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Biomedical subjects

M Charnock

Publications and source records attributed to M Charnock.

At least 19 recordsLinked to original sources

CD44 expression in cervical intraepithelial neoplasia (CIN) and carcinoma.

BACKGROUND: The expression of the CD44 gene is markedly changed in many neoplastic tissues. The identification of tumor-specific CD44 expression patterns may aid tumor diagnosis. METHODS AND RESULTS: The transcription and translation of the CD44 gene were analyzed by reverse transcription polymerase chain reaction (RT-PCR), in situ hybridization and by immunohistochemistry. Samples were obtained from 24 normal and 24 neoplastic or malignant human cervical tissues. Southern blot hybridization analysis of RT-PCR products revealed an increase in the size and number of CD44 standard and variant transcripts in malignant cervical tissues compared with corresponding normal tissues. Misprocessing of mRNA was indicated in cervical carcinoma cells by the retention of intronic sequences. Multiple CD44 mRNA and protein isoforms were present throughout carcinoma tissues, whereas localization was restricted to the basal epithelium in normal cervical tissue. Analysis of desquamated cervical cells from cases of cervical intraepithelial neoplasia stages I-III showed progressively deranged patterns of CD44 expression, with more alterations being detected in the more advanced stages. CONCLUSIONS: Marked alterations in CD44 expression occur in cervical tissues during progression to malignancy. CD44 expression analysis could aid the early diagnosis of cervical malignancy using minimally invasive methods.

Antigens, Neoplasm

Telomerase activity in human gynaecological malignancies.

AIM: To evaluate whether increased telomerase activity can be clinically useful for detecting malignant cells in a variety of gynaecological specimens. METHODS: Telomerase activity was examined in frozen tissue samples of histologically confirmed lesions of the endometrium, ovary, and cervix. It was also assessed in exfoliated cells in cervical smears from patients with premalignant and malignant lesions and in ascitic fluid obtained from cases with malignant or non-malignant ovarian tumours. RESULTS: Solid tissues from carcinomas were telomerase positive in all specimens of endometrial (6/6) and cervical (6/6) origin, and in almost all from the ovary (12/13). Normal tissues from the cervix (0/5) and the ovary (0/5) were telomerase negative, but samples from normal endometrium were found to show telomerase activity, possibly due to the cyclical regenerative nature of this tissue. Conversely, dissociated cells in cervical smears from preneoplastic and frankly neoplastic lesions rarely showed detectable telomerase activity. Thus smears from patients with malignant tumours were only positive in one of two patients, whereas those from CIN-2 (0/5) and CIN-3 (1/17) lesions and from normal (0/10) samples were almost all negative. Telomerase activity was also scarcely detectable in cells obtained from ascitic fluid from patients with ovarian tumours. CONCLUSIONS: As in many other organs, telomerase activity is increased in solid tissue specimens from malignant tumours of the female reproductive tract, but it is not yet a reliable indicator of the presence of exfoliated cancerous or precancerous cells in clinical specimens from such lesions. Interpretation should be guarded until more extensive studies have been conducted. The data on solid tissues presented here confirm that activation of this enzyme is a major hallmark of the neoplastic process.

Ascites

The basement membrane zone in lichen sclerosus: an immunohistochemical study.

The alteration in expression of basement membrane zone (BMZ) components in lichen sclerosus was investigated by immunohistochemical staining of skin biopsies from seven patients with histologically confirmed disease compared with controls. Monoclonal antibodies and polyclonal sera directed against proteins of the hemidesmosomes, anchoring fibrils, lamina lucida, lamina densa and BMZ collagens were used. Characteristic histological appearances at the dermo-epidermal junction were reflected in widespread alterations in antigen expression in the epidermal basement membrane and the papillary dermis. Expression of the proteins which constitute the structural scaffold (collagen IV and VII) were increased in lichen sclerosus. Expression of hemidesmosomal proteins which mediate adhesion and cell to matrix interaction (alpha 6 beta 4 and bullous pemphigoid antigen) and expression of anchoring filament components were markedly reduced, suggesting that the epidermal cells are exposed to selective damage.

Antibodies, Monoclonal

Detection and typing of human papillomavirus infection of the uterine cervix by dot blot hybridisation: comparison of scrapes and biopsies.

Paired scrapes and biopsies from 100 women attending a routine colposcopy clinic were examined by dot blot DNA hybridisation for infection with human papillomavirus (HPV) types 6/11, 16, 18, and 31; 51% of the scrapes and 50% of the biopsies were positive for HPV infection. Scrapes detected more HPV 18 (10% vs. 2%, P = less than 0.05) and HPV 31 (7% vs. 3%, not significant) than did the biopsies, but biopsies detected more HPV 16 (42% vs. 33%, not significant). Comparison of the results for each patient revealed that the correlation between scrapes and biopsies was not very close: only 34 patients were HPV-positive by both sampling methods, whereas 67 were positive if the results were combined. This report discusses the implications of these findings.

Adolescent

Evaluation of colposcopy in the postmenopausal woman.

Cytology, colposcopy and histology findings in 121 postmenopausal and 120 premenopausal women referred to the Oxford colposcopy clinic were compared; 88% of postmenopausal and 69% of premenopausal women were referred by their general practitioners. Cervical smear reports, within the preceding 5 years, were available for 21% of the postmenopausal and 54% of the premenopausal women. Colposcopic assessment was technically unsatisfactory in 53% of the postmenopausal women because the transformation zone was not completely visible, this contributed to a cone biopsy rate of 71% in this group. Only 17% of postmenopausal women with cervical intraepithelial neoplasia (CIN) were managed with local ablative techniques compared with their use in 61% premenopausal patients overall and in over 70% of the women under 35 years. Local ablation was used in 10 of 14 women using hormone replacement therapy. The cytological false negative rate for postmenopausal Papanicolaou class III, IV and V smears was 9% but for persistent class II inflammatory smears it was 43%. Nine of 23 postmenopausal women with persistent inflammatory dyskariosis despite antibiotic or antifungal treatment were found to have colposcopic appearances of CIN and four had microinvasion or invasion. Colposcopy revealed probable microinvasive or invasive disease in 17 postmenopausal women, seven of whom had class II or III cytology.

Aged

Use of immunocytochemical staining to identify cells in peritoneal fluid and washings at laparoscopy and laparotomy.

Specimens of peritoneal fluid or peritoneal washings from a series of 106 patients who had had laparotomy or laparoscopy for gynaecological complaints were studied "blind" by conventional cytology and immunocytochemical staining. The antibodies used were Ca 1 or Ca 2, anti-CEA, and HMFG-2 or E29. All these are directed against epithelial antigens and are expressed on most malignant epithelial cells and weakly or not at all on mesothelial cells. It was hoped that these reactions would confirm diagnoses made by conventional cytology and possibly show malignant cells which had not already been identified. Of 28 patients with malignant disease (chosen to exclude any with frank ascites), eight gave positive immunochemical reactions, only four having been reported positive from conventional examination. Of 77 patients without malignant disease, HMFG-2 or E29 gave positive reactions in seven, Ca 1 or Ca 2 in two, and anti-CEA in two (reactions with plasma cells being disregarded). Some misleading reactions were probably due to endometrial cells. It was concluded that the antibodies used in this study are not sufficiently specific or sensitive to allow immunocytochemical staining to replace conventional cytological diagnosis but are a useful supplementary aid.

Adult

Cervical wart virus infection, intraepithelial neoplasia and carcinoma; an immunohistological study using a panel of monoclonal antibodies.

The pattern of epithelial antigen expression has been examined in normal and disordered cervical squamous epithelium using immunohistological methods and a range of monoclonal antibodies. It was demonstrated that wart virus infection (WVI) is associated with disordered staining for a keratin-associated component and for HLA-DR antigen. Furthermore, wart-infected epithelium shows strong labelling for carcinoembryonic antigen (CEA) and for human milk fat globule antigens 1 and 2 (HMFG1 and 2). In addition these antigens (CEA, HMFG1 and 2) are also expressed in mixed WVI and cervical intraepithelial neoplasia (CIN), CIN III and in carcinoma. While these findings do not allow immunohistological discrimination between non-neoplastic and neoplastic cervical epithelia, they do provide support for the view that cellular proliferation of the type induced by papilloma virus may represent an initiator stage in the process of neoplastic transformation.

Adenocarcinoma

Endosalpingiosis in pregnancy. Case report.

At caesarean section, an unusual cystic lesion was found on the anterior uterine surface and on both ovaries. Biopsy established a diagnosis of endosalpingiosis. The pathogenesis and possible significance of the lesion are discussed, this being the first time this condition has been described in pregnancy.

Adult

Sensitivity differences displayed by Drosophila melanogaster larvae of different ages to the toxic effects of growth on media containing aflatoxin B1.

Using Drosophila melanogaster, the relative sensitivities of various larval stages to the toxic effects of growth on media supplemented with either 0.44 or 0.88 ppm aflatoxin B1 (AFB1) were determined. Two strains of fruit flies were tested: strain A-11 which is relatively resistant to AFB1 induced toxicity, and strain A-9 which is quite sensitive. Eggs, mid-first, mid-second and early-, mid- and late-third instar larvae were transferred onto AFB1 media and allowed to complete larval and pupal development and eclose as adults. At the 0.44 ppm concentration, strain A-11 showed no effect, while only first instar larvae of strain A-9 showed significant mortality rates for first instar larvae, but the A-9 larvae die at higher rates than the A-11 larvae. In addition, second and third instar larvae of strain A-9 show significant mortality rates when grown at 0.88 ppm AFB1, while these stages are not affected in strain A-11.

Aflatoxins

Placental protein 5 in fetal and maternal compartments.

Placental protein 5 is produced by the syncytiotrophoblast and secreted into the maternal peripheral circulation reaching levels of approximately 30 micrograms per litre in normal pregnancy at term. In the present study the distribution of PP5 was examined in maternal and fetal compartments in 13 patients at delivery.

Amniotic Fluid