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Biomedical subjects

P Londesborough

Publications and source records attributed to P Londesborough.

16 recordsLinked to original sources
PubMed2006

The expression of FHIT, PCNA and EGFR in benign and malignant breast lesions.

Immunohistochemical staining for FHIT and PCNA proteins was carried out in 451 breast lesions showing nonproliferative benign breast disease (BBD) (n=263), proliferative BBD without atypia (n=128), proliferative BBD with atypia (n=11), carcinoma in situ (n=15) or invasive carcinoma (n=34) and for EGFR protein in a subset of 71 of these cases. FHIT underexpression was not detected in nonproliferative lesions, but occurred in 2% of proliferative BBD without atypia, 10% proliferative BBD with atypia, 27% of carcinoma in situ and 41% of invasive carcinoma, which suggests that it could be useful in assessing those carcinoma in situ lesions (ductal, DCIS and lobular, LCIS) that are more likely to progress to malignancy. Preliminary microarray comparisons on DCIS and invasive carcinoma samples dissected from formalin-fixed paraffin sections showed a consistent downregulation of two previously identified FHIT-related genes, caspase 1 and BRCA1 in lesions underexpressing FHIT.

Acid Anhydride Hydrolases↗
PubMed2004

The role of human papillomavirus type 16 and the fragile histidine triad gene in the outcome of cervical neoplastic lesions.

The presence of high-risk human papillomavirus, loss of heterozygosity on chromosome 3p and fragile histidine triad gene expression were assessed as potential markers of cancer and CIN progression in 83 cervical cancers and 74 cervical intraepithelial neoplasia grade 1 lesions. Human papillomavirus type 16 was an indicator of vascular involvement in cancers. Loss of heterozygosity, especially in the fragile histidine triad gene intron 5, was an indicator of high-grade tumours, greater tumour depth and lymph node involvement. Abnormal fragile histidine triad gene expression was more frequent in cervical intraepithelial neoplasia grade 1 lesions with increased risk of disease progression.

Acid Anhydride Hydrolases↗
PubMed2002

Abnormal FHIT expression profiles in cervical intraepithelial neoplastic (CIN) lesions.

Abnormal fragile histidine triad transcripts were found in 20-30% of CIN2/3 lesions and 11% of normal cervical biopsies by RT-PCR. Bi-allelic loss of the fragile histidine triad gene and the loss of fragile histidine triad protein expression detectable by immunochemical staining with a polyclonal fragile histidine triad specific antibody was rare. The genomic changes showed no association with the presence of human papillomavirus types which carry high risk for cervical cancer (high risk human papillomavirus) as assessed by a type-specific multiplex PCR. The presence of abnormal fragile histidine triad transcripts in a subset of CIN2/3 lesions with no high risk human papillomavirus suggests that this could be an independent risk factor associated with an alternative carcinogenic pathway.

Acid Anhydride Hydrolases↗
PubMed2001

Detection of high-risk HPV types by the hybrid capture 2 test.

A hybrid capture test that can be used to detect at least 13 high-risk HPV types (referred to collectively as HPV-HR) in cervical scrapes (Hybrid Capture 2 probe set B, HC2-B) was evaluated. The HC2-B test is accurate and highly reproducible and the results obtained show excellent agreement with those obtained by a multiplexed type-specific polymerase chain reaction (mts-PCR). An additional assay to identify a subset of HPV-HR types may improve specificity without compromising sensitivity in HC2-B positive specimens with a test result close to the cut-off value given by 1 pg/ml HPV DNA.

Cervix Uteri↗
PubMed2000

The construction of defective interfering rubella virus particles.

Two defective viral vectors containing nucleic acid sequences from rubella virus strains RJ and RS linked to the reporter gene luciferase have been constructed. The vector RNAs are shown to replicate and interfere with wildtype virus in co-infected cells. The interference is associated with a polymorphic nucleotide at nt34 in the 5' stem-loop. The use of these constructs as expression vectors is discussed.

Animals↗
PubMed1996

Human papillomavirus genotype as a predictor of persistence and development of high-grade lesions in women with minor cervical abnormalities.

Women referred for colposcopy with mild and moderate dyskaryosis and found to have only minor cervical abnormalities were screened for oncogenic human papilloma virus (HPV) types. The natural development of these abnormalities in 42 HPV-positive women was assessed by cytology and colposcopy at 6-month intervals for up to 2 years. As is the case with cancers and high-grade cervical intra-epithelial neoplasia (CIN), minor cervical abnormalities were frequently found to be associated with HPV16, -18, -31 and -33. Viral persistence and the development of high-grade lesions were found to be closely associated with HPV16; 56% of HPV16 isolates were persistent compared to 7% of other HPV types, and all 4 subsequent CIN 3 lesions were in women with persistent infection. A striking association of persistence with a variant of HPV16 having a base change at nucleotide 350 was observed. Ten of 12 women with this variant had persistent infection compared to only 1 of 16 women infected with the HPV16 prototype.

Adult↗
PubMed1995

Sequence variation and biological activity of rubella virus isolates.

Haemagglutination (HA) by rubella virus is mediated by the E1 glycoprotein. Rubella isolates which haemagglutinate with different avidity have been characterised. A significant reduction of HA titre at pH 6.0 was observed in one isolate in which isoleucine is substituted for threonine at rubella E1 residue 280. This residue is located in an epitope (EP1) which we have previously identified and shown to bind HA inhibiting (HA1) monoclonal antibodies. The isolates studied are also distinguishable by plaque size but no sequence variations in the immunogenic region of E1 were identified which might account for this difference. No correlation was observed between infectivity and binding affinity of neutralising monoclonal antibodies for different rubella virus strains.

Animals↗
PubMed1992

Reactivity of a recombinant rubella E1 antigen expressed in E. coli.

The E1 nucleic acid sequence of rubella virus strain Judith (RJ) has been cloned into an E. coli expression vector LB03. The reactivity of the expressed unglycosylated antigen (E1J) was compared with its glycosylated counterpart in native virus (RJ) using rabbit and human sera. Rabbit antisera raised against RJ and E1J reacted differently with wild type, RJ (laboratory strain) and RA27/3 (vaccine virus) strains in a kinetic neutralisation test. Reciprocally, human post RA27/3 vaccination sera were also found to differ from post infection or post re-infection sera in their reactivity with RJ and E1J antigens. Our observations suggest that E1, in the conformation adopted in the RA27/3 virion may have unique antigenic properties.

Animals↗
PubMed1990

Diagnosis of foetal rubella virus infection by polymerase chain reaction.

We have used the polymerase chain reaction (PCR) to provide a very sensitive and unequivocal test for diagnosis of foetal rubella virus infection. RNA extracted from biopsy specimens (chorionic villi), placenta or products of conception was reverse-transcribed using a rubella virus-specific oligonucleotide primer and the cDNA was amplified by PCR. The specificity of the amplified fragment was confirmed by Southern blotting. Detection of rubella virus infection in five out of 41 clinical specimens examined by this approach was shown to be entirely consistent with clinical history and other methods of laboratory diagnosis in current use. The sensitivity of the test and the unequivocal nature of the results obtained could be invaluable in providing prenatal counselling following rubella virus infection during pregnancy.

Animals↗
PubMed1989

A bio-engineered rubella E1 antigen.

The major rubella envelope protein, E1, and a segment of it, comprising amino acids 207-353, have been separately expressed as fusion proteins with the IgG binding region of Staphylococcus aureus protein A in Escherichia coli. The proteins carry E1-specific antigenicity recognized by monoclonal antibodies raised against whole virus confirming that correct glycosylation is not required for antigenicity. The use of these bioengineered antigens in immunoassays for diagnosis of rubella infection and for immunization in experimental animals is described.

Amino Acid Sequence↗
PubMed1988

Diagnosis of fetal rubella infection by nucleic acid hybridization.

The efficacy of nucleic acid hybridization for the diagnosis of rubella infection in experimental and clinical materials was compared with immunoblot and virus isolation techniques. Our results showed that nucleic acid hybridization is specific and rapid but gives false-negative results when compared with conventional virus isolation in some experimental although not in clinical materials so far examined. For this reason, a failure to demonstrate rubella virus in fetal specimens by this method alone cannot yet be taken as a sole criterion for ruling out fetal rubella infection.

Abortion, Spontaneous↗
PubMed1988

Localization of the rubella E1 epitopes.

Three epitopes which react with haemagglutination inhibition and neutralizing antibodies have been located between amino acids 245-285 in the predicted amino acid sequence of rubella envelope glycoprotein E1.

Amino Acid Sequence↗
PubMed1986

Immunological characterisation of the rubella E 1 glycoprotein. Brief report.

Three epitopes have been identified on rubella virion envelope polypeptide E 1 using monoclonal antibodies. Antibodies to two of the epitopes, E 1EP1 and E 1EP2, show both haemagglutination inhibition and neutralization activities whereas antibodies to the remaining epitope, E 1EP3, show neutralizing activity only.

Animals↗
PubMed1985

Rubella virus RNA: effect of high multiplicity passage.

Evidence for the amplification of defective interfering particles of rubella virus after passage at high multiplicity has been obtained. The process is associated with the production of subgenomic rubella RNA species.

Animals↗