Biomedical subjects
J Cason
Publications and source records attributed to J Cason.
Perinatal infection and persistence of human papillomavirus types 16 and 18 in infants.
Perinatal transmission of genital human papillomaviruses (HPVs), including HPV-16 and -18 which are associated with anogenital carcinomas have been described previously [Pakarian et al. (1994): British Journal of Obstetrics and Gynaecology 101:514-517; Kaye et al. (1994) Journal of Medical Virology 44:415-421]. A study was undertaken to investigate whether HPV-16 and -18 DNA in infants contaminated at delivery persists until they are 6 months of age. Of 61 pregnant women recruited, 42 (68.8%) were HPV-16 and 13 (21.3%) were HPV-18 DNA positive. At 24 hr there were transmission rates from HPV DNA positive mothers to their infants of about 73% (HPV-16: 69%; HPV-18: 76.9%). Ten mothers who were both HPV-16 and -18 DNA positive produced six (60%) infants who were also doubly positive at 24 hr. HPV DNA persisted to 6 weeks in 79.5% (HPV-16: 84%; HPV-18: 75%) of those infants who were positive at birth. At 6 months of age, persistent HPV-16 DNA was detected in 83.3% of cases, but HPV-18 DNA persistence at this time was 20%. To extend these observations over a greater age range of children HPV-16 L1 and L2 proteins were expressed in insect cells via recombinant baculoviruses and sera from 229 children were examined to determine at what age IgM antibodies to HPV were acquired. There was a bimodal distribution of IgM seropositivity which peaked between 2 and 5 and 13 and 16 years of age, suggesting that two distinct modes of transmission may occur. The observation that infection with high cancer risk genital HPVs may occur in early life and persist is of considerable importance for HPV vaccine strategies.
Cancer associated human papillomaviruses: perinatal transmission and persistence.
Explore the source record for details and available documents.
Viral load as a determinant for transmission of human papillomavirus type 16 from mother to child.
Whilst genital papillomaviruses are commonly believed to be sexually transmitted, transmission of human papillomavirus type 16 (HPV-16) from mother to child at delivery has been described previously [Pakarian et al. (in press) British Journal of Obstetrics and Gynaecology]. In order to determine whether viral load in cervical/vaginal cells was an important determinant of transmission 15 pregnant women with HPV-16 infections were studied. Eight of these women had infants who were positive for HPV-16 DNA at genital and/or buccal sites. Viral load was estimated by laser densitometry of polymerase chain reaction (PCR) products. The eight mothers--four with a previous history of abnormal smears and two with previous genital warts--who transmitted infection to their infants had significantly higher viral loads (P < 0.05) than those who did not. It is concluded that viral load is an important, but not the sole, determinant for the transmission of HPV-16 from mother to infant.
Strategies for mapping and imitating viral B-cell epitopes.
Identification of viral B-cell epitopes is of importance in the selection of peptides for inclusion into subunit vaccines, the development of virus-specific serological tests and understanding the interaction of antibodies with viruses at a molecular level. B-cell epitopes can often be determined unequivocally by X-ray analyses of antibody-antigen complexes. This technique is, however, time-consuming and alternative strategies have now been developed for identifying epitopes. This article provides an overview of approaches which are currently available for mapping and imitating B-cell epitopes.
Use of a viral and cellular oncogenes to immortalise endothelial cells.
Explore the source record for details and available documents.
Cellular proteins associated with the E5 oncoprotein of human papillomavirus type 16.
Explore the source record for details and available documents.
Analysis of the physical state of human papillomavirus type-16 in early cervical intraepithelial neoplasia.
Explore the source record for details and available documents.
Detection of protein aggregates, but not virus-like particles, when the major (L1) coat protein of a wild-type human papillomavirus type 16 (HPV-16) is expressed in insect cells.
Explore the source record for details and available documents.
Expression of human papillomavirus type 16 (HPV-16) major (L1) and minor (L2) capsid proteins in insect cells as polyhistidine fusion proteins.
Explore the source record for details and available documents.
Hypothetical structure of the membrane-associated E5 oncoprotein of human papillomavirus type 16.
Explore the source record for details and available documents.
Detection of E5 oncoprotein in human papillomavirus type 16-positive cervical scrapes using antibodies raised to synthetic peptides.
Polyclonal antibodies were raised to partial and full-length synthetic peptides of human papillomavirus type 16 (HPV-16) E5. Antisera specificity for HPV-16 E5 was demonstrated by their ability to recognize not only their peptide immunogens but also full-length peptide and a glutathione S-transferase-E5 fusion protein. The most reactive antiserum, PE-6, raised to a full-length peptide, was used in Western blot analysis to identify HPV-16 E5 protein from exfoliated cervical cells. A strong, single band at approximately 20K was detected in two of six HPV-16-positive samples from women with a history of low-grade cervical intraepithelial neoplasia. The apparent M(r) by SDS-PAGE suggests that HPV-16 E5 forms homodimers in vivo, but not through cysteine linkage.
Cancer associated human papillomaviruses: perinatal transmission and persistence.
OBJECTIVE: To demonstrate the perinatal transmission and persistence of the cancer associated human papillomavirus types 16, 18, 31 and 33. DESIGN: Cervical swabs were taken from pregnant women between 20 and 38 weeks of gestation. Buccal and genital swabs were taken from infants at 24 h and at six weeks after delivery and examined for HPV-16, -18, -31 and -33 DNA by the polymerase chain reaction. SETTING: Maternity Unit at St Thomas's Hospital, London. SUBJECTS: Thirty-one pregnant women, 16 with a previous history of cervical intraepithelial neoplasia or genital warts, or both, and their 32 infants (one set of twins). RESULTS: Twenty of the 31 (65%) women were positive for HPV-DNA prior to delivery. Twelve of 32 (38%) and eight of 31 (26%) infants were HPV-DNA positive at 24 h and six weeks respectively. Swabs taken at 24 h demonstrated HPV type 16 in five mother-infant pairs and HPV type 18 in two mother-infant pairs. Dual infections with HPV types 16 and 18 were demonstrated in swabs from three mother-infant pairs. At six weeks, HPV-16 was demonstrated in swabs from six infants and HPV-18 in swabs from two infants. CONCLUSIONS: Perinatal transmission of human papillomavirus types 16 and 18 occurred in 55% cases. Persistent human papillomavirus infection was demonstrated at six weeks of age. Whether acquisition of human papillomavirus during the perinatal period predisposes to an increased risk of cervical intraepithelial neoplasia among female infants in later life remains to be established. Information on the persistence of perinatally acquired human papillomavirus is required before rational vaccination programmes can be considered.
Towards vaccines against human papillomavirus type-16 genital infections.
Human papillomavirus type-16 (HPV-16) is strongly associated with cervical carcinoma and cervical intraepithelial neoplasia. It may soon be possible to develop prophylactic vaccines designed to induce neutralizing antibodies to HPV-16 virions in genital secretions and therapeutic vaccines to induce cytotoxic T-cell responses against HPV-16 early proteins in cervical intraepithelial neoplasia and cervical cancers. Although significant advances have been achieved, problems remain before such vaccines can be used routinely.
Mapping of linear B cell epitopes on capsid proteins of bovine papillomavirus: identification of three external type-restricted epitopes.
Immunodominant, conserved and type-restricted external epitopes of bovine papillomavirus (BPV) major (L1) capsid protein have been identified using BPV particles and synthetic peptides. Antisera to disrupted BPV-1 recognized BPV-1 and BPV-2 particles in immune electron microscopy (IEM) studies and inhibited BPV-2-induced focus formation of NIH/3T3 cells. Thus BPV-1/BPV-2 cross-reactive epitopes occur on the surface of virions. The L1 protein appeared to be immunodominant as the antisera reacted with three dominant BPV-1/BPV-2 conserved B cell epitopes (amino acids 111 to 125, 131 to 145 and 191 to 205) in Pepscan assays of BPV-1 L1, whereas no common epitopes and less frequent antibody binding to peptides were detected in Pepscans of the L2 protein of BPV-1. Four discrete variable regions were identified in the sequences of L1 proteins of BPV-1 and BPV-2. Antisera against synthetic peptides corresponding to three of the four variable regions (amino acids 42 to 56, 435 to 449 and 485 to 499) of BPV-2 L1 caused clumping of BPV-2, but not of BPV-1, particles as examined by IEM, and antisera to one peptide (amino acids 485 to 499) inhibited BPV-2-induced focus formation of NIH/3T3 cells. These data suggest that these regions are type-specific BPV-2 L1 epitopes and that they occur on the virion surface. Although conformation-dependent epitopes remain to be identified on papillomaviruses, the linear epitopes identified in this study may be worthy of further study as constituents of experimental prophylactic vaccines.
Detection of antibodies to a linear epitope on the major coat protein (L1) of human papillomavirus type-16 (HPV-16) in sera from patients with cervical intraepithelial neoplasia and children.
Antibodies to the major (L1) coat protein of human papillomavirus type 16 (HPV-16) in sera from patients with cervical intra-epithelial neoplasia (CIN) have been investigated by means of recombinant proteins and synthetic peptides. When L1-HPV-16 fusion proteins were used in immunoblot assays, no antibody reactivity was found in sera from 52 patients with CIN or from 21 unrelated children. Amino-acid sequence analyses indicated that L1-HPV-16 amino acids 473 to 492 may contain an HPV-16 type-restricted epitope since the greatest diversity occurs in this region. In the ELISA, seropositivity to peptides 473 to 492 was more common among CIN patients whose biopsies contained HPV-16 DNA (91%, 21 of 23) than among their children (24%, 5 of 21; p less than 0.001) or other CIN patients with HPV-16 DNA-negative biopsies (66%, 19 of 29; p less than 0.05), but was unrelated to the severity of the CIN lesion. Antibodies to L1-HPV-16 peptide 473 to 492 among seropositive CIN patients cross-reacted with the analogous L1-HPV-33, but not with the L1-HPV-6b peptide, and were predominantly IgM. In contrast, antibodies which recognized a less variable region of L1-HPV-16 (amino acids 279 to 293) showed no association with HPV-16 DNA status. Seropositivity to the L1-HPV-6b (amino acids 473-492) was less frequent (33%) among CIN patients and unassociated with HPV-16 DNA status (p greater than 0.1); however 51% (37 of 72) of patients with genital warts had antibodies to this peptide.
The influence of zinc status and malnutrition on immunological function in Crohn's disease.
Cellular immunity is likely to be important in the pathogenesis of Crohn's disease; whether it is abnormal is not clear. The heterogeneity of patients with Crohn's disease probably underlies the disparity of reports, but attempts to determine which clinical features influence cellular immunity have been largely unsuccessful. This is probably caused by the omission of nutritional status as a potential factor, even though zinc deficiency has frequently been linked with abnormal immunity. Therefore, a detailed study of nutritional and tissue zinc status, nonspecific cellular immunity, and a measure of phagocytic function was performed in 32 patients with Crohn's disease and in a control group of 18 normal subjects and 12 patients with anorexia nervosa. Fourteen patients with Crohn's disease, all patients with anorexia nervosa, but none of the normal controls were malnourished. Peripheral blood lymphocyte population levels were normal in patients with Crohn's disease and in normal controls, but there was a small decrease in the levels of patients with anorexia nervosa. In vivo delayed hypersensitivity skin test responses were profoundly depressed in patients with anorexia nervosa and decreased in patients with Crohn's disease who were malnourished or receiving systemic glucocorticoids. In vitro lymphocyte transformation was reduced in malnourished patients with Crohn's disease, but there were only minor changes in patients with anorexia nervosa. There were alterations of in vitro immunoregulation in Crohn's disease, but they were not responsible for the abnormal lymphocyte transformation responses in malnourished patients. In vitro phagocytic function was reduced in patients with active Crohn's disease. These findings suggest that depressed in vivo and in vitro cellular immunity in malnourished patients with Crohn's disease is caused by a qualitative lymphocyte defect and that depressed in vivo but normal in vitro cellular immunity in anorexia nervosa is caused by a quantitative defect. Thus, malnutrition in Crohn's disease resembles kwashiorkor; in anorexia nervosa, it resembles marasmus. Tissue zinc status was mostly normal in Crohn's disease and anorexia nervosa, and zinc deficiency was not responsible for depressed nonspecific cellular immunity in either condition.