations tested in the LPA. Of 282 patients, 144 (50.1%) showed ELISA indices (E.I.) greater than one to HPV-1 and/or HPV-2 antigens prepared by disruption of purified virions. No correlation was found between positive responses in either test and the presence in cervical biopsies of koilocytes (considered pathognomonic for HPV infections), or between positive responses and the degree of dysplasia observed. Rather, positive antibody and T-cell responses corresponded with a history of past or present skin warts. Although antibody was detected in 42/86 (48.8%) women who thought they had never had warts, only 2/24 (8.3%) with no known history gave a positive S.I. in LPA.

Antibodies, Viral↗
PubMed1988

Synthetic oligonucleotide probes for the detection of human papilloma viruses by in situ hybridisation.

Using the published nucleotide sequence data for human papilloma virus (HPV) types 1, 6 and 16, sequences of 30 bases in length from the beginning of the E6 open reading frame (ORF) were selected. Oligonucleotides were synthesised on an Oswel Gene Synthesizer and labelled at the 3' end with biotin using the enzyme terminal transferase. In situ hybridisation was carried out on paraffin sections of wart and cervical tissues mounted on silanated slides. A 2 h hybridisation step allowed the whole process to be completed within one working day. The technique successfully demonstrated the presence of HPV-1 in skin warts, and of HPV-6 and HPV-16 in genital warts and cervical lesions. This simple approach has diagnostic potential for the detection and typing of papilloma viruses in biopsy material.

Base Sequence↗
PubMed1988

Immune responses to herpes simplex virus in patients with facial herpes simplex and those with eczema herpeticum.

The immune response to herpes simplex virus (HSV) was studied in 59 patients with primary and recrudescent facial HSV infections. The patients included nine with atopic eczema, seven of whom had eczema herpeticum (EH). All patients had antibodies to HSV (measured by ELISA) and all but three had HSV-specific cell mediated immunity (CMI) (measured by in vitro lymphoproliferation). Thirteen control subjects were negative for both tests. All three patients with absent CMI to HSV had suffered from severe EH and had depressed CMI to HSV for several months following an attack. In two of these EH patients, a positive CMI response was produced by in vitro removal of CD8 + ve T lymphocytes from peripheral blood mononuclear cells using a panning technique. Thus the absence of CMI to HSV in these patients was due to suppressor cell function rather than a lack of specifically responsive cells. The other four EH patients with normal CMI to HSV had suffered less severe EH, but no association between the absence of CMI to HSV and serum IgE level or activity of the eczema was apparent in the atopic patients. No specific anti-HSV IgE antibody was detectable.

Adolescent↗
PubMed1988

Significance of smoking and detection of serum antibodies to cytomegalovirus in cervical dysplasia.

Cervical biopsy specimens from 422 women attending a colposcopy clinic showed various grades of dysplasia in 387 and no evidence of dysplasia in 35. Of the women with dysplasia (CIN I, II or III) 67% were smokers and 33% were non-smokers compared with 43% smokers and 57% non-smokers in those without evidence of dysplasia. Of the women with CIN I 56% were smokers and 44% were non-smokers; 66% of those with CIN II were smokers and 34% were non-smokers (P less than 0.02), and 71% of those with CIN III were smokers (P less than 0.01). There were no significant differences between the smokers and non-smokers in the proportion of women who had had either a miscarriage or an abortion, in the prevalence of condylomata acuminata, and the use of oral contraception or barrier methods. Neither were there any significant differences in numbers of patients seropositive for cytomegalovirus or in CMV antibody titres among the groups. The detection of koilocytic cells in cervical biopsies showed a significant difference between smoking and non-smoking groups which reflected a significant increase in koilocytosis in smokers with CIN III.

Adult↗
PubMed1988

Expression of major histocompatibility class II antigens by Langerhans' cells in cervical intraepithelial neoplasia.

Cervical biopsy samples from 67 patients who had various grades of cervical intraepithelial neoplasia (CIN) or who showed evidence, in the form of koilocytosis, of human papillomavirus (HPV) infection of the uterine cervix, and from 10 women with normal cervices were examined. Cryostat sections from the biopsy samples were stained using monoclonal antibodies to T6, a Langerhans' cell marker, and to major histocompatibility complex (MHC) class II antigens (HLA-DP, DQ, and DR). Epithelial Langerhans' cells were reduced in number and showed changed morphology and distribution in koilocytic lesions and in all grades of CIN (p less than 0.01) except CIN I. HLA-DR expression by Langerhans' cells was significantly increased in koilocytic lesions and in CIN grades I and II (p less than 0.05); HLA-DQ expression was significantly increased in all grades of CIN (p less than 0.05) with the increase being most pronounced in CIN I (p less than 0.01). Columnar epithelium expressed MHC class II antigens in all samples tested and squamous epithelium in four of 29 cases of CIN III. These findings support the view that there is a localised disturbance of immune function in both neoplastic cervical epithelium and that infected with papillomavirus.

Adult↗
PubMed1988

The role of antigen presentation in the ontogeny of immune responses to herpes simplex virus.

The ability of epidermal antigen presenting cells (APC) to induce immune responses to herpes simplex virus (HSV) has been studied in mice of differing ages. Using an in vivo model of HSV infection we have demonstrated that neonatal epidermal cells (EC) induce specific suppression of DH to HSV in normal syngeneic adult mice. The suppression is transferable and mediated by T cells of the Lyt1+, Lyt2-, L3T4+ phenotype. The ability of EC to induce suppression persists up to 4 weeks of age, whereas EC from mice 6 weeks of age or older induce positive DH responses to the virus. This correlates with the susceptibility of mice of the different ages to HSV infection and their ability to mount DH responses to the virus.

Aging↗
PubMed1988

Quantification of urocanic acid isomers in murine skin during development and after irradiation with UVB light.

Urocanic acid has been postulated as the photoreceptor mediator of immunosuppression induced by ultraviolet-B (UVB) irradiation. We have shown previously that transplanted epidermal cells from neonatal mice, irradiated mice or mice skin painted with cis-urocanic acid suppress the immune responses to herpes simplex virus. Dorsal skin from foetal mice at 3 weeks gestation and from neonatal mice within 1 day of birth were assayed for the presence of cis- and trans-urocanic acid and compared with the amounts in the ears of 2, 4, 6 and 8-week old mice. Foetal mice had a low skin urocanic acid content (11.9 ng/mg wet weight), neonatal mice 227 ng/mg, while the other ages had at least 340 ng/mg. Neonatal mice were found to have 11.4% urocanic acid as the cis-isomer, whereas foetal mice had undetectable amounts and all remaining ages had about 4%. Irradiation of 7-week-old mice with 96 mJ/cm2 UVB light resulted in the presence within the ears of 31.1% urocanic acid as the cis-isomer. This level was maintained for at least 16 h, then declined slowly until, after 7 days, 16.2% was in the cis-form. Nonirradiated ears contained 4.7% cis-isomer. It is known that UVB irradiation of mice suppresses the delayed type hypersensitivity response to HSV. The suppression was found to be dependent on the time interval between irradiation and infection with virus; this had to be longer than 5 h and less than 14 days.(ABSTRACT TRUNCATED AT 250 WORDS)

Aging↗
PubMed1988

The immune response to glycoproteins of herpes simplex virus.

Herpes simplex virus commonly causes 'cold sores', the virus often becoming latent after the primary infection and recrudescing at intervals. Six glycoproteins have been described in the virion and in the membranes of infected cells; much of the host's immune response is directed against these molecules. The functions of individual glycoproteins in the disease process and in the induction of different components of the immune response are beginning to be unravelled, which should help provide a strategy for the creation of an effective subunit vaccine against the virus.

Antibodies, Bacterial↗
PubMed1988

Systemic administration of urocanic acid generates suppression of the delayed type hypersensitivity response to herpes simplex virus in a murine model of infection.

Urocanic acid (UCA), the putative photoreceptor for ultraviolet radiation (UV)-induced immunosuppression, undergoes a UV-dependent trans to cis isomerization. When UCA, containing a known proportion of the cis isomer, is administered by the intravenous route and live herpes simplex virus is given subcutaneously shortly afterwards, suppression of the delayed type hypersensitivity response to the virus is induced. Two T suppressor cell subsets are generated, one [Ly2+, L3T4-] and the other [Ly2-, L3T4+]. The results are discussed with regard to the differences indicated between local (epidermal) and systemic immunosuppression.

Animals↗
PubMed1988

The effect of tamoxifen on tumours induced by cells from a canine mammary carcinoma cell line in athymic nude mice.

Tumours were induced in CBA athymic nude mice by subcutaneous injection of REM 134 cells. These cells were from a continuous line derived from a canine mammary carcinoma and have no detectable oestrogen receptors. In vitro, the anti-oestrogen tamoxifen was growth inhibitory at a concentration of 10(-6) M and adding 10(-8) M oestradiol-17 beta did not reverse this effect. The relative rate of growth of the tumours induced by the cultured cells was the same in male and female mice. Oral tamoxifen at a dose of 1 mg mouse-1 week-1 suppressed the early growth rate significantly and to the same extent in male and female mice; conversely subcutaneous tamoxifen at 2 mg mouse-1 week-1 had only a transient early effect. These results argue against tamoxifen acting solely as an antagonist for oestrogen.

Animals↗
PubMed1987

Nuclear DNA analysis of koilocytic and premalignant lesions of the uterine cervix.

Cervical biopsy samples were taken from 79 patients who had various grades of cervical intraepithelial neoplasia or who showed evidence, in the form of koilocytosis, of human papillomavirus infection of the uterine cervix and from 10 women with normal cervices. The DNA content of the cells in the samples was analysed by flow cytometry. Analysis of the data obtained showed that the biopsy samples from women with cervical intraepithelial neoplasia and human papillomavirus lesions contained significantly more dividing cells (31.2% of cells from human papillomavirus lesions with no cervical intraepithelial neoplasia and 33.06%, 29.89%, and 31.76% of cells from cervical intraepithelial neoplasia grades I, II, and III, respectively) than those from women with normal cervices (21.6%). The proportion of aneuploid samples from the group who showed evidence of human papillomavirus infection only (18.2%) did not differ significantly from the group with cervical intraepithelial neoplasia grade III (21.2%). Aneuploidy and an increased rate of cellular proliferation are recognised characteristics of malignancy. These results therefore support the view that human papillomavirus plays an important part in the aetiology of cervical carcinoma and are relevant to the clinical management of patients.

Adult↗
PubMed1987

Advances in the use of nucleic acid probes in diagnosis of viral diseases of man. Brief review.

A variety of methods are now available for the preparation and labelling of viral nucleic acids for use as probes in diagnostic virology. Some of these are assessed including the use of synthetic oligonucleotides in place of molecularly cloned nucleic acids, and alternatives to labelling with radioactive isotopes such as biotin, enzymes and fluorochromes. Dot blot, sandwich, indirect sandwich and in situ hybridization are covered, and examples given of the current use of nucleic acid probes in detection of human viral infections. The potential and limitations of nucleic acid hybridization are discussed in the light of these new methods.

DNA, Viral↗
PubMed1987

A murine model of herpes simplex virus recrudescence.

A murine model is described in which recrudescence of herpes simplex virus (HSV) type 1 was achieved. C3H mice were shaved and irradiated with u.v. B light 3 days before being infected epidermally with a clinical isolate of HSV. Seven weeks or longer following the primary infection, the survivors were again shaved, irradiated with u.v. and mildly tape-stripped. Recrudescent lesions occurred in up to 80% of mice at the site of the original lesion in most cases, but also occasionally at other sites. Skin painting with u.v.-irradiated urocanic acid (a substance suggested to be a photomediator of the immunosuppressive effects of u.v.) in place of u.v.-irradiation induced some recrudescence but was not as efficient as u.v.-irradiation. Antibody titres to HSV had no value in predicting whether recrudescence would occur but lymphoproliferative responses in draining lymph nodes may provide some indication of viral activity at the epidermal site. A hypothesis is developed that u.v.-irradiation before primary infection with HSV induces a suppressive immune response to the virus which affects the virus-host interaction and accounts for a high incidence of recrudescent lesions on subsequent stimulus.

Animals↗