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This thesis is concerned with cervical cancer amongst New Zealand women, particularly Maori women. Maori women have an alarmingly high incidence of cervical cancer, approximately three times higher than non-Maori women. Maori women experience one of the highest rates of cervical cancer in the world. Chapter one, two and three form the introductory section of the thesis, Section A. Chapter one provides an overview of cervical cancer incidence in the world, followed by a more detailed analysis of the occurrence of cervical cancer in New Zealand and a discussion of the aetiological factors of cervical cancer. Cervical screening is discussed in Chapter two. The ethnic differences in incidence and mortality of cervical cancer between Maori and non-Maori and possible reasons for these differences are studied in Chapter three. Section B consists of the original work undertaken. A pilot study (Chapter four) was conducted to trial the methods for the national study (Chapter five). The national study was a retrospective review of the cervical smear histories of Maori women first diagnosed with invasive cervical cancer over a recent two year period in order to investigate why Maori women have not had their disease detected by screening and treated at the intraepithelial stage. Maori women�s knowledge of and attitudes towards cervical screening were obtained in a survey in Ruatoria (Chapter six). Section C concludes with a chapter (Chapter seven) on the conclusions and recommendations based on the material reviewed and the work undertaken.

Title page, abstract and table of contents only. The complete thesis in print form is available from the University of Adelaide Library. / In mice and other mammalian species, deposition of semen into the female reproductive tract elicits a local inflammatory response. Whether a comparable response occurs within the human cervix has not previously been studied. The experiments described in this thesis demonstrate, using cervical tissue biopsies taken before and after intercourse, that exposure to semen elicits an infiltration of leukocytes into the cervical tissue of peri-ovulatory women. Immunohistochemical analysis identified macrophages and dendritic cells as the predominant leukocytes recruited into the cervical epithelium and stroma following intercourse. Cytotoxic / suppressor T lymphocytes and memory T cells were also increased. Comparable responses were not detected following condom-protected intercourse. Quantitative real-time PCR was performed on duplicate tissue biopsies to investigate the molecular regulation of this response. Expression of GM-CSF, a potent stimulator of myeloid cell recruitment, was found to increase by 2.5-fold following unprotected intercourse. Trends towards increased IL-6 and IL-8 mRNA were also observed. Condom-protected intercourse did not activate cytokine expression, further suggesting that exposure to semen, as opposed to mechanical trauma, provides the inflammatory stimulus. In an in vitro model using the immortalised Ect-1 cell line, TGFβ was identified as a candidate active seminal factor. All three TGFβ isoforms were capable of mimicking the stimulatory ability of seminal plasma in Ect-1 cells and were comparable in their capacity to stimulate both GM-CSF and IL-6 expression in a dose-responsive manner. The addition of TGFβ isoform-specific neutralising antibodies inhibited seminal plasma-induced increases in these cytokines. However TGFβ was unable to stimulate IL-8 production. Addition of IFNƴ was found to strongly inhibit TGFβ-stimulated GM-CSF production, and 19-0H PGE₁ was found to increase IL-6 and IL-8, but not GM-CSF production. Responses to seminal plasma constituents were almost exactly replicated in primary cultures of human ectocervical cells. These results identify TGFβ as the major active constituent in human seminal plasma and indicate that other seminal agents, 19-0H PGE₁ and IFNƴ, interact with TGFβ to differentially regulate cervical cytokine expression. Finally, whether human seminal plasma cytokine content was associated with fertility in men was examined. No relationship between seminal plasma TGFβ₁, TGFβ₂, TGFβ₃, IL-8 or bacterial endotoxin content and fertility status was observed. However, there was an increased likelihood of high IFNƴ content in the male partners of couples experiencing infertility, most notable in recurrent miscarriage. The discriminating value of IFNƴ was increased when evaluated as a ratio of total TGFβ content. Inflammatory changes after exposure of the female reproductive tract to seminal plasma are implicated in 'conditioning' the maternal immune response, to facilitate successful embryo implantation and pregnancy. The studies described in this thesis provide a mechanistic basis for the observations linking exposure to semen with pregnancy success in humans and have expanded our knowledge of the cellular and molecular events that occur within the female reproductive tract following intercourse. Seminal plasma can therefore no longer be thought of as merely a transport medium for spermatozoa, rather as a means for communication between the male and female reproductive tissues, potentially required for optimal pregnancy success. / http://proxy.library.adelaide.edu.au/login?url= http://library.adelaide.edu.au/cgi-bin/Pwebrecon.cgi?BBID=1213820 / Thesis (Ph.D.) -- University of Adelaide, Medical School, 2005

Title page, abstract and table of contents only. The complete thesis in print form is available from the University of Adelaide Library. / In mice and other mammalian species, deposition of semen into the female reproductive tract elicits a local inflammatory response. Whether a comparable response occurs within the human cervix has not previously been studied. The experiments described in this thesis demonstrate, using cervical tissue biopsies taken before and after intercourse, that exposure to semen elicits an infiltration of leukocytes into the cervical tissue of peri-ovulatory women. Immunohistochemical analysis identified macrophages and dendritic cells as the predominant leukocytes recruited into the cervical epithelium and stroma following intercourse. Cytotoxic / suppressor T lymphocytes and memory T cells were also increased. Comparable responses were not detected following condom-protected intercourse. Quantitative real-time PCR was performed on duplicate tissue biopsies to investigate the molecular regulation of this response. Expression of GM-CSF, a potent stimulator of myeloid cell recruitment, was found to increase by 2.5-fold following unprotected intercourse. Trends towards increased IL-6 and IL-8 mRNA were also observed. Condom-protected intercourse did not activate cytokine expression, further suggesting that exposure to semen, as opposed to mechanical trauma, provides the inflammatory stimulus. In an in vitro model using the immortalised Ect-1 cell line, TGFβ was identified as a candidate active seminal factor. All three TGFβ isoforms were capable of mimicking the stimulatory ability of seminal plasma in Ect-1 cells and were comparable in their capacity to stimulate both GM-CSF and IL-6 expression in a dose-responsive manner. The addition of TGFβ isoform-specific neutralising antibodies inhibited seminal plasma-induced increases in these cytokines. However TGFβ was unable to stimulate IL-8 production. Addition of IFNƴ was found to strongly inhibit TGFβ-stimulated GM-CSF production, and 19-0H PGE₁ was found to increase IL-6 and IL-8, but not GM-CSF production. Responses to seminal plasma constituents were almost exactly replicated in primary cultures of human ectocervical cells. These results identify TGFβ as the major active constituent in human seminal plasma and indicate that other seminal agents, 19-0H PGE₁ and IFNƴ, interact with TGFβ to differentially regulate cervical cytokine expression. Finally, whether human seminal plasma cytokine content was associated with fertility in men was examined. No relationship between seminal plasma TGFβ₁, TGFβ₂, TGFβ₃, IL-8 or bacterial endotoxin content and fertility status was observed. However, there was an increased likelihood of high IFNƴ content in the male partners of couples experiencing infertility, most notable in recurrent miscarriage. The discriminating value of IFNƴ was increased when evaluated as a ratio of total TGFβ content. Inflammatory changes after exposure of the female reproductive tract to seminal plasma are implicated in 'conditioning' the maternal immune response, to facilitate successful embryo implantation and pregnancy. The studies described in this thesis provide a mechanistic basis for the observations linking exposure to semen with pregnancy success in humans and have expanded our knowledge of the cellular and molecular events that occur within the female reproductive tract following intercourse. Seminal plasma can therefore no longer be thought of as merely a transport medium for spermatozoa, rather as a means for communication between the male and female reproductive tissues, potentially required for optimal pregnancy success. / http://proxy.library.adelaide.edu.au/login?url= http://library.adelaide.edu.au/cgi-bin/Pwebrecon.cgi?BBID=1213820 / Thesis (Ph.D.) -- University of Adelaide, Medical School, 2005

Title page, abstract and table of contents only. The complete thesis in print form is available from the University of Adelaide Library. / In mice and other mammalian species, deposition of semen into the female reproductive tract elicits a local inflammatory response. Whether a comparable response occurs within the human cervix has not previously been studied. The experiments described in this thesis demonstrate, using cervical tissue biopsies taken before and after intercourse, that exposure to semen elicits an infiltration of leukocytes into the cervical tissue of peri-ovulatory women. Immunohistochemical analysis identified macrophages and dendritic cells as the predominant leukocytes recruited into the cervical epithelium and stroma following intercourse. Cytotoxic / suppressor T lymphocytes and memory T cells were also increased. Comparable responses were not detected following condom-protected intercourse. Quantitative real-time PCR was performed on duplicate tissue biopsies to investigate the molecular regulation of this response. Expression of GM-CSF, a potent stimulator of myeloid cell recruitment, was found to increase by 2.5-fold following unprotected intercourse. Trends towards increased IL-6 and IL-8 mRNA were also observed. Condom-protected intercourse did not activate cytokine expression, further suggesting that exposure to semen, as opposed to mechanical trauma, provides the inflammatory stimulus. In an in vitro model using the immortalised Ect-1 cell line, TGFβ was identified as a candidate active seminal factor. All three TGFβ isoforms were capable of mimicking the stimulatory ability of seminal plasma in Ect-1 cells and were comparable in their capacity to stimulate both GM-CSF and IL-6 expression in a dose-responsive manner. The addition of TGFβ isoform-specific neutralising antibodies inhibited seminal plasma-induced increases in these cytokines. However TGFβ was unable to stimulate IL-8 production. Addition of IFNƴ was found to strongly inhibit TGFβ-stimulated GM-CSF production, and 19-0H PGE₁ was found to increase IL-6 and IL-8, but not GM-CSF production. Responses to seminal plasma constituents were almost exactly replicated in primary cultures of human ectocervical cells. These results identify TGFβ as the major active constituent in human seminal plasma and indicate that other seminal agents, 19-0H PGE₁ and IFNƴ, interact with TGFβ to differentially regulate cervical cytokine expression. Finally, whether human seminal plasma cytokine content was associated with fertility in men was examined. No relationship between seminal plasma TGFβ₁, TGFβ₂, TGFβ₃, IL-8 or bacterial endotoxin content and fertility status was observed. However, there was an increased likelihood of high IFNƴ content in the male partners of couples experiencing infertility, most notable in recurrent miscarriage. The discriminating value of IFNƴ was increased when evaluated as a ratio of total TGFβ content. Inflammatory changes after exposure of the female reproductive tract to seminal plasma are implicated in 'conditioning' the maternal immune response, to facilitate successful embryo implantation and pregnancy. The studies described in this thesis provide a mechanistic basis for the observations linking exposure to semen with pregnancy success in humans and have expanded our knowledge of the cellular and molecular events that occur within the female reproductive tract following intercourse. Seminal plasma can therefore no longer be thought of as merely a transport medium for spermatozoa, rather as a means for communication between the male and female reproductive tissues, potentially required for optimal pregnancy success. / http://proxy.library.adelaide.edu.au/login?url= http://library.adelaide.edu.au/cgi-bin/Pwebrecon.cgi?BBID=1213820 / Thesis (Ph.D.) -- University of Adelaide, Medical School, 2005

Diss. (sammanfattning) Uppsala : Univ., 2004. / Härtill 5 uppsatser.

Diss. (sammanfattning) Stockholm : Univ., 2004. / Härtill 4 uppsatser.

Thesis (Ph.D.)--Kent State University, 2007. / Title from PDF t.p. (viewed Mar. 11, 2009). Advisor: Angelo L. DeLucia. Keywords: human papillomavirus, E6 oncogene, lignan, p53, apoptosis. Includes bibliographical references (p. 132-144).