RESUMO
Milk fat globule epidermal growth-factor 8 (MFG-E8) has not been previously linked to endometrial physiology. We reported on MFG-E8 mRNA up-regulation in the human endometrium during the window of implantation (WOI) using microarrays. Prolactin (PRL) secreted by stromal cells has been suggested to modulate protein expression. The objective of this study was to characterize the endometrial expression of MFG-E8 and its ligand αvß3 integrin during the menstrual cycle and its possible regulation by PRL. MFG-E8 mRNA (real-time RT-PCR) and protein expression (immunohistochemistry and immunoblotting) were analyzed in human endometrial biopsies at different times of the menstrual cycle, as well as in primary endometrial cell cultures. In primary cultures of epithelial cells, MFG-E8 intracellular protein expression was evaluated in absence or presence of PRL (0.2 and 1 µg/ml). The results show that MFG-E8 protein is almost exclusively localized to the epithelium in whole endometrial biopsies. Both MFG-E8 mRNA and protein expression increased in the luteal phase and were highest during the WOI; epithelial protein location of αvß3 integrin also peaked on cycle Day 24. Cultured epithelial cells showed a diffuse staining of MFG-E8 over the cytoplasmic area; however, some cells presented a punctuated staining pattern. PRL treatment of epithelial cells for 72 h in vitro significantly increased MFG-E8 protein intracellular expression. This is the first report on MFG-E8 protein localization to the human endometrial epithelium and its up-regulation during the WOI. The pattern of glandular expression of its ligand αvß3 integrin was remarkably similar. In vitro data support a modulatory role for PRL as a stromal/epithelial paracrine factor controlling MFG-E8.
Assuntos
Antígenos de Superfície/metabolismo , Endométrio/metabolismo , Epitélio/metabolismo , Glicolipídeos/metabolismo , Glicoproteínas/metabolismo , Integrina alfaV/metabolismo , Integrina beta3/metabolismo , Proteínas do Leite/metabolismo , Prolactina/farmacologia , Antígenos de Superfície/genética , Biópsia , Técnicas de Cultura de Células , Implantação do Embrião/fisiologia , Endométrio/citologia , Endométrio/efeitos dos fármacos , Células Epiteliais/citologia , Células Epiteliais/metabolismo , Feminino , Perfilação da Expressão Gênica , Regulação da Expressão Gênica/efeitos dos fármacos , Glicolipídeos/genética , Glicoproteínas/genética , Humanos , Immunoblotting , Imuno-Histoquímica , Integrina alfaV/genética , Integrina beta3/genética , Gotículas Lipídicas , Ciclo Menstrual/efeitos dos fármacos , Ciclo Menstrual/fisiologia , Proteínas do Leite/genética , Ligação Proteica , RNA Mensageiro/biossíntese , Células Estromais/citologia , Células Estromais/metabolismo , Regulação para Cima , Adulto JovemRESUMO
STUDY OBJECTIVES: REM sleep behavior disorder (RBD) is characterized by dream enactment behavior and is a premotoric sign associated with parkinsonism and dementia. We previously found contrast sensitivity visual acuity (CSVA) deficiencies in earliest stages of Parkinson disease (PD), plausibly associated with alpha-synuclein deposits in the inner retinal layers. We speculated that individuals with REM sleep behavior without clinical signs of parkinsonism might also show similar deficiencies. METHODS: Twenty-three patients with RBD and 28 healthy control patients. Eleven with PD and 12 with idiopathic RBD (iRBD). Twelve patients with RBD were re-evaluated after 1 year. Evaluations consisted of CSVA SLOAN low contrast acuity charts, optical coherence topography, Unified Parkinson's Disease Rating Scale (UPDRS), and general neurologic and ophthalmologic examinations. Data analyzed between groups using a one-way analysis of variance, and a paired samples t test for returning patients. RESULTS: Participants were classified into three groups: controls (n = 28), iRBD (n = 12), and RBD+PD (n = 11). Analysis of variance revealed CSVA scores were statistically significantly different between the three groups F2, 50 = 7.037, P = .002. Longitudinal analysis of RBD group showed CSVA decreased significantly at 1 year (P = .0141). To date, PD has developed in three individuals with iRBD based on progression of their UPDRS scores. CONCLUSIONS: CSVA is reduced in individuals with RBD and declines over time. It is plausible that patients with iRBD may show early loss in dopaminergic lateral inhibition in the retina, evidenced by their progressive loss of CSVA. This may represent a global loss of dopaminergic neurons similar to PD.
Assuntos
Doença de Parkinson , Transtorno do Comportamento do Sono REM , Sensibilidades de Contraste , Humanos , Doença de Parkinson/complicações , Transtorno do Comportamento do Sono REM/complicações , Sono REM , Acuidade VisualRESUMO
OBJECTIVE: The objective of this study was to evaluate basal anti-Müllerian hormone as a marker for ovarian responsiveness to fertility treatment. STUDY DESIGN: Frozen basal menstrual cycle day 3 serum samples were evaluated retrospectively for anti-Müllerian hormone, inhibin B, and follicle-stimulating hormone levels in 123 in vitro fertilization cycles (93 patients) and compared with in vitro fertilization records. RESULTS: Anti-Müllerian hormone values correlated the best with the number of retrieved oocytes (r = 0.539; P < .001) relative to age (r = -0.323; P < .01), follicle-stimulating hormone (r = -0.317; P < .01), inhibin B (P > .05), luteinizing hormone (P > .05), and estradiol (r = -0.190; P < .05). Receiver operating characteristic curve analysis demonstrated that, for the prediction of <4 oocytes retrieved, anti-Müllerian hormone had the largest area under the curve (AUC = 0.81; P = .0001) relative to age (r = 0.74; P = .005), follicle-stimulating hormone (0.71; P = .02), inhibin B (0.66; P = .03), and estradiol (0.54; P > .05). Similarly, for the prediction of >or=15 retrieved oocytes, anti-Müllerian hormone had the largest area under the curve (0.80; P = .0001) relative to age (0.63; P = .02), follicle-stimulating hormone (0.64; P = .005), inhibin B (r = 0.57; P > .05), and estradiol (0.58; P > .05). CONCLUSION: Anti-Müllerian hormone correlates better than age, follicle-stimulating hormone, luteinizing hormone, inhibin B, and estradiol with the number of retrieved oocytes. Receiver operating characteristic curves estimated that anti-Müllerian hormone accurately predicts ovarian responsiveness to controlled ovarian stimulation with high sensitivity and specificity.
Assuntos
Hormônio Antimülleriano/sangue , Hormônio Foliculoestimulante/sangue , Inibinas/sangue , Recuperação de Oócitos , Indução da Ovulação , Adulto , Fatores Etários , Feminino , Humanos , Técnicas Imunoenzimáticas , Hormônio Luteinizante/sangue , Valor Preditivo dos Testes , Curva ROC , Estudos RetrospectivosRESUMO
BACKGROUND: Kaposi's sarcoma is the most common malignancy among HIV patients. This systemic disease has an unpredictable clinical course and commonly manifests as a cutaneous face, trunk or lower extremity lesion. CASE: A 38-year-old, multiparous woman and AIDS patient presented with left vulvar edema and pain. The patient subsequently underwent surgery for incision and drainage of a possible abscess. Operative biopsy demonstrated Kaposi's sarcoma, which was treated with palliative radiation therapy. The patient was discharged in the care of hospice. CONCLUSION: Vulvar lesions may be thefirst sign of systemic Kaposi's sarcoma in the immunocompromised woman. Most vulvar lesions warrant careful evaluation and biopsy.
Assuntos
Infecções Oportunistas Relacionadas com a AIDS/etiologia , Síndrome da Imunodeficiência Adquirida/complicações , Sarcoma de Kaposi/etiologia , Neoplasias Vulvares/etiologia , Adulto , Feminino , HumanosRESUMO
OBJECTIVE: To study the regulation of apoptosis in human endometrial cells. The specific aims were to determine whether milk fat globule-epidermal growth factor 8 (MFG-E8), a novel endometrial epithelial protein, modulates caspase activation and DNA fragmentation; and to examine whether hCG, an early embryonic product, regulates Bax and Bcl-2 equilibrium, as well as MFG-E8 expression. DESIGN: Primary cultures of human endometrial epithelial cells (EECs) and endometrial stromal cells (ESCs). SETTING: Academic center. PATIENT(S): Ovulatory women aged 21-30 years. INTERVENTION(S): Treatment with MFG-E8 and hCG. MAIN OUTCOME MEASURE(S): Apoptotic activity was quantified using a luciferase assay. Deoxyribonucleic acid fragmentation was detected by TUNEL assay. Bax, Bcl-2, and MFG-E8 messenger RNA expression levels were determined by quantitative reverse transcription-polymerase chain reaction. Immunocytochemistry was used to establish cell purity and presence of MFG-E8 and hCG-R (receptor) proteins. RESULT(S): Endometrial epithelial cells were cytokeratin(+), vimentin(-), MFG-E8(+), and hCG-R(+), whereas ESC were vimentin(+), cytokeratin(-), MFG-E8(-), and hCG-R(+). Treatment of ESC with MFG-E8 resulted in a 13-fold increase in caspase activity and a 30-fold increase in TUNEL. On the other hand, hCG decreased messenger RNA expression of Bax in ESC. CONCLUSION(S): Milk fat globule-epidermal growth factor 8 has proapoptotic activity, suggesting participation in endometrial remodeling via an epithelial-stromal cell paracrine effect. Conversely, pregnancy levels of hCG has opposite effects on stromal cells.
Assuntos
Antígenos de Superfície/metabolismo , Gonadotropina Coriônica/metabolismo , Endométrio/citologia , Endométrio/metabolismo , Células Epiteliais/metabolismo , Proteínas do Leite/metabolismo , Adulto , Apoptose/fisiologia , Caspases/metabolismo , Células Cultivadas , Ativação Enzimática , Feminino , Humanos , Proteínas Proto-Oncogênicas c-bcl-2/metabolismo , Células Estromais/citologia , Adulto Jovem , Proteína X Associada a bcl-2RESUMO
The objective of this retrospective cross-sectional study was to evaluate the value of basal serum anti-Müllerian hormone (AMH) levels as a predictor of ovarian response and pregnancy outcome in a donor egg program. The study showed that AMH was superior to other biomarkers of ovarian reserve in predicting low and high response in young women selected as oocyte donors, but that it was not predictive of embryo morphology or pregnancy outcome in the recipient population.
Assuntos
Hormônio Antimülleriano/sangue , Biomarcadores/sangue , Doação de Oócitos , Indução da Ovulação/métodos , Resultado da Gravidez , Adulto , Blastocisto , Transferência Embrionária , Feminino , Humanos , Oócitos/citologia , Valor Preditivo dos Testes , Gravidez , Curva ROCRESUMO
OBJECTIVE: To evaluate the impact of cryopreservation storage duration on embryo survival, implantation competence, and pregnancy outcome. DESIGN: Retrospective study. SETTING: Academic tertiary-referral infertility center. PATIENT(S): In vitro fertilization patients and recipients of oocyte donation cycles who had cryopreserved embryos and underwent at least one thaw cycle from 1986 to 2007. INTERVENTION(S): None. MAIN OUTCOME MEASURE(S): Postthaw survival proportion and implantation, clinical pregnancy, miscarriage, and live birth rates. RESULT(S): Length of storage time did not have a significant effect on postthaw survival for IVF or oocyte donation cycles, or for embryos frozen at the pronuclear or cleavage stages. There was no significant impact of the duration of storage on clinical pregnancy, miscarriage, implantation, or live birth rate, whether from IVF or oocyte donation cycles. Logistic regression analysis demonstrated that the length of storage time or developmental stage at freezing were not predictive of embryo survival or pregnancy outcome. Only oocyte age, survival proportion, and number of transferred embryos were positive predictors of pregnancy outcome. CONCLUSION(S): Cryostorage duration did not adversely affect postthaw survival or pregnancy outcome in IVF or oocyte donation patients.