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Biomedical subjects

D J McCance

Publications and source records attributed to D J McCance.

71 records · Page 4Linked to original sources

Human papillomavirus type 16 recombinant DNA is maintained as an autonomously replicating episome in monkey kidney cells.

Human papillomavirus type 16 (HPV16) DNA cloned in the expression vector pSV2-neo has been shown to be maintained in transfected monkey kidney cells as an autonomously replicating episome at a level of 2 to 10 copies per cell. Integration of pSV2-neo/HPV16 DNA with the host genome occurred in transfected mouse fibroblasts. Neither type of cell appeared to be phenotypically transformed.

Animals↗

Human papillomavirus types 6 and 16 in multifocal intraepithelial neoplasias of the female lower genital tract.

Five women with multifocal intraepithelial neoplasia of the lower genital tract were investigated for the presence of human papillomavirus (HPV) infection by the method of DNA-DNA hybridization which detects the viral DNA. The DNA sequences of HPV types 6 and 16 were detected in each of the five patients and in each of the areas biopsied: cervix, vagina and vulva. DNA sequences of both viral types were also found in vulval intraepithelial neoplasia grades I-III and in cervical intraepithelial neoplasia grades I and III. The detection of HPV DNAs in multifocal lesions suggests a possible common aetiology for the lower genital tract intraepithelial neoplasias.

Adult↗

Prevalence of human papillomavirus type 16 DNA sequences in cervical intraepithelial neoplasia and invasive carcinoma of the cervix.

The frequency of human papillomavirus (HPV) type 16 in premalignant and malignant lesions of the cervix was investigated and compared with the detection of HPV type 6. In cervical intraepithelial neoplasia (CIN) grades I-III HPV 6 was detected in 28% and HPV 16 in 62% of patients whereas 90% of malignant lesions contained HPV 16 only. In the CIN lesions there was an increase in HPV 16 detection as the severity of disease increased while the level of detection of HPV 6 decreased. Only three (18%) of the cervices that were colposcopically and histologically normal contained HPV genomes; although two of these three women had either a history of genital warts or a sexual partner with penile warts.

Adolescent↗

Human papillomavirus.

Whilst papillomaviruses mainly induce epithelial proliferations in man and in different animal species, the association of this group of viruses with malignant tumours has become increasingly evident. Despite the heterogeneity of human papillomavirus (HPV), only a small number are identified within carcinomas, implying a different, oncogenic potential for different HPV types.

Adult↗

Presence of human papillomavirus DNA sequences in cervical intraepithelial neoplasia.

Twenty two patients referred to a district colposcopy clinic because of an abnormal cervical cytology report or a suspicious cervix and found to have a cervical epithelial abnormality were studied. The techniques of cytology, histology, immunohistochemistry, and DNA-DNA hybridisation were used to detect infection by human papillomavirus. Using an indirect immunoalkaline phosphatase technique human papillomavirus antigen was found in biopsy specimens from six of the 22 patients and DNA of papillomavirus type 6 in biopsy specimens from 13 of these women, including four out of six whose histological diagnosis was cervical intraepithelial neoplasia grade 3. In eight cases where cytological, colposcopical, and histological investigations all indicated the presence of wart virus infection, papillomavirus type 6 DNA was found in seven. Papillomavirus type 6 DNA was found in more than half of the proved cases of cervical intraepithelial neoplasia. The presence of this viral DNA in women with no cervical abnormality is to be studied.

Adolescent↗

Persistence of DNA sequences of BK virus and JC virus in normal human tissues and in diseased tissues.

Available evidence suggests that BK virus (BKV) and JC virus (JCV) persist in the kidneys of healthy individuals after primary infection and may reactivate when the host's immune response is impaired. Data supporting this hypothesis are presented. A previous study had shown BKV to be present in the kidneys of eight (57%) of 14 subjects. In the present study, which extended the investigation to a total of 30 subjects, BKV DNA was found in the renal tissues of 10 (33%) subjects, and JCV DNA was found in the renal tissues of three (10%) subjects. The viral DNA detected appeared not to be integrated with host DNA and to be isolated in foci. Investigation of normal and diseased brain tissue, including tissue from six subjects with multiple sclerosis, failed to reveal the presence of either JCV DNA or BKV DNA.

Adolescent↗

A paralytic disease in nude mice associated with polyoma virus infection.

Nude mice (nu/nu), heterotransplanted with human tumours and kept in isolators, were found to suffer from wasting and posterior paralysis. Electron microscopy of spinal cord tissue revealed virus particles in the oligodendrocytes consistent in size (35 to 40 nm), morphology and distribution with those of the polyoma--SV40 sub-group of papovaviruses. Serology and restriction enzyme analysis of the virus genome showed that the virus was the murine polyoma A2 strain. Inoculation of uninfected nude mice with 10(7) TCID50 of polyoma A2 strain virus produced a similar disease in these mice with wasting and, after 10 to 23 weeks, paralysis of the hind legs of all surviving mice. Extensive myelin disruption was seen throughout the brain stem and sacral region of the spinal cord and high titres of polyoma virus were found in the whole brain (10(8.8) TCID50/brain) and in the spinal cord (10(6.8) TCID50/spinal cord).

Animals↗

Persistence of animal and human papovaviruses in renal and nervous tissues.

The papovavirus polyoma persists in the kidneys of mice after a primary infection. In addition polyomavirus was found in a small percentage of normal mouse brains and in brains of mice exhibiting rear leg paralysis. Human papovaviruses JCV and BKV DNA sequences were found in 10% and 34%, respectively, of normal human kidneys from 29 cadavers, but no sequences from either of these viruses were found in brain tissue from 22 of these same cadavers.

Adolescent↗

The persistence of papovavirus BK DNA sequences in normal human renal tissue.

Evidence has accumulated indicating that BK virus, following an inapparent primary infection, persists in the renal organs of normal healthy individuals and reactivates upon immunosuppression. Data to support this hypothesis are presented and suggest that BK virus DNA sequences are present at very low levels in the kidneys of more than 50% of the population and that this persistence is localized in several foci within these organs.

Aged↗

Reactivation of polyoma virus in kidneys of persistently infected mice during pregnancy.

Female mice infected at birth with 10(7) 50% tissue culture infective doses of polyoma virus were mated when at least 6 weeks old. Polyoma was not detected in any tissues of 27 female mice before mating except for trace amounts in the kidneys of 2 mice, but late in gestation polyoma virus could be found in the kidneys of 21 of 38 mice with titers of 10(3.7) to 10(6.2) 50% tissue culture infective doses per gram of kidney. The virus was not detected in the brain, salivary gland, lung, liver, spleen, ovaries, placenta, or fetuses during gestation. Nonpregnant females were injected with female sex hormones over a period of 17 days, and polyoma was then detected in kidneys of 4 of 18 mice. Treatment of cultures of mouse embryo fibroblasts with either sexhormones or a glucocorticosteroid resulted in approximately a threefold increase in the rate of infection of cells with polyoma virus.

Animals↗

Transplacental transmission of polyoma virus in mice.

When pregnant mice were inoculated on day 1 of gestation with polyoma, some of them exhibited total resorption or reduced litter size, the extent depending on the dose of virus. Virus was detected in 4 out of 11 mouse embryo fibroblast (MEF) cultures made from infected mothers. After maternal infection on day 5 or 10 of gestation, virus titers of up to 10(7) 50% tissue culture infectious doses (TCID50)/g of fetus were found in all pools of fetuses tested 5 days later, with the titers falling by day 6. Hemagglutination-inhibiting antibodies against polyoma appeared in maternal serum by day 6 and rose to a maximum by day 14. Immunoglobulin G class antibodies were detected by day 7, with titers rising rapidly to a maximum at day 14. After maternal infection later in gestation (day 15), one out of three litters of newborn mice was found to have 10(5) TCID50 polyoma virus per g in pooled kidney samples.

Animals↗