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Biomedical subjects

H Merriman

Publications and source records attributed to H Merriman.

11 recordsLinked to original sources

Microinvasive cervical carcinoma: a retrospective study of cases presenting to the Oxford Colposcopy Unit between 1989 and 1996.

This a retrospective analysis of 65 cases of microinvasive disease and 5-8 years of follow-up (mean 6.2 years), evaluating the effectiveness of cytology and colposcopy in the diagnosis of microinvasive disease and the role of conservative surgery in its management. Cervical cytology reports indicated disease more severe than CIN III in 23% of cases. A further 7% at colposcopy were thought to have possible invasive disease despite no indication from the smear report, this impression correlated with increasing depth of invasion (>1.40 mm).

Journal Article↗

Sequence-specific DNA binding activities of nuclear matrix proteins of mammalian lens epithelial cells.

This study examines matrix and nonmatrix nuclear proteins of the rabbit lens epithelial cells. The nuclear matrix proteins were isolated by modified Penman technique, which requires presence of detergents and nucleases, whereas nonmatrix nuclear proteins were obtained by high salt extraction. The data from these experiments revealed presence of DNA binding activities for SP-1 and OCT-1 proteins in both matrix and non-matrix compartments of rabbit lens epithelial cells. Comparison of the relative abundance of SP-1 and OCT-1 binding activities in nuclear matrix and nonmatrix fractions suggest the distribution between these two compartments is cell type specific and possibly related to the control of cell growth.

Animals↗

Subnuclear distribution of the vitamin D receptor.

The subnuclear distribution of the vitamin D receptor was investigated to begin addressing the contribution of nuclear architecture to vitamin D-responsive control of gene expression in ROS 17/2.8 rat osteosarcoma cells. The nuclear matrix is an anastomosing network of filaments that is functionally associated with DNA replication, transcription, and RNA processing. The representation of vitamin D receptor in the nuclear matrix and nonmatrix nuclear fractions was determined by the combined application of 1) sequence-specific interactions with the vitamin D receptor binding element of the rat bone-specific osteocalcin gene promoter and 2) Western blot analysis. Both methods confirmed the presence of vitamin D receptor in the nonmatrix nuclear fraction and the absence of detectable vitamin D receptors associated with the nuclear matrix. In contrast, these same nuclear matrix proteins preparations exhibited association with the general transcription factor AP-1 and a bone tissue-specific promoter binding factor NMP2. NMP-2 exhibits recognition for a promoter domain contiguous to the vitamin D-responsive element of the osteocalcin gene, although the vitamin D receptor does not appear to be a component of the nuclear matrix proteins. Interrelationships between nuclear matrix proteins and nonmatrix nuclear proteins, in mediating steroid hormone responsiveness of a vitamin D-regulated promoter, are therefore suggested.

Animals↗

Parathyroid-responsive modifications in the nuclear matrix of ROS 17/2.8 rat osteosarcoma cells.

PTH is a mediator of skeletal development and remodeling that influences gene expression in osteoblastic cells. It is well established that PTH modulates the activity of membrane-associated second messenger signal transduction pathways. In these studies we have addressed the potential contribution of components of cell structure to the integration of PTH-related regulatory signals that influence the expression of bone cell genes. Chronic treatment of ROS 17/2.8 rat osteosarcoma cells with PTH is accompanied by changes in gene expression that are at least in part transcriptionally controlled. To explore the involvement of nuclear architecture in PTH-responsive modifications in gene expression, we investigated changes in the nuclear matrix after PTH treatment. Consistent with a role for the nuclear matrix in determining spatial organization and topology of chromatin as well as in the localization and targeting of transcription factors, we observed PTH-associated changes in a 200-kilodalton nuclear matrix protein in response to PTH. A significant down-regulation of synthesis was observed when nuclear matrix proteins were resolved electrophoretically in two-dimensional gels. This protein was restricted to the nuclear matrix and was not detected in the chromatin or cytoskeletal cellular fractions. These alterations in nuclear matrix proteins that occur after PTH treatment in osteosarcoma cells were phenotype related. They did not occur in UMR-106 POL or H4 hepatoma cells. Our findings support a role for the nuclear matrix in transducing PTH-mediated regulatory signals to facilitate the extent to which genes in osteoblasts are transcribed.

Animals↗

Large loop excision of the transformation zone (LLETZ) as an alternative to both local ablative and cone biopsy treatment: a series of 1000 patients.

One thousand patients, referred to the Oxford Colposcopy Clinic, were treated with either large loop excision of the transformation zone (LLETZ, 891 cases) or LLETZ cone (109 cases). Forty-five LLETZ cones were performed empirically, 64 under microcolposcopic guidance. Over 98% of patients were managed as outpatients under local anaesthesia, and 87% of new patients treated with LLETZ had treatment at their first visit. Ninety percent of patients had at least cervical intraepithelial neoplasia grade one (CIN I) and 73% had CIN II or worse. Seventeen cases of invasive or possibly invasive disease were detected, 6 of them unsuspected. The overall rate of complete excision of CIN or worse was 72%. Follow-up was cytologic with or without colposcopy depending on lesion severity. Ninety-one percent of 967 treated patients were free of dyskaryosis at a mean follow-up of 23 months, with complete excision of CIN or worse at LLETZ a significant predictive factor. No cases of invasive carcinoma have developed following treatment. Major morbidity was uncommon, with 3.8% severe hemorrhage. Stenosis was noted in 3.8% cases, mostly after LLETZ cone. One patient (0.1%) has reduced fertility possibly attributable to LLETZ. Questionnaire assessment revealed a very high degree of acceptability of the treatment to patients. LLETZ and LLETZ cone have proved highly acceptable and effective outpatient diagnostic and treatment alternatives to both local ablation and cone biopsy in the Oxford Colposcopy Clinic.

Adolescent↗

Secretory IgA antibody in cervicovaginal secretions from women with genital infection due to herpes simplex virus.

Sequential samples of cervicovaginal secretions from women with untreated first and recurrent episodes of genital infection due to herpes simplex virus type 2 (HSV-2) were assayed for IgA antibodies to HSV-2 by using fluorescent antibodies to human secretory piece (sIgA) and human IgA. Among women with first-episode genital herpes, sIgA antibody to HSV-2 was detected in 20 of 31 women from whom HSV was isolated from the cervix, compared with four of 13 women from whom it was not (P less than .05). Among women with first-episode genital herpes, the mean titer of sIgA antibody to HSV-2 peaked between days 9 and 16 of disease, whereas among women with recurrent genital HSV, the peak occurred at days 3-8 of disease. HSV-2 was not isolated from the cervix from any of 130 samples taken when titers of sIgA antibody to HSV-2 were greater than or equal to 1:2, compared with 98 of 259 samples taken when titers were less than or equal to 1:2 (P less than or equal to .01).

Adult↗