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P Maddox

Publications and source records attributed to P Maddox.

26 records · Page 2Linked to original sources
PubMed1997

Astral microtubule dynamics in yeast: a microtubule-based searching mechanism for spindle orientation and nuclear migration into the bud.

Localization of dynein-green fluorescent protein (GFP) to cytoplasmic microtubules allowed us to obtain one of the first views of the dynamic properties of astral microtubules in live budding yeast. Several novel aspects of microtubule function were revealed by time-lapse, three-dimensional fluorescence microscopy. Astral microtubules, about four to six in number for each pole, exhibited asynchronous dynamic instability throughout the cell cycle, growing at approximately 0.3-1.5 micron/min toward the cell surface then switching to shortening at similar velocities back to the spindle pole body (SPB). During interphase, a conical array of microtubules trailed the SPB as the nucleus traversed the cytoplasm. Microtubule disassembly by nocodozole inhibited these movements, indicating that the nucleus was pushed around the interior of the cell via dynamic astral microtubules. These forays were evident in unbudded G1 cells, as well as in late telophase cells after spindle disassembly. Nuclear movement and orientation to the bud neck in S/G2 or G2/M was dependent on dynamic astral microtubules growing into the bud. The SPB and nucleus were then pulled toward the bud neck, and further microtubule growth from that SPB was mainly oriented toward the bud. After SPB separation and central spindle formation, a temporal delay in the acquisition of cytoplasmic dynein at one of the spindle poles was evident. Stable microtubule interactions with the cell cortex were rarely observed during anaphase, and did not appear to contribute significantly to spindle alignment or elongation into the bud. Alterations of microtubule dynamics, as observed in cells overexpressing dynein-GFP, resulted in eventual spindle misalignment. These studies provide the first mechanistic basis for understanding how spindle orientation and nuclear positioning are established and are indicative of a microtubule-based searching mechanism that requires dynamic microtubules for nuclear migration into the bud.

Anaphase↗
PubMed1995

Human papillomavirus testing in primary cervical screening.

Several studies have examined the role of tests for human papillomavirus (HPV) in screening for cervical cancer but as yet the relevance is unclear. We looked at HPV testing for types 16, 18, 31, and 33 on material taken at the time of a cervical smear in 2009 eligible women having routine screening. Women with any degree of dyskaryosis or high levels of one of these HPV types were referred for colposcopy. 44% of the cervical intraepithelial neoplasia (CIN) lesions of grade 2/3 detected had negative cytology and were found only by HPV testing. A further 22% of the CIN 2/3 lesions were positive for HPV but showed only borderline or mild cytological changes. The positive predictive value of HPV testing was 42%, which was similar to that for moderate dyskaryosis. HPV types 16 and 31 were more sensitive and specific for CIN 2/3 than were types 18 or 33. However, 25% of the CIN 2/3 lesions were not detected by these four HPV tests. We suggest that HPV testing could usefully augment but not replace conventional cytology. These results should stimulate a much larger randomised trial to assess the impact of these improved CIN 2/3 detection rates on the subsequent incidence of invasive cancer.

Adult↗
PubMed1994

Cytokeratin expression and acetowhite change in cervical epithelium.

AIM: To investigate the distribution of cytokeratins 10, 13, 14 and 19 in biopsy specimens taken from acetowhite and non-acetowhite areas of the cervix. METHOD: Cervical biopsy specimens were taken from both acetowhite and non-acetowhite areas from 44 patients who presented with abnormal cervical cytology. The specimens were snap frozen in liquid nitrogen and multiple sections taken from each specimen. Staining was performed for cytokeratins 10, 13, 14, 19 and NADPH diaphorase enzyme. The areas of each section positive for the various markers were measured. RESULTS: Cytokeratin 10 positive cells were greatly increased in number in acetowhite biopsy specimens compared with non-acetowhite samples (45.1% v 2.8%; p < 0.0001). Cytokeratin 19 was also increased, but to a lesser extent (17.8% v 5.5%; p < 0.0001). In contrast, the almost universal expression of cytokeratin 13 was reduced in acetowhite biopsy specimens (86.2% v 96.9%; p < 0.0001). Cytokeratin 14 was found diffusely in the basal region of the stratified squamous epithelium and was marginally more apparent in the acetowhite biopsy specimens (p = 0.04). CONCLUSION: It is suggested that the presence of cytokeratin 10 may be an essential requirement for the formation of acetowhite change in association with the cellular swelling caused by acetic acid.

Acetates↗
PubMed1987

Subpopulations of Langerhans' cells in cervical neoplasia.

Multiple markers were used to count Langerhans' cells in the cervix. In the normal cervix, thymocyte antigen (T6) and adenosine triphosphatase (ATPase) demonstrated the largest population of Langerhans' cells. MHC Class II positive cells were equivalent to 60%, and S100 positive cells were equivalent to 35% of T6 or ATPase positive cells. Whereas Langerhans' cells demonstrated by T6, ATPase, and MHC Class II antigen were evenly distributed throughout the epithelium, the S100 positive cells were seen predominantly near lymphocytic aggregates and capillaries. In human papillomavirus infection and cervical intraepithelial neoplasia the numbers of T6, ATPase, or MHC Class II positive Langerhans' cells were reduced by 60% but the S100 positive cells were almost completely depleted. These findings suggested that there were different subpopulations of Langerhans' cells in the cervical epithelium. The depletion of Langerhans' cells, particularly the selective depletion of the S100 positive subpopulation, might cause a localized immunodeficiency that impairs immune surveillance and the cell-mediated immune response to human papillomavirus infection and cervical intraepithelial neoplasia.

Adult↗
PubMed1987

Lymphocyte phenotypes in cervical intraepithelial neoplasia and human papillomavirus infection.

Lymphocyte phenotypes in cervical mucosa were studied using a panel of monoclonal antibodies. T lymphocytes were predominant both within the epithelium and in the subepithelial stroma. In the normal cervix, both the T4+ (helper/inducer) and T8+ (suppressor/cytotoxic) subsets were present in a ratio similar to that in the peripheral circulation. In human papillomavirus (HPV) infection and cervical intraepithelial neoplasia (CIN) there was depletion of intraepithelial lymphocytes, especially of T4+ subset, with reversal of the ratio of T4+ to T8+ subsets to less than one. In contrast, there was no significant reduction in the number of lymphocytes in the subepithelial stroma. Tac+ (antigen primed and clonal expanding) lymphocytes were absent both within the epithelium and in the subepithelial stroma. These findings support our suggestion that there is a localized immunodeficiency in HPV infection and CIN. The aetiological and therapeutic implications are discussed.

Adolescent↗
PubMed1987

Tissue macrophage response in human papillomavirus infection and cervical intraepithelial neoplasia.

Tissue macrophages in the uterine cervix were studied immunocytochemically with monoclonal antibody (MoAb) 3.9 which reacts with the majority of macrophages, and E11 which is specific for the C3b receptor, CR1. Samples from five normal women, six with human papillomavirus (HPV) infection and 10 with cervical intraepithelial neoplasia (CIN) were tested. A small population of MoAb 3.9 positive and only occasional MoAb E11 positive macrophages were found in the normal cervix. In HPV infection and CIN there was a significant infiltration of MoAb 3.9 positive and MoAb E11 positive macrophages in both the epithelium and the stroma. The pattern of infiltration in these groups of women suggests that these macrophages were most likely to be functioning as the first line of defence against the spread of the virus infection, either through a direct anti-virus mechanism or non-specific phagocytosis.

Adult↗