Em experimento conduzido com o objetivo de avaliar os efeitos da concentração da dose de sêmen e o horário da inseminação artificial a tempo pré-fixado, foram utilizadas 516 fêmeas bovinas. Os animais, das raças Aberdeen Angus (Bos taurus) e Braford (Bos taurus 5/8 x Bos indicus 3/8) eram constituídos de 270 novilhas e 246 vacas multíparas. Os animais foram submetidos a um protocolo de sincronização de estros e ovulação através de implante vaginal contendo 250 mg de Acetato de Medroxiprogesterona (MAP) associado a duas aplicações de Benzoato de Estradiol (BE), sendo a primeira de 2 mg IM por ocasião da inserção do implante e a segunda de 1 mg IM vinte e quatro horas após a retirada do mesmo. Quando da remoção do implante foram administrados 500 mcg de Cloprostenol Sódico. As inseminações foram efetuadas às 48, 54 ou 60 horas após a retirada do implante, utilizando para cada momento duas concentrações distintas de espermatozóides viáveis, 10 e 20 milhões por dose. Verificou-se que as fêmeas (em especial as novilhas) inseminadas às 48 horas com 20 milhões de sptz/dose apresentaram índice de prenhez significativamente maior do que as inseminadas no mesmo momento com 10 milhões sptz/dose. As vacas inseminadas com 10 milhões de sptz às 60h apresentaram melhor taxa de prenhez (p<0,05) quando comparadas às inseminadas com 10 milhões de sptz às 48h. O percentual de prenhez encontrado nas vacas foi significativamente maior que o das novilhas, assim como o verificado nas fêmeas Aberdeen Angus, comparadas às Braford. A taxa de prenhez de novilhas inseminadas a tempo fixo pode ser incrementada utilizando-se maior número de espermatozóides viáveis por dose inseminante. / The objective of this study was to analyse the effects of semen concentration and moment of fixed timed insemination on pregnancy rates in 516 beef cattle females of the Aberdeen Angus (Bos taurus) and Braford (Bos taurus 5/8 x Bos indicus 3/8) breeds. The females were constituted of 270 heifers and 246 multiparous cows. The animals were all submitted to a synchronization program consisting of vaginal implants of 250mg of medroxiprogesterone acetate (MPA) associated to application of 2mg IM of estradiol benzoate (EB).After 7 days the implants were removed and 500 mg of cloprostenol were injected at the time. After 24hs of implant removal 1mg IM of EB was injected. The inseminations were done 48, 54 and 60 hours after the removal of the implants and semen with 10 and 20 million viable spermatozoa per dosis was used. The females (specially the heifers) of the group inseminated 48 hours after implant removal and using semen with 20 million viable sptz showed a significant higher percentage of pregnancy than the inseminated 48 hours using 10 million viable sptz. The cows inseminated at 60 hours with 10 million sptz showed higher pregnancy rates (p<0,05) than cows inseminated at 48 hours with 10 million sptz. The total pregnancy rate achieved on the cows was significantly higher than on the heifers. The females of the A. Angus group had higher pregnancy rates than the females of the Braford breed. The pregnancy rate of heifers fixed-timed inseminated can be increased using a higher semen concentration.

A presença do marsúpio fechado possibilitou aos isópodos terrestres a total independência do meio aquático para a reprodução, permitindo aos mesmos a colonização de habitats terrestres variados. Em seu interior, a prole é nutrida e oxigenada através de estruturas temporárias, chamadas cotilédones, as quais surgem durante o período ovígero das fêmeas e são exclusivas do grupo Crinocheta. O presente estudo teve como objetivo descrever padrões dos cotilédones, analisados em 37 espécies de isópodos terrestres distribuídas entre as famílias: Agnaridae, Armadillidae, Armadillidiidae, Balloniscidae, Bathytropidae, Detonidae, Dubioniscidae, Philosciidae, Platyarthridae, Porcellionidae, Pudeoniscidae, Scleropactidae e Trachelipodidae, verificando se ocorre variação de comprimento ao longo das fases de desenvolvimento embrionário, sendo que para isto foram selecionadas seis espécies: Armadillidium nasatum, A. vulgare, Atlantoscia floridana, Balloniscus sellowii, Benthana cairensis e Porcellio scaber. Armadillidium vulgare e B. sellowii também foram estimados quanto à proporção comprimento dos cotilédones/ tamanho da fêmea. Entre as 13 famílias estudadas foram identificados seis formatos (tipos) de cotilédones e sete arranjos diferentes de número e distribuição. O comprimento foi estabelecido como: curto, médio e longo. Armadillidium vulgare, A. floridana e B. cairensis não apresentaram diferença no comprimento dos cotilédones durante os estágios embrionários sendo que este foi evidenciado para as demais espécies, uma vez que B. sellowii e P. scaber apresentaram aumento da fase de ovo para embrião, diminuindo na fase de manca. Já em A. nasatum ocorre um aumento gradual até a fase de manca, onde então regridem drasticamente. O comprimento dos cotilédones de A. vulgare e B. sellowii é proporcional ao tamanho da fêmea. Durante os estudos realizados outra novidade foi registrada: a presença de uma “extensão marsupial”. Para maiores informações sobre esta estrutura, foi necessário identificar quais espécies a apresentavam, o número de indivíduos abrigados em seu interior e diferenças na estrutura entre as espécies que portavam tal extensão e as que possuem o marsúpio fechado restrito aos cinco pares de oostegitos. Seis espécies apresentaram extensão marsupial, a qual possibilita o abrigo de aproximadamente ¼ do total da prole. XI Este marsúpio não apresenta formato distendido como o encontrado nas demais espécies o que vem a influenciar diretamente a alimentação da fêmea, pois com o desenvolvimento da prole ocorrendo em direção aos órgãos desta, conforme avançam as fases, aumenta a pressão interna, comprimindo seu interior. As diferenças morfológicas registradas aqui representam estratégias reprodutivas adotadas pelas espécies, ao longo da evolução, podendo estar relacionadas (ou não) à filogenia dos grupos. / The presence of the closed brood pouch made it possible for terrestrial isopods to have full independence of the aquatic environment for reproduction, allowing them to colonize varied terrestrial habitats. Inside, the offspring is nourished and oxygenated by temporary structures, called cotyledons, which emerge during the ovigerous period of females and are unique to the group Crinocheta. This study aims to describe patterns of cotyledons, analyzed in 37 species of terrestrial isopods distributed among the families: Agnaridae, Armadillidae, Armadillidiidae, Balloniscidae, Bathytropidae, Detonidae, Dubioniscidae, "Philoscidae" Platyarthridae, Porcellionidae, Pudeoniscidae, Scleropactidae and Trachelipodidae , checking if there is variation in length along the stages of embryonic development, and for this, six species were selected as models: Armadillidium nasatum, A. vulgare, Atlantoscia floridana Balloniscus sellowii, Porcellio scaber and Benthana cairensis. Armadillidium vulgare and B. sellowii were also estimated concerning the proportion of cotyledon length / female size. Among the 13 studied families six formats (types) of cotyledons were identified as well as seven different arrangements of numbers and distribution. The length was established as: short, medium and long. Armadillidium vulgare, A. floridana and B. cairensis showed no difference in the length of the cotyledons during the embryonic stages while this was evidenced for the other species, since B. sellowii and P. scaber showed increased egg stage to the embryo, decreasing during the manca. Nevertheless in A. nasatum a gradual increase until the phase of manca occurs, which then regresses dramatically. The length of the cotyledons of A. vulgare and B. sellowii is proportional to female size. XIII During the carried out studies another new feature was recorded: the presence of an " marsupial extension." For obtaining further information about this structure it was necessary to identify the species that presented it, the number of individuals housed within, and differences in structure between species that harbored such extension and the others which had the closed pouch restricted to five pairs of oostegits. Six species showed marsupial extension, which provides shelter for approximately a quarter of the total offspring. This brood pouch does not have a distended format as the one found in other species, which directly influences the feeding of the female, because due to the fact that the offspring development occurs towards its organs as the stages advance, internal pressure increases, compressing its interior. The morphological differences reported here represent reproductive strategies adopted by the species, through evolution and could be related (or not) to the phylogeny of the groups.

abstract: There is a lack of music therapy services for college students who have problems with depression and/or anxiety. Even among universities and colleges that offer music therapy degrees, there are no known programs offering music therapy to the institution's students. Female college students are particularly vulnerable to depression and anxiety symptoms compared to their male counterparts. Many students who experience mental health problems do not receive treatment, because of lack of knowledge, lack of services, or refusal of treatment. Music therapy is proposed as a reliable and valid complement or even an alternative to traditional counseling and pharmacotherapy because of the appeal of music to young women and the potential for a music therapy group to help isolated students form supportive networks. The present study recruited 14 female university students to participate in a randomized controlled trial of short-term group music therapy to address symptoms of depression and anxiety. The students were randomly divided into either the treatment group or the control group. Over 4 weeks, each group completed surveys related to depression and anxiety. Results indicate that the treatment group's depression and anxiety scores gradually decreased over the span of the treatment protocol. The control group showed either maintenance or slight worsening of depression and anxiety scores. Although none of the results were statistically significant, the general trend indicates that group music therapy was beneficial for the students. A qualitative analysis was also conducted for the treatment group. Common themes were financial concerns, relationship problems, loneliness, and time management/academic stress. All participants indicated that they benefited from the sessions. The group progressed in its cohesion and the participants bonded to the extent that they formed a supportive network which lasted beyond the end of the protocol. The results of this study are by no means conclusive, but do indicate that colleges with music therapy degree programs should consider adding music therapy services for their general student bodies. / Dissertation/Thesis / M.M. Music Therapy 2013

O presente estudo teve como objetivo identificar a soroprevalência da leptospirose bovina no Estado de São Paulo, estratificado em sete regiões produtoras. Foram utilizados o delineamento estatístico, as amostras sorológicas e as informações contidas nos questionários empregados no Programa Nacional de Brucelose e Tuberculose (PNCEBT) instituído pelo Ministério de Agricultura, Pecuária e Abastecimento (MAPA, 2001), levando-se em consideração a utilização de fêmeas bovinas com idade igual ou superior a 24 meses, excluindo-se os machos, os diferentes tipos de produção, as práticas de manejo, as finalidades de reprodução, o tamanho dos rebanhos e o sistema de comercialização. Realizou-se a Soroaglutinação Microscópica (SAM) em 8.216 amostras sorológicas provenientes de 1021 propriedades. Os resultados da SAM foram confrontados com os possíveis fatores de risco e ocorrência de abortamentos. A infecção por Leptospira spp. está presente em todo o Estado de São Paulo, com soroprevalência de 49,4%, distribuída pelas sete regiões em que o estado foi sub-dividido, a prevalência por propriedade foi de 71,3% , a prevalência dos sorovares estabelecida por animal foi Hardjo (46%), associação dos sorovares Hardo e Wolffi (21%) , sorovares Shermani (8,9%), Autumnalis (4,46%) e Grippotyphosa (3,9%), a prevalência dos sorovares estabelecida por propriedade foi Hardjo (55,18%), associação dos sorovares Hardo e Wolffi (20,18%), sorovares Shermani (7,97%), Grippotyphosa (4,41%) e Autumnalis (3,17%). Denota-se que a distribuição da Leptospira sorovar Hardjo é praticamente homogênea em todas as regiões do estado de São Paulo e independente do tipo de exploração, manejo e das práticas de reprodução adotadas nos rebanhos. O tamanho do rebanho, a compra de animais, o compartilhamento de pastagem, a criação de ovinos e suínos e o uso de inseminação artificial foram apontados como fatores de risco em algumas regiões do estado, entretanto os fatores - tamanho de rebanho e uso de inseminação artificial- foram discutidos e devem considerados com cautela. A utilização de piquetes maternidade constituiu-se num fator de proteção contra a leptospirose e não houve correlação entre a ocorrência de abortamentos elacionados à infecção por qualquer sorovar de Leptospira spp., com exceção da região 3 onde este fator despontou significativamente. / The objective of the present study was to determine the seroprevalence of bovine leptospirosis in São Paulo State, stratified in seven cattle production regions. It was based on the statistic delineation, the serological samples and the responses of the survey employed on National Program for Control and Eradication of Brucelosis and Tuberculosis established by Ministry of Agriculture (2001). From the herds selected it was serologically analyzed only the cows &ge; 24 months old, excluding the males. It was taking into consideration the herd size, the type of productive exploration, reproductive handling, bovine practices and the commercialization system. Microscopic Agglutination Test (MAT) was applied on 8,216 serum samples from 1,021 different farms. The MAT results were analyzed against the possible risk factors and reproductive disorders due to leptospire infection. It was evidenced that leptospire infection occurs all over the seven regions of São Paulo, with 49,4% animal seroprevalence and 71,3% herd seroprevalence. Serovar Hardjo (46,4%) was the prevalent considering all the animaIs examined, followed by Hardjo/Wolfti association (21%), Shermani (8,9%), Autumnalis (4,46%) and Grippotyphosa (3,9%). Herd seroprevalence was Hardjo (55,18%), Hardjo/Wolfti association (20,18%), Shermani (7,97%), Grippotyphosa (4,41 %) and Autumnalis (3,17%). Serovar Hardjo is present in all regions of the State of São Paulo and its occurrence is independent of the handling conditions and reproductive practices adopted in the herds. Herds with &ge;.24 animaIs, introduction of new animaIs, contact or pasture shared with other animal species as ovine and swine and the use of artificial insemination were considered risk factors for leptospirosis infection. The existence of specific calving area in the farm was associated as a preventive measure for leptospirosis. In this study it was not observed correlation of any Leptospira spp. sorovars infection and serologic MAT status with the abortion; except in region 3, where it was significant.

Em experimento conduzido com o objetivo de avaliar os efeitos da concentração da dose de sêmen e o horário da inseminação artificial a tempo pré-fixado, foram utilizadas 516 fêmeas bovinas. Os animais, das raças Aberdeen Angus (Bos taurus) e Braford (Bos taurus 5/8 x Bos indicus 3/8) eram constituídos de 270 novilhas e 246 vacas multíparas. Os animais foram submetidos a um protocolo de sincronização de estros e ovulação através de implante vaginal contendo 250 mg de Acetato de Medroxiprogesterona (MAP) associado a duas aplicações de Benzoato de Estradiol (BE), sendo a primeira de 2 mg IM por ocasião da inserção do implante e a segunda de 1 mg IM vinte e quatro horas após a retirada do mesmo. Quando da remoção do implante foram administrados 500 mcg de Cloprostenol Sódico. As inseminações foram efetuadas às 48, 54 ou 60 horas após a retirada do implante, utilizando para cada momento duas concentrações distintas de espermatozóides viáveis, 10 e 20 milhões por dose. Verificou-se que as fêmeas (em especial as novilhas) inseminadas às 48 horas com 20 milhões de sptz/dose apresentaram índice de prenhez significativamente maior do que as inseminadas no mesmo momento com 10 milhões sptz/dose. As vacas inseminadas com 10 milhões de sptz às 60h apresentaram melhor taxa de prenhez (p<0,05) quando comparadas às inseminadas com 10 milhões de sptz às 48h. O percentual de prenhez encontrado nas vacas foi significativamente maior que o das novilhas, assim como o verificado nas fêmeas Aberdeen Angus, comparadas às Braford. A taxa de prenhez de novilhas inseminadas a tempo fixo pode ser incrementada utilizando-se maior número de espermatozóides viáveis por dose inseminante. / The objective of this study was to analyse the effects of semen concentration and moment of fixed timed insemination on pregnancy rates in 516 beef cattle females of the Aberdeen Angus (Bos taurus) and Braford (Bos taurus 5/8 x Bos indicus 3/8) breeds. The females were constituted of 270 heifers and 246 multiparous cows. The animals were all submitted to a synchronization program consisting of vaginal implants of 250mg of medroxiprogesterone acetate (MPA) associated to application of 2mg IM of estradiol benzoate (EB).After 7 days the implants were removed and 500 mg of cloprostenol were injected at the time. After 24hs of implant removal 1mg IM of EB was injected. The inseminations were done 48, 54 and 60 hours after the removal of the implants and semen with 10 and 20 million viable spermatozoa per dosis was used. The females (specially the heifers) of the group inseminated 48 hours after implant removal and using semen with 20 million viable sptz showed a significant higher percentage of pregnancy than the inseminated 48 hours using 10 million viable sptz. The cows inseminated at 60 hours with 10 million sptz showed higher pregnancy rates (p<0,05) than cows inseminated at 48 hours with 10 million sptz. The total pregnancy rate achieved on the cows was significantly higher than on the heifers. The females of the A. Angus group had higher pregnancy rates than the females of the Braford breed. The pregnancy rate of heifers fixed-timed inseminated can be increased using a higher semen concentration.

CoordenaÃÃo de AperfeiÃoamento de NÃvel Superior / O cÃncer de vulva corresponde a aproximadamente 1% das neoplasias malignas da mulher e de 3% a 5% de tumores genitais femininos. 90% destes sÃo carcinomas espino-celulares, curÃveis quando diagnosticado precocemente. O tratamento radical inclui o esvaziamento inguinal bilateral na maioria dos casos. Aproximadamente 30% das pacientes operÃveis tÃm disseminaÃÃo linfonodal, as 70% restantes tÃm mutilaÃÃo desnecessÃria. A possibilidade de aplicar o conceito de linfonodo sentinela, na conservaÃÃo dos linfonodos regionais da vulva, ainda nÃo à consenso. O modelo experimental na vulva da cadela à um passo importante no reconhecimento das peculiaridades da drenagem linfÃtica deste ÃrgÃo pela similaridade com a drenagem em humanos. Este trabalho experimental, em modelo canino tem como objetivo apresentar o modelo para a pesquisa do linfonodo sentinela na vulva da cadela usando o Azul Patente e Fitato de TecnÃcio; avaliar o Azul Patente como marcador do linfonodo sentinela da vulva da cadela; avaliar o Fitato de TecnÃcio como marcador do linfonodo sentinela na vulva da cadela, comparar os mÃtodos obtidos pelas duas tÃcnicas. Foram utilizados nos procedimentos 25 cadelas, adultas, sadias, com peso variando entre 10 e 12kg. InjeÃÃo de 5ÂCI de TecnÃcio na regiÃo vulvar, com espera de 30â. Rastreamento com probe das regiÃes de drenagem vulvar, injeÃÃo de 0,5mL de azul patente na regiÃo vulvar, com espera de 15â. Definidos os pontos âquentesâ com o probe, por incisÃes inguinais abordou-se o linfonodo, avaliando-se com o probe o linfonodo sentinela in-vivo e ex-vivo, anotando-se os valores; registrados os linfonodos corados e nÃo corados com azul patente; comparados os dois mÃtodos. Em 88% dos linfonodos houve presenÃa da lateralidade, tal diferenÃa foi significante (&#61539; = 28.88 e p<0,0001). NÃo houve diferenÃa significante (p>0,05) entre os lados direito e esquerdo, quanto à intercessÃo dos dois mÃtodos. Os nÃveis de radiaÃÃo detectados foram idÃnticos em ambos os lados (p>0,05), tambÃm nÃo foi verificada diferenÃa significante (p>0,05) em ambos os lados, nas contagens in vivo e ex vivo, e no nÃmero de linfonodo corado com azul patente. O modelo experimental apresentado foi capaz de definir o linfonodo sentinela utilizando o Azul Patente e TecnÃcio(99mTc). A identificaÃÃo do linfonodo sentinela à exequÃvel com Azul Patente no mapeamento da cadeia linfÃtica; o mapeamento linfÃtico com TecnÃcio(99mTc), permite identificar com detalhes o sistema de drenagem linfÃtica; nÃo houve diferenÃa significante entre os dois mÃtodos (p=1,0), Azul Patente e TecnÃcio(99mTc).

A hipóxia crônica intermitente (HCI) promove hipertensão arterial e aumento da atividade simpática em ratos jovens. Nestes animais, o aumento da atividade simpática ocorre durante uma fase específica da respiração e está correlacionada com o aumento da atividade expiratória. Estas evidências mostram que, após a HCI, os ratos jovens desenvolvem alterações no acoplamento simpático-respiratório, um mecanismo que pode contribuir, pelo menos em parte, para o desenvolvimento da hipertensão observada nestes animais. Em diversos modelos experimentais de hipertensão, os níveis de pressão arterial são menores nas fêmeas do que nos machos, portanto elas são resistentes ao desenvolvimento da hipertensão. Levando em conta essas informações, a hipótese do presente projeto foi a seguinte: fêmeas submetidas à HCI seriam resistentes ao desenvolvimento da hipertensão arterial. Para tanto, ratas jovens e adultas foram submetidas à HCI e seus parâmetros cardiovasculares e respiratórios foram avaliados na condição dos animais acordados e com livre movimentação. Além disso, as alterações na atividade simpática e respiratória também foram avaliadas na preparação coração tronco-cerebral isolados. Os resultados mostram que as fêmeas desenvolvem hipertensão semelhante aos machos submetidos ao mesmo protocolo, contudo as alterações no acoplamento entre a atividade simpática e respiratória são diferentes entre os sexos. Estes dados sugerem que embora os machos e fêmeas desenvolvam um nível similar de hipertensão após a HCI, os mecanismos envolvidos na geração da atividade simpática podem ser diferentes. / Chronic intermittent hypoxia (CIH) produces hypertension and sympathetic overactivity in juvenile male rats. The increase in sympathetic activity occurs during the expiratory phase of respiration, which is correlated with an augmented expiratory activity. This information indicates that after CIH, juvenile rats develop changes in the respiratory sympathetic-coupling, which could explain, at least in part, the hypertension observed in these animals. Female rats are known to be more resistant to the development of hypertension in several experimental models of this pathology. Take in consideration these facts, we hypothesized that female rats exposed to CIH were resistant to the development of hypertension. To test this hypothesis, we studied the cardiovascular and respiratory changes in female rats after the CIH in awake freely moving condition. In another group of animals, we studied the sympathetic and respiratory activity in female rats after the CIH, using for this, the working heartbrainstem preparation. The results show that juvenile female rats develop hypertension similarly to that observed in juvenile male rats submitted to the same protocol. However, juvenile female rats presented changes in the respiratory-sympathetic coupling different from that observed in juvenile male rats. Together, these results suggest that even if the level of hypertension after CIH is similar between males and females, the mechanisms underlying the generation of sympathetic overactivity are different.

The Aronson Cognitive Residual Evaluation Scale (ACRES), designed to assess residual cognitive functioning with potential loss due to age or CNS disorder, was examined with a male subject group. The five ACRES subtests were administered to 45 elderly males. Results were compared with a previously reported subject group of 48 elderly females. Measures of the subjects' levels of independent functioning and their performances on selected Wechsler Memory Scale Revised (WMS-R) subtests were related to ACRES scores. Intercorrelations among ACRES subtests suggest that more than one cognitive factor is assessed. WMS-R subtests showed moderately significant correlations with ACRES for verbal tasks and for nonverbal tasks. Findings were discussed within a framework of lateralization of CNS functions.

Doctor of Philosophy / Curriculum and Instruction Programs / Marjorie R. Hancock / Linda P. Thurston / The purpose of this qualitative collective case study was to examine the sociocultural and gender role expectation factors that contributed to the success of 10 Latina/Hispanic female high school graduates now attending a large university in the Midwest. Additionally, the study investigated the characteristics of resilience and persistence that helped these women continue their pursuit of higher education in spite of the challenges they faced. The participants in this study were identified as recent immigrants from Mexico or Mexican-Americans born in the United States of Mexican immigrant parents. All of these respondents graduated from a midwestern K-12 public school system and are now attending a large Midwestern university. This study used a qualitative paradigm and open-ended, in-depth interviews for data collection. The 17 question interview focused on the areas of sociocultural backgrounds, resilience/persistence factors, and gender role expectations. Demographic data about the participants’ life histories and educational experiences were collected during the 90-minute interviews. Findings in the study indicated that Latinas are faced with many conflicts. They have specific gender role expectations placed on them and are limited by cultural rules and norms. Along with these conflicts they learn to build resilience/persistence attributes to help them succeed in their academic careers. The seven factors that contributed to the lived experiences and factors of resilience/persistence of Latina/Hispanic female academic success included: 1) lived discrimination; 2) the need to obtain an education that would lead to a better life; 3) active involvement in extracurricular activities in school; 4) strict and protective parents; 5) positive role models from family and other Latinas; 6) traumatic life experiences; 7) and strong familial/parental support. Additionally, the study also revealed six more contributing factors to the sociocultural and gender role expectations and pressures that impact the success of Latina/Hispanic female students in a K-12 public school system. Those factors included traditional Hispanic households, living in two worlds, traditional gender role expectations, independence from family, transference of parental gender role expectations, and the behavioral expectations for Latinas. The study offers recommendations for future studies and implications for practice advising and encouraging Hispanic females to pursue their academic goals.

Endometrial carcinoma, which is preceded by non-malignant hyperplasia, is the fifth most common cancer in women worldwide. Various genetic alterations appear to be early events in the pathogenesis of endometrial cancer. The PTEN/MMAC1/TEP1 gene is most commonly mutated in endometrioid adenocarcinoma. This gene, on chromosome 10q23, codes for a tumour suppressor protein which displays lipid and dual-specific protein phosphatase activity. It has been implicated in several signal transduction pathways and seems to be involved in the negative regulation of the PI3K-, the MAPK- and the FAK pathways. Studies have shown that caucasian Americans have a 4-fold higher frequency of PTEN mutations than African Americans. An association of PTEN mutation status with clinical outcome has been found, where patients with PTEN mutation-positive endometrial carcinoma had a better prognosis than those without PTEN mutations. It has been hypothesized that the molecular pathogenesis of endometrial carcinoma within Caucasians and Black African groups may be different. The present study aimed to investigate the PTEN gene in caucasians and Black South African women with endometrial hyperplasia and carcinoma. The correlation between the frequency and type of mutations and the pathological features of the cancers (stage and grade) were also assessed. Paraffin¬embedded tissue samples from patients with endometrial hyperplasia [n=10] and cancer [n=47] were analysed for PTEN mutations using exon-by-exon PCR-SSCP. Thirty-two mutations were detected of which 24 were pathogenic (23 in the adenocarcinomas, one in the hyperplasias). These included 10 frameshift, 7 nonsense, 4 missense and 3 splice site mutations. Pathogenic mutations were located throughout the gene with the highest frequency observed in exon 5 (39.1%; 9/23), followed by exons 1 and 8 (both 17.4%; 4/23). This data does not differ significantly from published findings (P>0.05; x2-test). Pathogenic mutations were present in 54% (20/37) of the endometrioid adenocarcinomas and 10% (1/10) of the hyperplasias. No mutations were detected in the serous papillary cancers and poorly differentiated carcinomas. Fifty-five % (6/11) of tumours from Caucasians and 52% (13/25) of the tumours from Black South Africans had genetic alterations. When comparing the African and caucasian groups there were no significant differences with regards to PTEN mutation frequency (P>0.05; x2-test). Mutations occurred in early and advanced stage endometrial carcinomas, although the majority of the samples were stage 1 endometrioid adenocarcinomas. In the present study no association between the frequency of PTEN mutations and the grade and stage of the endometrial cancer were found (P>0.05; x2-test). To validate these observations, however, a larger sample size representative of all the grades and stages of endometrial carcinoma needs to be analyzed. / Dissertation (MSc (Human Genetics))--University of Pretoria, 2006. / Genetics / unrestricted