Biomedical subjects

C Wickenden

Publications and source records attributed to C Wickenden.

24 records · Page 2Linked to original sources

PubMed1986

Association of human papillomavirus with squamous carcinoma of the uterine cervix.

The frequent association of human papillomavirus infection with preinvasive and invasive cancers of the cervix has led to speculation that the viruses may be involved in the neoplastic process. We have carried out some epidemiological studies of the prevalence of human papillomavirus infection in the female genital tract to evaluate more fully the oncogenic potential of these viruses in the cervix. A non-invasive method of detecting the virus has been developed for this purpose using DNA hybridization of cervical scrapings. The technique has been used to carry out prospective studies of patients with cervical intraepithelial neoplasia (CIN) and to investigate infection in women treated by laser therapy for CIN. We have also studied women with normal cervices to determine the prevalence of human papillomaviruses in the normal population. Further studies have involved the investigation of the effect of interferon on virus replication and epithelial proliferation in women with CIN III.

Carcinoma in Situ↗

PubMed1986

The effect of interferon on human papillomaviruses associated with cervical intraepithelial neoplasia.

A double-blind, placebo-controlled, trial of leucocyte interferon showed that, contrary to previous reports, interferon had no significant effect on cervical intraepithelial neoplasia (CIN) when applied topically in a gel. DNA hybridization of cervical scrapes was used to monitor the effect of interferon on the human papillomaviruses (HPV) associated with CIN. There was, however, no significant difference in the expression of HPV 6 or 16 in the cervical epithelium of patients treated with interferon compared with those given a placebo. By using superficial cells scraped from the surface of the cervical epithelium as a source of DNA for viral studies, we were able to investigate the relation between HPV and CIN without interfering with the natural history of the disease. HPV 16 was detected in lesions which persisted while HPV 6 only was detected in one lesion that regressed. Regression was clearly associated with reduction in the number of copies of viral DNA per cell in this case. Dual infection with HPV types 6 and 16 were recorded in two patients with persistent lesions. In one patient, hybridization studies indicated that infection with HPV 16 could have occurred after infection with type 6 was established, and it is postulated that this may have changed the nature of the cervical lesion.

Adolescent↗

PubMed1985

Screening for wart virus infection in normal and abnormal cervices by DNA hybridisation of cervical scrapes.

Cervical scrapings from 78 women attending a sexually transmitted diseases (STD) clinic, family planning clinic, and colposcopy clinic were assayed for human papillomavirus type 6 (HPV-6) by DNA hybridisation. Results of hybridisation were compared with clinical, colposcopic, and cytological findings. Scrapings from 2 of the 4 women with genital warts gave positive results with the HPV probe. No HPV-6 DNA was detected in scrapings from 18 women attending an FPC whereas scrapings from 2 of 19 STD clinic patients with normal colposcopic and cytological examination were positive-this means that DNA hybridisation detected wart virus infection where previously none was suspected. HPV-6 DNA was detected in about 10% of cervical scrapings from women with cervical intraepithelial neoplasia (CIN) both before and after treatment. Indeed in 2 patients in whom viral DNA persisted after laser therapy, it was associated with local recurrence of neoplasia. This non-invasive technique is suitable for use as a screening test for HPV infection. In this study it identified women who have a high risk of developing CIN and in whom close cytological and colposcopic surveillance is indicated.

Animals↗

PubMed1985

Laboratory assessment of hepatic injury in the woodchuck (Marmota monax).

Normal reference values for total serum protein, albumin, cholesterol, alanine aminotransferase (ALT), aspartate aminotransferase (AST), sorbitol dehydrogenase (SDH), gamma glutamyl transferase (GGT), alkaline phosphatase (AP), and total bilirubin were established in 48 clinically healthy woodchucks. To validate the use of these biochemical tests in the woodchuck for assessment of liver injury, carbon tetrachloride was administered to produce hepatocellular necrosis and the common bile duct was surgically occluded to produce cholestasis. Biochemical tests were performed prior to experimental treatment and thereafter in surviving woodchucks for a period of 6 weeks. There were marked increases in the serum activities of AST, ALT, and SDH following carbon tetrachloride administration and all 3 enzymes appeared to be useful markers of acute hepatocellular injury. The predominate biochemical abnormalities in woodchucks with bile duct obstruction were hyperbilirubinemia, hypercholesterolemia and increased serum AP and GGT activities. The increase of GGT occurred earlier following bile duct obstruction and the magnitude of increase was greater than that of AP, suggesting that GGT would be the preferred serum enzyme test in the woodchuck for assessment of cholestatic liver injury.

Alanine Transaminase↗

PubMed1984

Proteolysis of ankyrin and of band 3 protein in chemically induced cell fusion. Ca2+ is not mandatory for fusion.

Human erythrocytes were fused by incubation with 0.5-2 mM-chlorpromazine hydrochloride at pH 6.8-7.6. Fusogenic preparations of chlorpromazine were cloudy suspensions of microdroplets, and below pH 6.8 chlorpromazine gave clear solutions that were inactive. Unlike control cells, the lateral mobility of the intramembranous particles of the PF-fracture face of chlorpromazine-treated cells was relatively unrestricted, since the particles were partly clustered at 37 degrees C and they exhibited extensive cold-induced clustering. Ca2+ stimulated fusion, but fusion was only very weakly inhibited by EGTA (10 mM) and by N-ethylmaleimide (50 mM); pretreatment of the cells with Tos-Lys-CH2Cl (7-amino-1-chloro-3-L-tosylamidoheptan-2-one) (7.5 mM) markedly inhibited fusion. Changes in the membrane proteins of erythrocytes fused by chlorpromazine, before and after treatment with chymotrypsin to remove band 3 protein, were investigated. The several observations made indicate that the Ca2+-insensitive component of fusion is associated with degradation of ankyrin (band 2.1 protein) to band 2.3-2.6 proteins and to smaller polypeptides by a serine proteinase that is inhibited by Tos-Lys-CH2Cl, and that the component of fusion inhibited by EGTA and N-ethylmaleimide is associated with degradation of band 3 protein to band 4.5 protein by a Ca2+-activated cysteine proteinase. Proteolysis of ankyrin appeared to be sufficient to permit the chlorpromazine-induced fusion of human erythrocytes, but fusion occurred more rapidly when band 3 protein was also degraded in the presence of Ca2+. Since other cells have structures comparable with the spectrin-actin skeleton of the erythrocyte membrane, the observations reported may be relevant to the initiation of naturally occurring fusion reactions in biomembranes. It is also suggested that, should polypeptides with fusogenic properties be produced from integral and skeletal membrane proteins by endogenous proteolysis, their formation would provide a general mechanism for the fusion of lipid bilayers in biomembrane fusion reactions.

Anion Exchange Protein 1, Erythrocyte↗

PubMed1984

Monoclonal antibodies for the histopathological diagnosis of cervical neoplasia.

Five monoclonal antibodies (Ca1, HMFG 1 and 2, 8.30.3 and 77.1) were used to study the distribution of antibody binding sites in cervical tissue with a view to identifying a marker which would distinguish between benign and malignant cervical epithelium. Both benign tissue (mature and immature metaplastic squamous epithelium, congenital transformation zone and glandular epithelium) and neoplastic tissue (cervical intraepithelial neoplasia, 1, 2 and 3 and invasive squamous cell carcinoma) were stained by these antibodies. Although immature metaplastic epithelium stained strongly with all the antibodies, the intensity and distribution of staining in general did not distinguish between benign and neoplastic conditions. All five antibodies, raised against three different antigens, stained cervical tissue in a similar way and thus were unsuitable for use as specific tumour markers in equivocal cases. Further studies on other tumour markers are indicated in view of the potential value of this approach.

Antibodies, Monoclonal↗