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J A Tidy

Publications and source records attributed to J A Tidy.

27 records · Page 2Linked to original sources
PubMed1991

Degradation of p53 can be targeted by HPV E6 sequences distinct from those required for p53 binding and trans-activation.

Human papillomavirus (HPV) types 16 and 18 appear to play a role in the development of ano-genital malignancies, whereas HPV 6 and 11 are usually associated with benign lesions. One HPV16 oncoprotein, E6, complexes with and promotes degradation of the cellular tumor suppressor p53. Here we show that E6 proteins of both oncogenic and benign HPV types associate in vitro with p53, but binding by E6 proteins of benign HPV types cannot target p53 for degradation. A C-terminal region of E6 conserved among all HPV types is important for p53 binding. However, N-terminal sequences of E6 conserved only between oncogenic HPV types are necessary to direct p53 degradation. p53 binding by E6 appears necessary but not sufficient for this activity. All E6 proteins tested showed comparable transcriptional trans-activating activity, a property that does not require the ability to bind or direct degradation of p53.

Amino Acid Sequence↗
PubMed1991

Expression of RB and p53 proteins in HPV-positive and HPV-negative cervical carcinoma cell lines.

Mutations within the tumor suppressor genes Rb-1 and p53 are commonly found in many human malignancies, and loss of wild-type function of both p53 and RB appear to be important events in the development of these malignancies. Interference with normal RB and p53 function in the cell has apparently also been exploited by the oncogenic genital human papillomaviruses (HPVs), which encode transforming proteins capable of binding cellular RB and p53 proteins. We have investigated the expression of RB and p53 in a series of eight cervical carcinoma cell lines, six of which contain HPV sequences and two of which have arisen apparently independently of HPV infection. In the six HPV-positive lines, no evidence of abnormal RB or p53 protein could be detected. However, there was evidence for abnormal RB and p53 in the two HPV-negative lines. These data are consistent with the hypothesis that loss of wild-type RB and p53 function is necessary for tumor development and that such loss can occur either by mutation within the cellular gene or by expression of viral proteins capable of complexing wild-type cellular proteins.

Carcinoma↗
PubMed1989

Relation between infection with a subtype of HPV16 and cervical neoplasia.

A variant (HPV16b) of the previously described human papillomavirus (HPV)16 (now called HPV16a) has been identified by polymerase chain reaction assays. Compared with HPV16a, HPV16b has a 21bp deletion and several point mutations within the upstream regulatory region. All cervical carcinoma samples studied contained only HPV16a. HPV16b was found only rarely in cervical neoplasia but was common in the normal population.

Carcinoma↗
PubMed1989

A new and sensitive method of screening for human papillomavirus infection.

Human papillomaviruses (HPVs) have been implicated in the development of cervical cancer, and HPV screening may one day supplement cytologic analysis of cervical samples. Detection of the small amounts of HPV DNA in cervical scrapes has been very difficult. The polymerase chain reaction is a new technique that can specifically amplify target DNA to facilitate its detection. We have amplified a region of HPV type 16 DNA using this technique and have shown the method to be both specific and sensitive (a tenfold improvement when compared with Southern blotting). Among 21 cervical scrapes, five from women with normal smears and 16 from women with dyskaryotic smears, HPV 16 DNA was present in scrapes from two women (40%) with normal smears and in scrapes from 12 women (75%) with dyskaryotic smears. The polymerase chain reaction technique is rapid, requires no radioactive probes, and should be the method of choice in future studies to determine the prevalence of HPV infection of the cervix.

DNA, Viral↗
PubMed1989

Laser excision rather than vaporization: the treatment of choice for cervical intraepithelial neoplasia.

We are concerned that the use of ablative therapy in the treatment of cervical intraepithelial neoplasia may lead to a failure to diagnose early invasive carcinoma. In view of this, since June 1986, 196 patients considered suitable for laser vaporization were treated by a shallow laser excision cone biopsy instead. The mean age of the women treated was 31 years, and the mean length of the excised specimen, measured after fixation, was 14 mm. All procedures were completed in the colposcopy clinic and took no longer to perform than vaporization. The complication rate was low, and an excellent specimen was available for pathologic examination. In this series, histology on the excised cone revealed that two patients had microinvasive carcinoma and one had adenocarcinoma in situ. In addition, 16 patients had a lesion two or three grades worse on the laser excision biopsy than was predicted by the colposcopically directed biopsy. Because of the inaccuracy of colposcopic biopsy, we now recommend a small laser excision cone biopsy as the treatment of choice for all patients with cervical intraepithelial neoplasia.

Adolescent↗
PubMedDate not supplied

The clinical presentation, treatment, and outcome of patients diagnosed with possible ectopic molar gestation.

The objective of this study was to determine the clinical presentation, treatment, and outcome of patients diagnosed with possible ectopic molar gestation registered with the Trophoblastic Disease Screening and Treatment Centre, Weston Park Hospital, Sheffield between 1986 and 2000. From the 5581 women registered, those with a diagnosis of ectopic molar pregnancy were identified from a computer database. Information regarding the relevant history of each patient and the clinical presentation, treatment, and outcomes of gestational trophoblastic disease (GTD) was determined by reviewing referral forms, case notes, and pro formas completed by the referring gynecologist. Histological review of the cases was undertaken where possible. Suspected ectopic molar gestations comprised 31/5581 (0.55%) of registrations. Known risk factors for ectopic pregnancy were identified in 79% of cases. Central histological review confirmed only six cases of GTD: three choriocarcinoma and three early complete moles. Four patients subsequently required chemotherapy. All patients are now in complete remission. We conclude that ectopic GTD is uncommon, with a UK incidence of approximately 1.5 per 1,000,000 births. Initial management is usually surgical removal of the conceptus, pathological suspicion of the diagnosis and registration with a screening center. Chemotherapy may be required and the prognosis is excellent.

England↗
PubMedDate not supplied

Upregulation of CD44 expression by interleukins 1, 4, and 13, transforming growth factor-beta1, estrogen, and progestogen in human cervical adenocarcinoma cell lines.

Although cervical adenocarcinoma constitutes approximately 10-20% of primary malignant tumors of the uterine cervix, its pathogenesis is less well understood than that of the corresponding squamous cancer. CD44 is a cell surface glycoprotein postulated to play a role in many biologic processes including tumor growth and metastasis. We have previously reported from immunohistochemical studies that a particular CD44 variant (CD44v5) is consistently overexpressed in endocervical neoplasia. It thus has potential as a diagnostic marker and even as a target for therapeutic approaches directed against specific epitopes. The aim of this study was to investigate which cytokines and hormones are capable of modulating CD44v5 expression, using a cell culture model. The effects of interleukin (IL)-1alpha, IL-1beta, IL-4, IL-13, transforming growth factor (TGF)-beta1, estrogen, and progestogen on CD44v5 expression were examined in cultures of three human cervical adenocarcinoma cell lines (HeLa, HeLa229, and HS588T). Expression was assessed using dual fluorescence-labeled flow cytometry and western blotting techniques. It was found that incubation of cultures for 72 h with IL-1alpha, IL-1beta, IL-4, IL-13, TGF-beta1 (all at 0.1-10 ng/mL), estrogen (5-10 ng/mL), or progestogen (5-20 ng/mL) induced significant upregulation of CD44v5. These factors are likely to exert a similar stimulatory influence in vivo and may contribute to the process of carcinogenesis.

Adenocarcinoma↗
PubMedDate not supplied

The use of electrical impedance spectroscopy in the detection of cervical intraepithelial neoplasia.

The objective of this study was to assess the performance of cervical impedance spectroscopy in the detection of cervical intraepithelial neoplasia (CIN) using the new MKIII impedance probe. A prospective observational study recruited women referred to colposcopy with an abnormal Papanicolaou smear. A pencil probe incorporating four gold electrodes was used to measure electrical impedance spectra from cervical epithelium. Colposcopy examinations, including probe positioning, were video recorded to allow for correlation between results obtained from colposcopic impression, histopathologic examination of colposcopic punch biopsies, and impedance measurements. Cervical impedance-derived parameters R, S, R/S, C, and Fc were assessed to see if significant difference in values obtained in CIN and normal epithelium existed. The performance of the probe in identifying women with CIN was also assessed. One hundred seventy-six women were recruited and 1168 points analyzed. Parameters R, S, and Fc showed significant separation of CIN or squamous intraepithelial lesion (SIL) from squamous, mature metaplastic, and columnar epithelium. Sensitivities of 74% and specificity of 53% can be achieved in identifying CIN 2/3 (High-grade SIL) in screened women. We conclude that cervical impedance spectrometry provides a potentially promising real-time screening tool for CIN with similar sensitivity and specificity to currently used screening tests. Further research is ongoing to develop the probe for potential clinical use.

Cervix Uteri↗