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Sample records for gestational trophoblastic neoplasia

  1. Chemotherapy for resistant or recurrent gestational trophoblastic neoplasia.

    LENUS (Irish Health Repository)

    Alazzam, Mo'iad

    2012-12-01

    Gestational trophoblastic neoplasia (GTN) is a highly curable group of pregnancy-related tumours; however, approximately 25% of GTN tumours will be resistant to, or will relapse after, initial chemotherapy. These resistant and relapsed lesions will require salvage chemotherapy with or without surgery. Various salvage regimens are used worldwide. It is unclear which regimens are the most effective and the least toxic.

  2. Gestational trophoblastic neoplasia: A 6 year retrospective study

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    Sushruta Shrivastava

    2014-01-01

    Full Text Available Aims and Objectives: To study the clinical presentations of gestational trophoblastic neoplasia and its response to chemotherapy. Materials and Methods: This is a retrospective study of 28 women of gestational trophoblastic neoplasia evaluated over a period of 6 years from January 2004 to December 2009. Patients were evaluated on the basis of their age, number of deliveries, history of abortion or molar pregnancy, and the treatment received. All patients were scored on the basis of WHO scoring system. Patients with low risk (score /=7 received multiple agent chemotherapy with EMACO regimen. After completion of chemotherapy patients were followed for a minimum of 2 years. The response to treatment was evaluated during follow-up by clinical examination, beta hCG levels and imaging as and when required. Results: Out of 28 women only 27 could be evaluated, because 1 patient was lost to follow-up. Out of 27 patients, 18 patients (66.67% achieved complete remission with the first-line chemotherapy and additional 25.92% (7/27 achieved complete remission with second line chemotherapy resulting in complete remission of 92.5% (25/27. Conclusion: Gestational trophoblastic neoplasia is curable if patient is properly evaluated and scored. It shows good response to chemotherapy.

  3. Gestational trophoblastic neoplasia: efficacy of color doppler ultrasound

    International Nuclear Information System (INIS)

    Song, Sun Wha; Jee, Won Hee; Choe, Bo Young; Byun, Jae Young; Choi, Byung Gil; Shinn, Kyung Sub

    1997-01-01

    To evaluate the efficacy of color Doppler ultrasound (US) in the diagnosis of gestational trophoblastic neoplasia (GTN). Intralesional color flows and resistive index (RI) on color Doppler US were prospectively analyzed in 21 consecutive suspected GTN cases. RI of the intralesional artery was investigated on the basis of the presence or absence of mass and metastasis. Correlation between RI of intralesional artery and urinary β-hCG was also investigated. Intralesional color flows were identified in 15 patients with GTN. On operation, intralesional color flows were observed in one of two patients in whom the presence of completely necrotic tissue was confirmed. Intralesional color flows, however, were not detected in four patients who were proved not to be GTN sufferers. Sensitivity, specificity, accuracy, positive and negative predictive values, and accuracy were 100%, 83%, 95%, 94% and 100%, respectively. Significant correlation between RI of the intralesional artery and urinary β-hCG was not established (p=0.49, r=0.19). RI of this artery was not substantially different between groups with and without mass, and between groups with and without metastasis (p=0.32, p=0.82). The current study demonstrates that color Doppler US is a sensitive and useful method for the diagnosis of GTN

  4. Postmolar gestational trophoblastic neoplasia: beyond the traditional risk factors.

    Science.gov (United States)

    Bakhtiyari, Mahmood; Mirzamoradi, Masoumeh; Kimyaiee, Parichehr; Aghaie, Abbas; Mansournia, Mohammd Ali; Ashrafi-Vand, Sepideh; Sarfjoo, Fatemeh Sadat

    2015-09-01

    To investigate the slope of linear regression of postevacuation serum hCG as an independent risk factor for postmolar gestational trophoblastic neoplasia (GTN). Multicenter retrospective cohort study. Academic referral health care centers. All subjects with confirmed hydatidiform mole and at least four measurements of β-hCG titer. None. Type and magnitude of the relationship between the slope of linear regression of β-hCG as a new risk factor and GTN using Bayesian logistic regression with penalized log-likelihood estimation. Among the high-risk and low-risk molar pregnancy cases, 11 (18.6%) and 19 cases (13.3%) had GTN, respectively. No significant relationship was found between the components of a high-risk pregnancy and GTN. The β-hCG return slope was higher in the spontaneous cure group. However, the initial level of this hormone in the first measurement was higher in the GTN group compared with in the spontaneous recovery group. The average time for diagnosing GTN in the high-risk molar pregnancy group was 2 weeks less than that of the low-risk molar pregnancy group. In addition to slope of linear regression of β-hCG (odds ratio [OR], 12.74, confidence interval [CI], 5.42-29.2), abortion history (OR, 2.53; 95% CI, 1.27-5.04) and large uterine height for gestational age (OR, 1.26; CI, 1.04-1.54) had the maximum effects on GTN outcome, respectively. The slope of linear regression of β-hCG was introduced as an independent risk factor, which could be used for clinical decision making based on records of β-hCG titer and subsequent prevention program. Copyright © 2015 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.

  5. RISK FACTORS FOR GESTATIONAL TROPHOBLASTIC NEOPLASIA: A CASE CONTROL STUDY IN A TERTIARY HOSPITAL

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    Hema Sreedharan Nair

    2016-10-01

    Full Text Available BACKGROUND Gestational trophoblastic disease is a spectrum of proliferative abnormalities of the trophoblast. GTD represents a benign form of the disease while GTN is the malignant often metastatic lesion. 75-80 per cent of patients initially diagnosed as GTD will follow a benign course after dilatation and curettage. 15-20 per cent develop locally invasive disease and 3-5 per cent develop metastatic lesions. The study aims to assess the proportion of gestational trophoblastic neoplasia among women with gestational trophoblastic disease and identify the risk factors for chemotherapy in gestational trophoblastic neoplasia. MATERIALS AND METHODS This is a case-control study conducted in a tertiary hospital during a 5-year period. Cases are gestational trophoblastic neoplasia diagnosed by either rising beta-HCG levels or plateauing beta-HCG levels or by histological evidence of choriocarcinoma. Controls are cases of gestational trophoblastic disease post evacuation with normal HCG regression at 8 weeks. There were 306 controls and 57 cases. RESULTS Tabulated and analysed using SPSS package. Of the 363 patients of gestational trophoblastic disease, 57 (15.7% needed chemotherapy. 98.2% belonged to the age group of 20-35 years. 63% had gestational age of more than 12 weeks, 56.1% had pre-evacuation HCG of more than 40,000. 15.7% needed combination therapy. CONCLUSION 1. 83.1% of patients belonged to age group of 20-30 years. 2. Blood group distribution of patients with gestational trophoblastic disease did not show any significance. 3. 15.7% of total patients were diagnosed to have gestational trophoblastic neoplasia that necessitated chemotherapy. 4. When uterine size was more than 12 weeks, a statistically significant number of patients needed chemotherapy compared to non-chemotherapy group. 5. When BHCG values were more than 40,000, a statistically significant number of patients needed chemotherapy. 6. A risk score of seven or more was found to

  6. The role of surgery in the management of gestational trophoblastic neoplasia.

    Science.gov (United States)

    Doll, Kemi M; Soper, John T

    2013-07-01

    Although sensitive human chorionic gonadotropin assays and advances in chemotherapy have assumed primary importance in the management of gestational trophoblastic neoplasia, surgery remains important in the overall care of these patients. Management of molar pregnancies consists of surgical evacuation and subsequent monitoring. Hysterectomy decreases the risk of post-molar trophoblastic disease in appropriate patients and, when incorporated to primary management of gestational trophoblastic neoplasia, can decrease the chemotherapy requirements of patients with low-risk disease. In patients with high-risk disease, surgical intervention is frequently required to control complications of disease or as therapy to stabilize patients during chemotherapy. Hysterectomy, thoracotomy, or other extirpative procedures may be integrated into the management of patients with chemorefractory disease. Interventional procedures are useful adjuncts to control bleeding from metastases.

  7. Prophylactic chemotherapy for hydatidiform mole to prevent gestational trophoblastic neoplasia.

    Science.gov (United States)

    Wang, Qiuyi; Fu, Jing; Hu, Lina; Fang, Fang; Xie, Lingxia; Chen, Hengxi; He, Fan; Wu, Taixiang; Lawrie, Theresa A

    2017-09-11

    This is an update of the original Cochrane Review published in Cochrane Library, Issue 10, 2012.Hydatidiform mole (HM), also called a molar pregnancy, is characterised by an overgrowth of foetal chorionic tissue within the uterus. HMs may be partial (PM) or complete (CM) depending on their gross appearance, histopathology and karyotype. PMs usually have a triploid karyotype, derived from maternal and paternal origins, whereas CMs are diploid and have paternal origins only. Most women with HM can be cured by evacuation of retained products of conception (ERPC) and their fertility preserved. However, in some women the growth persists and develops into gestational trophoblastic neoplasia (GTN), a malignant form of the disease that requires treatment with chemotherapy. CMs have a higher rate of malignant transformation than PMs. It may be possible to reduce the risk of GTN in women with HM by administering prophylactic chemotherapy (P-Chem). However, P-Chem given before or after evacuation of HM to prevent malignant sequelae remains controversial, as the risks and benefits of this practice are unclear. To evaluate the effectiveness and safety of P-Chem to prevent GTN in women with a molar pregnancy. To investigate whether any subgroup of women with HM may benefit more from P-Chem than others. For the original review we performed electronic searches in the Cochrane Gynaecological Cancer Specialised Register, the Cochrane Central Register of Controlled Trials (CENTRAL, Issue 2, 2012), MEDLINE (1946 to February week 4, 2012) and Embase (1980 to 2012, week 9). We developed the search strategy using free text and MeSH. For this update we searched the Cochrane Central Register of Controlled Trials (CENTRAL, Issue 5, 2017), MEDLINE (February 2012 to June week 1, 2017) and Embase (February 2012 to 2017, week 23). We also handsearched reference lists of relevant literature to identify additional studies and searched trial registries. We included randomised controlled trials

  8. First-line chemotherapy in low-risk gestational trophoblastic neoplasia.

    LENUS (Irish Health Repository)

    Alazzam, Mo'iad

    2012-01-01

    This is an update of a Cochrane review that was first published in Issue 1, 2009. Gestational trophoblastic neoplasia (GTN) is a rare but curable disease arising in the fetal chorion during pregnancy. Most women with low-risk GTN will be cured by evacuation of the uterus with or without single-agent chemotherapy. However, chemotherapy regimens vary between treatment centres worldwide and the comparable benefits and risks of these different regimens are unclear.

  9. Quality of life of gestational trophoblastic neoplasia survivors: a study of patients at the Philippine General Hospital trophoblastic disease section.

    Science.gov (United States)

    Cagayan, M Stephanie Fay S; Llarena, Raquel T

    2010-01-01

    To evaluate the quality of life (QOL) of patients who were diagnosed with gestational trophoblastic neoplasia (GTN) at the Philippine General Hospital Trophoblastic Disease Section and who were in remission at the time of this study. A cross-sectional descriptive study designed to measure the QOL of all patients diagnosed as having GTN in remission and following up at the Philippine General Hospital Trophoblastic Disease Outpatient Clinic from May-August 2008 (N = 46). This study used the short form 12-question (SF-12) survey forms to evaluate the QOL of patients diagnosed with GTN. Scores from the SF-12 were analyzed using Pearson's correlation. Statistical significance was assumed for p values educational level and physical functioning. A negative correlation was found between the stage of GTN and patients' general health. In conclusion, the survivors' age, educational level and type of treatment had impact on the QOL among GTN survivors in terms of physical functioning. No relationship was established between the demographic variables and mental status. SF-12 appears to be a reliable instrument, suggesting its potential in measuring health status in GTN survivors. Age, educational attainment and type of treatment were shown to have an impact on the QOL of the surviving GTN patients.

  10. Gestational trophoblastic neoplasia after spontaneous human chorionic gonadotropin normalization following molar pregnancy evacuation.

    Science.gov (United States)

    Braga, Antonio; Maestá, Izildinha; Matos, Michelle; Elias, Kevin M; Rizzo, Julianna; Viggiano, Maurício Guilherme Campos

    2015-11-01

    To evaluate the risk of gestational trophoblastic neoplasia (GTN) after spontaneous human chorionic gonadotropin normalization in postmolar follow-up. Retrospective chart review of 2284 consecutive cases of hydatidiform mole with spontaneous normalization of hCG following uterine evacuation treated at one of five Brazilian reference centers from January 2002 to June 2013. After hCG normalization, GTN occurred in 10/2284 patients (0.4%; 95% CI 0.2%-0.8%). GTN developed in 9/1424 patients (0.6%; 95% CI 0.3%-1.2%) after a complete hydatidiform mole, in 1/849 patients (0.1%; 95% CInormalization was 18months, and no diagnoses were made before six months of postmolar surveillance. Patients who required more than 56days to achieve a normal hCG value had a ten-fold increased risk of developing GTN after hCG normalization (9/1074; 0.8%; 95% CI 0.4%-1.6%) compared to those who reached a normal hCG level in fewer than 56days (1/1210;0.08%; 95% CInormalization following molar pregnancy is exceedingly rare, and the few patients who do develop GTN after achieving a normal hCG value are likely to be diagnosed after completing the commonly recommended six months of postmolar surveillance. Current recommendations for surveillance after hCG normalization should be revisited. Copyright © 2015 Elsevier Inc. All rights reserved.

  11. Pregnancy outcomes after chemotherapy for trophoblastic neoplasia.

    Science.gov (United States)

    Garcia, Mila Trementosa; Lin, Lawrence Hsu; Fushida, Koji; Francisco, Rossana Pulcineli Vieira; Zugaib, Marcelo

    2016-12-01

    The successful development of chemotherapy enabled a fertilitysparing treatment for patients with trophoblastic neoplasia. After disease remission, the outcome of a subsequent pregnancy becomes a great concern for these women. To analyze existing studies in the literature that describe the reproductive outcomes of patients with trophoblastic neoplasia treated with chemotherapy. Systematic review was performed searching for articles on Medline/ Pubmed, Lilacs and Cochrane Library databases, using the terms "gestational trophoblastic disease" and "pregnancy outcome". A total of 18 articles were included. No evidence of decreased fertility after chemotherapy for trophoblastic neoplasia was observed. The abortion rates in patients who conceived within 6 months after chemotherapy was higher compared to those who waited longer. Some studies showed increased rates of stillbirth and repeat hydatidiform moles. Only one work showed increased congenital abnormalities. The pregnancies conceived after chemotherapy for trophoblastic neoplasia should be followed with clinical surveillance due to higher rates of some pregnancy complications. However, studies in the literature provide reassuring data about reproductive outcomes of these patients.

  12. Pregnancy outcomes after chemotherapy for trophoblastic neoplasia

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    MILA TREMENTOSA GARCIA

    Full Text Available SUMMARY Introduction The successful development of chemotherapy enabled a fertilitysparing treatment for patients with trophoblastic neoplasia. After disease remission, the outcome of a subsequent pregnancy becomes a great concern for these women. Objective To analyze existing studies in the literature that describe the reproductive outcomes of patients with trophoblastic neoplasia treated with chemotherapy. Method Systematic review was performed searching for articles on Medline/ Pubmed, Lilacs and Cochrane Library databases, using the terms “gestational trophoblastic disease” and “pregnancy outcome”. Results A total of 18 articles were included. No evidence of decreased fertility after chemotherapy for trophoblastic neoplasia was observed. The abortion rates in patients who conceived within 6 months after chemotherapy was higher compared to those who waited longer. Some studies showed increased rates of stillbirth and repeat hydatidiform moles. Only one work showed increased congenital abnormalities. Conclusion The pregnancies conceived after chemotherapy for trophoblastic neoplasia should be followed with clinical surveillance due to higher rates of some pregnancy complications. However, studies in the literature provide reassuring data about reproductive outcomes of these patients.

  13. Uterine Rupture Due to Invasive Metastatic Gestational Trophoblastic Neoplasm

    Science.gov (United States)

    Bruner, David I.; Pritchard, Amy M.; Clarke, Jonathan

    2013-01-01

    While complete molar pregnancies are rare, they are wrought with a host of potential complications to include invasive gestational trophoblastic neoplasia. Persistent gestational trophoblastic disease following molar pregnancy is a potentially fatal complication that must be recognized early and treated aggressively for both immediate and long-term recovery. We present the case of a 21-year-old woman with abdominal pain and presyncope 1 month after a molar pregnancy with a subsequent uterine rupture due to invasive gestational trophoblastic neoplasm. We will discuss the complications of molar pregnancies including the risks and management of invasive, metastatic gestational trophoblastic neoplasia. PMID:24106538

  14. Is Doppler ultrasound useful for evaluating gestational trophoblastic disease?

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    Lawrence H. Lin

    Full Text Available Doppler ultrasound is a non-invasive method for evaluating vascularization and is widely used in clinical practice. Gestational trophoblastic neoplasia includes a group of highly vascularized malignancies derived from placental cells. This review summarizes data found in the literature regarding the applications of Doppler ultrasound in managing patients with gestational trophoblastic neoplasia. The PubMed/Medline, Web of Science, Cochrane and LILACS databases were searched for articles published in English until 2014 using the following keywords: “Gestational trophoblastic disease AND Ultrasonography, Doppler.” Twenty-eight articles met the inclusion criteria and were separated into the 4 following groups according to the aim of the study. (1 Doppler ultrasound does not seem to be capable of differentiating partial from complete moles, but it might be useful when evaluating pregnancies in which a complete mole coexists with a normal fetus. (2 There is controversy in the role of uterine artery Doppler velocimetry in the prediction of development of gestational trophoblastic neoplasia. (3 Doppler ultrasound is a useful tool in the diagnosis of gestational trophoblastic neoplasia because abnormal myometrial vascularization and lower uterine artery Doppler indices seem to be correlated with invasive disease. (4 Lower uterine artery Doppler indices in the diagnosis of gestational trophoblastic neoplasia are associated with methotrexate resistance and might play a role in prognosis. CONCLUSION: Several studies support the importance of Doppler ultrasound in the management of patients with gestational trophoblastic neoplasia, particularly the role of Doppler velocimetry in the prediction of trophoblastic neoplasia and the chemoresistance of trophoblastic tumors. Doppler findings should be used as ancillary tools, along with human chorionic gonadotropin assessment, in the diagnosis of gestational trophoblastic neoplasia.

  15. Is Doppler ultrasound useful for evaluating gestational trophoblastic disease?

    Science.gov (United States)

    Lin, Lawrence H; Bernardes, Lisandra S; Hase, Eliane A; Fushida, Koji; Francisco, Rossana P V

    2015-12-01

    Doppler ultrasound is a non-invasive method for evaluating vascularization and is widely used in clinical practice. Gestational trophoblastic neoplasia includes a group of highly vascularized malignancies derived from placental cells. This review summarizes data found in the literature regarding the applications of Doppler ultrasound in managing patients with gestational trophoblastic neoplasia. The PubMed/Medline, Web of Science, Cochrane and LILACS databases were searched for articles published in English until 2014 using the following keywords: "Gestational trophoblastic disease AND Ultrasonography, Doppler." Twenty-eight articles met the inclusion criteria and were separated into the 4 following groups according to the aim of the study. (1) Doppler ultrasound does not seem to be capable of differentiating partial from complete moles, but it might be useful when evaluating pregnancies in which a complete mole coexists with a normal fetus. (2) There is controversy in the role of uterine artery Doppler velocimetry in the prediction of development of gestational trophoblastic neoplasia. (3) Doppler ultrasound is a useful tool in the diagnosis of gestational trophoblastic neoplasia because abnormal myometrial vascularization and lower uterine artery Doppler indices seem to be correlated with invasive disease. (4) Lower uterine artery Doppler indices in the diagnosis of gestational trophoblastic neoplasia are associated with methotrexate resistance and might play a role in prognosis. Several studies support the importance of Doppler ultrasound in the management of patients with gestational trophoblastic neoplasia, particularly the role of Doppler velocimetry in the prediction of trophoblastic neoplasia and the chemoresistance of trophoblastic tumors. Doppler findings should be used as ancillary tools, along with human chorionic gonadotropin assessment, in the diagnosis of gestational trophoblastic neoplasia.

  16. Gestational Trophoblastic Disease -Choriocarcinoma

    International Nuclear Information System (INIS)

    Bozik, M.

    2011-01-01

    Gestational trophoblastic tumors are a group of a diseases from the benign hydatidiform mole, through the invasive mole to the highly malignant form of a choriocarcinoma. Choriocarcinoma is a rare tumor and it is the most malignant and aggressive neoplasm of all the gestational trophoblastic diseases. It grows rapidly and metastasizes to the lung, liver, and, less frequently, to the brain. The author presents the case of a 26-year-old woman who is indicated to the CT examination for suspected brain tumor based on the previous examinations. The patient was diagnosed with metastatic choriocarcinoma to the brain, kidney and adrenal gland on the basis of an anamnesis by her husband, a high value of beta-hCG and a gynecological examination. (author)

  17. Gestational trophoblastic neoplasms

    International Nuclear Information System (INIS)

    Demas, B.E.; Hricak, H.; Braga, C.

    1988-01-01

    Twenty-four women with suspected gestational trophoblastic neoplasms were evaluated prospectively to identify imaging algorithms optimal for treatment planning. All underwent chest radiography, chest CT, hepatic and cranial CT or MR imaging, and pelvic MR imaging. Ten also underwent pelvic CT, 13 pelvic US. The most sensitive imaging combination was chest CT, hepatic and cranial CT or MR imaging, and pelvic MR imaging. However, correct assignment to ACOG therapeutic categories was achieved by means of history, physical examination, beta subunit of human chorionic gonadotropin measurements, and chest radiography in 81% of patients. Hepatic and cranial imaging defined the need for radiation therapy. Chest CT was needed only when chest radiographs were negative. Pelvic imaging aided diagnosis but did not assist in treatment planning

  18. Uterine Rupture Due to Invasive Metastatic Gestational Trophoblastic Neoplasm

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    David I Bruner

    2013-09-01

    Full Text Available While complete molar pregnancies are rare, they are wrought with a host of potential complications to include invasive gestational trophoblastic neoplasia. Persistent gestational trophoblastic disease following molar pregnancy is a potentially fatal complication that must be recognized early and treated aggressively for both immediate and long-term recovery. We present the case of a 21-year-old woman with abdominal pain and presyncope 1 month after a molar pregnancy with a subsequent uterine rupture due to invasive gestational trophoblastic neoplasm. We will discuss the complications of molar pregnancies including the risks and management of invasive, metastatic gestational trophoblastic neoplasia. [West J Emerg Med. 2013;14(5:444–447.

  19. Gestational Trophoblastic Disease—Health Professional Version

    Science.gov (United States)

    Gestational trophoblastic disease (GTD) is a broad term encompassing both benign and malignant growths arising from products of conception in the uterus. GTDs contain paternal chromosomes and are placental in origin. Find evidence-based information on gestational trophoblastic disease treatment.

  20. Drugs Approved for Gestational Trophoblastic Disease

    Science.gov (United States)

    This page lists cancer drugs approved by the Food and Drug Administration (FDA) for gestational trophoblastic disease. The list includes generic names and brand names. The drug names link to NCI's Cancer Drug Information summaries.

  1. Gestational trophoblastic disease following complete hydatidiform ...

    African Journals Online (AJOL)

    Gestational trophoblastic disease following complete hydatidiform mole in Mulago Hospital, Kampala, Uganda. ... The main outcome measures were pre- and post-evacuation serum hCG levels and complications associated with oral methotrexate use. Results : The prevalence of CHM was 3.42 per 1,000 deliveries.

  2. Clinical and radiological correlations in patients with gestational trophoblastic disease

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    Lana de Lourdes Aguiar Lima

    Full Text Available Abstract Gestational trophoblastic disease is an abnormality of pregnancy that encompasses a group of diseases that differ from each other in their propensity for regression, invasion, metastasis, and recurrence. In the past, it was common for patients with molar pregnancy to present with marked symptoms: copious bleeding; theca lutein cysts; uterus larger than appropriate for gestational age; early preeclampsia; hyperemesis gravidarum; and hyperthyroidism. Currently, with early diagnosis made by ultrasound, most patients are diagnosed while the disease is still in the asymptomatic phase. In cases of progression to trophoblastic neoplasia, staging-typically with Doppler flow studies of the pelvis and chest X-ray, although occasionally with computed tomography or magnetic resonance imaging-is critical to the choice of an appropriate antineoplastic therapy regimen. Because it is an unusual and serious disease that affects women of reproductive age, as well as because its appropriate treatment results in high cure rates, it is crucial that radiologists be familiar with gestational trophoblastic disease, in order to facilitate its early diagnosis and to ensure appropriate follow-up imaging.

  3. Clinical and radiological correlations in patients with gestational trophoblastic disease

    International Nuclear Information System (INIS)

    Lima, Lana de Lourdes Aguiar; Parente, Raphael Camara Medeiros; Amim Junior, Joffre; Rezende Filho, Jorge Fonte de; Montenegro, Carlos Antonio Barbosa; Braga, Antonio; Maesta, Izildinha

    2016-01-01

    Gestational trophoblastic disease is an abnormality of pregnancy that encompasses a group of diseases that differ from each other in their propensity for regression, invasion, metastasis, and recurrence. In the past, it was common for patients with molar pregnancy to present with marked symptoms: copious bleeding; theca lutein cysts; uterus larger than appropriate for gestational age; early preeclampsia; hyperemesis gravidarum; and hyperthyroidism. Currently, with early diagnosis made by ultrasound, most patients are diagnosed while the disease is still in the asymptomatic phase. In cases of progression to trophoblastic neoplasia, staging-typically with Doppler flow studies of the pelvis and chest X-ray, although occasionally with computed tomography or magnetic resonance imaging-is critical to the choice of an appropriate antineoplastic therapy regimen. Because it is an unusual and serious disease that affects women of reproductive age, as well as because its appropriate treatment results in high cure rates, it is crucial that radiologists be familiar with gestational trophoblastic disease, in order to facilitate its early diagnosis and to ensure appropriate follow-up imaging. (author)

  4. Clinical and radiological correlations in patients with gestational trophoblastic disease

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    Lima, Lana de Lourdes Aguiar; Parente, Raphael Camara Medeiros; Amim Junior, Joffre; Rezende Filho, Jorge Fonte de; Montenegro, Carlos Antonio Barbosa; Braga, Antonio, E-mail: lanalima@hotmail.com [Universidade Federal do Rio de Janeiro (UFRJ), RJ (Brazil); Maesta, Izildinha [Universidade Estadual Paulista Julio de Mesquita Filho (UNESP), Botucatu, SP (Brazil). Faculdade de Medicina

    2016-07-15

    Gestational trophoblastic disease is an abnormality of pregnancy that encompasses a group of diseases that differ from each other in their propensity for regression, invasion, metastasis, and recurrence. In the past, it was common for patients with molar pregnancy to present with marked symptoms: copious bleeding; theca lutein cysts; uterus larger than appropriate for gestational age; early preeclampsia; hyperemesis gravidarum; and hyperthyroidism. Currently, with early diagnosis made by ultrasound, most patients are diagnosed while the disease is still in the asymptomatic phase. In cases of progression to trophoblastic neoplasia, staging-typically with Doppler flow studies of the pelvis and chest X-ray, although occasionally with computed tomography or magnetic resonance imaging-is critical to the choice of an appropriate antineoplastic therapy regimen. Because it is an unusual and serious disease that affects women of reproductive age, as well as because its appropriate treatment results in high cure rates, it is crucial that radiologists be familiar with gestational trophoblastic disease, in order to facilitate its early diagnosis and to ensure appropriate follow-up imaging. (author)

  5. Gestational trophoblastic disease with hyperthyroidism: Anesthetic management

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    Puneet Khanna

    2012-01-01

    Full Text Available The coexistence of hyperthyroidism with gestational trophoblastic disease is a known albeit rare clinical condition. We herein report the successful anesthetic management of such a case in our institute. There are only few case reports in literature of this association. Often, the diagnosis of hyperthyroid state is retrospective one, as it can be missed in the emergency scenario of patient requiring molar evacuation. This case report highlights the perioperative management and optimization of hyperthyroid state prior to surgical evacuation of the invasive hydatidiform mole.

  6. Minimally-aggressive gestational trophoblastic neoplasms.

    Science.gov (United States)

    Cole, Laurence A

    2012-04-01

    We have previously defined a new syndrome "Minimally-aggressive gestational trophoblastic neoplasms" in which choriocarcinoma or persistent hydatidiform mole has a minimal growth rate and becomes chemorefractory. Previously we described a new treatment protocol, waiting for hCG rise to >3000 mIU/ml and disease becomes more advanced, then using combination chemotherapy. Initially we found this treatment successful in 8 of 8 cases, here we find this protocol appropriate in a further 16 cases. Initially we used hyperglycosylated hCG, a limited availability test, to identify this syndrome. Here we propose also using hCG doubling rate to detect this syndrome. Minimally aggressive gestational trophoblastic disease can be detected by chemotherapy resistance or low hyperglycosylated hCG, disease by hyperglycosylated hCG and by hCG doubling test. All were recommended to hold off further chemotherapy until hCG >3000mIU/ml. One case died prior to the start of the study, one case withdrew because of a lung nodule and one withdrew refusing the suggested combination chemotherapy. The remaining 16 women were all successfully treated. A total of 8 plus 16 or 24 of 24 women were successfully treated using the proposed protocol, holding back on chemotherapy until hCG >3000mIU/ml. Copyright © 2011 Elsevier Inc. All rights reserved.

  7. The Gestational Trophoblastic Diseases: A Ten Year Retrospective Study

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    Razieh Mohammadjafari

    2010-01-01

    Full Text Available Background: Gestational trophoblastic disease (GTD defines a heterogenenous group ofinterrelated lesions that arise from the trophoblastic epithelium of the placenta. There are severalhistologically distinct types of GTD: hydatiform mole (complete or partial, persistant/invasivegestational trophoblastic neoplasia (GTN, choriocarcinoma and placenta site trophoblastictumors. The aim of this study was to determine the frequency and risk factors of GTD amongwomen admitted to Imam Khomeini Hospital in Ahvaz, Iran.Materials and Methods: This was a cross-sectional study conducted at Imam KhomeiniHospital in Ahvaz, Iran. All hospital records related to GTD (132 from 1996 until 2006 werereviewed. Demographic and histo-pathologic characteristics were extracted. Chi-square andFisher-exact tests were used to analyze all variables. P ≤ 0.05 was considered statisticallysignificant. SPSS, version 11 was used for statistical analysis.Results: The mean age of patients was 27.6 years. Most patients who presented with GTDwere of ages 18-35 years (71.3%. There was no relationship between age and hydatiformmole during the reproductive years. There were 28 (18.9% patients over the age 40, of which18 (15.90% of these had a complete hydatiform mole. Within this group, 9 (6.8% changedto a persistent mole. There was a significant relationship between age over 40 and completemole (p<0.02. The percentage of patients with blood groups A and O was the same (37.9%.There was a significant relationship between blood groups (O+ and A+ and complete mole(p<0.05.Conclusion: The most common age range for hydatiform mole was 18-35 years. Women overthe age of 40 had a more complete hydatiform mole, which is similar to the other countries.Age and blood group are two risk factors for hydatiform mole.

  8. A Rare Gestational Trophoblastic Disease: Placental Site Trophoblastic Tumor

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    Senem Yaman Tunç

    2016-12-01

    PSTT is a rare tumor. In contrast to other trophoblastic tumors, PSTT produces a small amount of ß-HCG and it is relatively insensitive to chemotherapy. Adjuvant chemotherapy is suggested to follow surgical treatment in the cases with metastasis.

  9. A five - year review of gestational trophoblastic diseases in Port ...

    African Journals Online (AJOL)

    Methods: A retrospective analysis of women treated for gestational ... persistent trophoblastic disease while 8(21.1%) had chemotherapy for choriocarcinoma. ... as well as proper counseling of patients treated on the benefits of follow up visits.

  10. Stages of Gestational Trophoblastic Tumors and Neoplasia

    Science.gov (United States)

    ... the blood of a woman who is not pregnant may be a sign of GTD. Urinalysis : A test to check the color of urine and its contents, such as sugar, protein , blood, bacteria , and the level of β-hCG. ...

  11. MR imaging of gestational trophoblastic tumor: role of gadolinium enhancement

    International Nuclear Information System (INIS)

    Choi, Si Young; Byun, Jae Young; Kim, Bum Su; Yun, Young Hyun; Mun, Kyung Mi; Park, Kyung Sin; Kim, Byung Kee; Bae, Seog Nyeon; Shinn, Kyung Sub.

    1997-01-01

    The purpose of this study is to investigate the role of gadolinium enhanced MR imaging in the evaluation of gestational trophoblastic tumors (invasive mole and choriocarcinoma). Pre-enhanced T1-and T2-weighted images and gadolinium enhanced T1-weighted images of 34 gestational trophoblastic tumors (15 choriocarcinomas, 19 invasive moles) were retrospectively evaluated and enhancement patterns were analyzed. Morphologica differences and structural characteristics were analyzed by the evaluation of tumor margin, patterns of hemorrhagic necroses, the development of intratumoral vascularity, and molar villi. Graded scores of MR findings between pre- and gadolinium enhanced images were based on the following criteria : 1) visualization of tumor margin 2) distinction between tumor necrosis and zone of trophoblastic proliferation ; and 3) molar villi. Statistical differences between graded scores of pre- and post-enhanced images were analyzed. Gadolinium enhanced MR imaging was helpful for the visualization of tumor characteristics in gestational trophoblastic tumors and in differential diagnosis between invasive mole and choriocarcinoma. (author). 16 refs., 4 tabs., 4 figs

  12. Feasibility of central co-ordinated EMA/CO for gestational trophoblastic disease in the Netherlands

    NARCIS (Netherlands)

    van der Houwen, Clasien; Rietbroek, Ron C.; Lok, Christianne A. R.; ten Kate-Booij, Marianne J.; Lammes, Frits B.; Ansink, Anca C.

    2004-01-01

    In the Netherlands, high risk gestational trophoblastic disease (GTD) patients are treated in different referral hospitals with a national working party on trophoblastic tumours having a co-ordinating function. Our purpose was to evaluate whether this policy is a satisfactory alternative to complete

  13. Gestational trophoblastic disease in Abuth Zaria, Nigeria: A 5‑year ...

    African Journals Online (AJOL)

    Gestational trophoblastic disease in Abuth Zaria, Nigeria: A 5‑year review. ... Abimbola O. Kolawole, John K. Nwajagu, Adekunle O. Oguntayo, Marliya S. ... The data obtained were expressed in percentages, means, and standard deviations.

  14. Gestational Trophoblastic Disease: A Multimodality Imaging Approach with Impact on Diagnosis and Management

    International Nuclear Information System (INIS)

    Dhanda, S.; Ramani, S.; Dhanda, S.; Ramani, S.; Thakur, M.

    2014-01-01

    Gestational trophoblastic disease is a condition of uncertain etiology, comprised of hydatiform mole (complete and partial), invasive mole, choriocarcinoma, and placental site trophoblastic tumor. It arises from abnormal proliferation of trophoblastic tissue. Early diagnosis of gestational trophoblastic disease and its potential complications is important for timely and successful management of the condition with preservation of fertility. Initial diagnosis is based on a multimodality approach: encompassing clinical features, serial quantitative β-hCG titers, and pelvic ultrasonography. Pelvic magnetic resonance imaging (MRI) is sometimes used as a problem-solving tool to assess the depth of myometrial invasion and extra uterine disease spread in equivocal and complicated cases. Chest radiography, body computed tomography (CT), and brain MRI have been recommended as investigative tools for overall disease staging. Angiography has a role in management of disease complications and metastases. Efficacy of PET (positron emission tomography) and PET/CT in the evaluation of recurrent or metastatic disease has not been adequately investigated yet. This paper discusses the imaging features of gestational trophoblastic disease on various imaging modalities and the role of different imaging techniques in the diagnosis and management of this entity. 1. Introduction Gestational trophoblastic disease (GTD) refers to an abnormal trophoblastic proliferation composed of a broad spectrum of lesions ranging from benign, albeit pre malignant hydatiform mole (complete and partial), through to the aggressive invasive mole, choriocarcinoma

  15. Gestational trophoblastic disease: experience at a tertiary care hospital of sindh

    International Nuclear Information System (INIS)

    Khaskheli, M.; Imdad, A.; Baloch, S.

    2007-01-01

    To determine the frequency, clinical presentation and management outcomes of Gestational Trophoblastic Disease (GTD). The case records of all the gestational trophoblastic cases during study period were analyzed regarding their illness history, clinical examination, investigations, treatment and follow-up. The main outcomes were measured in terms of duration, antecedent pregnancy, investigations, treatment and the follow-up. There were a total of 1030 obstetric admissions during the study period, which included 23 cases of trophoblastic disease. Hence, frequency of GTD was 1 per 45 live births. Of these 23 cases, 19 (82.6%) patients had hydatidiform mole and 4 patients had malignant trophoblastic disease. Eight patients (34.7%) received chemotherapy while rest of the patients had suction evacuation and follow-up. Among all patients, 21 (91.3%) fully recovered and 2 (8.69%) died because of extensive disease; metastasis extending upto brain. Frequency of trophoblastic disease was high in this series compared to world and national literature. Therefore, emphasis should be on the early diagnosis of disease as proper management in the early stages strongly influences the outcome of disease. Suction evacuation and follow-up are ideal treatments for benign trophoblastic disease. (author)

  16. Gestational trophoblastic disease: experience at a tertiary care hospital of sindh

    Energy Technology Data Exchange (ETDEWEB)

    Khaskheli, M; Imdad, A; Baloch, S [Liaquat Univ. of Medical and Health Sciences, Jamshoro (Pakistan). Dept. of Obstetrics and Gynaecology

    2007-02-15

    To determine the frequency, clinical presentation and management outcomes of Gestational Trophoblastic Disease (GTD). The case records of all the gestational trophoblastic cases during study period were analyzed regarding their illness history, clinical examination, investigations, treatment and follow-up. The main outcomes were measured in terms of duration, antecedent pregnancy, investigations, treatment and the follow-up. There were a total of 1030 obstetric admissions during the study period, which included 23 cases of trophoblastic disease. Hence, frequency of GTD was 1 per 45 live births. Of these 23 cases, 19 (82.6%) patients had hydatidiform mole and 4 patients had malignant trophoblastic disease. Eight patients (34.7%) received chemotherapy while rest of the patients had suction evacuation and follow-up. Among all patients, 21 (91.3%) fully recovered and 2 (8.69%) died because of extensive disease; metastasis extending upto brain. Frequency of trophoblastic disease was high in this series compared to world and national literature. Therefore, emphasis should be on the early diagnosis of disease as proper management in the early stages strongly influences the outcome of disease. Suction evacuation and follow-up are ideal treatments for benign trophoblastic disease. (author)

  17. Gestational Trophoblastic Disease: A Multimodality Imaging Approach with Impact on Diagnosis and Management

    Directory of Open Access Journals (Sweden)

    Sunita Dhanda

    2014-01-01

    Full Text Available Gestational trophoblastic disease is a condition of uncertain etiology, comprised of hydatiform mole (complete and partial, invasive mole, choriocarcinoma, and placental site trophoblastic tumor. It arises from abnormal proliferation of trophoblastic tissue. Early diagnosis of gestational trophoblastic disease and its potential complications is important for timely and successful management of the condition with preservation of fertility. Initial diagnosis is based on a multimodality approach: encompassing clinical features, serial quantitative β-hCG titers, and pelvic ultrasonography. Pelvic magnetic resonance imaging (MRI is sometimes used as a problem-solving tool to assess the depth of myometrial invasion and extrauterine disease spread in equivocal and complicated cases. Chest radiography, body computed tomography (CT, and brain MRI have been recommended as investigative tools for overall disease staging. Angiography has a role in management of disease complications and metastases. Efficacy of PET (positron emission tomography and PET/CT in the evaluation of recurrent or metastatic disease has not been adequately investigated yet. This paper discusses the imaging features of gestational trophoblastic disease on various imaging modalities and the role of different imaging techniques in the diagnosis and management of this entity.

  18. Efficacy of NETDC (New England Trophoblastic Disease Center prognostic index score to predict gestational trophoblastic tumor from hydatidiform mole

    Directory of Open Access Journals (Sweden)

    Khrismawan Khrismawan

    2004-03-01

    Full Text Available A prospective longitudinal analytic study assessing the efficacy of NETDC (New England Trophoblastic Disease Center prognostic index score in predicting malignancy after hydatidiform mole had been performed. Of the parameter evaluated; age of patients, type of hydatidiform mole, uterine enlargement, serum hCG level, lutein cyst, and presence of complicating factors were significant risk factors for malignancy after hydatidiform mole were evacuated (p<0.032. The study were done on 50 women diagnosed with hydatidiform mole with 1 year observation (January 2001-December 2002 at the Department of Obstetrics and Gynecology, Mohammad Hoesin Hospital, Palembang. The results showed that the NETDC prognostic index score predicted malignancy in 50% of high risk group and 10% in low risk group (p<0.05. This showed a higher number than that found by the WHO (19%-30%. The risk for incidence of  malignancy after hydatidiform mole in the high risk group is 9.0 times higher compared to that of the low risk group (CI: 1.769-45.786. (Med J Indones 2004; 13: 40-6 Keywords: New England Trophoblastic Disease Center (NETDC, gestational trophoblastic tumor, hydatidiform mole, high and low risk

  19. [Potential role of the angiogenic factor "EG-VEGF" in gestational trophoblastic diseases].

    Science.gov (United States)

    Boufettal, H; Feige, J-J; Benharouga, M; Aboussaouira, T; Nadifi, S; Mahdaoui, S; Samouh, N; Alfaidy, N

    2013-10-01

    Gestational trophoblastic disease (MGT) includes a wide spectrum of pathologies of the placenta, ranging from benign precancerous lesions, with gestational trophoblastic tumors. Metastases are the leading causes of death as a result of this tumor. They represent a major problem for obstetrics and for the public health system. To date, there is no predictor of the progression of molar pregnancies to gestational trophoblastic tumor (GTT). Only an unfavorable plasma hCG monitoring after evacuation of hydatidiform mole is used to diagnose a TTG. The causes of the development of this cancer are still poorly understood. Increasing data in the literature suggests a close association between the development of this tumor and poor placental vascularization during the first trimester of pregnancy. The development of the human placenta depends on a coordination between the trophoblast and endothelial cells. A disruption in the expression of angiogenic factors could contribute to uterine or extra-uterine tissue invasion by extravillous trophoblast, contributing to the development of TTG. This review sheds lights on the phenomenon of angiogenesis during normal and abnormal placentation, especially during the MGT and reports preliminary finding concerning, the variability of expression of "Endocrine Gland-Derived Vascular Endothelial Growth Factor" (EG-VEGF), a specific placental angiogenic factor, in normal and molar placentas, and the potential role of differentiated expressions of the main placental angiogenic factors in the scalability of hydatidiform moles towards a recovery or towards the development of gestational trophoblastic tumor. Deciphering the mechanisms by which the angiogenic factor influences these processes will help understand the pathophysiology of MGT and to create opportunities for early diagnosis and treatment of the latter. Copyright © 2013 Elsevier Masson SAS. All rights reserved.

  20. Lack of a Y-Chromosomal Complement in the Majority of Gestational Trophoblastic Neoplasms

    Directory of Open Access Journals (Sweden)

    Kai Lee Yap

    2010-01-01

    Full Text Available Gestational trophoblastic neoplasms (GTNs are a rare group of neoplastic diseases composed of choriocarcinomas, placental site trophoblastic tumors (PSTTs and epithelioid trophoblastic tumors (ETTs. Since these tumors are derivatives of fetal trophoblastic tissue, approximately 50% of GTN cases are expected to originate from a male conceptus and carry a Y-chromosomal complement according to a balanced sex ratio. To investigate this hypothesis, we carried out a comprehensive analysis by genotyping a relatively large sample size of 51 GTN cases using three independent sex chromosome genetic markers; Amelogenin, Protein Kinase and Zinc Finger have X and Y homologues that are distinguishable by their PCR product size. We found that all cases contained the X-chromosomal complement while only five (10% of 51 tumors harbored the Y-chromosomal complement. Specifically, Y-chromosomal signals were detected in one (5% of 19 choriocarcinomas, one (7% of 15 PSTTs and three (18% of 17 ETTs. The histopathological features of those with a Y-chromosome were similar to those without. Our results demonstrate the presence of a Y-chromosomal complement in GTNs, albeit a low 10% of cases. This shortfall of Y-chromosomal complements in GTNs may reinforce the notion that the majority of GTNs are derived from previous molar gestations.

  1. Proportion hyperglycosylated hCG: a new test for discriminating gestational trophoblastic diseases.

    Science.gov (United States)

    Cole, Laurence A

    2014-11-01

    Hyperglycosylated human chorionic gonadotropin (hCG) is a variant of hCG with large oligosaccharide side chains. Although hCG is produced by syncytiotrophoblast cells, hyperglycosylated hCG marks cytotrophoblast cell. Hyperglycosylated hCG signals placental implantation. Total hCG in serum and urine is measured by the Siemens Immulite hCG pregnancy test; the result is in milli-international unit per milliliter. Hyperglycosylated hCG is determined by the B152 microtiter plate assay; the result is in nanogram per milliliter. Hyperglycosylated hCG results can be converted to milli-international unit per milliliter equivalents by multiplying by 11. The test measures proportion hyperglycosylated hCG, hyperglycosylated hCG / total hCG. Proportion hyperglycosylated hCG marks cases intent on developing persistent hydatidiform mole (68% detection at 17% false detection). Proportion hyperglycosylated hCG also marks persistent hydatidiform mole (100% detection at 5.1% false detection). Proportion hyperglycosylated hCG distinguishes choriocarcinoma and gestational trophoblastic neoplasm cases, absolutely discriminating aggressive cases and minimally aggressive cases. Proportion hyperglycosylated hCG identifies quiescent gestational trophoblastic disease cases. It recognizes quiescent cases that become persistent disease (100% detection at 0% false positive). Proportion hyperglycosylated hCG is an invaluable test for discriminating gestational trophoblastic diseases.

  2. [Gestational trophoblastic diseases in cesarean scar: an analysis of 20 cases].

    Science.gov (United States)

    Zhang, Ge'er; Pan, Zimin

    2017-05-25

    To analyze the clinical features, diagnosis and treatment of gestational trophoblastic diseases in cesarean scar. Clinical data of three cases of gestational trophoblastic diseases in cesarean scar diagnosed in Women's Hospital, Zhejiang University School of Medicine during December 2011 and December 2016 were collected. And literature search was performed in Wanfang data, VIP, CNKI, PubMed, ISI Web of Knowledge and EMbase database. A total of 20 cases of gestational trophoblastic diseases were included in the analysis. Clinical features were mainly abnormal vaginal bleeding after menopause, artificial abortion or medical abortion, which might be accompanied by abdominal pain. Serum β-human chorionic gonadotropin (β-hCG) levels were increased in 19 patients. The sonographic features were increase of uterine volume, honeycomb-like abnormal intrauterine echo (or described as multiple cystic dark area, multiple anechoic area and multiple liquid dark area) or heterogeneity echo conglomeration, and no clear bound with muscular layer in some cases. There were abundant blood flow signals inside or around the lesions. The ultrasonography indicated that the lesions were located in the anterior side of the uterine isthmus with the involvement of cesarean section scar. In 12 cases with lesions in cesarean scar shown by preliminary diagnosis, 9 underwent uterine artery embolization (UAE) for pretreatment; the blood loss greater than 1500 mL was observed in only one case without UAE; no patient received hysterectomy. In 8 patients whose lesions were not shown in cesarean scar, only one case received UAE pretreatment, and hysterectomy was performed in 3 cases due to blood loss greater than 1500 mL. Two cases were lost in follow-up and no death was reported in remaining 18 cases. The serum β-hCG levels returned to normal or satisfactory level during the follow-up in 17 cases with increased β-hCG levels before treatment and no recurrence was observed. The misdiagnosis rate and

  3. Obstetric ultrasound aids prompt referral of gestational trophoblastic disease in marginalized populations on the Thailand-Myanmar border

    NARCIS (Netherlands)

    McGregor, Kathryn; Min, Aung Myat; Karunkonkowit, Noaeni; Keereechareon, Suporn; Tyrosvoutis, Mary Ellen; Tun, Nay Win; Rijken, Marcus J.; Hoogenboom, Gabie; Boel, Machteld; Chotivanich, Kesinee; Nosten, François; McGready, Rose

    2017-01-01

    Background: The use of obstetric ultrasound in the diagnosis of gestational trophoblastic disease (GTD) in high-income settings is well established, leading to prompt management and high survival rates. Evidence from low-income settings suggests ultrasound is essential in identifying complicated

  4. Role of ultrasound in the diagnosis and management of gestational trophoblastic disease in Rural health facilities- A case report

    International Nuclear Information System (INIS)

    Bach, J.F.H.

    2015-01-01

    Gestational trophoblastic disease (GTD) is a rare kind of proliferative disorder of trophoblastic cells which develops from the placenta in early pregnancy. It can be benign, premalignant or malignant. Molar pregnancy, also known as Hydatidiform Mole, is a form of benign GTD. The complete hydatidiform mole (CHM) sub-type which limited to endometrium is most common. It has excellent prognosis if early appropriate diagnosis and management are done. A well performed ultrasound(US) play a primordial role in the diagnosis of maternal health disorders during routine prenatal care. This helps in avoiding complications and consequently aids in achieving the objectives of the Millennium Development Goals (MDGs) in Rwanda. To understand the definition of Gestational trophoblastic disease(GTD) and to recognize key diagnostic findings of complete molar pregnancy on ultrasound and appropriate management in maternal follow up. Review the differential diagnosis for ultrasound findings seen with GTD and other modalities Ultrasound is the first modality to be used in all rural health facilities for diagnosis of suspected Gestational trophoblastic disease (GTD) for better results. It is available and free of radiation

  5. An investigative study into psychological and fertility sequelae of gestational trophoblastic disease: the impact on patients' perceived fertility, anxiety and depression.

    Directory of Open Access Journals (Sweden)

    Valentina E Di Mattei

    Full Text Available Gestational Trophoblastic Disease (GTD comprises a group of disorders that derive from the placenta. Even if full recovery is generally expected, women diagnosed with GTD have to confront: the loss of a pregnancy, a potentially life-threatening diagnosis and delays in future pregnancies. The aim of the study is to evaluate the psychological impact of GTD, focusing on perceived fertility, depression and anxiety.37 patients treated for GTD at San Raffaele Hospital, Milan, took part in the study. The STAI-Y (State-Trait Anxiety Inventory, the BDI-SF (Beck Depression Scale-Short Form and the FPI (Fertility Problem Inventory were used. Patients were grouped on the basis of presence of children (with or without, age (< or ≥35 and type of diagnosis (Hydatidiform Mole, HM, or Gestational Trophoblastic Neoplasia, GTN. Differences in the values between variables were assessed by a t-type test statistic. Three-way ANOVAs were also carried out considering the same block factors.The study highlights that women suffering from GTN had higher depression scores compared to women suffering from HM. A significant correlation was found between anxiety (state and trait and depression. Younger women presented higher Global Stress scores on the FPI, especially tied to Need for Parenthood and Relationship Concern subscales. Need for Parenthood mean scores significantly varied between women with and without children too.We can conclude that fertility perception seems to be negatively affected by GTD diagnosis, particularly in younger women and in those without children. Patients should be followed by a multidisciplinary team so as to be supported in the disease's psychological aspects too.

  6. Prognosis of patients treated with whole brain radiation therapy for metastatic gestational trophoblastic disease

    International Nuclear Information System (INIS)

    Schechter, Naomi R.; Mychalczak, Borys; Jones, Walter; Spriggs, David

    1996-01-01

    Purpose/Objective: To evaluate the effect of multiple treatment and disease related variables on the local control and survival of patients receiving whole brain radiation therapy for metastatic gestational trophoblastic disease. Materials and Methods: Between November 1967 and December 1994, 21 patients were treated at our institution for gestational trophoblastic disease metastatic to the brain. 29% ((6(21))) were diagnosed with their brain metastases before the onset of chemotherapy (early group). 79% ((15(21))) developed their brain metastases during or after the administration of first-line chemotherapy (late group). All patients were treated with whole brain radiation therapy. The total dose ranged from 200 cGy to 3600 cGy (median 2200 cGy). Sixteen patients (76%) received concurrent systemic chemotherapy. None of the patients received intrathecal chemotherapy as a component of their initial treatment. Survival and local control were calculated from the date of diagnosis of brain metastases. Follow-up ranged from 11 months to 170 months with a median of 77 months. Results: The median overall survival was 21 months, with 2- and 5-year actuarial survivals of 46% and 31%, respectively. Neither survival nor local control was significantly affected by age at diagnosis of brain metastases (<35 vs. ≥35 years), time of presentation of brain metastases (early vs. late), or use of concurrent chemotherapy. The total dose of radiation (<2200 cGy vs. ≥2200 cGy) significantly affected initial local control, but not survival. The 5-year actuarial local control of the initial brain metastases with ≥2200 cGy was 91%, as compared to 24% with <2200 cGy (p=0.05). Survival was significantly affected by control of disease at extracranial sites. The 2- and 5-year actuarial survivals of the 9 patients whose disease was controlled at extracranial sites were 100% and 83%, respectively, as compared to 8% and 0% for the 12 whose extracranial disease was not controlled (p=0

  7. Tegafur Substitution for 5-Fu in Combination with Actinomycin D to Treat Gestational Trophoblastic Neoplasm.

    Directory of Open Access Journals (Sweden)

    Mei Peng

    Full Text Available Although 5-fluorouracil (5-Fu combination chemotherapy provides a satisfactory therapeutic response in patients with gestational trophoblastic neoplasms (GTNs, it has severe side effects. The current study analyzed the therapeutic effects and side effects of tegafur plus actinomycin D (Act-D vs. 5-Fu plus Act-D for the treatment of GTNs based on controlled historical records. A total of 427 GTN cases that received tegafur and Act-D combination chemotherapy at the Second Xiangya Hospital of XiangYa Medical School between August 2003 and July 2013 were analyzed based on historical data. A total of 393 GTN cases that received 5-Fu plus Act-D between August 1993 and July 2003 at the same hospital were also analyzed, which constituted the control group. The therapeutic effects, toxicity and side effects after chemotherapy were compared between the groups. The overall response rate was 90.63% in the tegafur+Act-D group (tegafur group and 92.37% in the 5-Fu+Act-D group (5-Fu group; these rates were not significantly different (P > 0.05. However, the incidence rates of myelosuppression (white blood cell decline, gastrointestinal reactions (nausea, vomiting, dental ulcer, and diarrhea, skin lesions and phlebitis were lower in the tegafur group than in the 5-Fu group (P < 0.05. The results of this study may provide useful data for the clinical application of tegafur in GTN treatment.

  8. Usefulness of low-dose CT in the detection of pulmonary metastasis of gestational trophoblastic tumours

    International Nuclear Information System (INIS)

    Xu, X.J.; Lou, F.L.; Zhang, M.M.; Pan, Z.M.; Zhang, L.

    2007-01-01

    Aim: To determine whether a low-dose spiral chest computed tomography (CT) examination could replace standard-dose chest CT in detecting pulmonary metastases in patients with gestational trophoblastic tumour (GTT). Materials and methods: In a prospective investigation, 67 chest CT examinations of 39 GTT patients were undertaken. All the patients underwent CT examinations using standard-dose (150 mAs, pitch 1, standard reconstruction algorithm) and low-dose (40 mAs, pitch 2, bone reconstruction algorithm) protocols. Two radiologists interpreted images independently. A metastasis was defined as a nodule within lung parenchyma that could not be attributed to a pulmonary vessel. The number of metastases detected with each protocol was recorded. The size of each lesion was measured and categorized as <5, 5-9.9, and ≥10 mm. Wilcoxon's signed rank test was used to assess the difference between the numbers of lesion detected by the two protocols. Results: The CT dose index (CTDI) for the standard-dose and low-dose CT protocols was 10.4 mGy and 1.4 mGy, respectively. One thousand, six hundred, and eighty-two metastases were detected by standard-dose CT, and 1460 lesions by the low-dose protocol. The numbers detected by low-dose CT were significantly less than those detected by standard-dose CT (Z = -3.776, p < 0.001), especially for nodules smaller than 5 mm (Z = -4.167, p < 0.001). However, the disease staging and risk score of the patients were not affected by use of the low-dose protocol. Conclusion: Low-dose chest CT can be used as a staging and follow-up procedure for patients with GTT

  9. Management of gestational trophoblastic disease: a survey of New Zealand O&G practice.

    Science.gov (United States)

    Kladnitski, Maria; Kenwright, Diane

    2016-03-11

    The aim of the study was to obtain information on pathways for diagnosis and management of molar pregnancy/gestational trophoblastic disease (GTD) across New Zealand, the protocols used, and, in addition, to consider the view of O&G Specialists on a national GTD reference centre. An electronic survey approved by the RANZCOG Continues Professional Development Committee was distributed amongst registered O&G Specialists currently working in New Zealand. Data were analysed using Microsoft Excel 2011. Frequency distributions were used to determine the percentage of participants responding to the listed alternatives for each question. There were 234 potential responders, but only 68 complete questionnaires were received and available for analysis. The diagnosis of GTD requires histopathological analysis of pregnancy tissue, however only 79.7% of participants request this test routinely. Sixty-five percent of Fellows thought that a number of molar pregnancies can be missed with increasing proportion of medically-managed miscarriages, reliance on ultrasound and appearance of the tissue being contributing factors. Sixty-six percent of specialists were directly involved in the management of patients with GTD to various degrees. Follow-up responsibilities were divided between designated O&G specialists (52.3%), specialised gynaecology clinics (29.2%), acute assessment units (13.8%), nurse specialists (12%), O&G registrars (10.8%), GPs (6.2%), and others (6.2%). NZGCG guidelines were used by the majority of responders (54.8%), followed by local (29%) and RCOG (27.4%) guidelines. Seventy-two percent of specialists felt that some form of centralisation in the management of GTD is needed. In spite of the low response rate, our research demonstrates existing practice heterogeneity at every level of care. It also confirms that there is a desire for some form of centralisation in diagnosis and management of GTD, and a definite need for data collection in the form of a national

  10. Outcome of pregnancy subsequent to chemotherapy with actinomycin-D in low risk gestational trophoblastic neoplasia

    Directory of Open Access Journals (Sweden)

    Soheila Aminimoghaddam

    2017-07-01

    Methods: A retrospective cohort study was conducted on patients with GTN who were referred to Firoozgar and Mirza Koochak Khan teaching hospitals during 10 years, starting from 2004. The inclusion criterion was patients with low-risk persistent GTN after molar pregnancy, EP, and abortion, that treated with single agent chemotherapy actinomycin-D. After following the patients for 12 months, patients with serum βHCG lower than 5 mIU/ml, who intended to have child were allowed to become pregnant. The following items were observed in the study: age, body mass index (BMI, parity, chemotherapy duration, and pregnancy outcomes such as spontaneous abortion or preterm labor, pre-eclampsia, stillbirth, fetal malformation, and repeated molar pregnancy. Results: 74 patients were monitored, 83.78% of them had uncomplicated pregnancy and labor, 4.05% had the abortion, 4.05% had second molar pregnancy, 2.7% had pre-eclampsia, 5.40% had preterm labor. Moreover, stillbirth and malformation did not occur in this study even after chemotherapy treatment. There was not any significant correlation between age, BMI, parity, and chemotherapy duration with pregnancy outcomes. Conclusion: The outcomes of pregnancy after chemotherapy with actinomycin-D is similar to the general population who did not have chemotherapy. The abortion rate and repeated molar pregnancy were similar between population and sample too. Thus, the study shows that the cured patients with low-risk GTN have as much chance of having a normal pregnancy as normal women. In other words, treatment with actinomycin-D does not have any adverse effect in future pregnancies.

  11. Qualitative and quantitative analysis of diffusion-weighted imaging of gestational trophoblastic disease: Can it predict progression of molar pregnancy to persistent form of disease?

    Energy Technology Data Exchange (ETDEWEB)

    Sefidbakht, Sepideh [Medical imaging research center, Department of Radiology and Imaging, Shiraz University of Medical Sciences, Shiraz (Iran, Islamic Republic of); Hosseini, Fatemeh, E-mail: f.hoseini88@gmail.com [Medical imaging research center, Department of Radiology and Imaging, Shiraz University of Medical Sciences, Shiraz (Iran, Islamic Republic of); Bijan, Bijan [Abdominal Imaging/MR and Nonvascular Interventional Division, University of California, Davis, CA (United States); Hamedi, Bahareh; Azizi, Tayyebeh [Obstetrics& Gynecology Department, Medical School, Shiraz University of Medical Sciences, Shiraz (Iran, Islamic Republic of)

    2017-03-15

    Highlights: • The incidence of GTD in Iran is significantly higher than America and Europe. • ADC value of GTD is (1.96 ± 0.32 × 10{sup −3} mm{sup 2}/s). • GTD in T1 and T2-weighted images shows heterogeneous “snow-storm” appearance. • Focal intratumoral hemorrhage is bright in DWI and low signal in the ADC map. • ADC value and DWI are not helpful to predict progression of HM to persistent disease. - Abstract: Purpose: To describe the diffusion-weighted imaging (DWI) appearance of gestational trophoblastic disease (GTD) and to determine its apparent diffusion coefficient (ADC) values. To evaluate the feasibility of DWI to predict progression of hydatidiform mole (HM) to persistent disease. Methods: During a period of 6 months, women with preliminary diagnosis of GTD, based on ultrasound and ßhCG levels, underwent 1.5T MRI (T2 high-resolution and DWI; b values 50, 400, 800; sagittal and perpendicular to the endometrium; and T1, T2 Turbo Spin Echo [TSE] axial images). Patients were followed for 6–12 months to monitor progression to persistent form of the disease. ADC values and image characteristics were compared between HM and persistent neoplasia and between GTD and non-molar pregnancy using Mann–Whitney U and Fisher’s exact tests, respectively. Results: Among the 23 studied patients, 19 (83%) were classified as molar and 4 (17%) as non-molar, based on pathology reports. After 6–12 months of follow-up, 5 (26%) cases progressed to persistent disease and 14 (74%) cases were benign HM. There was no significant difference between ADC values for HM (1.93 ± 0.33 × 10{sup −3} mm{sup 2}/s) and persistent neoplasia (2.03 ± 0.28 × 10{sup −3} mm{sup 2}/s) (P = 0.69). The ADC of non-molar pregnancies was (0.96 ± 0.46 × 10{sup −3} mm{sup 2}/s), which was significantly different from GTD (1.96 ± 0.32 × 10{sup −3} mm{sup 2}/s) (P = 0.001). Heterogeneous snowstorm appearance, focal intratumoral hemorrhage, myometrial contraction, and

  12. The role of {sup 18}F-fluorodeoxyglucose positron emission tomography in gestational trophoblastic tumours: a pilot study

    Energy Technology Data Exchange (ETDEWEB)

    Chang, Ting Chang; Wu, Yen Ching; Wu, Tzu I. [University College of Medicine, Division of Gynecologic Oncology, Taoyuan (Taiwan); Yen, Tzu Chen; Chang, Yu.Cheng [Chang Gung Memorial Hospital, Department of Nuclear Medicine, Taoyuan (Taiwan); Li, Yiu Tai [Kuo General Hospital, Department of Obstetrics and Gynecology, Tainan (Taiwan); Ng, Koon Kwan [Chang Gung University College of Medicine, Departments of Diagnostic Radiology, Taoyuan (Taiwan); Jung, Shih Ming [Chang Gung Memorial Hospital, Anatomic Pathology, Taoyuan (Taiwan); Lai, Chyong Huey [University College of Medicine, Division of Gynecologic Oncology, Taoyuan (Taiwan); Chang Gung Memorial Hospital Linkou Medical Center, Department of Obstetrics and Gynecology, Taoyuan (Taiwan)

    2006-02-01

    We conducted a pilot trial to evaluate the value of {sup 18}F-fluorodeoxyglucose ({sup 18}F-FDG) positron emission tomography (PET) in gestational trophoblastic tumours (GTTs). Patients with placental site trophoblastic tumour (PSTT), high-risk GTT (World Health Organisation score {>=}8, disease onset at postpartum or greater than 6 months after antecedent pregnancy), metastatic GTT, recurrent/resistant GTT after chemotherapy, or post-molar GTT with unexplained abnormal {beta}-hCG regression and patients undergoing re-evaluation after salvage treatment were enrolled. PET was undertaken within 1 week after computed tomography (CT). Clinical impacts of additional PET were determined on a scan basis. A total of 14 patients were recruited. Sixteen PET scans were performed, with one patient having three serial studies. Benefits of additional PET were seen in 7 of 16 (43.8%) scans; these benefits included disclosure of chemotherapy-resistant lesions (n=2), exclusion of false-positive CT lesions (n=1), detection of an additional lesion not found by conventional imaging (n=1) in high-risk GTT at the start of primary chemotherapy, and confirmation of complete response to treatment for PSTT or to salvage therapy for recurrent/resistant GTT (n=3). On the other hand, in two instances there were false-negative PET findings, six scans yielded no benefit, and one showed an indeterminate lesion. Our preliminary results suggest that {sup 18}F-FDG PET is potentially useful in selected patients with GTT by providing precise mapping of metastases and tumour extent upfront, by monitoring treatment response and by localising viable tumours after chemotherapy. A larger study is necessary to further define the role of {sup 18}F-FDG PET in GTT. (orig.)

  13. The role of 18F-fluorodeoxyglucose positron emission tomography in gestational trophoblastic tumours: a pilot study

    International Nuclear Information System (INIS)

    Chang, Ting Chang; Wu, Yen Ching; Wu, Tzu I.; Yen, Tzu Chen; Chang, Yu.Cheng; Li, Yiu Tai; Ng, Koon Kwan; Jung, Shih Ming; Lai, Chyong Huey

    2006-01-01

    We conducted a pilot trial to evaluate the value of 18 F-fluorodeoxyglucose ( 18 F-FDG) positron emission tomography (PET) in gestational trophoblastic tumours (GTTs). Patients with placental site trophoblastic tumour (PSTT), high-risk GTT (World Health Organisation score ≥8, disease onset at postpartum or greater than 6 months after antecedent pregnancy), metastatic GTT, recurrent/resistant GTT after chemotherapy, or post-molar GTT with unexplained abnormal β-hCG regression and patients undergoing re-evaluation after salvage treatment were enrolled. PET was undertaken within 1 week after computed tomography (CT). Clinical impacts of additional PET were determined on a scan basis. A total of 14 patients were recruited. Sixteen PET scans were performed, with one patient having three serial studies. Benefits of additional PET were seen in 7 of 16 (43.8%) scans; these benefits included disclosure of chemotherapy-resistant lesions (n=2), exclusion of false-positive CT lesions (n=1), detection of an additional lesion not found by conventional imaging (n=1) in high-risk GTT at the start of primary chemotherapy, and confirmation of complete response to treatment for PSTT or to salvage therapy for recurrent/resistant GTT (n=3). On the other hand, in two instances there were false-negative PET findings, six scans yielded no benefit, and one showed an indeterminate lesion. Our preliminary results suggest that 18 F-FDG PET is potentially useful in selected patients with GTT by providing precise mapping of metastases and tumour extent upfront, by monitoring treatment response and by localising viable tumours after chemotherapy. A larger study is necessary to further define the role of 18 F-FDG PET in GTT. (orig.)

  14. Management of gestational trophoblastic tumours: a five-year clinical experience

    International Nuclear Information System (INIS)

    Rauf, B.; Hassan, L.; Ahmed, S.

    2004-01-01

    Objective: An analysis of a 5-year clinical experience in the management of gestational trophobIastic tumours in a tertiary care hospital. Patients and Methods: A total of 30 cases were managed and a detailed analysis of these patients were done. Of these 13 followed Hydatidiform Mole, 10 after abortion and 7 after a term pregnancy. Results: Out of 30 cases of gestational trophobIastic tumour, 63.3% were between 21 and 38 years of age. Ninety percent of the patients presented with vaginal bleeding, while life-threatening hemorrhage occurred in 23.3% of the cases. 43.3% of the patients had hydatidiform mole as an antecedent pregnancy and 36.7% of the patients presented within four months of the antecedent pregnancy. Blood groups O and B were most frequently encountered i.e. in 40% and 33.3% of the cases. Metastatic disease was present in 46.6% of the cases, of which 8 were high risk and one was of medium risk group. Major sites of metastasis were lungs (33.3%) and vagina (30%). Serum BHCG of 40,000 miu/ml and above was present in 53.3% of the cases (P=0.016) and number of metastasis >8 were found in 16.7% cases (P=0.001). Prior chemotherapy was given in only 2 patients and both of them died due to resistance. Chemotherapy was given to 100% of patients; survival was 100% in low-risk group and 50% in high-risk group (P=0.004). Overall mortality was 20% i.e. 6 patients died of the disease. Major side effects of chemotherapy were stomatitis (66.6%), alopecia (56.6%), low hemoglobin (60%), weight loss and recurrent infection. Conclusion: Late diagnosis, previously failed chemotherapy and high WHO prognostic scores are major risk factors affecting outcome in these patients. Hence every female in reproductive age group with unexplained bleeding per vaginum should be investigated with serum BHCG (Beta human chorionic gonadotrophin). (author)

  15. Obstetric ultrasound aids prompt referral of gestational trophoblastic disease in marginalized populations on the Thailand-Myanmar border.

    Science.gov (United States)

    McGregor, Kathryn; Myat Min, Aung; Karunkonkowit, Noaeni; Keereechareon, Suporn; Tyrosvoutis, Mary Ellen; Tun, Nay Win; Rijken, Marcus J; Hoogenboom, Gabie; Boel, Machteld; Chotivanich, Kesinee; Nosten, François; McGready, Rose

    2017-01-01

    The use of obstetric ultrasound in the diagnosis of gestational trophoblastic disease (GTD) in high-income settings is well established, leading to prompt management and high survival rates. Evidence from low-income settings suggests ultrasound is essential in identifying complicated pregnancies, but with limited studies reviewing specific conditions including GTD. The aim of this study is to review the role of ultrasound in diagnosis and management of GTD in a marginalized population on the Thailand-Myanmar border. Antenatal ultrasound became available in this rural setting in 2001 and care for women with GTD has been provided by Thailand public hospitals for 20 years. Retrospective record review. The incidence of GTD was 103 of 57,004 pregnancies in Karen and Burmese women on the Thailand-Myanmar border from 1993-2013. This equates to a rate of 1.8 (95% CI 1.5-2.2) per 1000 or 1 in 553 pregnancies. Of the 102 women with known outcomes, one (1.0%) died of haemorrhage at home. The median number of days between first antenatal clinic attendance and referral to hospital was reduced from 20 (IQR 5-35; range 1-155) to 2 (IQR 2-6; range 1-179) days (p = 0.002) after the introduction of ultrasound. The proportion of severe outcomes (death and total abdominal hysterectomy) was 25% (3/12) before ultrasound compared to 8.9% (8/90) with ultrasound (p = 0.119). A recurrence rate of 2.5% (2/80) was observed in the assessable population. The presence of malaria parasites in maternal blood was not associated with GTD. The rate of GTD in pregnancy in this population is comparable to rates previously reported within South-East Asia. Referral time for uterine evacuation was significantly shorter for those women who had an ultrasound. Ultrasound is an effective method to improve diagnosis of GTD in low-income settings and an effort to increase availability in marginalized populations is required.

  16. Gestational Trophoblastic Disease Treatment

    Science.gov (United States)

    ... the blood of a woman who is not pregnant may be a sign of GTD. Urinalysis : A test to check the color of urine and its contents, such as sugar, protein , blood, bacteria , and the level of β-hCG. ...

  17. Malformação arteriovenosa uterina após doença trofoblástica gestacional Uterine arteriovenous malformation after gestational trophoblastic disease

    Directory of Open Access Journals (Sweden)

    Paulo Belfort

    2006-02-01

    Full Text Available OBJETIVO: investigar a presença e resultados de malformações vasculares uterinas (MAVU após doença trofoblástica gestacional (DTG. MÉTODOS: estudo retrospectivo com inclusão de casos diagnosticados entre 1987 e 2004; 2764 pacientes após DTG foram acompanhadas anualmente com ultra-sonografia transvaginal e Doppler colorido no Centro de Neoplasia Trofoblástica Gestacional da Santa Casa da Misericórdia (Rio de Janeiro, RJ, Brasil. Sete pacientes tiveram diagnóstico final de MAVU baseado em análise ultra-sonográfica - índice de pulsatilidade (IP, índice de resistência (IR e velocidade sistólica máxima (VSM - e achados de imagens de ressonância nuclear magnética (RNM. Dosagens negativas de beta-hCG foram decisivas para estabelecer o diagnóstico diferencial com DTG recidivante. RESULTADOS: a incidência de MAVU após DTG foi 0,2% (7/2764. Achados ultra-sonográficos de MAVU: IP médio de 0,44±0,058 (extremos: 0,38-0,52; IR médio de 0,36±0,072 (extremos: 0,29-0,50; VSM média de 64,6±23,99 cm/s (extremos: 37-96. A imagem de RNM revelou útero aumentado, miométrio heterogêneo, espaços vasculares tortuosos e vasos parametriais com ectasia. A apresentação clínica mais comum foi hemorragia transvaginal, presente em 52,7% (4/7 dos casos. Tratamento farmacológico com 150 mg de acetato de medroxiprogesterona foi empregado para controlar a hemorragia, após a estabilização hemodinâmica. Permanecem as pacientes em seguimento, assintomáticas até hoje. Duas pacientes engravidaram com MAVU, com gestações e partos exitosos. CONCLUSÃO: presente sangramento transvaginal em pacientes com beta-hCG negativo e história de DTG, deve-se considerar a possibilidade de MAVU e solicitar avaliação ultra-sonográfica com dopplervelocimetria. O tratamento conservador é a melhor opção na maioria dos casos de MAVU pós-DTG.PURPOSE: to investigate the presence and outcome of uterinevascular malformations (UVAM after gestational

  18. An investigative study into psychological and fertility sequelae of gestational trophoblastic disease: the impact on patients' perceived fertility, anxiety and depression.

    Science.gov (United States)

    Di Mattei, Valentina E; Carnelli, Letizia; Bernardi, Martina; Pagani Bagliacca, Elena; Zucchi, Paola; Lavezzari, Luca; Giorgione, Veronica; Ambrosi, Alessandro; Mangili, Giorgia; Candiani, Massimo; Sarno, Lucio

    2015-01-01

    Gestational Trophoblastic Disease (GTD) comprises a group of disorders that derive from the placenta. Even if full recovery is generally expected, women diagnosed with GTD have to confront: the loss of a pregnancy, a potentially life-threatening diagnosis and delays in future pregnancies. The aim of the study is to evaluate the psychological impact of GTD, focusing on perceived fertility, depression and anxiety. 37 patients treated for GTD at San Raffaele Hospital, Milan, took part in the study. The STAI-Y (State-Trait Anxiety Inventory), the BDI-SF (Beck Depression Scale-Short Form) and the FPI (Fertility Problem Inventory) were used. Patients were grouped on the basis of presence of children (with or without), age (statistic. Three-way ANOVAs were also carried out considering the same block factors. The study highlights that women suffering from GTN had higher depression scores compared to women suffering from HM. A significant correlation was found between anxiety (state and trait) and depression. Younger women presented higher Global Stress scores on the FPI, especially tied to Need for Parenthood and Relationship Concern subscales. Need for Parenthood mean scores significantly varied between women with and without children too. We can conclude that fertility perception seems to be negatively affected by GTD diagnosis, particularly in younger women and in those without children. Patients should be followed by a multidisciplinary team so as to be supported in the disease's psychological aspects too.

  19. Human chorionic gonadotrophin regression rate as a predictive factor of postmolar gestational trophoblastic neoplasm in high-risk hydatidiform mole: a case-control study.

    Science.gov (United States)

    Kim, Bo Wook; Cho, Hanbyoul; Kim, Hyunki; Nam, Eun Ji; Kim, Sang Wun; Kim, Sunghoon; Kim, Young Tae; Kim, Jae-Hoon

    2012-01-01

    The aim of this study was early prediction of postmolar gestational trophoblastic neoplasm (GTN) after evacuation of high-risk mole, by comparison of human chorionic gonadotrophin (hCG) regression rates. Fifty patients with a high-risk mole initially and spontaneously regressing after molar evacuation were selected from January 1, 1996 to May 31, 2010 (spontaneous regression group). Fifty patients with a high-risk mole initially and progressing to postmolar GTN after molar evacuation were selected (postmolar GTN group). hCG regression rates represented as hCG/initial hCG were compared between the two groups. The sensitivity and specificity of these rates for prediction of postmolar GTN were assessed using receiver operating characteristic curves. Multivariate analyses of associations between risk factors and postmolar GTN progression were performed. The mean regression rate of hCG between the two groups was compared. hCG regression rates represented as hCG/initial hCG (%) were 0.36% in the spontaneous regression group and 1.45% in the postmolar GTN group in the second week (p=0.003). Prediction of postmolar GTN by hCG regression rate revealed a sensitivity of 48.0% and specificity of 89.5% with a cut-off value of 0.716% and area under the curve (AUC) of 0.759 in the 2nd week (pfactor for postmolar GTN. Crown Copyright © 2011. Published by Elsevier Ireland Ltd. All rights reserved.

  20. Fatores de risco para doença trofoblástica gestacional persistente Risk factors for persistent gestational trophoblastic disease

    Directory of Open Access Journals (Sweden)

    Daniel Guimarães Tiezzi

    2005-06-01

    selecionar pacientes que não necessitariam de seguimento na forma realizada atualmente e impede também a seleção com precisão de casos com indicação de quimioterapia profilática.PURPOSE: to evaluate the epidemiologic data and signs of trophoblastic hyperplasia in patients with complete hydatidiform mole (CHM and to estimate the risk associated with the persistence of the disease. METHODS:: we evaluated 214 patients with CHM submitted to uterine evacuation between 1980 and 2001. The patients were included prospectively. All patients were followed until negative bHCG with weekly clinical evaluation and bHCG quantification. We considered persistence when the patient needed another treatment after uterine evacuation. The risk factors for persistence were evaluated through univariate and multivariate analysis, and the odds ratio (OR was calculated for each one. RESULTS: among the epidemiologic factors, only negative Rh was significant (OR=2.28. All signs of trophoblastic hyperplasia, represented by uterine size larger than expected, sonographic uterine volume, tecaluteinic cysts, and betaHCG higher than 10(5 were associated with risk for the presistence of the disease. The presence of at least one sign of trophoblastic hyperplasia showed sensitivity of 82% and predictive positive value of 35.1% (OR=4.8. The logistic regression identified larger uterine size than expected and bHCG higher than 10(5 as risk factors for persistence of the gestational trophoblastic disease (OR=4.1 and 5.5, respectively. CONCLUSIONS: the signs of trophoblastic hyperplasia showed good sensitivity to predict persistence of the disease; however, the low predictive positive value does not allow using these criteria to change treatment. It is very important to reinforce the importance of serial betaHCG quantification in these high-risk patients.

  1. A curva de regressão da gonadotrofina coriônica humana é útil no diagnóstico precoce da neoplasia trofoblástica gestacional pós-molar? Are curves of human chorionic gonadotropin useful in the early diagnosis of post-molar trophoblastic neoplasia?

    Directory of Open Access Journals (Sweden)

    Lúcia Regina Marques Gomes Delmanto

    2007-10-01

    Full Text Available OBJETIVO: avaliar a utilidade da curva de regressão normal da gonadotrofina coriônica humana (hCG no diagnóstico precoce de neoplasia trofoblástica gestacional pós-molar (NTG. MÉTODOS: estudo longitudinal, incluindo 105 pacientes com mola hidatiforme completa (MHC acompanhadas no Centro de Doenças Trofoblásticas de Botucatu, entre 1998 e 2005. Os títulos da hCG sérica foram mensurados quinzenalmente em todas as pacientes. Curvas individuais de regressão da hCG das 105 pacientes foram estabelecidas. A comparação entre a curva de regressão normal estabelecida em nosso serviço com as curvas individuais da hCG foi usada no rastreamento e diagnóstico (platô/ascensão de NTG. O número de semanas pós-esvaziamento quando a hCG excedeu o limite normal foi comparado com o número semanas em que a hCG apresentou platô/ascensão. RESULTADOS: das 105 pacientes com MHC, 80 apresentaram remissão espontânea (RE e 25 desenvolveram NTG. Das 80 pacientes com RE, 7 (8,7% apresentaram, inicialmente, dosagem da hCG acima do normal, mas, no devido tempo, alcançaram a remissão. Todas as 25 pacientes com NTG apresentaram desvio da curva normal da hCG em 3,8±2,5 semanas e mostraram platô ou ascensão em 8,4±2,9 semanas (pPURPOSE: to evaluate the usefulness of the normal human chorionic gonadotropin (hCG regression curve in the early diagnosis of post-molar trophoblastic neoplasia (GTN. METHODS: a longitudinal study including 105 patients with complete hydatidiform mole (CHM followed up at the Botucatu Center of Trophoblastic Diseases from 1998 to 2005. Serial serum hCG titers were measured fortnightly in all patients. Individual curves of the 105 patients were built. Comparison between the normal regression curve established at our center with individual hCG curves was used to screen and diagnose (plateau/rise GTN. The number of weeks postevacuation when hCG levels exceeded the normal limits was compared with the number of weeks when h

  2. Sonographic image of cervix epithelioid trophoblastic tumor coexisting with mucinous adenocarcinoma in a postmenopausal woman: A case report.

    Science.gov (United States)

    Zhu, Yi; Zhang, Guo-Nan; Zhang, Rui-Bo; Shi, Yu; Wang, Deng-Feng; He, Rong

    2017-09-01

    Epithelioid trophoblastic tumor (ETT) is a distinctive but rare gestational trophoblastic neoplasia (GTN) composed of chorionic-type intermediate trophoblast cells. Approximately 50% ETT arose from the uterine cervix or lower uterine segment following a previous pregnancy with vaginal bleeding. With its unusual ability to simulate an invasive epithelioid neoplasm, ETT frequently poses a diagnostic challenge, especially involving the uterine cervix. We herein report the case of a 60-year-old female with persistent vaginal bleeding and middle-level elevation of serum human chorionic gonadotropin (hCG). Ultrasound revealed a 3.0 × 2.7 cm well-circumscribed, strongly echogenic lesion in the cervix, with a peripheral pattern of Doppler signals. The enhanced pattern by contrast-enhanced ultrasound displayed strong peripheral enhancement accompanied with globular appearance, then centripetal filling completely, and fading away rapidly. The final pathological diagnosis was ETT accompanying mucinous adenocarcinoma. Due to the pre-operative evaluation of a presumed IB2 cervix mucinous adenocarcinoma, the patient was treated with 2 courses of neoadjuvant chemotherapy followed by radical hysterectomy. The patient is currently disease-free for the past 1 year. This case report demonstrates that sonographic image of tumor shapes and blood flow could be helpful in differentiating ETT from another GTN and enable more accurate diagnosis before treatment.

  3. Persistência da imagem metastática pulmonary após tratamento de doença trofoblástica gestacional Persisting metastatic pulmonar imaging after treatment of gestational trophoblastic disease

    Directory of Open Access Journals (Sweden)

    Eddie Fernando Candido Murta

    1999-01-01

    Full Text Available O objetivo deste relato é a apresentação de um caso de doença trofoblástica gestacional com metástases pulmonares, cujas imagens persistiram após a normalização dos títulos de fração beta do hormônio da gonadotrofina coriônica (beta-hCG após cinco ciclos de quimioterapia (metotrexato, 20 mg/dia por 5 dias a cada 14 dias. A paciente foi submetida a ressecção das lesões por toracoscopia vídeo-assistida. O exame histológico demonstrou necrose sem evidência de tumor residual. É importante reconhecer que a persistência de nódulos pulmonares em pacientes com doença trofoblástica gestacional metastática após tratamento e normalização do beta-hCG pode não representar tumor viável mas somente necrose e/ou fibrose.The aim of this report is to present one case of gestational trophoblastic disease with pulmonary metastases apparently persisting despite the return of beta-human chorionic gonadotropin (beta-hCG to normal levels after five cycles of chemotherapy (20 mg methotrexate/day for 5 days. The patient was submitted to a video-assisted thoracoscopy and the nodules were excised. Histological examination showed tissue necrosis without evidence of residual tumor. It is important to recognize that persistent nodules in the lungs of patients with metastatic gestational disease after treatment and normal beta-hCG titers may not represent viable tumor but rather necrosis and/or fibrosis.

  4. Preditores Clínicos e Histopatológicos de Tumor Trofoblástico Gestacional pós-Mola Hidatiforme Completa Clinical and Histopathological Predictors of Gestational Trophoblastic Tumor +after Complete Hydatidiform Mole

    Directory of Open Access Journals (Sweden)

    Izildinha Maestá

    2000-04-01

    Full Text Available Objetivo: definir os preditores clínicos e histopatológicos mais eficientes da evolução da mola hidatiforme completa (MHC para tumor trofoblástico gestacional (TTG. Métodos: estudo prospectivo clínico e histopatológico de todas as portadoras de MHC, atendidas entre 1990 e 1998 no Hospital das Clínicas de Botucatu -- UNESP. A avaliação clínica pré-esvaziamento molar classificou a gravidez molar em: MHC de alto risco e MHC de baixo risco. Foram analisados os preditores clínicos para TTG, estabelecidos por Goldstein et al.¹ e por outros autores2--10. A avaliação histopatológica incluiu a determinação do diagnóstico de MHC, segundo os critérios de Szulman e Surti11, e o reconhecimento dos fatores de risco para TTG, de Ayhan et al.8. Os preditores clínicos e histopatológicos foram correlacionados com o desenvolvimento de TTG pós-molar. Resultados: em 65 portadoras de MHC, cistos do ovário maiores que 6 cm e tamanho uterino maior que 16 cm foram os preditores clínicos mais eficientes de TTG. A proliferação trofoblástica, a atipia nuclear, a necrose/hemorragia, a maturação trofoblástica e a relação cito/sinciciotrofoblasto não foram preditores significativos para TTG. A correlação entre preditor clínico e histopatológico para o desenvolvimento de TTG não foi possível porque nenhum parâmetro histopatológico foi significativo. Conclusões: mais estudos são necessários para avaliar possíveis preditores de persistência (TTG e sua aplicação no contexto clínico das MHC. Enquanto isso, a determinação seriada de hCG sérico permanece o único indicador prognóstico seguro para TTG pós-MHC.Purpose: to determine the most efficient clinical and histopathological predictors of complete hydatidiform mole (CHM after gestational trophoblastic tumors (GTT. Methods: a prospective clinical and histopathological study was performed on all patients with CHM treated at the University Hospital of Botucatu between 1990

  5. General Information about Gestational Trophoblastic Disease

    Science.gov (United States)

    ... the blood of a woman who is not pregnant may be a sign of GTD. Urinalysis : A test to check the color of urine and its contents, such as sugar, protein , blood, bacteria , and the level of β-hCG. ...

  6. Human placental trophoblast invasion and differentiation: a particular focus on Wnt signalling

    Directory of Open Access Journals (Sweden)

    Martin eKnöfler

    2013-09-01

    Full Text Available Wingless ligands, a family of secreted proteins, are critically involved in organ development and tissue homeostasis by ensuring balanced rates of stem cell proliferation, cell death and differentiation. Wnt signalling components also play crucial roles in murine placental development controlling trophoblast lineage determination, chorioallantoic fusion and placental branching morphogenesis. However, the role of the pathway in human placentation, trophoblast development and differentiation is only partly understood. Here, we summarize our present knowledge about Wnt signalling in the human placenta and discuss its potential role in physiological and aberrant trophoblast invasion, gestational diseases and choriocarcinoma formation. Differentiation of proliferative first trimester cytotrophoblasts into invasive extravillous trophoblasts is associated with nuclear recruitment of β-catenin and induction of Wnt-dependent T-cell factor 4 suggesting that canonical Wnt signalling could be important for the formation and function of extravillous trophoblasts. Indeed, activation of the pathway was shown to promote trophoblast invasion in different in vitro trophoblast model systems as well as trophoblast cell fusion. Methylation-mediated silencing of inhibitors of Wnt signalling provided evidence for epigenetic activation of the pathway in placental tissues and choriocarcinoma cells. Similarly, abundant nuclear expression of β-catenin in invasive trophoblasts of complete hydatidiform moles suggested a role for hyper-activated Wnt signalling. In contrast, upregulation of Wnt inhibitors was noticed in placentae of women with preeclampsia, a disease characterized by shallow trophoblast invasion and incomplete spiral artery remodelling. Moreover, changes in Wnt signalling have been observed upon cytomegalovirus infection and in recurrent abortions. In summary, the current literature suggests a critical role of Wnt signalling in physiological and abnormal

  7. Differential Effects of Sodium Butyrate and Lithium Chloride on Rhesus Monkey Trophoblast Differentiation.

    Directory of Open Access Journals (Sweden)

    Priyadarsini Kumar

    Full Text Available Trophoblast differentiation during early placental development is critical for successful pregnancy and aberrant differentiation causes preeclampsia and early pregnancy loss. During the first trimester, cytotrophoblasts are exposed to low oxygen tension (equivalent to~2%-3% O2 and differentiation proceeds along an extravillous pathway (giving rise to invasive extravillous cytotrophoblasts and a villous pathway (giving rise to multinucleated syncytiotrophoblast. Interstitial extravillous cytotrophoblasts invade the decidua, while endovascular extravillous cytotrophoblasts are involved in re-modelling uterine spiral arteries. We tested the idea that sodium butyrate (an epigenetic modulator induces trophoblast differentiation in early gestation rhesus monkey trophoblasts through activation of the Wnt/β-catenin pathway. The results show that syncytiotrophoblast formation was increased by butyrate, accompanied by nuclear accumulation of β-catenin, and increased expression of EnvV2 and galectin-1 (two factors thought to be involved in trophoblast fusion. Surprisingly, the expression of GCM1 and syncytin-2 was not affected by sodium butyrate. When trophoblasts were incubated with lithium chloride, a GSK3 inhibitor that mimics Wnt activation, nuclear accumulation of β-catenin also occurred but differentiation into syncytiotrophoblast was not observed. Instead the cells differentiated to mononucleated spindle-shaped cells and showed molecular and behavioral characteristics of endovascular trophoblasts. Another highly specific inhibitor of GSK3, CHIR99021, failed to induce endovascular trophoblast characteristics. These observations suggest that activation of the Wnt/β-catenin pathway correlates with both trophoblast differentiation pathways, but that additional factors determine specific cell fate decisions. Other experiments suggested that the differential effects of sodium butyrate and lithium chloride might be explained by their effects on TNF

  8. Early embryonic demise: no evidence of abnormal spiral artery transformation or trophoblast invasion.

    Science.gov (United States)

    Ball, E; Robson, S C; Ayis, S; Lyall, F; Bulmer, J N

    2006-03-01

    Invasion by extravillous trophoblast of uterine decidua and myometrium and the associated spiral artery 'transformation' are essential for the development of normal pregnancy. Small pilot studies of placental bed and basal plate tissues from miscarriages have suggested that impaired interstitial and endovascular trophoblast invasion may play a role in the pathogenesis of miscarriage. The hypothesis that early miscarriage is associated with reduced extravillous trophoblast invasion and spiral artery transformation was tested in a large series of placental bed biopsies containing decidua and myometrium and at least one spiral artery from early, karyotyped embryonic miscarriages (gestation; n = 50) dated from the last menstrual period and ultrasound scan dated normal pregnancies (n = 78). Frozen sections were immunostained to demonstrate trophoblast (cytokeratin), myometrium and spiral artery medial smooth muscle (desmin), and endothelium (von Willebrand factor). Trophoblast invasion and individual features of spiral artery transformation were assessed histologically in spiral arteries of miscarriages (n = 176) and controls (n = 246) and analysed statistically using a logistic regression model. Trophoblast invasion of uterine tissues and spiral artery transformation did not differ between euploid and aneuploid early miscarriage and also did not differ significantly from normal pregnancy. These findings suggest that failed trophoblast invasion and spiral artery transformation do not have a pivotal role in the pathogenesis of early miscarriage.

  9. Expression of urokinase receptors by human trophoblast. A histochemical and ultrastructural analysis

    DEFF Research Database (Denmark)

    Multhaupt, H A; Mazar, A; Cines, D B

    1994-01-01

    BACKGROUND: Through their ability to invade endometrium, remodel the uterine spiral arteries, and sustain placental blood fluidity, trophoblast cells play a central role in establishing and maintaining the integrity of the uteroplacental vasculature. The expression of urokinase receptors by troph......BACKGROUND: Through their ability to invade endometrium, remodel the uterine spiral arteries, and sustain placental blood fluidity, trophoblast cells play a central role in establishing and maintaining the integrity of the uteroplacental vasculature. The expression of urokinase receptors...... at the leading edge of migrating extravillous trophoblast cells. Receptors were also abundantly expressed during the first and second trimesters of gestation by villous trophoblast, where they were located on apical villous projections and within intracellular vacuoles, a subset of which were lysosomes...

  10. Increased placental trophoblast inclusions in placenta accreta.

    Science.gov (United States)

    Adler, E; Madankumar, R; Rosner, M; Reznik, S E

    2014-12-01

    Trophoblast inclusions (TIs) are often found in placentas of genetically abnormal gestations. Although best documented in placentas from molar pregnancies and chromosomal aneuploidy, TIs are also associated with more subtle genetic abnormalities, and possibly autism. Less than 3% of non-aneuploid, non-accreta placentas have TIs. We hypothesize that placental genetics may play a role in the development of placenta accreta and aim to study TIs as a potential surrogate indicator of abnormal placental genetics. Forty cases of placenta accreta in the third trimester were identified in a search of the medical records at one institution. Forty two third trimester control placentas were identified by a review of consecutively received single gestation placentas with no known genetic abnormalities and no diagnosis of placenta accreta. Forty percent of cases with placenta accreta demonstrated TIs compared to 2.4% of controls. More invasive placenta accretas (increta and percreta) were more likely to demonstrate TIs than accreta (47% versus 20%). Prior cesarean delivery was more likely in accreta patients than controls (67% versus 9.5%). Placenta accreta is thought to be the result of damage to the endometrium predisposing to abnormal decidualization and invasive trophoblast growth into the myometrium. However, the etiology of accreta is incompletely understood with accreta frequently occurring in women without predisposing factors and failing to occur in predisposed patients. This study has shown that TIs are present at increased rates in cases of PA. Further studies are needed to discern what underlying pathogenic mechanisms are in common between abnormal placentation and the formation of TIs. Published by Elsevier Ltd.

  11. Placental Trophoblast Responses to Porphyromonas gingivalis Mediated by Toll-like Receptor-2 and -4

    Directory of Open Access Journals (Sweden)

    Banun Kusumawardani

    2013-09-01

    Full Text Available Trophoblast participates in preventing allorecognition and controlling pathogens that compromise fetal wellbeing. Toll-like receptors recognize conserved sequences on the pathogens surface and trigger effector cell functions. Porphyromonas gingivalis is thought to spread to the umbilical cord and cause fetal growth restriction. Objective: To characterize expression and function of TLR-2 and TLR-4 in trophoblast cells from Porphyromonas gingivalisinfected pregnant rats. Methods: Live Porphyromonas gingivalis were challenged into the maxillary first molar subgingival sulcus of female rats before and/or during pregnancy and sacrified on gestational day (GD 14 and 20. Porphyromonas gingivalis was detected by API-ZYM system in the maternal blood of the retro-orbital venous plexus and the umbilical cord. TLR-2 and TLR-4 expressions in trophoblast cells was detected by immunohistochemistry. Results: Porphyromonas gingivalis was first detected in the maternal blood and finally spread to the umbilical cord. Syncytiotrophoblast, spongitrophoblast and trophoblastic giant cell in treated groups had significantly higher expression of TLR-2 and TLR-4 than control group (p<0.05. Conclusion: Syncytiotrophoblast, spongitrophoblast and trophoblastic giant cell are able to recognize Porphyromonas gingivalis through TLR-2 and TLR-4 expression. The ligation of TLR-2 and TLR-4 promoted cytokine production and induced trophoblast cell death. These findings strengthen links between periodontal disease and fetal growth restriction.DOI: 10.14693/jdi.v20i2.150

  12. CASE REPORT A recurrent gestational choriocarcinoma case ...

    African Journals Online (AJOL)

    Admin

    molar pregnancy (Luna Russo et al., 2015). To our knowledge recurrence resulting in rupture 14 month following a live pregnancy is an extremely rare event. Management of gestational trophoblastic disease in our setup poses multiple challenges as seen in this particular case. Serum β-HCG follow up for these patients ...

  13. Imaging and Clinical Data of Placental Site Trophoblastic Tumor: A Case Report

    International Nuclear Information System (INIS)

    Niknejadi, Maryam; Ahmadi, Firoozeh; Akhbari, Farnaz

    2016-01-01

    Placental site trophoblastic tumor (PSTT) is a very rare variant of gestational trophoblastic tumor. It can occur after normal termination of pregnancy or spontaneous abortion and ectopic or molar pregnancy. There is a wide range of clinical manifestations from a benign condition to an aggressive disease with fatal outcome. One of the most important characteristics of PSTT, unlike other forms of gestational trophoblastic diseases (GTD) is the presence of low beta-subunit of human chorionic gonadotropin (β-hCG) levels because it is a neoplastic proliferation of intermediate trophoblastic cells. However, human placental lactogen (hPL) is increased on histologic section and in the serum of patients too. We present a case of PSTT and discuss the differential diagnosis in order to further familiarize physicians with the diagnosis and treatment of this disease. It has a varied clinical spectrum and usually presents with irregular vaginal bleeding or amenorrhea. Diagnosis is confirmed by dilatation and curettage (D and C) and hysterectomy. Because chemotherapy is not effective, surgery is the cornerstone of treatment. This case is presented because it is a rare neoplasm with different treatments and it should be differentiated from molar pregnancy

  14. Function of caspase-14 in trophoblast differentiation

    Directory of Open Access Journals (Sweden)

    Charles Adrian K

    2009-09-01

    Full Text Available Abstract Background Within the human placenta, the cytotrophoblast consists of a proliferative pool of progenitor cells which differentiate to replenish the overlying continuous, multi-nucleated syncytiotrophoblast, which forms the barrier between the maternal and fetal tissues. Disruption to trophoblast differentiation and function may result in impaired fetal development and preeclampsia. Caspase-14 expression is limited to barrier forming tissues. It promotes keratinocyte differentiation by cleaving profilaggrin to stabilise keratin intermediate filaments, and indirectly providing hydration and UV protection. However its role in the trophoblast remains unexplored. Methods Using RNA Interference the reaction of control and differentiating trophoblastic BeWo cells to suppressed caspase-14 was examined for genes pertaining to hormonal, cell cycle and cytoskeletal pathways. Results Transcription of hCG, KLF4 and cytokeratin-18 were increased following caspase-14 suppression suggesting a role for caspase-14 in inhibiting their pathways. Furthermore, hCG, KLF4 and cytokeratin-18 protein levels were disrupted. Conclusion Since expression of these molecules is normally increased with trophoblast differentiation, our results imply that caspase-14 inhibits trophoblast differentiation. This is the first functional study of this unusual member of the caspase family in the trophoblast, where it has a different function than in the epidermis. This knowledge of the molecular underpinnings of trophoblast differentiation may instruct future therapies of trophoblast disease.

  15. Hormones of Adipose Tissue and Gestational Diabetes

    Directory of Open Access Journals (Sweden)

    O.S. Payenok

    2013-10-01

    Full Text Available Obesity and gestational diabetes are the risk factors for complications both in the mother and in the fetus. Adipose tissue hormones (leptin, adiponectin, resistin are secreted by the human placenta and regulate the function of trophoblast. The review presents data from the literature on the role of adipocytokines in the development of gestational diabetes and preeclampsia in obese women. The article considers the criteria and algorithms for the diagnosis of gestational diabetes recommended by the World Health Organization and the International Association of Diabetes and Pregnancy Study Group.

  16. Endoarterial pulmonary metastasis of malignant trophoblast associated with a term intrauterine pregnancy.

    Science.gov (United States)

    Carlson, J A; Day, T G; Kuhns, J G; Howell, R S; Masterson, B J

    1984-02-01

    A previously healthy gravida 4, para 3, developed preclampsia and progressive dyspnea at the 37th gestational week and had bilateral pulmonary infiltrates on chest roentgenogram. She delivered a healthy, term, male infant with a normal appearing placenta. Postpartum, her respiratory status gradually worsened. A lung biopsy on the 20th postpartum day revealed intravascular trophoblasts, diffuse arteriolar thrombosis with pulmonary infarction, and subacute interstitial pneumonitis. Combination chemotherapy was instituted, but the patient died from respiratory insufficiency.

  17. Gestational trophoblastic neoplasm and women living with HIV and ...

    African Journals Online (AJOL)

    2015-07-03

    Jul 3, 2015 ... smart phone or mobile device to read online. .... problematic and a continuous positive airway pressure ... that survival is prolonged with the use of ART.3,7 ... relationships which may have inappropriately influenced them in ...

  18. Gestational Trophoblastic Neoplasm and Women Living With HIV ...

    African Journals Online (AJOL)

    The overall cure rate is about 90%. Response to treatment for GTN is generally favourable; but the sequelae of HIV and/or AIDS, the resultant low CD4 counts, comorbidities, poor performance status and the extent of metastatic disease in patients receiving chemotherapy, compromise the prognosis and survival.

  19. Gestational Trophoblastic Disease (GTD): a 10 year review of ...

    African Journals Online (AJOL)

    GTD) are common among Nigerian women in their reproductive life. They are important in that they present a unique opportunity for early detection and cure. This study aimed at identifying the various histological types encountered in Benin ...

  20. Trophoblast retrieval and isolation from the cervix: origins of cervical trophoblasts and their potential value for risk assessment of ongoing pregnancies.

    Science.gov (United States)

    Moser, Gerit; Drewlo, Sascha; Huppertz, Berthold; Armant, D Randall

    2018-03-28

    invasive routes taken by EVT cells at the fetal-maternal interface that could displace them into the reproductive tract. Since the 1970s, investigators have attempted to recover trophoblast cells from the uterus or cervix for prenatal diagnostics. Trophoblast cells from Pap smears obtained at 5-20 weeks of gestation have been purified (>95% β-hCG positive) by immunomagnetic isolation with nanoparticles linked to anti-HLA-G (TRIC). The isolated cells contain the fetal genome, and have an EVT-like expression profile. Similar EVT-like cells appear in the lumen of uterine glands and can be observed entering the uterine cavity along the margins of the placenta, suggesting that they are the primary source of cervical trophoblast cells. Cells isolated by TRIC can be used to accurately genotype the embryo/fetus by targeted next-generation sequencing. Biomarker protein expression quantified in cervical trophoblast cells after TRIC correlates with subsequent pregnancy loss, pre-eclampsia and fetal growth restriction. A key remaining question is the degree to which EVT cells in the cervix might differ from those in the basal plate and placental bed. TRIC could one day provide a method of risk assessment for maternal and fetal disease, and reveal molecular pathways disrupted during the first trimester in EVT cells associated with placental maldevelopment. As perinatal interventions emerge for pregnancy disorders and inherited congenital disorders, TRIC could provide a key diagnostic tool for personalized precision medicine in obstetrics.

  1. Deep trophoblast invasion and spiral artery remodelling in the placental bed of the lowland gorilla

    DEFF Research Database (Denmark)

    Pijnenborg, R; Vercruysse, L; Carter, Anthony Michael

    2011-01-01

    In contrast to baboon or rhesus macaque, trophoblast invasion in the human placental bed occurs by the interstitial as well as the endovascular route and reaches as deep as the inner myometrium. We here describe two rare specimens of gorilla placenta. In the light of recent findings in the chimpa......In contrast to baboon or rhesus macaque, trophoblast invasion in the human placental bed occurs by the interstitial as well as the endovascular route and reaches as deep as the inner myometrium. We here describe two rare specimens of gorilla placenta. In the light of recent findings...... in the chimpanzee, we postulated the occurrence of deep invasion in gorilla pregnancy. Tissues were processed for histology (PAS, orcein), lectin staining (Ulex europaeus agglutinin 1) and immunohistochemistry (cytokeratin 7/17, α-actin). A specimen of young but undetermined gestational age included deep placental...... no definite conclusions about the origin of the intramural trophoblast and the time-course of spiral artery invasion. A different late second trimester placenta specimen showed scattered extravillous trophoblast in the basal plate and underlying decidua, as well as a remodelled spiral artery containing...

  2. [Fetomaternal transfusion and diagnosis of gestational choriocarcinoma].

    Science.gov (United States)

    Emin, L; Izard, A; Schiavone, S; Kermanach, P; Deramecourt, M; Duclusaud, A; Gertych, W; Girard, S

    2015-03-01

    Choriocarcinoma is a rare but agressive malignant trophoblastic neoplasm. Fetomaternal transfusion can be the first sign of choriocarcinoma. We describe two cases of gestational choriocarinoma whose first manifestation was a fetomaternal transfusion. Fetomaternal transfusion is a rare demonstration of choriocarcinoma but its diagnosis must lead to a placenta examination with specific research of choriocarcinoma. The more the therapeutic care is precise, the better is the forecast. Copyright © 2015 Elsevier Masson SAS. All rights reserved.

  3. Trophoblast lineage cells derived from human induced pluripotent stem cells

    Energy Technology Data Exchange (ETDEWEB)

    Chen, Ying, E-mail: ying.chen@hc.msu.edu [Department of Obstetrics, Gynecology and Reproductive Biology, Michigan State University, 333 Bostwick NE, Grand Rapids, MI 49503 (United States); Wang, Kai; Chandramouli, Gadisetti V.R. [Department of Obstetrics, Gynecology and Reproductive Biology, Michigan State University, 333 Bostwick NE, Grand Rapids, MI 49503 (United States); Knott, Jason G. [Developmental Epigenetics Laboratory, Department of Animal Science, Michigan State University (United States); Leach, Richard, E-mail: Richard.leach@hc.msu.edu [Department of Obstetrics, Gynecology and Reproductive Biology, Michigan State University, 333 Bostwick NE, Grand Rapids, MI 49503 (United States); Department of Obstetrics, Gynecology and Women’s Health, Spectrum Health Medical Group (United States)

    2013-07-12

    Highlights: •Epithelial-like phenotype of trophoblast lineage cells derived from human iPS cells. •Trophoblast lineage cells derived from human iPS cells exhibit trophoblast function. •Trophoblasts from iPS cells provides a proof-of-concept in regenerative medicine. -- Abstract: Background: During implantation, the blastocyst trophectoderm attaches to the endometrial epithelium and continues to differentiate into all trophoblast subtypes, which are the major components of a placenta. Aberrant trophoblast proliferation and differentiation are associated with placental diseases. However, due to ethical and practical issues, there is almost no available cell or tissue source to study the molecular mechanism of human trophoblast differentiation, which further becomes a barrier to the study of the pathogenesis of trophoblast-associated diseases of pregnancy. In this study, our goal was to generate a proof-of-concept model for deriving trophoblast lineage cells from induced pluripotency stem (iPS) cells from human fibroblasts. In future studies the generation of trophoblast lineage cells from iPS cells established from patient’s placenta will be extremely useful for studying the pathogenesis of individual trophoblast-associated diseases and for drug testing. Methods and results: Combining iPS cell technology with BMP4 induction, we derived trophoblast lineage cells from human iPS cells. The gene expression profile of these trophoblast lineage cells was distinct from fibroblasts and iPS cells. These cells expressed markers of human trophoblasts. Furthermore, when these cells were differentiated they exhibited invasive capacity and placental hormone secretive capacity, suggesting extravillous trophoblasts and syncytiotrophoblasts. Conclusion: Trophoblast lineage cells can be successfully derived from human iPS cells, which provide a proof-of-concept tool to recapitulate pathogenesis of patient placental trophoblasts in vitro.

  4. Trophoblast lineage cells derived from human induced pluripotent stem cells

    International Nuclear Information System (INIS)

    Chen, Ying; Wang, Kai; Chandramouli, Gadisetti V.R.; Knott, Jason G.; Leach, Richard

    2013-01-01

    Highlights: •Epithelial-like phenotype of trophoblast lineage cells derived from human iPS cells. •Trophoblast lineage cells derived from human iPS cells exhibit trophoblast function. •Trophoblasts from iPS cells provides a proof-of-concept in regenerative medicine. -- Abstract: Background: During implantation, the blastocyst trophectoderm attaches to the endometrial epithelium and continues to differentiate into all trophoblast subtypes, which are the major components of a placenta. Aberrant trophoblast proliferation and differentiation are associated with placental diseases. However, due to ethical and practical issues, there is almost no available cell or tissue source to study the molecular mechanism of human trophoblast differentiation, which further becomes a barrier to the study of the pathogenesis of trophoblast-associated diseases of pregnancy. In this study, our goal was to generate a proof-of-concept model for deriving trophoblast lineage cells from induced pluripotency stem (iPS) cells from human fibroblasts. In future studies the generation of trophoblast lineage cells from iPS cells established from patient’s placenta will be extremely useful for studying the pathogenesis of individual trophoblast-associated diseases and for drug testing. Methods and results: Combining iPS cell technology with BMP4 induction, we derived trophoblast lineage cells from human iPS cells. The gene expression profile of these trophoblast lineage cells was distinct from fibroblasts and iPS cells. These cells expressed markers of human trophoblasts. Furthermore, when these cells were differentiated they exhibited invasive capacity and placental hormone secretive capacity, suggesting extravillous trophoblasts and syncytiotrophoblasts. Conclusion: Trophoblast lineage cells can be successfully derived from human iPS cells, which provide a proof-of-concept tool to recapitulate pathogenesis of patient placental trophoblasts in vitro

  5. Detection of colorectal neoplasia

    DEFF Research Database (Denmark)

    Wilhelmsen, Michael; Christensen, Ib J; Rasmussen, Louise

    2017-01-01

    Serological biomarkers may be an option for early detection of colorectal cancer (CRC). The present study assessed eight cancer-associated protein biomarkers in plasma from subjects undergoing first time ever colonoscopy due to symptoms attributable to colorectal neoplasia. Plasma AFP, CA19-9, CEA...... value was 18% and the negative predictive value was 97%. Combinations of serological protein biomarkers provided a significant identification of subjects with high risk of the presence of colorectal neoplasia. The present set of biomarkers could become important adjunct in early detection of CRC....

  6. Effect of proline rich 15-deficiency on trophoblast viability and survival.

    Directory of Open Access Journals (Sweden)

    Katherine C Gates

    Full Text Available Deviations from the normal program of gene expression during early pregnancy can lead to early embryonic loss as well as dysfunctional placentation, which can cause significant morbidity and mortality. Proline rich 15 (PRR15 is a low molecular weight nuclear protein expressed by the trophoblast during early gestation. Lentivirus-mediated knockdown of PRR15 mRNA in ovine trophectoderm led to demise of the embryo by gestational day 15, providing compelling evidence that PRR15 expression is critical during this precarious window of development. Our objective was to determine the effect of PRR15 knockdown on trophoblast gene expression, proliferation, and survival. The first-trimester human trophoblast cell line, ACH-3P, was infected with control lentivirus or a lentivirus expressing a short hairpin (shRNA to target PRR15 mRNA for degradation, resulting in a 68% reduction in PRR15 mRNA. Microarray analysis of these cell lines revealed differential expression of genes related to cancer, focal adhesion, and p53 signaling. These changes included significant up-regulation of GDF15, a cytokine increased in pregnancies with preeclampsia. Viability and proliferation decreased in PRR15-deficient cells, which was consistent with down-regulation of cell cycle-related genes CCND1 and CDK6 and an up-regulation of CCNG2 and CDKN1A in the PRR15-deficient cells. TNFSF10, a tumor necrosis factor superfamily member known to induce apoptosis increased significantly in the PRR15-deficient cells. Migration through a basement membrane matrix decreased and an increased population of apoptotic cells was present when treated with shRNA to target PRR15. These results suggest that PRR15 enhances trophoblast viability and survival during early implantation and placentation.

  7. The psychoactive compound of Cannabis sativa, Δ(9)-tetrahydrocannabinol (THC) inhibits the human trophoblast cell turnover.

    Science.gov (United States)

    Costa, M A; Fonseca, B M; Marques, F; Teixeira, N A; Correia-da-Silva, G

    2015-08-06

    The noxious effects of cannabis consumption for fertility and pregnancy outcome are recognized for years. Its consumption during gestation is associated with alterations in foetal growth, low birth weight and preterm labor. The main psychoactive molecule of cannabis, Δ(9)-tetrahydrocannabinol (THC) impairs the production of reproductive hormones and is also able to cross the placenta barrier. However, its effect on the main placental cells, the trophoblasts, are unknown. Actually, the role of THC in cell survival/death of primary human cytotrophoblasts (CTs) and syncytiotrophoblasts (STs) and in the syncytialization process remains to be explored. Here, we show that THC has a dual effect, enhancing MTT metabolism at low concentrations, whereas higher doses decreased cell viability, on both trophoblast phenotypes, though the effects on STs were more evident. THC also diminished the generation of oxidative and nitrative stress and the oxidized form of glutathione, whereas the reduced form of this tripeptide was increased, suggesting that THC prevents ST cell death due to an antioxidant effect. Moreover, this compound enhanced the mitochondrial function of STs, as observed by the increased MTT metabolism and intracellular ATP levels. These effects were independent of cannabinoid receptors activation. Besides, THC impaired CT differentiation into STs, since it decreased the expression of biochemical and morphological biomarkers of syncytialization, through a cannabinoid receptor-dependent mechanism. Together, these results suggest that THC interferes with trophoblast turnover, preventing trophoblast cell death and differentiation, and contribute to disclose the cellular mechanisms that lead to pregnancy complications in women that consume cannabis-derived drugs during gestation. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

  8. [Trophoblast: conductor of the maternal immune tolerance].

    Science.gov (United States)

    Mesdag, V; Salzet, M; Vinatier, D

    2014-11-01

    Pregnancy is a temporary semi-allograft that survives for nine months. The importance of this event for the survival of the species justifies several tolerance mechanisms that are put into place at the beginning of pregnancy, some of which occur even at the time of implantation. The description of these mechanisms underlines the leadership of the trophoblast. The trophoblast is the conductor of the events, protects himself by expressing specific antigens and regulates the environment of the decidua according to the calendar of the events of the pregnancy The trophoblast and the decidual environment attract the effectors of immunity, almost all present in the decidua. The immunological atmosphere of the decidua evolves during the pregnancy modulating the level of activation of the immunological cells and adapting the level of activation to the stage of the pregnancy. Copyright © 2014 Elsevier Masson SAS. All rights reserved.

  9. Gestational diabetes

    Science.gov (United States)

    ... this page: //medlineplus.gov/ency/article/000896.htm Gestational diabetes To use the sharing features on this page, please enable JavaScript. Gestational diabetes is high blood sugar (glucose) that starts or ...

  10. Persistent trophoblast disease following partial molar pregnancy.

    NARCIS (Netherlands)

    Wielsma, S.; Kerkmeijer, L.G.W.; Bekkers, R.L.M.; Pyman, J.; Tan, J.; Quinn, M.

    2006-01-01

    OBJECTIVE: Human chorionic gonadotrophin (hCG) follow-up data were analysed retrospectively in all patients registered in the Hydatidiform Mole Registry at the Royal Women's Hospital, Melbourne from January 1992 to January 2001 to determine the risk of persistent trophoblast disease following

  11. Trophoblastic progranulin expression is upregulated in cases of fetal growth restriction and preeclampsia.

    Science.gov (United States)

    Stubert, Johannes; Schattenberg, Florian; Richter, Dagmar-Ulrike; Dieterich, Max; Briese, Volker

    2012-05-13

    The expression of the anti-inflammatory glycoprotein progranulin and the hypoxia-induced transcription factor 1α (HIF-1α) in the villous trophoblast was compared between placentae from patients with preeclampsia (PE), fetal growth restriction (FGR), and normal controls. Matched pairs analysis of third trimester placentae specimens (mean gestational age 36+2) was performed by semiquantitative measurements of the immunohistochemical staining intensities for progranulin and HIF-1α expression (PE n=13, FGR n=9 and controls n=11). Further, placental progranulin mRNA expression was analyzed by qRT-PCR on term placentae (n=3 for each group). Compared to controls, villous trophoblast revealed a significantly higher expression of progranulin in cases of PE (Pprogranulin protein was not accompanied by an increase of the progranulin mRNA in term placentae. Increased expression of progranulin protein in villous trophoblast cells in cases of PE and FGR may result from disturbed placental development and, therefore, may be of pathogenetic importance. The increase was correlated to HIF-1α expression. Further evaluation of this potential mechanism of regulation is required.

  12. Rac1/β-Catenin Signalling Pathway Contributes to Trophoblast Cell Invasion by Targeting Snail and MMP9

    Directory of Open Access Journals (Sweden)

    Minghua Fan

    2016-03-01

    Full Text Available Background/Aims: Preeclampsia is an idiopathic and serious complication during gestation in which placental trophoblast cells differentiate into several functional subtypes, including highly invasive extravillous trophoblasts (EVTs. Although the cause and pathogenesis of preeclampsia have remained unclear, numerous studies have suggested that the inadequacy of EVT invasion leads to imperfect uterine spiral artery remodelling, which plays a crucial role in the development of preeclampsia. Rac1, or Ras-related C3 botulinum toxin substrate 1, was found to be a key regulator of the migration, invasion uand apoptosis of various tumour cells. Because EVTs share similar invasive and migratory biological behaviours with malignant cells, this study aimed to determine whether the Rac1 signalling pathway affects trophoblast invasion and is thus involved in the pathogenesis of preeclampsia. Methods: We measured the activity of Rac1 and its downstream targets, β-catenin, Snail and MMP9 in placental tissues from patients experiencing a normal pregnancy and those with preeclampsia. Furthermore, we treated HTR-8/SVneo cells with a shRNA Rac1 vector and the β-catenin inhibitor IWP-2 and explored Rac1 signalling pathway activation as well as the effects of Snail and β-catenin on trophoblast invasion. Results: In placental samples from patients experiencing a normal pregnancy and those with preeclampsia, active Rac1 levels and MMP9 protein and mRNA levels were significantly decreased in term pregnancy samples compared to early pregnancy samples. Lower levels were found in preeclampsia samples than in normal term pregnancy samples, and these levels significantly declined in severe preeclampsia samples compared with mild preeclampsia samples. Further analyses demonstrated that both Rac1 shRNA and the β-catenin inhibitor significantly suppressed MMP9 and Snail activation in trophoblasts, thus impairing trophoblast invasion. Notably, silencing Rac1 down

  13. MiR-519d-3p suppresses invasion and migration of trophoblast cells via targeting MMP-2.

    Directory of Open Access Journals (Sweden)

    Jie Ding

    Full Text Available Our study was approved by the Medical Ethics Committee of Tang Du Hospital, Fourth Military Medical University and complied strictly with national ethical guidelines. Preeclampsia (PE is a specific clinical disorder characterized by gestational hypertension and proteinuria and is a leading cause of maternal and perinatal mortality worldwide. The miR-519d-3p is upregulated in the maternal plasma of patients with PE which indicates a possible association between this microRNA and the pathogenesis of PE. No studies to date have addressed the effect of miR-519d-3p on the invasion and migration of trophoblast cells. In our study, we found that miR-519d-3p expression was elevated in placental samples from patients with PE. In vitro, overexpression of miR-519d-3p significantly inhibited trophoblast cell migration and invasion, whereas transfection of a miR-519d-3p inhibitor enhanced trophoblast cell migration and invasion. Luciferase assays confirmed that matrix metalloproteinase-2 (MMP-2 is a direct target of miR-519d-3p. Quantitative real-time PCR and western blot assays showed that overexpression of miR-519d-3p downregulated MMP-2 mRNA and protein expression. Knockdown of MMP-2 using a siRNA attenuated the increased trophoblast migration and invasion promoted by the miR-519d-3p inhibitor. In placentas from patients with PE or normal pregnancies, a negative correlation between the expression of MMP-2 and miR-519d-3p was observed using the Pearson correlation and linear regression analysis. Our present findings suggest that upregulation of miR-519d-3p may contribute to the development of PE by inhibiting trophoblast cell migration and invasion via targeting MMP-2; miR-519d-3p may represent a potential predictive and therapeutic target for PE.

  14. Triazole fungicide tebuconazole disrupts human placental trophoblast cell functions

    International Nuclear Information System (INIS)

    Zhou, Jinghua; Zhang, Jianyun; Li, Feixue; Liu, Jing

    2016-01-01

    Highlights: • Tebuconazole (TEB) inhibited the proliferation of human placental trophoblasts. • TEB changed cell cycle distribution of G1 and G2 phases of trophoblasts. • TEB induced apoptosis of trophoblasts via mitochondrial pathway. • TEB decreased the invasive and migratory capacities of trophoblasts. • TEB altered the mRNA levels of key regulatory genes in trophoblasts - Abstract: Triazole fungicides are one of the top ten classes of current-use pesticides. Although exposure to triazole fungicides is associated with reproductive toxicity in mammals, limited information is available regarding the effects of triazole fungicides on human placental trophoblast function. Tebuconazole (TEB) is a common triazole fungicide that has been extensively used for fungi control. In this work, we showed that TEB could reduce cell viability, disturb normal cell cycle distribution and induce apoptosis of human placental trophoblast cell line HTR-8/SVneo (HTR-8). Bcl-2 protein expression decreased and the level of Bax protein increased after TEB treatment in HTR-8 cells. The results demonstrated that this fungicide induced apoptosis of trophoblast cells via mitochondrial pathway. Importantly, we found that the invasive and migratory capacities of HTR-8 cells decreased significantly after TEB administration. TEB altered the expression of key regulatory genes involved in the modulation of trophoblast functions. Taken together, TEB suppressed human trophoblast invasion and migration through affecting the expression of protease, hormones, angiogenic factors, growth factors and cytokines. As the invasive and migratory abilities of trophoblast are essential for successful placentation and fetus development, our findings suggest a potential risk of triazole fungicides to human pregnancy.

  15. Triazole fungicide tebuconazole disrupts human placental trophoblast cell functions

    Energy Technology Data Exchange (ETDEWEB)

    Zhou, Jinghua [Key Laboratory of Environmental Remediation and Ecological Health, Ministry of Education, Zhejiang University, Hangzhou 310058 (China); Zhang, Jianyun [Research Center for Air Pollution and Health, College of Environmental and Resource Sciences, Zhejiang University, Hangzhou 310058 (China); Li, Feixue [Zhejiang Key Laboratory of Organ Development and Regeneration, Institute of Developmental and Regenerative Biology, College of Life and Environmental Sciences, Hangzhou Normal University, Hangzhou 310036 (China); Liu, Jing, E-mail: jliue@zju.edu.cn [Key Laboratory of Environmental Remediation and Ecological Health, Ministry of Education, Zhejiang University, Hangzhou 310058 (China); Research Center for Air Pollution and Health, College of Environmental and Resource Sciences, Zhejiang University, Hangzhou 310058 (China)

    2016-05-05

    Highlights: • Tebuconazole (TEB) inhibited the proliferation of human placental trophoblasts. • TEB changed cell cycle distribution of G1 and G2 phases of trophoblasts. • TEB induced apoptosis of trophoblasts via mitochondrial pathway. • TEB decreased the invasive and migratory capacities of trophoblasts. • TEB altered the mRNA levels of key regulatory genes in trophoblasts - Abstract: Triazole fungicides are one of the top ten classes of current-use pesticides. Although exposure to triazole fungicides is associated with reproductive toxicity in mammals, limited information is available regarding the effects of triazole fungicides on human placental trophoblast function. Tebuconazole (TEB) is a common triazole fungicide that has been extensively used for fungi control. In this work, we showed that TEB could reduce cell viability, disturb normal cell cycle distribution and induce apoptosis of human placental trophoblast cell line HTR-8/SVneo (HTR-8). Bcl-2 protein expression decreased and the level of Bax protein increased after TEB treatment in HTR-8 cells. The results demonstrated that this fungicide induced apoptosis of trophoblast cells via mitochondrial pathway. Importantly, we found that the invasive and migratory capacities of HTR-8 cells decreased significantly after TEB administration. TEB altered the expression of key regulatory genes involved in the modulation of trophoblast functions. Taken together, TEB suppressed human trophoblast invasion and migration through affecting the expression of protease, hormones, angiogenic factors, growth factors and cytokines. As the invasive and migratory abilities of trophoblast are essential for successful placentation and fetus development, our findings suggest a potential risk of triazole fungicides to human pregnancy.

  16. Cytotoxicant-induced trophoblast dysfunction and abnormal pregnancy outcomes: role of zinc and metallothionein.

    Science.gov (United States)

    McAleer, Mary Frances; Tuan, Rocky S

    2004-12-01

    Normal trophoblast function, including implantation, hormone production, and formation of the selectively permeable maternofetal barrier, is essential for the establishment and maintenance of the fetoplacental unit and proper fetal development. Maternal cytotoxicant exposure causes the destruction of these cells, especially the terminally differentiated syncytiotrophoblasts, and results in a myriad of poor pregnancy outcomes. These outcomes range from intrauterine growth retardation and malformation to spontaneous abortion or stillbirth. There is recent evidence that the metal-binding protein, metallothionein, is involved in the protection of human trophoblastic cells from heavy metal-induced and severe oxidative stress-induced apoptosis. Metallothionein, with its unique biochemical structure, can both bind essential metal ions, such as the transcription modulator zinc, and yet allow their ready displacement by toxic nonessential metal ions or damaging free radicals. These properties suggest that metallothionein may be responsible not only for sequestering the cytotoxic agents, but also for altering signal transduction in the affected cells. Here, we review several identified causes of adverse pregnancy outcomes (specifically, prenatal exposure to cigarette smoke and alcohol, gestational infection, and exposure to environmental contaminants), discuss the role of zinc in modulating the cellular response to these toxic insults, and then propose how metallothionein may function to mediate this protective response. Published 2005 Wiley-Liss, Inc.

  17. Pomegranate juice and punicalagin attenuate oxidative stress and apoptosis in human placenta and in human placental trophoblasts

    Science.gov (United States)

    Tuuli, Methodius G.; Longtine, Mark S.; Shin, Joong Sik; Lawrence, Russell; Inder, Terrie; Michael Nelson, D.

    2012-01-01

    The human placenta is key to pregnancy outcome, and the elevated oxidative stress present in many complicated pregnancies contributes to placental dysfunction and suboptimal pregnancy outcomes. We tested the hypothesis that pomegranate juice, which is rich in polyphenolic antioxidants, limits placental trophoblast injury in vivo and in vitro. Pregnant women with singleton pregnancies were randomized at 35∼38 wk gestation to 8 oz/day of pomegranate juice or apple juice (placebo) until the time of delivery. Placental tissues from 12 patients (4 in the pomegranate group and 8 in the control group) were collected for analysis of oxidative stress. The preliminary in vivo results were extended to oxidative stress and cell death assays in vitro. Placental explants and cultured primary human trophoblasts were exposed to pomegranate juice or glucose (control) under defined oxygen tensions and chemical stimuli. We found decreased oxidative stress in term human placentas from women who labored after prenatal ingestion of pomegranate juice compared with apple juice as control. Moreover, pomegranate juice reduced in vitro oxidative stress, apoptosis, and global cell death in term villous explants and primary trophoblast cultures exposed to hypoxia, the hypoxia mimetic cobalt chloride, and the kinase inhibitor staurosporine. Punicalagin, but not ellagic acid, both prominent polyphenols in pomegranate juice, reduced oxidative stress and stimulus-induced apoptosis in cultured syncytiotrophoblasts. We conclude that pomegranate juice reduces placental oxidative stress in vivo and in vitro while limiting stimulus-induced death of human trophoblasts in culture. The polyphenol punicalagin mimics this protective effect. We speculate that antenatal intake of pomegranate may limit placental injury and thereby may confer protection to the exposed fetus. PMID:22374759

  18. lessons from a hybrid epithelioid trophoblastic tumor and chorio

    African Journals Online (AJOL)

    (36,900 mIU/ml) and examination showed a bleeding cervical mass. An initial ... characterized by abnormal proliferation of placental trophoblasts and include .... MRI is invaluable to assess extra uterine disease spread and complications.

  19. Trophoblast cells of ruminant placentas - A mini review

    International Nuclear Information System (INIS)

    Igwebuike, U.M.

    2004-09-01

    Understanding of ruminant placental structure and function is essential for veterinarians and researchers. The ruminant placenta is classified as cotyledonary and synepitheliochorial on the bases of its gross anatomical features and histological characteristics respectively. The richly vascularized embryonic chorioallantois is lined on its outer surface by cells of the trophectodermal epithelium. These cells which assume specialized functions are referred to as trophoblast cells. Two morphologically and functionally distinct cell types have been recognized in the trophectoderm of the placenta of ruminant animals. These are the mononucleate trophoblast cells and the binucleate trophoblast cells. The occurrence, morphological characteristics, and specialized functions of these trophoblast cells, in relation to conceptus nutrition and survival in utero are discussed in this review. (author)

  20. Immunolocalization of progesterone receptors in binucleate trophoblast cells of the buffalo placenta (Bubalus bubalis

    Directory of Open Access Journals (Sweden)

    Carlos Eduardo Ambrósio

    2007-06-01

    Full Text Available The binucleate trophoblast cells (CTBs of the water buffalo placenta (Bubalus bubalis were studied with emphasis on the presence of progesterone receptor. Placentomal tissues from 27 buffalos (2-10 months of pregnancy were processed and embedded in paraplast (Paraplast Embedding Media – Paraplast Plus to locate the progesterone receptors using the immunohistochemistry technique. The immunohistochemical reaction for progesterone receptor through monoclonal antibody PgR Ab2 showed staining of CTBs, caruncular epithelial and estromal cells and blood vessel estromal pericitos present in the placentome throughout the entire gestational period analyzed. These results indicate the production of progesterone with autocrine and paracrine action in the placentome growth, differentiation and functional regulation.

  1. Intrathoracic neoplasia: Epidemiology and etiology

    Energy Technology Data Exchange (ETDEWEB)

    Weller, R.E.

    1992-05-01

    Neoplasms of the thorax encompass those derived from the thoracic wall, trachea, mediastinum, lungs and pleura. They represent a wide variety of lesions including benign and malignant tumors arising from many tissues. The large surface area, 60 to 90 m{sup 2} in man, represented by the respiratory epithelium and associated thoracic structures are ideal targets for carcinogens carried by inspired air. The topic of discussion in this report is the epidemiology, etiology, and mechanisms of spontaneous intrathoracic neoplasia in animals and man. Much of what we know or suspect about thoracic neoplasia in animals has been extrapolated from experimentally-induced neoplasms.

  2. Pulmonary preinvasive neoplasia.

    Science.gov (United States)

    Kerr, K M

    2001-04-01

    Advances in molecular biology have increased our knowledge of the biology of preneoplastic lesions in the human lung. The recently published WHO lung tumour classification defines three separate lesions that are regarded as preinvasive neoplasia. These are (1) squamous dysplasia and carcinoma in situ (SD/CIS), (2) atypical adenomatous hyperplasia (AAH), and (3) diffuse idiopathic pulmonary neuroendocrine cell hyperplasia (DIP-NECH). SD/CIS is graded in four stages (mild, moderate, severe, and CIS), based upon the distribution of atypical cells and mitotic figures. Most airways showing SD/CIS demonstrate a range of grades; many epithelia are hard to assess and the reproducibility of this complex system remains to be established. Detailed criteria are, however, welcome and provide an objective framework on which to compare various molecular changes. Alterations in gene expression and chromosome structure known to be associated with malignant transformation can be demonstrated in CIS, less so in dysplasias, but also in morphologically normal epithelium. The changes might be sequential, and their frequency and number increase with atypia. Less is known of the "risk of progression" of SD/CIS to invasive "central" bronchial carcinoma. It may take between one and 10 years for invasion to occur, yet the lesion(s) may be reversible if carcinogen exposure ceases. AAH may be an important precursor lesion for peripheral "parenchymal" adenocarcinoma of the lung: the "adenoma" in an adenoma-carcinoma sequence. There is good morphological evidence that AAH may progress from low to high grade to bronchioloalveolar carcinoma (BAC; a non-invasive lesion by definition). Invasion then develops within BAC and peripheral lung adenocarcinoma evolves. The molecular events associated with this progression are not well understood and studies are hampered by a lack of clear criteria to distinguish high grade AAH from BAC. Nonetheless, as with SD/CIS, the patterns of expression of tumour

  3. Gestational surrogacy.

    Science.gov (United States)

    Brinsden, Peter R

    2003-01-01

    Gestational surrogacy is a treatment option available to women with certain clearly defined medical problems, usually an absent uterus, to help them have their own genetic children. IVF allows the creation of embryos from the gametes of the commissioning couple and subsequent transfer of these embryos to the uterus of a surrogate host. The indications for treatment include absent uterus, recurrent miscarriage, repeated failure of IVF and certain medical conditions. Treatment by gestational surrogacy is straightforward and follows routine IVF procedures for the commissioning mother, with the transfer of fresh or frozen-thawed embryos to the surrogate host. The results of treatment are good, as would be expected from the transfer of embryos derived from young women and transferred to fit, fertile women who are also young. Clinical pregnancy rates achieved in large series are up to 40% per transfer and series have reported 60% of hosts achieving live births. The majority of ethical or legal problems that have arisen out of surrogacy have been from natural or partial surrogacy arrangements. The experience of gestational surrogacy has been largely complication-free and early results of the follow-up of children, commissioning couples and surrogates are reassuring. In conclusion, gestational surrogacy arrangements are carried out in a few European countries and in the USA. The results of treatment are satisfactory and the incidence of major ethical or legal complications has been limited. IVF surrogacy is therefore a successful treatment for a small group of women who would otherwise not be able to have their own genetic children.

  4. Glucose metabolism in cultured trophoblasts from human placenta

    International Nuclear Information System (INIS)

    Moe, A.J.; Farmer, D.R.; Nelson, D.M.; Smith, C.H.

    1990-01-01

    The development of appropriate placental trophoblast isolation and culture techniques enables the study of pathways of glucose utilization by this important cell layer in vitro. Trophoblasts from normal term placentas were isolated and cultured 24 hours and 72 hours in uncoated polystyrene culture tubes or tubes previously coated with a fibrin matrix. Trophoblasts cultured on fibrin are morphologically distinct from those cultured on plastic or other matrices and generally resemble in vivo syncytium. Cells were incubated up to 3 hours with 14 C-labeled glucose and reactions were stopped by addition of perchloric acid. 14 CO 2 production by trophoblasts increased linearly with time however the largest accumulation of label was in organic acids. Trophoblasts cultured in absence of fibrin utilized more glucose and accumulated more 14 C in metabolic products compared to cells cultured on fibrin. Glucose oxidation to CO 2 by the phosphogluconate (PG) pathway was estimated from specific yields of 14 CO 2 from [1- 14 C]-D-glucose and [6- 14 C]-D-glucose. Approximately 6% of glucose oxidation was by the PG pathway when cells were cultured on fibrin compared to approximately 1% by cells cultured in the absence of fibrin. The presence of a fibrin growth matrix appears to modulate the metabolism of glucose by trophoblast from human placenta in vitro

  5. Multiple endocrine neoplasia type I

    International Nuclear Information System (INIS)

    Fischer, H.J.; Lois, J.F.; Gomes, A.S.

    1985-01-01

    A case of multiple endocrine neoplasia (Men) consisting of an unusual combination of an insulin-producing islet cell tumour and an adrenal adenoma is reported. CT clearly demonstrated the adrenal mass whereas the pancreatic lesion remained questionable. Conversely angiography located the pancreatic tumour but the adrenal findings were subtle. (orig.)

  6. Fibrobronchoscopy in the lung neoplasia

    International Nuclear Information System (INIS)

    Machin Gonzalez, Victoriano; Vieito Espinneira, Rodolfo; Freyre Serentill, Juan C.; Benito Soler, Isabel

    1997-01-01

    160 patients with a clinical-radiological picture suggesting lung neoplasia was conducted. Fibrobronchoscopy was performed as a reliable method to detect this disease. Punch biopsy, exfoliative cytology, and bronchial lavage Webre used to obtain specimens for the histological study. Of all the patients studied, 112 cases Webre positive and a proper diagnosis by biopsy was attained in 90 of them

  7. Extravillous trophoblast invasion in placenta accreta is associated with differential local expression of angiogenic and growth factors: a cross-sectional study.

    Science.gov (United States)

    Duzyj, C M; Buhimschi, I A; Laky, C A; Cozzini, G; Zhao, G; Wehrum, M; Buhimschi, C S

    2018-02-22

    Placenta accreta is clinically associated with maternal uterine scar. Our objective was to investigate the biochemical contribution of maternal scarring to hyperinvasive trophoblast. We hypothesised that trophoblast over-invasion in placenta accreta is associated with aberrant invasion-site signalling of growth and angiogenic factors known to be involved in wound healing and promotion of cell invasion through the epithelial to mesenchymal cellular programme. Cross-sectional series. Yale-New Haven Hospital. Women with histologically confirmed normal and abnormal placentation. Placental invasion site tissue sections were immunostained for endoglin and other angiogenic regulators, and transforming growth factor β (TGFβ) proteins. Maternal serum endoglin, and the vascular endothelial growth factor (VEGF) mediators hypoxia-inducible factor-1α (HIF1α) and endostatin, were assessed using immunoassay. Differences in median H-score by immunostaining and in mean serum level by immunoassay. By immunostaining, placenta accreta samples demonstrated intervillous endoglin shedding and increased trophoblast expression of its cleavage protein matrix metalloproteinase-14. Absent decidual HIF1α and endostatin were observed in areas of VEGF upregulation. TGFβ1 was present in myocytes but not in collagen bundles into which accreta trophoblast invaded. Maternal serum endoglin decreased in praevia and accreta when corrected for gestational age. Angiogenic and growth factors at the placental invasion site are altered in accreta, both by decidual absence and within myometrial scar. We postulate this promotes the invasive phenotype of placenta accreta by activating hyperinvasive trophoblast and by dysregulating placental vascular remodelling. Yale Department of Obstetrics, Gynecology and Reproductive Sciences funds. Placenta accreta histology shows dysregulation of angiogenic and growth factors. © 2018 Royal College of Obstetricians and Gynaecologists.

  8. Variation in macrophage migration inhibitory factor [MIF] immunoreactivity during bovine gestation

    DEFF Research Database (Denmark)

    Paulesu, L.; Pfarrer, C.; Romagnoli, R.

    2012-01-01

    and hemochorial human and mouse placentae. Here we studied the bovine placenta being multiplex, villous and synepitheliochorial with a low degree of invasion, to see if MIF could be involved. Placental tissues sampled from 12 cows at 9 stages of gestation (days 18-250), and endometrial tissues from two non......-pregnant animals were processed for immunohistochemistry. Bovine MIF was detected by Western blot using anti-human MIF monoclonal antibodies. An immunoreactive band of approximately 12kDa confirmed similarities between bovine and human MIFs. Compared to the non-pregnant stage with very faint staining...... both caruncular and trophoblast epithelium of the placentomes were positive with different intensity in relation to the gestational stage. In the uterine glands, some strongly stained cells were present. The mature binucleated trophoblast giant cells were negative throughout pregnancy. During...

  9. Diagnostics of trophoblast disease and the control of therapeutic efficiency based on definition of chorionic gonadotrapin and trophoblastic beta1-glycoprotein

    International Nuclear Information System (INIS)

    Yugrinova, L.G.; Olefirenko, G.A.; Dotsenko, Yu.S.

    1982-01-01

    A comparative estimation of markers of trophoblast disease, chorionic gonadotropin (CG) and trophoblastic beta 1 -glycoprotein defined by different methods is given. It is found that diagnostics and control of therapeutic efficiency for patients having trophoblast disease based on CG definition are possible. In 86% of cases the clinical diagnosis was confirmed by the immunoradioautography, and in 33% - by the immunodiffusion method. The dependence of marker detection frequency on the therapeutic efficiency is found

  10. Clinical characteristics and outcomes of placental site trophoblastic tumor: experience of single institution in Korea.

    Science.gov (United States)

    Lee, Hye-Joo; Shin, Wonkyo; Jang, Yun Jeong; Choi, Chel Hun; Lee, Jeong-Won; Bae, Duk-Soo; Kim, Byoung-Gie

    2018-05-01

    Placental site trophoblastic tumor (PSTT) is the rarest form of gestational trophoblastic disease (GTD) and the optimum management is still controversial. In this study, we analyzed the clinical features, treatment, and outcomes of 6 consecutive patients with PSTT treated in our institution. The electronic medical record database of Samsung Medical Center was screened to identify patients with PSTT from 1994 to 2017. Medical records for the details of each patient's clinical features and treatment were extracted and reviewed. This study was approved Institutional Review Board of our hospital. A total of 418 cases of GTD, 6 (1.4%) patients with PSTT were identified. The median age of the patients was 31 years. The antecedent pregnancy was term in all 5 cases with available antecedent pregnancy information and the median interval from pregnancy to diagnosis of PSTT was 8 months. The median titer of serum beta human chorionic gonadotropin (β-hCG) at diagnosis was 190.9 mIU/mL. Five (83.3%) patients presented with irregular vaginal bleeding and one (16.7%) had amenorrhea. All patients had disease confined to the uterus without metastasis at diagnosis and were successfully treated by hysterectomy alone. All of them were alive without disease during the follow-up period. In this study, we observed low level serum β-hCG titer and irregular vaginal bleeding with varying interval after antecedent term pregnancy were most common presenting features of PSTT. In addition, we demonstrated hysterectomy alone was successful for the treatment of stage I disease of PSTT.

  11. The invasive phenotype of placenta accreta extravillous trophoblasts associates with loss of E-cadherin.

    Science.gov (United States)

    Duzyj, C M; Buhimschi, I A; Motawea, H; Laky, C A; Cozzini, G; Zhao, G; Funai, E F; Buhimschi, C S

    2015-06-01

    Epithelial-to-mesenchymal transition (EMT) is a process of molecular and phenotypic epithelial cell alteration promoting invasiveness. Loss of E-cadherin (E-CAD), a transmembrane protein involved in cell adhesion, is a marker of EMT. Proteolysis into N- and C-terminus fragments by ADAM10 and presenilin-1 (PSEN-1) generates soluble (sE-CAD) and transcriptionally active forms. We studied the protein expression patterns of E-CAD in the serum and placenta of women with histologically-confirmed over-invasive placentation. The patterns of expression and levels of sE-CAD were analyzed by Western blot, immunoassay, and immunoprecipitation. Tissue immunostaining for E-CAD, cytokeratin-7 (epithelial marker), vimentin (mesenchymal marker), ADAM10, PSEN-1 and β-catenin expression were investigated in parallel. N-terminus cleaved 80 kDa sE-CAD fragments were present in serum of pregnant women with gestational age regulation of the circulatory levels. Women with advanced trophoblast invasion did not display circulatory levels of sE-CAD different from those of women with normal placentation. Histologically, extravillous trophoblasts (EVT) closer to the placental-myometrial interface demonstrated less E-CAD staining than those found deeper in the myometrium. These cells expressed both vimentin and cytokeratin, an additional feature of EMT. EVT of placentas with advanced invasion displayed intracellular E-CAD C-terminus immunoreactivity predominating over that of the extracellular N-terminus, a pattern consistent with preferential PSEN-1 processing. Local processing of E-CAD may be an important molecular mechanism controlling the invasive phenotype of accreta EVT. Copyright © 2015 Elsevier Ltd. All rights reserved.

  12. Let-7i-Induced Atg4B Suppression Is Essential for Autophagy of Placental Trophoblast in Preeclampsia.

    Science.gov (United States)

    Xu, Yinyan; Huang, Xinyan; Xie, Juan; Chen, Yanni; Fu, Jing; Wang, Li

    2017-09-01

    Autophagy, identified as type II programmed cell death, has already been known to be involved in the pathophysiology of preeclampsia (PE), which is a gestational disease with high morbidity. The present study aims to investigate the functional role of let-7i, a miRNA, in trophoblastic autophagy. Placental tissue used in this study was collected from patients with severe preeclampsia (SPE) or normal pregnant women. A decreased level of let-7i was found in placenta of SPE. In addition, autophagic vacuoles were observed in SPE and the expression of microtubule associated protein 1 light chain 3 (LC3) II/I was elevated. In vitro, let-7i mimics suppressed the autophagic activities in human HTR-8/SVneo trophoblast cell line (HTR-8) and human placental choriocarcinoma cell line JEG-3, whereas let-7i inhibitor enhanced the activities. As a potential target of let-7i, autophagy-related 4B cysteine peptidase (Atg4B) had an increased expression level in SPE. As expected, the increased expression of Atg4B was negatively regulated by let-7i using dual luciferase reporter assay. Furthermore, these trophoblast-like cells transfected with the let-7i mimic or inhibitors resulted in a significant change of Atg4B in both mRNA and protein level. More importantly, Atg4B overexpression could partly reverse let-7i mimic-reduced LC3II/I levels; whereas Atg4B silencing partly attenuated let-7i inhibitor-induced the level of LC3II/I expression. Taken together, these findings suggest that let-7i is able to regulate autophagic activity via regulating Atg4B expression, which might contribute to the pathogenesis of PE. J. Cell. Physiol. 232: 2581-2589, 2017. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

  13. Galectin-1 influences trophoblast immune evasion and emerges as a predictive factor for the outcome of pregnancy.

    Science.gov (United States)

    Tirado-González, Irene; Freitag, Nancy; Barrientos, Gabriela; Shaikly, Valerie; Nagaeva, Olga; Strand, Magnus; Kjellberg, Lennart; Klapp, Burghard F; Mincheva-Nilsson, Lucia; Cohen, Marie; Blois, Sandra M

    2013-01-01

    Galectin-1 (gal-1) is expressed at the feto-maternal interface and plays a role in regulating the maternal immune response against placental alloantigens, contributing to pregnancy maintenance. Both decidua and placenta contribute to gal-1 expression and may be important for the maternal immune regulation. The expression of gal-1 within the placenta is considered relevant to cell-adhesion and invasion of trophoblasts, but the role of gal-1 in the immune evasion machinery exhibited by trophoblast cells remains to be elucidated. In this study, we analyzed gal-1 expression in preimplantation human embryos and first-trimester decidua-placenta specimens and serum gal-1 levels to investigate the physiological role played by this lectin during pregnancy. The effect on human leukocyte antigen G (HLA-G) expression in response to stimulation or silencing of gal-1 was also determined in the human invasive, proliferative extravillous cytotrophoblast 65 (HIPEC65) cell line. Compared with normal pregnant women, circulating gal-1 levels were significantly decreased in patients who subsequently suffered a miscarriage. Human embryos undergoing preimplantation development expressed gal-1 on the trophectoderm and inner cell mass. Furthermore, our in vitro experiments showed that exogenous gal-1 positively regulated the membrane-bound HLA-G isoforms (HLA-G1 and G2) in HIPEC65 cells, whereas endogenous gal-1 also induced expression of the soluble isoforms (HLA-G5 and -G6). Our results suggest that gal-1 plays a key role in pregnancy maternal immune regulation by modulating HLA-G expression on trophoblast cells. Circulating gal-1 levels could serve as a predictive factor for pregnancy success in early human gestation.

  14. Esophagectomy for Superficial Esophageal Neoplasia.

    Science.gov (United States)

    Watson, Thomas J

    2017-07-01

    Endoscopic therapies have become the standard of care for most cases of Barrett's esophagus with high-grade dysplasia or intramucosal adenocarcinoma. Despite a rapid and dramatic evolution in treatment paradigms, esophagectomy continues to occupy a place in the therapeutic armamentarium for superficial esophageal neoplasia. The managing physician must remain cognizant of the limitations of endoscopic approaches and consider surgical resection when they are exceeded. Esophagectomy, performed at experienced centers for appropriately selected patients with early-stage disease can be undertaken with the expectation of cure as well as low mortality, acceptable morbidity, and good long-term quality of life. Copyright © 2017 Elsevier Inc. All rights reserved.

  15. Monoclonal antibodies against human trophoblast in female infertility

    Czech Academy of Sciences Publication Activity Database

    Sedláková, Alena; Elzeinová, Fatima; Bukovský, A.; Madar, J.; Ulčová-Gallová, Z.; Pěknicová, Jana

    2005-01-01

    Roč. 54, č. 3 (2005), s. 159 ISSN 0271-7352. [European Congress of Reproductive Immunology /3./. 05.09.11-05.09.15, Essex] R&D Projects: GA MZd(CZ) NR7838 Institutional research plan: CEZ:AV0Z50520514 Keywords : monoclonal antibodies * female infertility * trophoblast Subject RIV: EB - Genetics ; Molecular Biology

  16. TNF-α inhibits trophoblast integration into endothelial cellular networks.

    Science.gov (United States)

    Xu, B; Nakhla, S; Makris, A; Hennessy, A

    2011-03-01

    Preeclampsia has been linked to shallow trophoblast invasion and failure of uterine spiral artery transformation. Interaction between trophoblast cells and maternal uterine endothelium is critically important for this remodelling. The aim of our study was to investigate the effect of TNF-α on the interactions of trophoblast-derived JEG-3 cells into capillary-like cellular networks. We have employed an in vitro trophoblast-endothelial cell co-culture model to quantify trophoblast integration into endothelial cellular networks and to investigate the effects of TNF-α. Controlled co-cultures were also treated with anti-TNF-α antibody (5 μg/ml) to specifically block the effect of TNF-α. The invasion was evaluated by performing quantitative PCR (Q-PCR) to analyse gene expression of matrix metalloproteinases-2 (MMP-2), MMP-9, tissue inhibitor of matrix metalloproteinase (TIMP)-1, integrins (α(1)β(1) and α(6)β(4)), plasminogen activator inhibitor (PAI)-1, E-cadherin and VE-cadherin. JEG-3 cell integration into endothelial networks was significantly inhibited by exogenous TNF-α. The inhibition was observed in the range of 0.2-5 ng/ml, to a maximum 56% inhibition at the highest concentration. This inhibition was reversed by anti-TNF-α antibody. Q-PCR analysis showed that mRNA expression of integrins α(1)β(1) and MMP-2 was significantly decreased. VE-cadherin mRNA expression was significantly up-regulated (32-80%, p integration into maternal endothelial cellular networks, and this process involves the inhibition of MMP-2 and a failure of integrins switch from α(6)β(4) to α(1)β(1.) These molecular correlations reflect the changes identified in human preeclampsia. Copyright © 2011 Elsevier Ltd. All rights reserved.

  17. Evidence for Differential Glycosylation of Trophoblast Cell Types*

    Science.gov (United States)

    Chen, Qiushi; Pang, Poh-Choo; Cohen, Marie E.; Longtine, Mark S.; Schust, Danny J.; Haslam, Stuart M.; Blois, Sandra M.; Dell, Anne; Clark, Gary F.

    2016-01-01

    Human placental villi are surfaced by the syncytiotrophoblast (STB), with a layer of cytotrophoblasts (CTB) positioned just beneath the STB. STB in normal term pregnancies is exposed to maternal immune cells in the placental intervillous space. Extravillous cytotrophoblasts (EVT) invade the decidua and spiral arteries, where they act in conjunction with natural killer (NK) cells to convert the spiral arteries into flaccid conduits for maternal blood that support a 3–4 fold increase in the rate of maternal blood flow into the placental intervillous space. The functional roles of these distinct trophoblast subtypes during pregnancy suggested that they could be differentially glycosylated. Glycomic analysis of these trophoblasts has revealed the expression of elevated levels of biantennary N-glycans in STB and CTB, with the majority of them bearing a bisecting GlcNAc. N-glycans terminated with polylactosamine extensions were also detected at low levels. A subset of the N-glycans linked to these trophoblasts were sialylated, primarily with terminal NeuAcα2–3Gal sequences. EVT were decorated with the same N-glycans as STB and CTB, except in different proportions. The level of bisecting type N-glycans was reduced, but the level of N-glycans decorated with polylactosamine sequences were substantially elevated compared with the other types of trophoblasts. The level of triantennary and tetraantennary N-glycans was also elevated in EVT. The sialylated N-glycans derived from EVT were completely susceptible to an α2–3 specific neuraminidase (sialidase S). The possibility exists that the N-glycans associated with these different trophoblast subpopulations could act as functional groups. These potential relationships will be considered. PMID:26929217

  18. Evidence for Differential Glycosylation of Trophoblast Cell Types.

    Science.gov (United States)

    Chen, Qiushi; Pang, Poh-Choo; Cohen, Marie E; Longtine, Mark S; Schust, Danny J; Haslam, Stuart M; Blois, Sandra M; Dell, Anne; Clark, Gary F

    2016-06-01

    Human placental villi are surfaced by the syncytiotrophoblast (STB), with a layer of cytotrophoblasts (CTB) positioned just beneath the STB. STB in normal term pregnancies is exposed to maternal immune cells in the placental intervillous space. Extravillous cytotrophoblasts (EVT) invade the decidua and spiral arteries, where they act in conjunction with natural killer (NK) cells to convert the spiral arteries into flaccid conduits for maternal blood that support a 3-4 fold increase in the rate of maternal blood flow into the placental intervillous space. The functional roles of these distinct trophoblast subtypes during pregnancy suggested that they could be differentially glycosylated. Glycomic analysis of these trophoblasts has revealed the expression of elevated levels of biantennary N-glycans in STB and CTB, with the majority of them bearing a bisecting GlcNAc. N-glycans terminated with polylactosamine extensions were also detected at low levels. A subset of the N-glycans linked to these trophoblasts were sialylated, primarily with terminal NeuAcα2-3Gal sequences. EVT were decorated with the same N-glycans as STB and CTB, except in different proportions. The level of bisecting type N-glycans was reduced, but the level of N-glycans decorated with polylactosamine sequences were substantially elevated compared with the other types of trophoblasts. The level of triantennary and tetraantennary N-glycans was also elevated in EVT. The sialylated N-glycans derived from EVT were completely susceptible to an α2-3 specific neuraminidase (sialidase S). The possibility exists that the N-glycans associated with these different trophoblast subpopulations could act as functional groups. These potential relationships will be considered. © 2016 by The American Society for Biochemistry and Molecular Biology, Inc.

  19. Intrahepatic splenosis mimicking hepatic neoplasia

    Directory of Open Access Journals (Sweden)

    Gabriel Neves Saad Teles

    Full Text Available Introduction: Splenosis is defined as the heterotopic autoimplantation of splenic tissue following trauma to or surgery on the spleen. Clinical case: We present a case of an asymptomatic 73-year-old male in whom hypervascular lesions were detected during routine exams. The patient reported a history of carotid artery surgery and cholecystectomy; he had a laparotomy incision from childhood but was unaware of the reason for it. The patient exhibited slightly elevated carcinoembryonic antigen (CEA levels. Histopathology revealed intrahepatic heterotopic splenic parenchyma, with no evidence of neoplasia in either of the two lesions, the diameters of which were 1.5 cm and 3.6 cm. Patient received outpatient follow-up care for 24 months and experienced no complications. Discussion: Our clinical, laboratory, and imaging exams failed to reveal the etiology of the lesion. Because the masses were hypervascular lesions, a percutaneous liver biopsy was not feasible. Conclusion: Through this report, we emphasize the importance of considering intrahepatic splenosis as a remote possibility in patients with hepatic nodules who have a history of splenectomy. Keywords: Splenosis, Neoplasia, Liver, Splenectomy

  20. Elsevier Trophoblast Research Award lecture: Molecular mechanisms underlying estrogen functions in trophoblastic cells--focus on leptin expression.

    Science.gov (United States)

    Gambino, Y P; Maymó, J L; Pérez Pérez, A; Calvo, J C; Sánchez-Margalet, V; Varone, C L

    2012-02-01

    The steroid hormone 17β-estradiol is an estrogen that influences multiple aspects of placental function and fetal development in humans. During early pregnancy it plays a role in the regulation of blastocyst implantation, trophoblast differentiation and invasiveness, remodeling of uterine arteries, immunology and trophoblast production of hormones such as leptin. Estradiol exerts some effects through the action of classical estrogen receptors ERα and ERβ, which act as ligand-activated transcription factors and regulate gene expression. In addition, estradiol can elicit rapid responses from membrane-associated receptors, like activation of protein-kinase pathways. Thus, the cellular effects of estradiol will depend on the specific receptors expressed and the integration of their signaling events. Leptin, the 16,000MW protein product of the obese gene, was originally considered an adipocyte-derived signaling molecule for the central control of metabolism. However, pleiotropic effects of leptin have been identified in reproduction and pregnancy. The leptin gene is expressed in placenta, where leptin promotes proliferation and survival of trophoblastic cells. Expression of leptin in placenta is highly regulated by key pregnancy molecules as hCG and estradiol. The aim of this paper is to review the molecular mechanisms underlying estrogen functions in trophoblastic cells; focusing on mechanisms involved in estradiol regulation of placental leptin expression. Copyright © 2012 Elsevier Ltd. All rights reserved.

  1. miR-518b Enhances Human Trophoblast Cell Proliferation Through Targeting Rap1b and Activating Ras-MAPK Signal

    Directory of Open Access Journals (Sweden)

    Ming Liu

    2018-03-01

    Full Text Available Preeclampsia is a pregnancy-specific complication defined as newly onset gestational hypertension and proteinuria. Deficiency in placental development is considered as the predominant cause of preeclampsia. Our previous study found that the expression of miR-518b increased significantly in the preeclamptic placentas, indicating the potential participation of this small RNA in the occurrence of preeclampsia. In this study, data analysis using multiple databases predicted Rap1b as a candidate target of miR-518b. An evident decrease in Rap1b expression was observed in preeclamptic placentas when compared with the control placentas, which was negatively correlated with the level of miR-518b. Based on the data of in situ hybridization and immunohistochemistry showing that Rap1b exhibited similar localization with miR-518b in villous cytotrophoblast cells and column trophoblasts, we further explored their function in regulating trophoblast cell proliferation. In HTR8/SVneo cells, exogenous transfection of miR-518b reduced the expression of Rap1b, and dual-luciferase reporter assay validated Rap1b as the direct target of miR-518b. The small RNA could increase the BrdU incorporation and the ratio of cells at S phase, and enhance the phosphorylation of Raf-1 and ERK1/2. Such growth-promoting effect could be efficiently reversed by Rap1b overexpression. The data indicate that miR-518b can promote trophoblast cell proliferation via Rap1b–Ras–MAPK pathway, and the aberrant upregulation of miR-518b in preeclamptic placenta may contribute to the excessive trophoblast proliferation. The study provides new evidence to further understand the etiology of preeclampsia.

  2. Hepatitis C Virus Sensing by Human Trophoblasts Induces Innate Immune Responses and Recruitment of Maternal NK Cells: Potential Implications for Limiting Vertical Transmission.

    Science.gov (United States)

    Giugliano, Silvia; Petroff, Margaret G; Warren, Bryce D; Jasti, Susmita; Linscheid, Caitlin; Ward, Ashley; Kramer, Anita; Dobrinskikh, Evgenia; Sheiko, Melissa A; Gale, Michael; Golden-Mason, Lucy; Winn, Virginia D; Rosen, Hugo R

    2015-10-15

    Hepatitis C virus (HCV) is the world's most common blood-borne viral infection for which there is no vaccine. The rates of vertical transmission range between 3 and 6% with odds 90% higher in the presence of HIV coinfection. Prevention of vertical transmission is not possible because of lack of an approved therapy for use in pregnancy or an effective vaccine. Recently, HCV has been identified as an independent risk factor for preterm delivery, perinatal mortality, and other complications. In this study, we characterized the immune responses that contribute to the control of viral infection at the maternal-fetal interface (MFI) in the early gestational stages. In this study, we show that primary human trophoblast cells and an extravillous trophoblast cell line (HTR8), from first and second trimester of pregnancy, express receptors relevant for HCV binding/entry and are permissive for HCV uptake. We found that HCV-RNA sensing by human trophoblast cells induces robust upregulation of type I/III IFNs and secretion of multiple chemokines that elicit recruitment and activation of decidual NK cells. Furthermore, we observed that HCV-RNA transfection induces a proapoptotic response within HTR8 that could affect the morphology of the placenta. To our knowledge, for the first time, we demonstrate that HCV-RNA sensing by human trophoblast cells elicits a strong antiviral response that alters the recruitment and activation of innate immune cells at the MFI. This work provides a paradigm shift in our understanding of HCV-specific immunity at the MFI as well as novel insights into mechanisms that limit vertical transmission but may paradoxically lead to virus-related pregnancy complications. Copyright © 2015 by The American Association of Immunologists, Inc.

  3. Preeclampsia: novel insights from global RNA profiling of trophoblast subpopulations.

    Science.gov (United States)

    Gormley, Matthew; Ona, Katherine; Kapidzic, Mirhan; Garrido-Gomez, Tamara; Zdravkovic, Tamara; Fisher, Susan J

    2017-08-01

    The maternal signs of preeclampsia, which include the new onset of high blood pressure, can occur because of faulty placentation. We theorized that transcriptomic analyses of trophoblast subpopulations in situ would lend new insights into the role of these cells in preeclampsia pathogenesis. Our goal was to enrich syncytiotrophoblasts, invasive cytotrophoblasts, or endovascular cytotrophoblasts from the placentas of severe preeclampsia cases. Total RNA was subjected to global transcriptional profiling to identify RNAs that were misexpressed compared with controls. This was a cross-sectional analysis of placentas from women who had been diagnosed with severe preeclampsia. Gestational age-matched controls were placentas from women who had a preterm birth with no signs of infection. Laser microdissection enabled enrichment of syncytiotrophoblasts, invasive cytotrophoblasts, or endovascular cytotrophoblasts. After RNA isolation, a microarray approach was used for global transcriptional profiling. Immunolocalization identified changes in messenger RNA expression that carried over to the protein level. Differential expression of non-protein-coding RNAs was confirmed by in situ hybridization. A 2-way analysis of variance of non-coding RNA expression identified particular classes that distinguished trophoblasts in cases vs controls. Cajal body foci were visualized by coilin immunolocalization. Comparison of the trophoblast subtype data within each group (severe preeclampsia or noninfected preterm birth) identified many highly differentially expressed genes. They included molecules that are known to be expressed by each subpopulation, which is evidence that the method worked. Genes that were expressed differentially between the 2 groups, in a cell-type-specific manner, encoded a combination of molecules that previous studies associated with severe preeclampsia and those that were not known to be dysregulated in this pregnancy complication. Gene ontology analysis of the

  4. MTA3 regulates CGB5 and Snail genes in trophoblast

    Energy Technology Data Exchange (ETDEWEB)

    Chen, Ying [Department of Obstetrics, Gynecology and Reproductive Biology, Michigan State University, Grand Rapids, MI 49503 (United States); Miyazaki, Jun [Department of Obstetrics and Gynecology, Fujita Health University School of Medicine, Fujita Health University, Toyoake (Japan); Division of Molecular Genetics, Institute for Comprehensive Medical Science, Fujita Health University, Toyoake (Japan); Nishizawa, Haruki [Department of Obstetrics and Gynecology, Fujita Health University School of Medicine, Fujita Health University, Toyoake (Japan); Kurahashi, Hiroki [Division of Molecular Genetics, Institute for Comprehensive Medical Science, Fujita Health University, Toyoake (Japan); Leach, Richard, E-mail: Richard.Leach@hc.msu.edu [Department of Obstetrics, Gynecology and Reproductive Biology, Michigan State University, Grand Rapids, MI 49503 (United States); Department of Obstetrics, Gynecology and Women’s Health, Spectrum Health Medical Group, Grand Rapids, MI 49503 (United States); Wang, Kai, E-mail: Kai.Wang@hc.msu.edu [Department of Obstetrics, Gynecology and Reproductive Biology, Michigan State University, Grand Rapids, MI 49503 (United States)

    2013-04-19

    Highlights: •Impaired MTA3, raised CGB5 and Snail expression are associated with preeclampsia. •Knock-down of MTA3 causes up-regulation of CGB5 and Snail genes in BeWo cells. •MTA3 occupies CGB5 and Snail gene promoters in BeWo cells. -- Abstract: Secreted by the placental trophoblast, human chorionic gonadotropin (hCG) is an important hormone during pregnancy and is required for the maintenance of pregnancy. Previous studies have shown that dys-regulation of hCG expression is associated with preeclampsia. However, the exact relationship between altered hCG levels and development of preeclampsia is unknown. Metastasis associated protein 3 (MTA3), a chromatin remodeling protein, is abundantly expressed in the placental trophoblasts, but its function is unknown. In breast cancer, MTA3 has been shown to repress the expression of Snail and cell migration. However, whether MTA3 acts similarly in the trophoblast has not been investigated. In the present study, we examined the role of MTA3 in regulating the hCG β-subunit gene (gene name: CGB5) and Snail expression in the trophoblast cell line, BeWo, as well as its relevance to the high hCG expression levels seen in preeclampsia. First, we investigated MTA3 expression in preeclamptic placenta as compared to normal control placenta via gene expression microarray and qRT-PCR and found that MTA3 was significantly down-regulated, whereas both CGB5 and Snail were up-regulated in preeclamptic placenta. Secondly, we knocked down MTA3 gene in trophoblast cell line BeWo and found Snail and hCG were both up-regulated, suggesting that MTA3 represses Snail and hCG gene expression in trophoblasts. Next, we cloned the CGB5 and Snail promoters into the pGL3-basic vector individually and found that silencing of MTA3 by siRNA resulted in an increase of both CGB5 and Snail promoter activities. To confirm that this MTA3 inhibition is a direct effect, we performed a chromatin immune-precipitation (ChIP) assay and found that MTA3

  5. MTA3 regulates CGB5 and Snail genes in trophoblast

    International Nuclear Information System (INIS)

    Chen, Ying; Miyazaki, Jun; Nishizawa, Haruki; Kurahashi, Hiroki; Leach, Richard; Wang, Kai

    2013-01-01

    Highlights: •Impaired MTA3, raised CGB5 and Snail expression are associated with preeclampsia. •Knock-down of MTA3 causes up-regulation of CGB5 and Snail genes in BeWo cells. •MTA3 occupies CGB5 and Snail gene promoters in BeWo cells. -- Abstract: Secreted by the placental trophoblast, human chorionic gonadotropin (hCG) is an important hormone during pregnancy and is required for the maintenance of pregnancy. Previous studies have shown that dys-regulation of hCG expression is associated with preeclampsia. However, the exact relationship between altered hCG levels and development of preeclampsia is unknown. Metastasis associated protein 3 (MTA3), a chromatin remodeling protein, is abundantly expressed in the placental trophoblasts, but its function is unknown. In breast cancer, MTA3 has been shown to repress the expression of Snail and cell migration. However, whether MTA3 acts similarly in the trophoblast has not been investigated. In the present study, we examined the role of MTA3 in regulating the hCG β-subunit gene (gene name: CGB5) and Snail expression in the trophoblast cell line, BeWo, as well as its relevance to the high hCG expression levels seen in preeclampsia. First, we investigated MTA3 expression in preeclamptic placenta as compared to normal control placenta via gene expression microarray and qRT-PCR and found that MTA3 was significantly down-regulated, whereas both CGB5 and Snail were up-regulated in preeclamptic placenta. Secondly, we knocked down MTA3 gene in trophoblast cell line BeWo and found Snail and hCG were both up-regulated, suggesting that MTA3 represses Snail and hCG gene expression in trophoblasts. Next, we cloned the CGB5 and Snail promoters into the pGL3-basic vector individually and found that silencing of MTA3 by siRNA resulted in an increase of both CGB5 and Snail promoter activities. To confirm that this MTA3 inhibition is a direct effect, we performed a chromatin immune-precipitation (ChIP) assay and found that MTA3

  6. Gestational trophoblastic disease in Abuth Zaria, Nigeria: A 5‑year ...

    African Journals Online (AJOL)

    (teenagers) and older than 40 years of age (40–50 years).[1,3‑5] ... economic status and in women whose diets are deficient in protein, folic ... The absence of fetal heart tones, a uterus too large for the ..... proper management of this condition.

  7. A case report of treating a high-risk gestational trophoblastic disease (GTD

    Directory of Open Access Journals (Sweden)

    Zhi Hao Liew

    2017-12-01

    Full Text Available Background: GTD developing after a normal pregnancy is reported in 25% of patients and it is usually choriocarcinoma. It occurs in approximately 5 per 100,000 pregnancies in Southeast Asia. Case: A 34 year-old Malay lady, gravida 4 para 4+0 presented with vaginal bleeding in two weeks after the delivery of her fourth child who was born as full term through LSCS. She admitted to hospital and underwent Suction and curettage. The histopathology came back as choriocarcinoma. On post-op day 7, she developed massive hemoperitoneum due to uterine perforation caused by tumour rupture. Therefore, total abdominal hysterectomy was performed. Post-surgery serum beta hCG was 209,320 IU/L. Thyroid function test was normal. Histopathology examination revealed choriocarcinoma at the fundus with haemorrhagic necrotic areas, infiltrating myometrial wall and right fallopian tube stump with serosal breach. CT imaging showed normal brain and multiple bilateral lung nodules in upper and lower lobes. She was given first cycle of EMA-CO (Etoposide, Methotrexate, Actinomycin D, Vincristine, Cyclophosphamid in view of high-risk choriocarcinoma with lungs metastasis, stage III with WHO prognostic scoring 11. Her pre-chemotherapy beta hCG was 263,753 IU/L which gradually went down and became less than 0.1 after cycle-5. CT scan was also normal. After that, another two more cycles of chemotherapy were proceeded. Therefore, she has completed seven cycles of chemotherapy in March 2016. She has been monitored under oncology follow-up for one year. Monthly βhCG was always normal until now without signs and symptoms of recurrence. Conclusion: Generally, high-risk GTDs are resistant to single agent chemotherapy and multiple chemotherapy regimens are necessary. Although this patient is a case of choriocarcinoma having high risk features, such as antecedent full-term pregnancy and pre-treatment beta-hCG of 263,753 IU/L (more than 100,000, she gained complete remission after seven cycles with EMA-CO. Once the patient has achieved complete remission for one year with normal serum beta-hCG, the probability of a late recurrence is less than 1%. Therefore, risk stratification with WHO criteria and appropriate choice of chemotherapy are very important for long-term outcomes.   

  8. Gestational trophoblastic diseases - clinical guidelines for diagnosis, treatment, follow-up, and counselling

    DEFF Research Database (Denmark)

    Niemann, Isa; Vejerslev, Lars O; Frøding, Ligita

    2015-01-01

    months once or twice a month, thereafter every second to third month. Patients with PSTT and ETT are monitored with measurement of hCG throughout their lifetimes (C). In genetically verified twin pregnancy with hydatidiform mole and a living foetus, the pregnancy can continue if serum hCG is monitored...

  9. Decidual Stromal Cell Response to Paracrine Signals from the Trophoblast: Amplification of Immune and Angiogenic Modulators

    DEFF Research Database (Denmark)

    Hess, AP; Hamilton, AE; Talbi, S

    2007-01-01

    During the invasive phase of implantation, trophoblasts and maternal decidual stromal cells secrete products that regulate trophoblast differentiation and migration into the maternal endometrium. Paracrine interactions between the extravillous trophoblast and the maternal decidua are important...... a functional genomics approach to investigate these paracrine interactions. Human endometrial stromal cells were decidualized with progesterone and were further treated with conditioned media (CM) from human trophoblasts (TCM) or, as a control, with conditioned media (CCM) from non-decidualized stromal cells...... regulated groups. The data demonstrate a significant induction of pro-inflammatory cytokines and chemokines, as well as angiogenic/static factors in decidualized endometrial stromal cells in response to trophoblast-secreted products. The data suggest that the trophoblast acts to alter the local immune...

  10. Roles of CDX2 and EOMES in human induced trophoblast progenitor cells

    Energy Technology Data Exchange (ETDEWEB)

    Chen, Ying, E-mail: ying.chen@hc.msu.edu [Department of Obstetrics, Gynecology and Reproductive Biology, College of Human Medicine, Michigan State University, Grand Rapids, MI 49503 (United States); Wang, Kai [Department of Obstetrics, Gynecology and Reproductive Biology, College of Human Medicine, Michigan State University, Grand Rapids, MI 49503 (United States); Gong, Yun Guo; Khoo, Sok Kean [Genomic Microarray Core Facility, Van Andel Research Institute, Grand Rapids, MI 49503 (United States); Leach, Richard, E-mail: Richard.Leach@hc.msu.edu [Department of Obstetrics, Gynecology and Reproductive Biology, College of Human Medicine, Michigan State University, Grand Rapids, MI 49503 (United States); Department of Obstetrics, Gynecology and Women’s Health, Spectrum Health Medical Group, Grand Rapids, MI 49503 (United States)

    2013-02-08

    Highlights: ► CDX2 and EOMES play critical roles in human induced trophoblast progenitors (iTP). ► iTP cells directly transformed from fibroblasts. ► Differentiation of iTP cells into extravillous trophoblasts and syncytiotrophoblasts. -- Abstract: Abnormal trophoblast lineage proliferation and differentiation in early pregnancy have been associated with the pathogenesis of placenta diseases of pregnancy. However, there is still a gap in understanding the molecular mechanisms of early placental development due to the limited primary trophoblast cultures and fidelity of immortalized trophoblast lines. Trophoblasts stem (TS) cells, an in vitro model of trophectoderm that can differentiate into syncytiotrophoblasts and extravillous trophoblasts, can be an attractive tool for early pregnancy research. TS cells are well established in mouse but not in humans due to insufficient knowledge of which trophoblast lineage-specific transcription factors are involved in human trophectoderm (TE) proliferation and differentiation. Here, we applied induced pluripotent stem cell technique to investigate the human trophoblast lineage-specific transcription factors. We established human induced trophoblast progenitor (iTP) cells by direct reprogramming the fibroblasts with a pool of mouse trophoblast lineage-specific transcription factors consisting of CDX2, EOMES, and ELF5. The human iTP cells exhibit epithelial morphology and can be maintained in vitro for more than 2 months. Gene expression profile of these cells was tightly clustered with human trophectoderm but not with human neuron progenitor cells, mesenchymal stem cells, or endoderm cells. These cells are capable of differentiating into cells with an invasive capacity, suggesting extravillous trophoblasts. They also form multi-nucleated cells which secrete human chorionic gonadotropin and estradiol, consistent with a syncytiotrophoblast phenotype. Our results provide the evidence that transcription factors CDX2 and

  11. Gestational Diabetes and Pregnancy

    Science.gov (United States)

    ... Pregnant Avoiding Pregnancy Zika and Pregnancy Articles Gestational Diabetes and Pregnancy Language: English (US) Español (Spanish) Recommend ... diabetes must also take insulin. Problems of Gestational Diabetes in Pregnancy Blood sugar that is not well ...

  12. TROPHOBLASTIC β1 – GLYCOPROTEIN SYNTHESIS IN SEROPOSITIVE PREGNANT WOMEN

    Directory of Open Access Journals (Sweden)

    R. N. Bogdanovich

    2005-01-01

    Full Text Available Abstract. The level of trophoblastic β1 – glycoprotein (SP–1 was determined in the blood sera of 200 healthy pregnant women and 184 women with threatened abortions in term till 20 weeks of pregnancy. In group of women experiencing recurrent abortions in 38 % cases antibodies to chorionic gonadotropin, in 39,5 % cases antibodies to phospholipids, in 25,5 % – antibodies to tireoglobulin were revealed in significant amounts. In 20,65 % lupus anticoagulant was found. The majority of women in this group had changes in homeostasis. The presence of autoantibodies during pregnancy is the unfavourable factor in the development of placental insufficiency. This is proved by the decreased secretion of trophoblastic β1 – glycoprotein – a marker of the fetal part of placenta. (Med. Immunol., 2005, vol.7, № 1, pp. 85588

  13. Hydatidiform mole in Aminu Kano teaching hospital, northwestern ...

    African Journals Online (AJOL)

    Background: Hydatidiform mole is a benign tumour of the trophoblast tissue and a relatively common gynaecological emergency. It could resolve spontaneously following evacuation, however 9-20% of patients with complete hydatidiform mole go on to have gestational trophoblast neoplasia. It is potentially curable once the ...

  14. MSX2 Induces Trophoblast Invasion in Human Placenta.

    Directory of Open Access Journals (Sweden)

    Hao Liang

    Full Text Available Normal implantation depends on appropriate trophoblast growth and invasion. Inadequate trophoblast invasion results in pregnancy-related disorders, such as early miscarriage and pre-eclampsia, which are dangerous to both the mother and fetus. Msh Homeobox 2 (MSX2, a member of the MSX family of homeobox proteins, plays a significant role in the proliferation and differentiation of various cells and tissues, including ectodermal organs, teeth, and chondrocytes. Recently, MSX2 was found to play important roles in the invasion of cancer cells into adjacent tissues via the epithelial-mesenchymal transition (EMT. However, the role of MSX2 in trophoblastic invasion during placental development has yet to be explored. In the present study, we detected MSX2 expression in cytotrophoblast, syncytiotrophoblast, and extravillous cytotrophoblast cells of first or third trimester human placentas via immunohistochemistry analysis. Furthermore, we found that the in vitro invasive ability of HTR8/SVneo cells was enhanced by exogenous overexpression of MSX2, and that this effect was accompanied by increased protein expression of matrix metalloproteinase-2 (MMP-2, vimentin, and β-catenin. Conversely, treatment of HTR8/SVneo cells with MSX2-specific siRNAs resulted in decreased protein expression of MMP-2, vimentin, and β-catenin, and reduced invasion levels in a Matrigel invasion test. Notably, however, treatment with the MSX2 overexpression plasmid and the MSX2 siRNAs had no effect on the mRNA expression levels of β-catenin. Meanwhile, overexpression of MSX2 and treatment with the MSX2-specific siRNA resulted in decreased and increased E-cadherin expression, respectively, in JEG-3 cells. Lastly, the protein expression levels of MSX2 were significantly lower in human pre-eclamptic placental villi than in the matched control placentas. Collectively, our results suggest that MSX2 may induce human trophoblast cell invasion, and dysregulation of MSX2 expression may

  15. Live cell imaging of in vitro human trophoblast syncytialization.

    Science.gov (United States)

    Wang, Rui; Dang, Yan-Li; Zheng, Ru; Li, Yue; Li, Weiwei; Lu, Xiaoyin; Wang, Li-Juan; Zhu, Cheng; Lin, Hai-Yan; Wang, Hongmei

    2014-06-01

    Human trophoblast syncytialization, a process of cell-cell fusion, is one of the most important yet least understood events during placental development. Investigating the fusion process in a placenta in vivo is very challenging given the complexity of this process. Application of primary cultured cytotrophoblast cells isolated from term placentas and BeWo cells derived from human choriocarcinoma formulates a biphasic strategy to achieve the mechanism of trophoblast cell fusion, as the former can spontaneously fuse to form the multinucleated syncytium and the latter is capable of fusing under the treatment of forskolin (FSK). Live-cell imaging is a powerful tool that is widely used to investigate many physiological or pathological processes in various animal models or humans; however, to our knowledge, the mechanism of trophoblast cell fusion has not been reported using a live- cell imaging manner. In this study, a live-cell imaging system was used to delineate the fusion process of primary term cytotrophoblast cells and BeWo cells. By using live staining with Hoechst 33342 or cytoplasmic dyes or by stably transfecting enhanced green fluorescent protein (EGFP) and DsRed2-Nuc reporter plasmids, we observed finger-like protrusions on the cell membranes of fusion partners before fusion and the exchange of cytoplasmic contents during fusion. In summary, this study provides the first video recording of the process of trophoblast syncytialization. Furthermore, the various live-cell imaging systems used in this study will help to yield molecular insights into the syncytialization process during placental development. © 2014 by the Society for the Study of Reproduction, Inc.

  16. Inflammatory Bowel Disease and Cervical Neoplasia

    DEFF Research Database (Denmark)

    Rungoe, Christine; Simonsen, Jacob; Riis, Lene

    2015-01-01

    BACKGROUND & AIMS: We examined the risk of cervical neoplasia (dysplasia or cancer) in women with ulcerative colitis (UC) or Crohn's disease (CD). We also calculated the reverse, the risk for diagnosis with cervical neoplasia before development of inflammatory bowel disease (IBD). METHODS: We...... established a national cohort of women diagnosed with UC (n = 18,691) or CD (n = 8717) between 1979 and 2011 and a control cohort of individually matched women from the general population (controls, n = 1,508,334). Incidence rate ratios (IRRs) of screening activity and diagnosis of cervical neoplasia in women...... with IBD were assessed by Cox proportional hazards regression analysis. Odds ratios (ORs) of cervical neoplasia before diagnosis of IBD were calculated by using conditional logistic regression. RESULTS: Women with CD underwent cervical cancer screening as often as women in the general population (IRR, 0...

  17. Current trends in follow-up of trophoblastic function in ruminant species.

    Science.gov (United States)

    Sousa, N M; Beckers, J F; Gajewski, Z

    2008-12-01

    During the pregnancy of ruminants, different hormones and proteins are secreted by placenta or corpus luteum allowing the follow up of gestation. Among them, progesterone (P4) and pregnancy-associated glycoproteins (PAG) were proposed as laboratory tools to establish or to confirm pregnancy diagnosis. In last years, PAG assay also provided useful information for researchers working in programs focused on the follow up of trophoblastic function. Concentrations of PAG appeared as altered after the use of embryo biotechnology (in vitro fertilization, cloning by nuclear transfer, inter-specific pregnancies), according to nutritional status of pregnant females (overnourished or undernourished), or consecutive to infectious diseases leading to pathologies affecting the pregnancy in cows (Actynomyces pyogenes and Neospora caninum) and goats (Toxoplasma gondii, Listeria monocytogenes and Trypanosoma congolense). As well, in numerous studies, the association of repeated ultrasound examinations with P4 and PAG determinations allowed a better understanding of mechanisms related to embryonic and fetal mortalities: failure after artificial insemination or embryo transfer techniques, large offspring syndrome after in vitro fecundation and cloning.

  18. COMPUTED TOMOGRAPHIC EVALUATION OF CANINE PHARYNGEAL NEOPLASIA

    OpenAIRE

    Carozzi, Gregorio

    2016-01-01

    Computed tomography (CT) is commonly used to investigate head tumours in dogs, and is a fundamental part of the diagnostic work-up, for diagnosis, staging and planning therapy in neoplastic disease. Nasal diseases, either neoplastic or non-neoplastic diseases, oral neoplasia, brain disease, thyroid or carotid body neoplasia have been extensively studied. However little information are available for lesions of the pharyngeal area. In this thesis, cases of dogs affected by pharyngeal neoplas...

  19. Ocular Surface Squamous Neoplasia in Xeroderma Pigmentosum

    Directory of Open Access Journals (Sweden)

    Rajesh R Nayak

    2013-11-01

    Full Text Available Xeroderma pigmentosum (XP is a rare genetic disorder associated with multiple oculocutaneous and neurological manifestations. It occurs due to deficiency of the enzymes responsible for repairing ultraviolet radiation-induced DNA damage. Persistence of un-repaired DNA results in somatic mutations, leading to neoplasia of the skin and ocular surface. As this condition is rare, only isolated case reports of XP with ocular surface squamous neoplasia (OSSN are found in literature.

  20. The Elsevier Trophoblast Research Award Lecture: Importance of metzincin proteases in trophoblast biology and placental development: a focus on ADAM12.

    Science.gov (United States)

    Aghababaei, Mahroo; Beristain, Alexander G

    2015-04-01

    Placental development is a highly regulated process requiring signals from both fetal and maternal uterine compartments. Within this complex system, trophoblasts, placental cells of epithelial lineage, form the maternal-fetal interface controlling nutrient, gas and waste exchange. The commitment of progenitor villous cytotrophoblasts to differentiate into diverse trophoblast subsets is a fundamental process in placental development. Differentiation of trophoblasts into invasive stromal- and vascular-remodeling subtypes is essential for uterine arterial remodeling and placental function. Inadequate placentation, characterized by defects in trophoblast differentiation, may underlie the earliest cellular events driving pregnancy disorders such as preeclampsia and fetal growth restriction. Molecularly, invasive trophoblasts acquire characteristics defined by profound alterations in cell-cell and cell-matrix adhesion, cytoskeletal reorganization and production of proteolytic factors. To date, most studies have investigated the importance of the matrix metalloproteinases (MMPs) and their ability to efficiently remodel components of the extracellular matrix (ECM). However, it is now becoming clear that besides MMPs, other related proteases regulate trophoblast invasion via mechanisms other than ECM turnover. In this review, we will summarize the current knowledge on the regulation of trophoblast invasion by members of the metzincin family of metalloproteinases. Specifically, we will discuss the emerging roles that A Disintegrin and Metalloproteinases (ADAMs) play in placental development, with a particular focus on the ADAM subtype, ADAM12. Copyright © 2015 Elsevier Ltd. All rights reserved.

  1. Fluorescence detection of esophageal neoplasia

    Science.gov (United States)

    Borisova, E.; Vladimirov, B.; Avramov, L.

    2008-06-01

    White-light endoscopy is well-established and wide used modality. However, despite the many technological advances that have been occurred, conventional endoscopy is suboptimal and usually detects advanced stage lesions. The limitations of standard endoscopy initiate development of spectroscopic techniques, additional to standard endoscopic equipment. One of the most sensitive approaches is fluorescence spectroscopy of gastrointestinal mucosa for neoplasia detection. In the recent study delta-aminolevulinic acid/Protoporphyrin IX (5-ALA/PpIX) is used as fluorescent marker for dysplasia and tumor detection in esophagus. The 5-ALA is administered per os six hours before measurements at dose 20 mg/kg weight. Excitation source has max of emission at 405 nm and light is delivered by the standard light guide of the endoscopic equipment. Through endoscopic instrumental channel a fiber is applied to return information about fluorescence to microspectrometer. Spectral features observed during endoscopic investigations could be distinct as the next regions: 450-630 nm region, where tissue autofluorescence is observed; 630-710 nm region, where fluorescence of PpIX is clearly pronounced; 530-580 nm region, where minima in the autofluorescence signal are observed, related to reabsorption of blood. The lack of fluorescence peaks in the red spectral area for normal mucosa is an indication for selective accumulation of 5-ALA/PpIX only in abnormal sites Very good correlation between fluorescence signals and histology examination of the lesions investigated is achieved.

  2. [Cells of immune system of mother and trophoblast cells: constructive cooperation for the sake of achievement of the joint purpose].

    Science.gov (United States)

    Aĭlamazian, E K; Stepanova, O I; Sel'kov, S A; Sokolov, D I

    2013-01-01

    In the present review modern data about change of morfo-functional properties of a trophoblast during pregnancy, and also about influence of the cytokines produced by cells of a microenvironment, including leucocytes of mother, on a functional state of trophoblast is cited. Features of interaction between trophoblast and immune cells of mother are described within physiological pregnancy and within pregnancy complicated by preeclampsia.

  3. GATA-2 and GATA-3 regulate trophoblast-specific gene expression in vivo.

    NARCIS (Netherlands)

    G.T. Ma (Grace); M.E. Roth (Matthew); J.C. Groskopf (John); F.G. Grosveld (Frank); J.D. Engel (Douglas); D.I.H. Linzer (Daniel); F.Y. Tsai (Fong-Ying); S.H. Orkin (Stuart)

    1997-01-01

    textabstractWe previously demonstrated that the zinc finger transcription factors GATA-2 and GATA-3 are expressed in trophoblast giant cells and that they regulate transcription from the mouse placental lactogen I gene promoter in a transfected trophoblast cell line. We present evidence here that

  4. Expression of extracellular matrix metalloproteinase inducer (EMMPRIN) and its expected roles in the bovine endometrium during gestation.

    Science.gov (United States)

    Mishra, B; Kizaki, K; Koshi, K; Ushizawa, K; Takahashi, T; Hosoe, M; Sato, T; Ito, A; Hashizume, K

    2012-02-01

    Extracellular matrix metalloproteinase inducer (EMMPRIN) and its induced matrix metalloproteinases (MMPs) play a crucial role in tissue remodeling during the peri-implantation period. However, the role of EMMPRIN in the bovine placenta is still unclear. We have postulated that EMMPRIN might play a regulatory role in trophoblastic cell functions during gestation by itself or through the regulation of MMP expression. In this study, EMMPRIN mRNA was detected in the bovine placentome and interplacentome throughout gestation, and its expression was significantly higher in the cotyledon during late gestation. In situ hybridization showed that EMMPRIN mRNA was expressed in the caruncular epithelium and the cotyledonary epithelium, including binucleate cells. Western blot analysis detected a band representing a protein of approximately 65 kDa in the caruncular and cotyledonary tissues, and the intensity of its expression was increased in both of these tissues during late gestation. The expression levels of MMP-2 and MMP-14 in the bovine placenta were higher during late gestation, as was observed for EMMPRIN. Therefore, EMMPRIN might regulate trophoblastic cell functions, especially those of binucleate cells, through MMP expression in the bovine placenta. Copyright © 2012 Elsevier Inc. All rights reserved.

  5. Unsaturated fatty acids protect trophoblast cells from saturated fatty acid-induced autophagy defects.

    Science.gov (United States)

    Hong, Ye-Ji; Ahn, Hyo-Ju; Shin, Jongdae; Lee, Joon H; Kim, Jin-Hoi; Park, Hwan-Woo; Lee, Sung Ki

    2018-02-01

    Dysregulated serum fatty acids are associated with a lipotoxic placental environment, which contributes to increased pregnancy complications via altered trophoblast invasion. However, the role of saturated and unsaturated fatty acids in trophoblastic autophagy has yet to be explored. Here, we demonstrated that prolonged exposure of saturated fatty acids interferes with the invasiveness of human extravillous trophoblasts. Saturated fatty acids (but not unsaturated fatty acids) inhibited the fusion of autophagosomes and lysosomes, resulting in the formation of intracellular protein aggregates. Furthermore, when the trophoblast cells were exposed to saturated fatty acids, unsaturated fatty acids counteracted the effects of saturated fatty acids by increasing degradation of autophagic vacuoles. Saturated fatty acids reduced the levels of the matrix metalloproteinases (MMP)-2 and MMP-9, while unsaturated fatty acids maintained their levels. In conclusion, saturated fatty acids induced decreased trophoblast invasion, of which autophagy dysfunction plays a major role. Copyright © 2017 Elsevier B.V. All rights reserved.

  6. Gestational Tubal Choriocarcinoma Presenting as a Pregnancy of Unknown Location following Ovarian Induction

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    Lawrence Hsu Lin

    2018-01-01

    Full Text Available The management of pregnancy of unknown location (PUL can be a challenging situation, since it can present as several different conditions. Here we describe a rare case of gestational choriocarcinoma arising in the fallopian tube after ovarian induction in an infertile patient. The patient received clomiphene for ovarian induction and had rising levels of human chorionic gonadotropin (hCG over nine months without sign of pregnancy. After referral to our center, the patient was diagnosed with a paraovarian tumor, which revealed a gestational choriocarcinoma arising in the fallopian tube; the final diagnosis was supported by pathological and cytogenomic analysis. Malignancies, such as gestational trophoblastic disease, should be in the differential diagnosis of PUL; the early recognition of these conditions is key for the proper treatment and favorable outcome.

  7. The Natural History of Neoplasia

    Science.gov (United States)

    Pitot, Henry C.

    1977-01-01

    The stages of initiation and promotion in the natural history of epidermal carcinogenesis have been known for many years. Recently, experimental systems other than skin have been shown to exhibit similar, if not completely analogous, stages in the natural history of neoplasia. In particular, the demonstration by Peraino and his associates that phenobarbital may enhance the production of hepatomas by a relatively subcarcinogenic dose of acetylaminofluorene was one of the first demonstrations of stages occurring in an extraepidermal neoplasm. Studies reported in this paper have demonstrated that administration of phenobarbital (0.05% in the diet) for 6 months following a single dose of diethylnitrosamine (5 to 10 mg/kg) given within 24 hours after partial hepatectomy resulted in a marked increase in the number of enzyme-altered foci in the liver as well as in the production of hepatocellular carcinomas. This was compared to animals receiving only a single dose of diethylnitrosamine following partial hepatectomy with no further treatment, in which only a relatively small number of foci were evident in the absence of phenobarbital feeding. Using three different enzyme markers, a distinct degree of phenotypic heterogeneity of the enzyme-altered foci in liver was demonstrated. These studies have shown that liver carcinogensis can be readily divided into two stages: a) initiation by a single dose of diethylnitrosamine following partial hepatectomy and b) promotion by the continuous feeding of phenobarbital. Furthermore, the immediate progeny of the initiated cells, the enzyme-altered focus, may be recognized by suitable microscopic means prior to the formation of gross lesions as required in the skin system. These initiated cell populations exhibit a degree of biochemical heterogeneity which reflects that seen in fully developed hepatic neoplasms, suggesting that promotion and progression in this system does not significantly alter the basic biochemical characteristics of

  8. Fractal analysis of cervical intraepithelial neoplasia.

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    Markus Fabrizii

    Full Text Available INTRODUCTION: Cervical intraepithelial neoplasias (CIN represent precursor lesions of cervical cancer. These neoplastic lesions are traditionally subdivided into three categories CIN 1, CIN 2, and CIN 3, using microscopical criteria. The relation between grades of cervical intraepithelial neoplasia (CIN and its fractal dimension was investigated to establish a basis for an objective diagnosis using the method proposed. METHODS: Classical evaluation of the tissue samples was performed by an experienced gynecologic pathologist. Tissue samples were scanned and saved as digital images using Aperio scanner and software. After image segmentation the box counting method as well as multifractal methods were applied to determine the relation between fractal dimension and grades of CIN. A total of 46 images were used to compare the pathologist's neoplasia grades with the predicted groups obtained by fractal methods. RESULTS: Significant or highly significant differences between all grades of CIN could be found. The confusion matrix, comparing between pathologist's grading and predicted group by fractal methods showed a match of 87.1%. Multifractal spectra were able to differentiate between normal epithelium and low grade as well as high grade neoplasia. CONCLUSION: Fractal dimension can be considered to be an objective parameter to grade cervical intraepithelial neoplasia.

  9. Differential Receptor for Advanced Glycation End Products Expression in Preeclamptic, Intrauterine Growth Restricted, and Gestational Diabetic Placentas.

    Science.gov (United States)

    Alexander, Kristen L; Mejia, Camilo A; Jordan, Clinton; Nelson, Michael B; Howell, Brian M; Jones, Cameron M; Reynolds, Paul R; Arroyo, Juan A

    2016-02-01

    Receptor for advanced glycation end products (RAGE) is a receptor implicated in the modulation of inflammation. Inflammation has been associated with pregnancy pathologies including preeclampsia (PE), intrauterine growth restriction (IUGR), and gestational diabetes mellitus (GDM). Our objective was to examine placental RAGE expression in PE, IUGR, and GDM complications. Human placental tissues were obtained for RAGE determination using Q-PCR, immunohistochemistry, and Western blot. Invasive trophoblast cells were cultured and treated with AGES for RAGE activation studies. Compared to control placenta, we observed: (i) decreased RAGE gene expression during GDM, (ii) increased RAGE protein in the PE placenta, and (iii) decreased RAGE protein in the IUGR placenta. In trophoblast cells exposed AGEs, we observed: (i) decreased trophoblast invasion, (ii) increased c-Jun N-terminal kinases (JNK) and Extracellular signal-regulated kinases (ERK), and (iii) increased TNF-α and IL-1β secretion. We conclude that placental RAGE is activated during PE and that RAGE-mediated inflammation in the trophoblast involves increased pro-inflammatory cytokine secretion. © 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  10. Immunomodulator expression in trophoblasts from the feline immunodeficiency virus (FIV-infected cat

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    Donaldson Janet R

    2011-07-01

    Full Text Available Abstract Background FIV infection frequently compromises pregnancy under experimental conditions and is accompanied by aberrant expression of some placental cytokines. Trophoblasts produce numerous immunomodulators that play a role in placental development and pregnancy maintenance. We hypothesized that FIV infection may cause dysregulation of trophoblast immunomodulator expression, and aberrant expression of these molecules may potentiate inflammation and compromise pregnancy. The purpose of this project was to evaluate the expression of representative pro-(TNF-α, IFN-γ, IL-1β, IL-2, IL-6, IL-12p35, IL-12p40, IL-18, and GM-CSF and anti-inflammatory cytokines (IL-4, IL-5, and IL-10; CD134, a secondary co-stimulatory molecule expressed on activated T cells (FIV primary receptor; the chemokine receptor CXCR4 (FIV co-receptor; SDF-1α, the chemokine ligand to CXCR4; and FIV gag in trophoblasts from early-and late-term pregnancy. Methods We used an anti-cytokeratin antibody in immunohistochemistry to identify trophoblasts selectively, collected these cells using laser capture microdissection, and extracted total RNA from the captured cell populations. Real time, reverse transcription-PCR was used to quantify gene expression. Results We detected IL-4, IL-5, IL-6, IL-1β, IL-12p35, IL-12p40, and CXCR4 in trophoblasts from early-and late-term pregnancy. Expression of cytokines increased from early to late pregnancy in normal tissues. A clear, pro-inflammatory microenvironment was not evident in trophoblasts from FIV-infected queens at either stage of pregnancy. Reproductive failure was accompanied by down-regulation of both pro-and anti-inflammatory cytokines. CD134 was not detected in trophoblasts, and FIV gag was detected in only one of ten trophoblast specimens collected from FIV-infected queens. Conclusion Feline trophoblasts express an array of pro-and anti-inflammatory immunomodulators whose expression increases from early to late pregnancy in

  11. Neurocutaneous spectrum of multiple endocrine neoplasia-1

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    Shireen Furtado

    2012-01-01

    Full Text Available Multiple endocrine neoplasia type I or Wermer syndrome is characterized by primary hyperparathyroidism, enteropancreatic endocrine tumor, and a pituitary pathology. A 35-year-old male presented with visual field defects, hyperprolactinemia, and hypogonadism. He also had multiple infraumbilical skin-colored nodules. A syndromal association of Wermer syndrome was derived using the dermal, pituitary, parathyroid, and gastrointestinal hormonal manifestations of the tumor. The radiological and histological findings of lesion which underwent biopsy are discussed. The presence of collagenomas, lipomas, and hypopigmented macules in a patient with neuroendocrine symptoms should raise the suspicion of an underlying multiple endocrine neoplasia.

  12. Circulating free soluble fms-like tyrosine kinase-1 during late first trimester in relation with placental volume as a surrogate for trophoblastic production: a physiology study in low-risk cohort.

    Science.gov (United States)

    Manthati, Sudtawin; Pratumvinit, Busadee; Hanyongyuth, Ratchaneekorn; Udompunthurak, Suthipol; Phaophan, Amprapha; Wataganara, Tuangsit

    2017-08-01

    Data on first-trimester circulating soluble fms-like tyrosine kinase-1 (sFlt-1) and ischemic placental disease is limited and conflicting. This study aimed to study its physiology in relation to trophoblastic mass as the source of production. Low-risk (representing normal placentation) women from 11 0/7 to 13 6/7 weeks' gestation were prospectively enrolled. Selective measurement of serum free sFlt-1 using a new automated assay from 100 eligible subjects was analyzed with gestational age, maternal weight, fetal crown-rump length (CRL), and mean uterine artery Doppler pulsatility index (PI). Placental volume (surrogate for trophoblastic mass) was estimated using 3-dimensional ultrasound and was assessed for its association with serum free sFlt-1. There was no significant association between serum free sFlt-1 and placental volume in either arithmetic (r = 0.053, p = 0.600), logarithmic (r = 0.005, p = 0.963), or quartile (p = 0.703) scale. There was a significant negative correlation between free sFlt-1 level and maternal weight (r=-0.213, p = 0.033). No significant correlation was found between free sFlt-1 level and gestational age (r = 0.007, p = 0.947), CRL (r = 0.027, p = 0.788), and uterine artery Doppler mean PI (r = 0.020, p = 0.828). Lack of correlation between circulating free sFlt-1 level and placental volume suggests that trophoblasts are not its major source during first trimester with presumably physiologic placentation.

  13. Immunochemical identification of human trophoblast membrane antigens using monoclonal antibodies

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    Brown, P J; Molloy, C M; Johnson, P M [Liverpool Univ. (UK). Dept. of Immunology

    1983-11-01

    Human trophoblast membrane antigens recognised by monoclonal antibodies (H310, H315, H316 and H317) have been identified using combinations of radioimmunoprecipitation, SDS-PAGE, electroblotting, chromatographic and ELISA-type techniques. H317 is known to identify heat-stable placental-type alkaline phosphatase and accordingly was shown to react with a protein of subunit Msub(r) of 68000. H310 and H316 both recognise an antigen with a subunit Msub(r) of 34000 under reducing conditions. In non-reducing conditions, the H310/316 antigen gave oligomers of a component of Msub(r) 62000. It is unknown whether this 62000 dalton component is a dimer of the 34000 dalton protein with either itself or a second protein chain of presumed Msub(r) around 28000. H315 recognises an antigen with subunit Msub(r) of 36000; in non-reducing conditions this component readily associates to oligomeric structures. The epitope recognised by H315 may be sensitive to SDS. The two proteins recognised by H310/316 and H315 have been termed the p34 and p36 trophoblast membrane proteins, respectively.

  14. Effects of Human Umbilical Cord Mesenchymal Stem Cells on Human Trophoblast Cell Functions In Vitro

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    Yajing Huang

    2016-01-01

    Full Text Available Trophoblast cell dysfunction is involved in many disorders during pregnancy such as preeclampsia and intrauterine growth restriction. Few treatments exist, however, that target improving trophoblast cell function. Human umbilical cord mesenchymal stem cells (hUCMSCs are capable of self-renewing, can undergo multilineage differentiation, and have homing abilities; in addition, they have immunomodulatory effects and paracrine properties and thus are a prospective source for cell therapy. To identify whether hUCMSCs can regulate trophoblast cell functions, we treated trophoblast cells with hUCMSC supernatant or cocultured them with hUCMSCs. Both treatments remarkably enhanced the migration and invasion abilities of trophoblast cells and upregulated their proliferation ability. At a certain concentration, hUCMSCs also modulated hCG, PIGF, and sEndoglin levels in the trophoblast culture medium. Thus, hUCMSCs have a positive effect on trophoblast cellular functions, which may provide a new avenue for treatment of placenta-related diseases during pregnancy.

  15. Generation of Elf5-Cre knockin mouse strain for trophoblast-specific gene manipulation.

    Science.gov (United States)

    Kong, Shuangbo; Liang, Guixian; Tu, Zhaowei; Chen, Dunjin; Wang, Haibin; Lu, Jinhua

    2018-04-01

    Placental development is a complex and highly controlled process during which trophoblast stem cells differentiate to various trophoblast subtypes. The early embryonic death of systemic gene knockout models hampers the investigation of these genes that might play important roles during placentation. A trophoblast specific Cre mouse model would be of great help for dissecting out the potential roles of these genes during placental development. For this purpose, we generate a transgenic mouse with the Cre recombinase inserted into the endogenous locus of Elf5 gene that is expressed specifically in placental trophoblast cells. To analyze the specificity and efficiency of Cre recombinase activity in Elf5-Cre mice, we mated Elf5-Cre mice with Rosa26 mT/mG reporter mice, and found that Elf5-Cre transgene is expressed specifically in the trophoectoderm as early as embryonic day 4.5 (E4.5). By E12.5, the activity of Elf5-Cre transgene was detected exclusively in all derivatives of trophoblast lineages, including spongiotrophoblast, giant cells, and labyrinth trophoblasts. In addition, Elf5-Cre transgene was also active during spermatogenesis, from spermatids to mature sperms, which is consistent with the endogenous Elf5 expression in testis. Collectively, our results provide a unique tool to delete specific genes selectively and efficiently in trophoblast lineage during placentation. © 2018 Wiley Periodicals, Inc.

  16. Development to term of sheep embryos reconstructed after inner cell mass/trophoblast exchange.

    Science.gov (United States)

    Loi, Pasqualino; Galli, Cesare; Lazzari, Giovanna; Matsukawa, Kazutsugu; Fulka, Josef; Goeritz, Frank; Hildebrandt, Thomas B

    2018-04-13

    Here we report in vitro and term development of sheep embryos after the inner cell mass (ICM) from one set of sheep blastocysts were injected into the trophoblast vesicles of another set. We also observed successful in vitro development of chimeric blastocysts made from sheep trophoblast vesicles injected with bovine ICM. First, we dissected ICMs from 35 sheep blastocysts using a stainless steel microblade and injected them into 29 re-expanded sheep trophoblastic vesicles. Of the 25 successfully micromanipulated trophoblastic vesicles, 15 (51.7%) re-expanded normally and showed proper ICM integration. The seven most well reconstructed embryos were transferred for development to term. Three ewes receiving manipulated blastocysts were pregnant at day 45 (42.8%), and all delivered normal offspring (singletons, two females and one male, average weight: 3.54 ± 0.358 kg). Next, we monitored in vitro development of sheep trophoblasts injected with bovine ICMs. Of 17 injected trophoblastic vesicles, 10 (58.8%) re-expanded after 4 h in culture, and four (40%) exhibited integrated bovine ICM. Our results indicate that ICM/trophoblast exchange is feasible, allowing full term development with satisfactory lambing rate. Therefore, ICM exchange is a promising approach for endangered species conservation.

  17. Primary Cilium-Regulated EG-VEGF Signaling Facilitates Trophoblast Invasion.

    Science.gov (United States)

    Wang, Chia-Yih; Tsai, Hui-Ling; Syu, Jhih-Siang; Chen, Ting-Yu; Su, Mei-Tsz

    2017-06-01

    Trophoblast invasion is an important event in embryo implantation and placental development. During these processes, endocrine gland-derived vascular endothelial growth factor (EG-VEGF) is the key regulator mediating the crosstalk at the feto-maternal interface. The primary cilium is a cellular antenna receiving environmental signals and is crucial for proper development. However, little is known regarding the role of the primary cilium in early human pregnancy. Here, we demonstrate that EG-VEGF regulates trophoblast cell invasion via primary cilia. We found that EG-VEGF activated ERK1/2 signaling and subsequent upregulation of MMP2 and MMP9, thereby facilitating cell invasion in human trophoblast HTR-8/SVneo cells. Inhibition of ERK1/2 alleviated the expression of MMPs and trophoblast cell invasion after EG-VEGF treatment. In addition, primary cilia were observed in all the trophoblast cell lines tested and, more importantly, in human first-trimester placental tissue. The receptor of EG-VEGF, PROKR1, was detected in primary cilia. Depletion of IFT88, the intraflagellar transporter required for ciliogenesis, inhibited primary cilium growth, thereby ameliorating ERK1/2 activation, MMP upregulation, and trophoblast cell invasion promoted by EG-VEGF. These findings demonstrate a novel function of primary cilia in controlling EG-VEGF-regulated trophoblast invasion and reveal the underlying molecular mechanism. J. Cell. Physiol. 232: 1467-1477, 2017. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

  18. Risk of metachronous neoplasia on surveillance colonoscopy in young patients with colorectal neoplasia.

    Science.gov (United States)

    Kim, Hyun Gun; Cho, Young-Seok; Cha, Jae Myung; Shin, Jeong Eun; Kim, Kyeong Ok; Yang, Hyo-Joon; Koo, Hoon Sup; Joo, Young-Eun; Boo, Sun-Jin

    2018-03-01

    Few prior reports exist that address the appropriate colonoscopy surveillance interval for individuals  .1). In the baseline low-risk adenoma group (n = 1869), the 5-year risk of metachronous advanced neoplasia was 4.9% in the younger patients on screening colonoscopy and 5.1% in the older patients (P > .1). Similarly, in the baseline no neoplasia group (n = 7013), the 5-year risk of metachronous advanced neoplasia was 4.1% in the younger patients on screening colonoscopy and 5.6% in the older patients (P > .1). Considering the similar risk of metachronous advanced neoplasia in younger and older individuals, we suggest a 3-year surveillance interval for high-risk adenoma and a 5-year surveillance interval for low-risk adenoma in young individuals without a strong family history. Copyright © 2018 American Society for Gastrointestinal Endoscopy. Published by Elsevier Inc. All rights reserved.

  19. ADAM28 localizes to HLA-G+ trophoblasts and promotes column cell outgrowth.

    Science.gov (United States)

    De Luca, L C; Le, H T; Mara, D L; Beristain, A G

    2017-07-01

    Trophoblast progenitor cell differentiation towards the extravillous trophoblast (EVT) lineage initiates within proximal regions of anchoring columns of first trimester placental villi. While molecular processes controlling the initial stages of progenitor cell differentiation along the EVT pathway have been described, much remains unknown about factors important in distal column cell differentiation into invasive EVTs. ADAMs are proteases that regulate growth factor signaling, cell-matrix adhesion, and matrix proteolysis, and thus impact many processes relevant in placentation. Global gene expression studies identified the ADAM subtype, ADAM28, to be highly expressed in EVT-like trophoblasts, suggesting that it may play a role in EVT function. This study aims to test the functional importance of ADAM28 in column cell outgrowth and maintenance. ADAM28 mRNA levels and protein localization were determined by qPCR and immunofluorescence microscopy analyses in purified placental villi cell populations and tissues. ADAM28 function in trophoblast column outgrowth was examined using ADAM28-targetting siRNAs in Matrigel-imbedded placental explant cultures. Within placental villi, ADAM28 mRNA levels were highest in HLA-G + column trophoblasts, and consistent with this, ADAM28 was preferentially localized to HLA-G + trophoblasts within distal anchoring columns and decidual tissue. siRNA-directed loss of ADAM28 impaired trophoblast column outgrowth and resulted in increased apoptosis in matrix-invading trophoblasts. Our findings suggest that ADAM28 promotes column outgrowth by providing survival cues within anchoring column cells. This study also provides insight into a possible role for ADAM28 in driving differentiation of column trophoblasts into invasive HLA-G + EVT subsets. Copyright © 2017 Elsevier Ltd. All rights reserved.

  20. How to Treat Gestational Diabetes

    Science.gov (United States)

    ... A Listen En Español How to Treat Gestational Diabetes Be sure to see the latest Diabetes Forecast ... and a healthy start for your baby. Gestational Diabetes – Looking Ahead Gestational diabetes usually goes away after ...

  1. Genetics Home Reference: gestational diabetes

    Science.gov (United States)

    ... Email Facebook Twitter Home Health Conditions Gestational diabetes Gestational diabetes Printable PDF Open All Close All Enable Javascript to view the expand/collapse boxes. Description Gestational diabetes is a disorder characterized by abnormally high blood ...

  2. Anal intraepithelial neoplasia in HIV+ men

    NARCIS (Netherlands)

    Richel, O.

    2014-01-01

    In this thesis we investigated several aspects of anal intraepithelial neoplasia (AIN) in HIV+ men who have sex with men (MSM). This condition has gained clinical interest because of the impressive increase of the anal cancer incidence in HIV+ MSM since the introduction of combination antiretroviral

  3. Microparticles and Exosomes in Gynecologic Neoplasias

    NARCIS (Netherlands)

    Nieuwland, Rienk; van der Post, Joris A. M.; Lok Gemma, Christianne A. R.; Kenter, G.; Sturk, Augueste

    2010-01-01

    This review presents an overview of the functions of microparticles and exosomes in gynecologic neoplasias. Growing evidence suggests that vesicles released from cancer cells in gynecologic malignancies contribute to the hypercoagulable state of these patients and contribute to tumor progression by

  4. Risk Factors for Cervical Intraepithelial Neoplasia

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    Estrella de la Caridad Armenteros Espino

    2016-09-01

    Full Text Available Background: cervix cancer constitutes the second cause of death worldwide, with new diagnosis each year. Objective: to determine the risk factors of cervical intraepithelial neoplasia in the municipality of Cruces. Methods: it was developed an analytical research with case and control design from November 2013 to November 2014. The group of cases was formed of the 34 women with this diagnosis. There were selected 64 females from the same environment with the same age for the control group. The data obtained by surveys and clinical records reviews were presented in absolute numbers and percentages. It was used Chi-squared test and odd ratio. Results: 52 % of women with neoplasia were less than 25 years old. Significant differences were found which associate neoplasia with early sexual intercourse, sexually transmitted infections by Papilloma virus, Plane genital condyloma, and the use of oral contraceptive pills. Multiple sex partner was a frequent antecedent. Conclusion: risk factors associated to cervical intraepithelial neoplasia in the group of women studied in the Cruces municipality were early sexual intercourse, mainly before 15 years old, multiple sex partner, sexually communicated diseases and the use of oral contraceptive pills for more than 5 years.

  5. Centrosome Clustering in the Development of Bovine Binucleate Trophoblast Giant Cells.

    Science.gov (United States)

    Klisch, Karl; Schraner, Elisabeth M; Boos, Alois

    2017-01-01

    Binucleate trophoblast giant cells (BNC) are the characteristic feature of the ruminant placenta. During their development, BNC pass through 2 acytokinetic mitoses and become binucleate with 2 tetraploid nuclei. In this study, we investigate the number and location of centrosomes in bovine BNC. Centrosomes typically consist of 2 centrioles surrounded by electron-dense pericentriolar material. Duplication of centrosomes is tightly linked to the cell cycle, which ensures that the number of centrosomes remains constant in proliferating diploid cells. Alterations of the cell cycle, which affect the number of chromosome sets, also affect the number of centrosomes. In this study, we use placentomal tissue from pregnant cows (gestational days 80-230) for immunohistochemical staining of γ-tubulin (n = 3) and transmission electron microscopy (n = 3). We show that mature BNC have 4 centrosomes with 8 centrioles, clustered in the angle between the 2 cell nuclei. During the second acytokinetic mitosis, the centrosomes must be clustered to form the poles of a bipolar spindle. In rare cases, centrosome clustering fails and tripolar mitosis leads to the formation of trinucleate "BNC". Generally, centrosome clustering occurs in polyploid tumor cells, which have an increased number of centrioles, but it is absent in proliferating diploid cells. Thus, inhibition of centrosome clustering in tumor cells is a novel promising strategy for cancer treatment. BNC are a cell population in which centrosome clustering occurs as part of the normal life history. Thus, they might be a good model for the study of the molecular mechanisms of centrosome clustering. © 2016 S. Karger AG, Basel.

  6. Mitotic and apoptotic activity in colorectal neoplasia.

    Science.gov (United States)

    Kohoutova, Darina; Pejchal, Jaroslav; Bures, Jan

    2018-05-18

    Colorectal cancer (CRC) is third most commonly diagnosed cancer worldwide. The aim of the prospective study was to evaluate mitosis and apoptosis of epithelial cells at each stage of colorectal neoplasia. A total of 61 persons were enrolled into the study: 18 patients with non-advanced colorectal adenoma (non-a-A), 13 patients with advanced colorectal adenoma (a-A), 13 patients with CRC and 17 controls: individuals with normal findings on colonoscopy. Biopsy samples were taken from pathology (patients) and healthy mucosa (patients and healthy controls). Samples were formalin-fixed paraffin-embedded and stained with haematoxylin-eosin. Mitotic and apoptotic activity were evaluated in lower and upper part of the crypts and in the superficial compartment. Apoptotic activity was also assessed using detection of activated caspase-3. In controls, mitotic activity was present in lower part of crypts, accompanied with low apoptotic activity. Mitotic and apoptotic activity decreased (to almost zero) in upper part of crypts. In superficial compartment, increase in apoptotic activity was observed. Transformation of healthy mucosa into non-a-A was associated with significant increase of mitotic activity in lower and upper part of the crypts and with significant increase of apoptotic activity in all three compartments; p colorectal neoplasia were observed. Detection of activated caspase-3 confirmed the above findings in apoptotic activity. Significant dysregulation of mitosis and apoptosis during the progression of colorectal neoplasia, corresponding with histology, was confirmed. In patients with sporadic colorectal neoplasia, healthy mucosa does not display different mitotic and apoptotic activity compared to mucosa in healthy controls and therefore adequate endoscopic/surgical removal of colorectal neoplasia is sufficient.

  7. ACCRETA COMPLICATING COMPLETE PLACENTA PREVIA IS CHARACTERIZED BY REDUCED SYSTEMIC LEVELS OF VASCULAR ENDOTHELIAL GROWTH FACTOR AND EPITHELIAL-TO-MESENCHYMAL TRANSITION OF THE INVASIVE TROPHOBLAST

    Science.gov (United States)

    Wehrum, Mark J.; Buhimschi, Irina A.; Salafia, Carolyn; Thung, Stephen; Bahtiyar, Mert O.; Werner, Erica F.; Campbell, Katherine H.; Laky, Christine; Sfakianaki, Anna K.; Zhao, Guomao; Funai, Edmund F.; Buhimschi, Catalin S.

    2011-01-01

    OBJECTIVE To characterize serum angiogenic factor profile of women with complete placenta previa and determine if invasive trophoblast differentiation characteristic of accreta, increta or percreta shares features of epitehelial-mesenchymal-transition (EMT). STUDY DESIGN We analyzed gestational age matched serum samples from 90 pregnant women with either complete placenta previa (n=45) or uncomplicated pregnancies (n=45). Vascular-endothelial-growth-factor (VEGF), placental-growth-factor (PlGF) and soluble fms-like-tyrosine-kinase-1 (sFlt-1) were immunoassayed. VEGF and phosphotyrosine (P-Tyr) immunoreactivity was surveyed in histological specimens relative to expression of vimentin and cytokeratin-7. RESULTS Women with previa and invasive placentation [accreta (n=5); increta (n=6); percreta (n=2)] had lower systemic VEGF (invasive previa: median [IQR]: 0.8[0.02–3.4] vs. control: 6.5[2.7–10.5] pg/mL, P=0.02). VEGF and P-Tyr immunostaining predominated in the invasive extravillous trophoblasts (EVT) which co-expressed vimentin and cytokeratin-7, a EMT feature and tumor-like cell phenotype. CONCLUSIONS Lower systemic free VEGF and a switch of the interstitial EVT to a metastable cell phenotype characterize placenta previa with excessive myometrial invasion. PMID:21316642

  8. Comparative experimental infection of Listeria monocytogenes and Listeria ivanovii in bovine trophoblasts.

    Science.gov (United States)

    Rocha, Cláudia E; Mol, Juliana P S; Garcia, Luize N N; Costa, Luciana F; Santos, Renato L; Paixão, Tatiane A

    2017-01-01

    Listeria monocytogenes is a Gram-positive, facultative intracellular and invasive bacterium that has tropism to the placenta, and causes fetal morbidity and mortality in several mammalian species. While infection with L. monocytogenes and L. ivanovii are known as important causes of abortion and reproductive failure in cattle, the pathogenesis of maternal-fetal listeriosis in this species is poorly known. This study used the bovine chorioallantoic membrane explant model to investigate the kinetics of L. monocytogenes, L. ivanovii, and L. innocua infections in bovine trophoblastic cells for up to 8 h post infection. L. monocytogenes and L. ivanovii were able to invade and multiply in trophoblastic cells without causing cell death or inducing expression of pro-inflammatory genes. Although L. innocua was unable to multiply in bovine trophoblastic cells, it induced transcription of the pro-inflammatory mediator CXCL6. This study demonstrated for the first time the susceptibility of bovine trophoblastic cells to L. monocytogenes and L. ivanovii infection.

  9. Immunomodulator expression in trophoblasts from the feline immunodeficiency virus FIV infected cat

    Science.gov (United States)

    FIV infection frequently compromises pregnancy under experimental conditions and is accompanied by aberrant expression of some placental cytokines. Trophoblasts produce numerous immunomodulators that play a role in placental development and pregnancy maintenance. We hypothesized that FIV infection m...

  10. Gestational Diabetes and Women

    Centers for Disease Control (CDC) Podcasts

    This women's health podcast focuses on gestational diabetes (GDM) to help educate women who may have been diagnosed with GDM now or in the past. GDM is a condition that can lead to pregnancy complications.

  11. Coexistence of prostate neoplasia in patients undergoing radical cystoprostatectomy due to vesical neoplasia

    Directory of Open Access Journals (Sweden)

    Frederico R. Romero

    2004-08-01

    Full Text Available OBJECTIVE: To assess the incidence of bladder carcinoma infiltrating the prostate and prostate adenocarcinoma in patients undergoing radical cystoprostatectomy due to bladder cancer, as well as to assess if the characteristics of the bladder neoplasia influence the prostatic involvement by this neoplasia. MATERIALS AND METHODS: We retrospectively assessed 60 male patients, who underwent radical cystoprostatectomy between July 1997 and December 2003. Mean age was 66.7 years (40 and 93 years. The product of radical cystoprostatectomies was checked for involvement of urethra and prostate parenchyma by the primary neoplasia, and for the presence of associated prostate adenocarcinoma. Bladder neoplasia characteristics, such as localization, size, multifocality, association with in situ carcinoma and histological grade, were studied in order to assess the possibility of using such characteristics as predictive factors of prostate infiltration by bladder urothelial carcinoma. RESULTS: We observed the presence of 20% of patients with bladder carcinoma infiltrating the prostatic urethra, 23.3% of patients with infiltration of the prostate parenchyma and 28.3% of patients with associate prostate adenocarcinoma, resulting in a total of 55% of patients with prostatic involvement (infiltrative bladder carcinoma and/or adenocarcinoma. We also observed a statistically significant correlation between tumor location in the trigone, the presence of in situ carcinoma and the histological grade of the bladder tumor with prostatic infiltration by the vesical neoplasia. CONCLUSION: The coexistence of prostatic neoplasia in patients operated for bladder neoplasia was frequent in our sample (55%. We observed that the prostatic infiltration by bladder tumors occurs more frequently with tumors located in the trigone, with associated in situ carcinoma and with high histological grade. There was no correlation between neoplastic infiltration of prostate and multifocality

  12. The role of invasive trophoblast in implantation and placentation of primates

    DEFF Research Database (Denmark)

    Carter, Anthony Michael; Enders, Allen C; Pijnenborg, Robert

    2015-01-01

    We here review the evolution of invasive placentation in primates towards the deep penetration of the endometrium and its arteries in hominoids. The strepsirrhine primates (lemurs and lorises) have non-invasive, epitheliochorial placentation, although this is thought to be derived from a more...... invasive type. In haplorhine primates, there is differentiation of trophoblast at the blastocyst stage into syncytial and cellular trophoblast. Implantation involves syncytiotrophoblast that first removes the uterine epithelium then consolidates at the basal lamina before continuing into the stroma...

  13. Alteration of Pituitary Tumor Transforming Gene-1 Regulates Trophoblast Invasion via the Integrin/Rho-Family Signaling Pathway.

    Directory of Open Access Journals (Sweden)

    Seung Mook Lim

    Full Text Available Trophoblast invasion ability is an important factor in early implantation and placental development. Recently, pituitary tumor transforming gene 1 (PTTG1 was shown to be involved in invasion and proliferation of cancer. However, the role of PTTG1 in trophoblast invasion remains unknown. Thus, in this study we analyzed PTTG1 expression in trophoblasts and its effect on trophoblast invasion activity and determined the mechanism through which PTTG1 regulates trophoblast invasion. Trophoblast proliferation and invasion abilities, regardless of PTTG1 expression, were analyzed by quantitative real-time polymerase chain reaction, fluorescence-activated cell sorting analysis, invasion assay, western blot, and zymography after treatment with small interfering RNA against PTTG1 (siPTTG1. Additionally, integrin/Rho-family signaling in trophoblasts by PTTG1 alteration was analyzed. Furthermore, the effect of PTTG1 on trophoblast invasion was evaluated by microRNA (miRNA mimic and inhibitor treatment. Trophoblast invasion was significantly reduced through decreased matrix metalloproteinase (MMP-2 and MMP-9 expression when PTTG1 expression was inhibited by siPTTG1 (p < 0.05. Furthermore, knockdown of PTTG1 increased expression of integrin alpha 4 (ITGA4, ITGA5, and integrin beta 1 (ITGB1; otherwise, RhoA expression was significantly decreased (p < 0.05. Treatment of miRNA-186-5p mimic and inhibitor controlled trophoblast invasion ability by altering PTTG1 and MMP expression. PTTG1 can control trophoblast invasion ability via regulation of MMP expression through integrin/Rho-family signaling. In addition, PTTG1 expression and its function were regulated by miRNA-186-5p. These results help in understanding the mechanism through which PTTG1 regulates trophoblast invasion and thereby implantation and placental development.

  14. Canine oral cavity neoplasias - Brief review

    Directory of Open Access Journals (Sweden)

    João Filipe Requicha

    2015-03-01

    Full Text Available ABSTRACT. Requicha J.F., Pires M. dos A., Albuquerque C.M. & Viegas C.A. [Canine oral cavity neoplasias - Brief review.] Neoplasias da cavidade oral do cão - Breve revisão. Revista Brasileira de Medicina Veterinária, 37(1:41-46, 2015. Faculdade de Medicina Veterinária, Universidade Lusófona de Humanidades e Tecnologias, Campo Grande, 1749-024 Lisboa, Portugal e Department of Veterinary Sciences, School of Agriculture and Veterinary Sciences, University of Trás-os-Montes e Alto Douro, P.O. Box 1013, 5001-801 Vila Real, Portugal. E-mail: jfrequicha@gmail.com Oral proliferative lesions are relatively common in domestic carnivores but, fortunately, a lot of these lesions are benign. The oral cavity is place of 6% of all tumours in dogs, being the sixth most important localization of neoplasias in this specie. The non-odontogenic tumors arise from structures of the oral cavity, except from dental tissue, and they are mostly malignant. Odontogenic tumors are those originated from the dental structures. In the case of tumors of non-odontogenic, will be described the oral papillomatosis, the melanoma, the squamous cell carcinoma, and the fibrosarcoma. Among the odontogenic tumors, the focus will be on the epulides, ameloblastoma, odontoma and dentigerous cysts.

  15. Spectrum of ocular surface squamous neoplasia

    International Nuclear Information System (INIS)

    Babar, T.F.; Khan, M.N.; Hussain, M.; Shah, S.A.

    2007-01-01

    To describe the pattern of ocular surface squamous neoplasia (OSSN), clinical presentations, the risk factors and treatment options. The study included 36 eyes of 35 patients with biopsy-proven ocular surface neoplasia. The details of patients regarding age, gender, laterality and risk factors were entered into a specially-designed proforma. Each patient was also assessed biomicroscopically for type and complications of ocular surface neoplasia. The frequency of OSSN was 0.37 among admitted hospital patients. Among 36 cases of OSSN, squamous cell carcinoma of the conjunctiva was the most common type of OSSN seen in 63.9%, followed by carcinoma in situ of conjunctiva in 25% and carcinoma in situ of cornea in 11.1%. Male patients outnumbered female (65.7% vs 34.3%) with 71.42% of patients above 60 years of age. The risk factors identified were: old age, ultraviolet B exposure and xeroderma pigmentosa. Treatment consisted of local resection with or without adjuvant therapy in 61.1%, exenteration in 30.5%, enucleation in 5.5% and chemo/radiotherapy in 2.7%. Intraocular invasion was seen in 5.5% and orbital spread in 30.5%. The frequency of OSSN was 0.37% among admitted patients. Identification of exact etiological factors will enable to formulate strategies that are likely to decrease the incidence of this disease and the associated morbidity and mortality. (author)

  16. TNF-α stimulates System A amino acid transport in primary human trophoblast cells mediated by p38 MAPK signaling.

    Science.gov (United States)

    Aye, Irving L M H; Jansson, Thomas; Powell, Theresa L

    2015-10-01

    Maternal obesity and gestational diabetes mellitus (GDM) increase the risk of delivering infants that are large for gestational age with greater adiposity, who are prone to the development of metabolic disease in childhood and beyond. These maternal conditions are also associated with increased levels of the proinflammatory cytokine TNF-α in maternal tissues and the placenta. Recent evidence suggests that changes in placental amino acid transport contribute to altered fetal growth. TNF-α was previously shown to stimulate System A amino acid transport in primary human trophoblasts (PHTs), however the molecular mechanisms remain unknown. In this study, we tested the hypothesis that TNF-α regulates amino acid uptake in cultured PHTs by a mitogen-activated protein kinase (MAPK)-dependent mechanism. Treatment of PHTs with TNF-α significantly increased System A amino acid transport, as well as Erk and p38 MAPK signaling. Pharmacological antagonism of p38, but not Erk MAPK activity, inhibited TNF-α stimulated System A activity. Silencing of p38 MAPK using siRNA transfections prevented TNF-α stimulated System A transport in PHTs. TNF-α significantly increased the protein expression of System A transporters SNAT1 and SNAT2, but did not affect their mRNA expression. The effects of TNF-α on SNAT1 and SNAT2 protein expression were reversed by p38 MAPK siRNA silencing. In conclusion, TNF-α regulates System A activity through increased SNAT1 and SNAT2 transporter protein expression in PHTs. These findings suggest that p38 MAPK may represent a critical mechanistic link between elevated proinflammatory cytokines and increased placental amino acid transport in obese and GDM pregnancies associated with fetal overgrowth. © 2015 The Authors. Physiological Reports published by Wiley Periodicals, Inc. on behalf of the American Physiological Society and The Physiological Society.

  17. Gestational Diabetes Mellitus

    DEFF Research Database (Denmark)

    McIntyre, H David; Jensen, Dorte M; Jensen, Richard C

    2018-01-01

    OBJECTIVE: To define the prevalence and pregnancy outcomes related to elevated fasting venous plasma glucose (FVPG) in a Danish pregnancy cohort. RESEARCH DESIGN AND METHODS: This was an observational cohort study including 1,516 women without gestational diabetes mellitus (GDM) by Danish criteria....... FVPG measured at 28 weeks' gestation was related to pregnancy outcomes. RESULTS: With use of the World Health Organization 2013 threshold of FVPG ≥5.1 mmol/L, 40.1% of the cohort qualified as having GDM. There was no evidence of excess fetal growth, hypertension in pregnancy, or caesarean delivery...

  18. Late gestational nutrient restriction

    DEFF Research Database (Denmark)

    Tygesen, Malin Plumhoff; Nielsen, Mette Olaf; Nørgaard, Peder

    2008-01-01

    We investigated the effect of 50% nutrient restriction during the last 6 weeks of gestation on twin-pregnant ewes' plasma glucose, non-esterified fatty acid, ß-hydroxybutyrate, insulin, IGF-1 and leptin concentrations and the effects on lamb birth weight and ewes' lactation performance. Plasma...

  19. Endoscopic submucosal dissection for early Barrett's neoplasia.

    Science.gov (United States)

    Barret, Maximilien; Cao, Dalhia Thao; Beuvon, Frédéric; Leblanc, Sarah; Terris, Benoit; Camus, Marine; Coriat, Romain; Chaussade, Stanislas; Prat, Frédéric

    2016-04-01

    The possible benefit of endoscopic submucosal dissection (ESD) for early neoplasia arising in Barrett's esophagus remains controversial. We aimed to assess the efficacy and safety of ESD for the treatment of early Barrett's neoplasia. All consecutive patients undergoing ESD for the resection of a visible lesion in a Barrett's esophagus, either suspicious of submucosal infiltration or exceeding 10 mm in size, between February 2012 and January 2015 were prospectively included. The primary endpoint was the rate of curative resection of carcinoma, defined as histologically complete resection of adenocarcinomas without poor histoprognostic factors. Thirty-five patients (36 lesions) with a mean age of 66.2 ± 12 years, a mean ASA score of 2.1 ± 0.7, and a mean C4M6 Barrett's segment were included. The mean procedure time was 191 ± 79 mn, and the mean size of the resected specimen was 51.3 ± 23 mm. En bloc resection rate was 89%. Lesions were 12 ± 15 mm in size, and 81% (29/36) were invasive adenocarcinomas, six of which with submucosal invasion. Although R0 resection of carcinoma was 72.4%, the curative resection rate was 66% (19/29). After a mean follow-up of 12.9 ± 9 months, 16 (45.7%) patients had required additional treatment, among whom nine underwent surgical resection, and seven further endoscopic treatments. Metachronous lesions or recurrence of cancer developed during the follow-up period in 17.2% of the patients. The overall complication rate was 16.7%, including 8.3% perforations, all conservatively managed, and no bleeding. The 30-day mortality was 0%. In this early experience, ESD yielded a moderate curative resection rate in Barrett's neoplasia. At present, improvements are needed if ESD is to replace piecemeal endoscopic mucosal resection in the management of Barrett's neoplasia.

  20. What is your diagnosis? [Intestinal neoplasia

    International Nuclear Information System (INIS)

    Uehlinger, P.; Glaus, T.; Stoeckli, R.; Flueckiger, M.; Leuch, F.

    1997-01-01

    Iron lack anemia due to chronic blood loss was diagnosed in a 12-year-old dog. Clinical abnormalities included weakness and episodic vomiting. Typical hematological abnormalities were moderate regenerative anemia (Hct 21 %) and microcytosis (MCV 39 fl.). Chronic occult blood loss in adult dogs most commonly occurs in the gastrointestinal tract, associated with ulcus or neoplasia. Possible diagnostic steps include radiographs, abdominal ultrasound, gastroduodenoscopy, and exploratory laparotomy. In the present case gastric and duodenal adenocarcinomata were found during necropsy, confirming the clinical suspicion of a bleeding gastrointestinal malignancy

  1. Mamary neoplasia in a closed beagle colony

    International Nuclear Information System (INIS)

    Taylor, G.N.; Shabestari, L.; Williams, J.; Mays, C.W.; Angus, W.; McFarland, S.

    1975-01-01

    The incidence rate of mammary neoplasia in a large colony of beagles and its relationship to internal skeletal and/or liver radiation, age, relatively late ovariectomy (4 years and older), endometritis, parity status, and adrenal weight was examined. Of these various factors, age was the only condition that was clearly correlated with changes in the mammary tumor incidence. The rate became significant at approximately eight years of age and increased progressively throughout the successively older age classes. Within the female dogs, the incidence of mammary cancer was higher that that of any other form of spontaneous malignancy

  2. Molecular signatures of thyroid follicular neoplasia

    DEFF Research Database (Denmark)

    Borup, R.; Rossing, M.; Henao, Ricardo

    2010-01-01

    The molecular pathways leading to thyroid follicular neoplasia are incompletely understood, and the diagnosis of follicular tumors is a clinical challenge. To provide leads to the pathogenesis and diagnosis of the tumors, we examined the global transcriptome signatures of follicular thyroid...... a mechanism for cancer progression, which is why we exploited the results in order to generate a molecular classifier that could identify 95% of all carcinomas. Validation employing public domain and cross-platform data demonstrated that the signature was robust and could diagnose follicular nodules...... and robust genetic signature for the diagnosis of FA and FC. Endocrine-Related Cancer (2010) 17 691-708...

  3. New Developments in Ocular Surface Squamous Neoplasia

    Directory of Open Access Journals (Sweden)

    Ayşe Yağcı

    2014-09-01

    Full Text Available Ocular surface squamous neoplasia originates from conjunctiva epithelium and covers a broad spectrum of disease ranging from dysplasia to squamous cell carcinoma. Clinical features may vary from case to case. Traditional treatment of excision with no-touch technique combined with adjuvant therapies because of high recurrence rate. Main adjuvant treatments are cryotherapy and chemotherapy. In this review, clinical forms, differential diagnosis, American Joint Committee on Cancer classification and recent approaches to the management of ocular surface squamous dysplasia were described. (Turk J Ophthalmol 2014; 44: Supplement 8-14

  4. Leukemia inhibitory factor promote trophoblast invasion via urokinase-type plasminogen activator receptor in preeclampsia.

    Science.gov (United States)

    Zheng, Qin; Dai, Kuixing; Cui, Xinyuan; Yu, Ming; Yang, Xuesong; Yan, Bin; Liu, Shuai; Yan, Qiu

    2016-05-01

    Preeclampsia is a pregnancy-related syndrome which can cause perinatal mortality and morbidity. Inadequate invasion by trophoblast cells may lead to poor perfusion of the placenta, even result in preeclampsia. Understanding the molecular mechanisms underlying placentation facilitates the better intervention of preeclampsia. Urokinase-type plasminogen activator receptor (uPAR) is involved in the physiological and pathological processes. Leukemia inhibitory factor (LIF) is an important regulator in the establishment of pregnancy. However, the expression of uPAR in preeclamptic patients and its relationship with LIF remains unclear. In the current study, we found that the level of uPAR was relatively lower in the placentas from preeclamptic patients as compared with normal pregnant women. LIF promoted trophoblast cell outgrowth by upregulating uPAR in an explants culture, and LIF also enhanced migration and invasion potential through uPAR in trophoblast JAR and JEG-3 cell lines, and with increased gelatinolytic activities of matrix metalloproteinase 2 (MMP-2). The effect of LIF and uPAR on trophoblast migration and invasion was mediated by PI3K/AKT signaling pathway. Our data indicates the roles of LIF in promoting trophoblast migration and invasion through uPAR and suggest that abnormal expression of uPAR might be associated with the etiology of preeclampsia. Copyright © 2016 Elsevier Masson SAS. All rights reserved.

  5. Quebec Trophoblastic Disease Registry: how to make an easy-to-use dynamic database.

    Science.gov (United States)

    Sauthier, Philippe; Breguet, Magali; Rozenholc, Alexandre; Sauthier, Michaël

    2015-05-01

    To create an easy-to-use dynamic database designed specifically for the Quebec Trophoblastic Disease Registry (RMTQ). It is now well established that much of the success in managing trophoblastic diseases comes from the development of national and regional reference centers. Computerized databases allow the optimal use of data stored in these centers. We have created an electronic data registration system by producing a database using FileMaker Pro 12. It uses 11 external tables associated with a unique identification number for each patient. Each table allows specific data to be recorded, incorporating demographics, diagnosis, automated staging, laboratory values, pathological diagnosis, and imaging parameters. From January 1, 2009, to December 31, 2013, we used our database to register 311 patients with 380 diseases and have seen a 39.2% increase in registrations each year between 2009 and 2012. This database allows the automatic generation of semilogarithmic curves, which take into account β-hCG values as a function of time, complete with graphic markers for applied treatments (chemotherapy, radiotherapy, or surgery). It generates a summary sheet for a synthetic vision in real time. We have created, at a low cost, an easy-to-use database specific to trophoblastic diseases that dynamically integrates staging and monitoring. We propose a 10-step procedure for a successful trophoblastic database. It improves patient care, research, and education on trophoblastic diseases in Quebec and leads to an opportunity for collaboration on a national Canadian registry.

  6. The role of invasive trophoblast in implantation and placentation of primates

    Science.gov (United States)

    Carter, Anthony M.; Enders, Allen C.; Pijnenborg, Robert

    2015-01-01

    We here review the evolution of invasive placentation in primates towards the deep penetration of the endometrium and its arteries in hominoids. The strepsirrhine primates (lemurs and lorises) have non-invasive, epitheliochorial placentation, although this is thought to be derived from a more invasive type. In haplorhine primates, there is differentiation of trophoblast at the blastocyst stage into syncytial and cellular trophoblast. Implantation involves syncytiotrophoblast that first removes the uterine epithelium then consolidates at the basal lamina before continuing into the stroma. In later stages of pregnancy, especially in Old World monkeys and apes, cytotrophoblast plays a greater role in the invasive process. Columns of trophoblast cells advance to the base of the implantation site where they spread out to form a cytotrophoblastic shell. In addition, cytotrophoblasts advance into the lumen of the spiral arteries. They are responsible for remodelling these vessels to form wide, low-resistance conduits. In human and great apes, there is additional invasion of the endometrium and its vessels by trophoblasts originating from the base of the anchoring villi. Deep trophoblast invasion that extends remodelling of the spiral arteries to segments in the inner myometrium evolved in the common ancestor of gorilla, chimp and human. PMID:25602074

  7. The role of invasive trophoblast in implantation and placentation of primates.

    Science.gov (United States)

    Carter, Anthony M; Enders, Allen C; Pijnenborg, Robert

    2015-03-05

    We here review the evolution of invasive placentation in primates towards the deep penetration of the endometrium and its arteries in hominoids. The strepsirrhine primates (lemurs and lorises) have non-invasive, epitheliochorial placentation, although this is thought to be derived from a more invasive type. In haplorhine primates, there is differentiation of trophoblast at the blastocyst stage into syncytial and cellular trophoblast. Implantation involves syncytiotrophoblast that first removes the uterine epithelium then consolidates at the basal lamina before continuing into the stroma. In later stages of pregnancy, especially in Old World monkeys and apes, cytotrophoblast plays a greater role in the invasive process. Columns of trophoblast cells advance to the base of the implantation site where they spread out to form a cytotrophoblastic shell. In addition, cytotrophoblasts advance into the lumen of the spiral arteries. They are responsible for remodelling these vessels to form wide, low-resistance conduits. In human and great apes, there is additional invasion of the endometrium and its vessels by trophoblasts originating from the base of the anchoring villi. Deep trophoblast invasion that extends remodelling of the spiral arteries to segments in the inner myometrium evolved in the common ancestor of gorilla, chimp and human. © 2015 The Author(s) Published by the Royal Society. All rights reserved.

  8. Membrane Protected Apoptotic Trophoblast Microparticles Contain Nucleic Acids

    Science.gov (United States)

    Orozco, Aaron F.; Jorgez, Carolina J.; Horne, Cassandra; Marquez-Do, Deborah A.; Chapman, Matthew R.; Rodgers, John R.; Bischoff, Farideh Z.; Lewis, Dorothy E.

    2008-01-01

    Microparticles (MPs) that circulate in blood may be a source of DNA for molecular analyses, including prenatal genetic diagnoses. Because MPs are heterogeneous in nature, however, further characterization is important before use in clinical settings. One key question is whether DNA is either bound to aggregates of blood proteins and lipid micelles or intrinsically associated with MPs from dying cells. To test the latter hypothesis, we asked whether MPs derived in vitro from dying cells were similar to those in maternal plasma. JEG-3 cells model extravillous trophoblasts, which predominate during the first trimester of pregnancy when prenatal diagnosis is most relevant. MPs were derived from apoptosis and increased over 48 hours. Compared with necrotic MPs, DNA in apoptotic MPs was more fragmented and resistant to plasma DNases. Membrane-specific dyes indicated that apoptotic MPs had more membranous material, which protects nucleic acids, including RNA. Flow cytometry showed that MPs derived from dying cells displayed light scatter and DNA staining similar to MPs found in maternal plasma. Quantification of maternal MPs using characteristics defined by MPs generated in vitro revealed a significant increase of DNA+ MPs in the plasma of women with preeclampsia compared with plasma from women with normal pregnancies. Apoptotic MPs are therefore a likely source of stable DNA that could be enriched for both early genetic diagnosis and monitoring of pathological pregnancies. PMID:18974299

  9. Primary pulmonary neoplasia in the dog and cat

    International Nuclear Information System (INIS)

    Mehlhaff, C.J.; Mooney, S.

    1985-01-01

    This article covers the pertinent clinical, physical, and radiographic findings in dogs and cats with primary pulmonary neoplasia. Diagnostic and treatment recommendations are made. Although primary pulmonary neoplasia is rare in both the dog and cat, it appears to be diagnosed with increasing frequency. Early detection and surgical treatment of carefully selected cases can prolong a good quality of life

  10. Zollinger-Ellison syndrome, acromegaly, and colorectal neoplasia

    NARCIS (Netherlands)

    Tobi, M; Cats, A; Maliakkal, BJ; Kinzie, JL; Maliakkal, R; Dullaart, RPF; Luk, GD

    Zollinger-Ellison syndrome (ZES) and acromegaly are two hypersecretory states in which colorectal neoplasia has been described, but the incidence in the former condition may not be increased. We describe four patients with colorectal neoplasia associated with the ZES and review other published

  11. Molecular diagnosis of multiple endocrine neoplasia type 2A ...

    African Journals Online (AJOL)

    Molecular diagnosis of multiple endocrine neoplasia type 2A. RJ Pegoraro, DJ Hacking, RH Buck, L Rom, PA Lanning, GMB Berger. Abstract. Objective. To identify by means of genetic analyses individuals who are at risk of developing medullary thyroid cancer that is a component of multiple endocrine neoplasia. Subjects.

  12. NEOPLASIA IN SNAKES AT ZOO ATLANTA DURING 1992-2012.

    Science.gov (United States)

    Page-Karjian, Annie; Hahne, Megan; Leach, Kate; Murphy, Hayley; Lock, Brad; Rivera, Samuel

    2017-06-01

    A retrospective study was conducted to review neoplasia of captive snakes in the Zoo Atlanta collection from 1992 to 2012. Of 255 snakes that underwent necropsy and histopathologic examination at Zoo Atlanta during the study period, 37 were observed with neoplasia at necropsy. In those 37 snakes, 42 neoplastic lesions of 18 primary cell types were diagnosed. Thirty-five of those neoplasms (83.3%) were malignant, and of those, 19 were of mesenchymal origin, whereas 14 were of epithelial origin. The median annual rate of neoplasia at necropsy was 12.5% (interquartile range = 2.8-19.5%) over the 21-yr study period. The mean estimated age at death for snakes with neoplasia was 13.2 yr (range, 1-24 yr). Investigating the incidence and clinical significance of neoplasia in captive snakes is vital for developing effective preventative and treatment regimes.

  13. Gestational surrogacy in India

    OpenAIRE

    Rozée , Virginie; Unisa , Sayeed; De La Rochebrochard , Elise

    2016-01-01

    International audience; While gestational surrogacy is illegal in France, it is authorized in other countries, such as India. Drawing upon a study of Indian surrogates, Indian and foreign intended parents pursuing surro­gacy, as well as physicians, lawyers and Indian clinic and agency managers, Virginie Rozée, Sayeed Unisa and Elise de La Rochebrochard describe how surrogacy services are organized in India and examine the expectations and rationales of the protagonists.

  14. Gestational Diabetes and Women

    Centers for Disease Control (CDC) Podcasts

    2009-05-12

    This women's health podcast focuses on gestational diabetes (GDM) to help educate women who may have been diagnosed with GDM now or in the past. GDM is a condition that can lead to pregnancy complications.  Created: 5/12/2009 by Office of Women’s Health (OWH) and National Center for Chronic Disease Prevention and Health Promotion (NCCDPHP).   Date Released: 5/12/2009.

  15. Gestational weight gain.

    Science.gov (United States)

    Kominiarek, Michelle A; Peaceman, Alan M

    2017-12-01

    Prenatal care providers are advised to evaluate maternal weight at each regularly scheduled prenatal visit, monitor progress toward meeting weight gain goals, and provide individualized counseling if significant deviations from a woman's goals occur. Today, nearly 50% of women exceed their weight gain goals with overweight and obese women having the highest prevalence of excessive weight gain. Risks of inadequate weight gain include low birthweight and failure to initiate breast-feeding whereas the risks of excessive weight gain include cesarean deliveries and postpartum weight retention for the mother and large-for-gestational-age infants, macrosomia, and childhood overweight or obesity for the offspring. Prenatal care providers have many resources and tools to incorporate weight and other health behavior counseling into routine prenatal practices. Because many women are motivated to improve health behaviors, pregnancy is often considered the optimal time to intervene for issues related to eating habits and physical activity to prevent excessive weight gain. Gestational weight gain is a potentially modifiable risk factor for a number of adverse maternal and neonatal outcomes and meta-analyses of randomized controlled trials report that diet or exercise interventions during pregnancy can help reduce excessive weight gain. However, health behavior interventions for gestational weight gain have not significantly improved other maternal and neonatal outcomes and have limited effectiveness in overweight and obese women. Copyright © 2017 Elsevier Inc. All rights reserved.

  16. Deep trophoblast invasion and spiral artery remodelling in the placental bed of the chimpanzee

    DEFF Research Database (Denmark)

    Pijnenborg, R; Vercruysse, L; Carter, Anthony Michael

    2011-01-01

    Deep trophoblast invasion is usually considered to be a unique feature of human placentation as compared to other primates. Because of the occasional occurrence of preeclampsia in great apes, which in the human is associated with impaired deep invasion, this uniqueness may be questioned. The avai......Deep trophoblast invasion is usually considered to be a unique feature of human placentation as compared to other primates. Because of the occasional occurrence of preeclampsia in great apes, which in the human is associated with impaired deep invasion, this uniqueness may be questioned...

  17. Mola hidatiforme e doença trofoblástica gestacional Hydatidiform mole and gestational trophoblastic disease

    Directory of Open Access Journals (Sweden)

    Jurandyr Moreira de Andrade

    2009-02-01

    Full Text Available A mola hidatiforme é uma complicação relativamente infrequente da gravidez, mas com potencial para evolução para formas que necessitam de tratamento sistêmico e podem ser ameaçadoras da vida. Sob a denominação de mola hidatiforme há duas entidades histopatológicas e clínicas: a mola parcial e a completa. As diferenças entre estas duas formas são importantes, devido ao risco de evolução para formas persistentes, ou seja, mais alto para as completas. O diagnóstico da mola hidatiforme, seu tratamento e seguimento após o tratamento inicial sofreram alterações importantes nos últimos anos. O número de pacientes assintomáticas tem aumentado devido ao emprego de ultrassonografia no início da gravidez. Para a resolução da mola hidatiforme é necessário evitar o emprego de medicamentos que induzam contrações uterinas e usar a vácuo-aspiração. Deve ser prescrito o método contraceptivo hormonal logo após o esvaziamento da mola. O seguimento é baseado nas dosagens seriadas semanais de gonadotrofinas coriônicas. É importante que o método empregado detecte todas as formas das gonadotrofinas coriônicas (molécula intacta, hiperglicosilada, subunidade β livre e fragmento central da subunidade β.The hydatiform mole is a relatively rare pregnancy complication, but with potential to evolve to forms which need systemic treatment and can be a threat to life. There are two histopathological and clinical entities under the name of hydatiform mole: the partial and the complete mole. The differences between the two forms are important due to risk of evolution to persistent forms, which is higher for the complete moles. The diagnosis, treatment and follow-up of hydatiform mole have been under important changes in the last years. The number of asymptomatic patients has increased, due to the use of ultrasonography at the onset of pregnancy. The use of medication that induces uterine contractions must be avoided, and vacuum aspiration should be used. Soon after emptying the mole, a hormonal contraceptive method should be prescribed. Follow-up should be based on weekly serial dosages of chorionic gonadotropin. It is important that the method employed detects all the forms of chorionic gonadotropins (intact molecule, with hyper glycol, free β subunit, and central fragment β subunit.

  18. Photodynamic therapy of cervical intraepithelial neoplasia

    Science.gov (United States)

    Inada, Natalia M.; Lombardi, Welington; Leite, Marieli F. M.; Trujillo, Jose R.; Kurachi, Cristina; Bagnato, Vanderlei S.

    2014-03-01

    Photodynamic therapy (PDT) is a technique that has been used for the treatment of tumors, especially in Gynecology. The photodynamic reaction is based on the production of reactive oxygen species after the activation of a photosensitizer. Advantages of the PDT in comparison to the surgical resection are: ambulatory treatment and tissue recovery highly satisfactory, through a non-invasive procedure. The cervical intraepithelial neoplasia (CIN) grades I and II presents potential indications for PDT. The aim of the proposed study is to evaluate the safety and efficacy of the PDT for the diagnostics and treatment of CIN I and II. The equipment and the photosensitizer are produced in Brazil with a representative low cost. It is possible to visualize the fluorescence of the cervix and to treat the lesions, without side effects. The proposed clinical protocol shows great potential to become a public health technique.

  19. Dermatologic symptoms associated with gastrointestinal neoplasia

    Directory of Open Access Journals (Sweden)

    Beata Młynarczyk-Bonikowska

    2017-03-01

    Full Text Available Gastrointestinal tumors are among the most common neoplastic causes of death worldwide. Presence of characteristic skin lesions can allow faster diagnosis and therapy and this way can increase the probability of a cure. In the paper we present the most important paraneoplastic syndromes that can coexist with gastrointestinal malignancy including colon, gastric, esophagus and pancreatic cancers. We take into account genetic syndromes such as Cowden syndrome, familial atypical multiple mole melanoma syndrome (FAMMM (melanoma/pancreatic cancer, Clarke Howel-Evans, Peutz-Jeghers, Muir-Torre, Gardner syndromes and acquired syndromes such as acantosis nigricans maligna, tripe palms, Leser-Trelat, Bazex, hypertrichosis languinosa, erythema gyratum repens , carcinoid and glucagonoma syndrome. We also include cutaneous metastases and coexistence of neoplasia in some cases of dermatomyositis.

  20. IFPA Meeting 2010 Workshops Report II: Placental pathology; trophoblast invasion; fetal sex; parasites and the placenta; decidua and embryonic or fetal loss; trophoblast differentiation and syncytialisation.

    Science.gov (United States)

    Al-Khan, A; Aye, I L; Barsoum, I; Borbely, A; Cebral, E; Cerchi, G; Clifton, V L; Collins, S; Cotechini, T; Davey, A; Flores-Martin, J; Fournier, T; Franchi, A M; Fretes, R E; Graham, C H; Godbole, G; Hansson, S R; Headley, P L; Ibarra, C; Jawerbaum, A; Kemmerling, U; Kudo, Y; Lala, P K; Lassance, L; Lewis, R M; Menkhorst, E; Morris, C; Nobuzane, T; Ramos, G; Rote, N; Saffery, R; Salafia, C; Sarr, D; Schneider, H; Sibley, C; Singh, A T; Sivasubramaniyam, T S; Soares, M J; Vaughan, O; Zamudio, S; Lash, G E

    2011-03-01

    Workshops are an important part of the IFPA annual meeting. At IFPA Meeting 2010 diverse topics were discussed in twelve themed workshops, six of which are summarized in this report. 1. The placental pathology workshop focused on clinical correlates of placenta accreta/percreta. 2. Mechanisms of regulation of trophoblast invasion and spiral artery remodeling were discussed in the trophoblast invasion workshop. 3. The fetal sex and intrauterine stress workshop explored recent work on placental sex differences and discussed them in the context of whether boys live dangerously in the womb.4. The workshop on parasites addressed inflammatory responses as a sign of interaction between placental tissue and parasites. 5. The decidua and embryonic/fetal loss workshop focused on key regulatory mediators in the decidua, embryo and fetus and how alterations in expression may contribute to different diseases and adverse conditions of pregnancy. 6. The trophoblast differentiation and syncytialisation workshop addressed the regulation of villous cytotrophoblast differentiation and how variations may lead to placental dysfunction and pregnancy complications. Copyright © 2011 Elsevier Ltd. All rights reserved.

  1. Relaxin, its receptor (RXFP1), and insulin-like peptide 4 expression through gestation and in placenta accreta.

    Science.gov (United States)

    Goh, William; Yamamoto, Sandra Y; Thompson, Karen S; Bryant-Greenwood, Gillian D

    2013-08-01

    This study was designed to show whether placental relaxin (RLN), its receptor (RXFP1), or insulin-like peptide 4 (INSL4) might have altered expression in patients with placenta accreta. The baseline expression of their genes through gestation (n = 34) was quantitated in the placental basal plate (BP) and villous trophoblast (TR), and compared to their expression in placenta accreta (n = 6). The proteins were also immunolocalized and quantitated in the accreta tissues. The messenger RNAs (mRNAs) of matrix metalloproteinase 9, -2, and tissue inhibitors of matrix metalloproteinase (TIMP)-1 were also measured. Results demonstrated that the BP and TR expressed low levels of RLN/RXFP1 and INSL4 through gestation. In accreta, increased RLN gene and protein in BP were associated with antepartum bleeding whereas INSL4 expression decreased throughout the TR. There were no changes in mRNAs for MMPs, but TIMP-1 was increased only in the invasive TR.

  2. Suppression of STAT3 Signaling by Δ9-Tetrahydrocannabinol (THC) Induces Trophoblast Dysfunction.

    Science.gov (United States)

    Chang, Xinwen; Bian, Yiding; He, Qizhi; Yao, Julei; Zhu, Jingping; Wu, Jinting; Wang, Kai; Duan, Tao

    2017-01-01

    Marijuana is a widely used illicit drug and its consumption during pregnancy has been associated with adverse reproductive outcomes. The purpose of this study was to determine the effects of chronic intake of Δ9-tetrahydrocannabinol (THC), the major component of marijuana, on trophoblast function, placental development, and birth outcomes. The pathological characteristics and distribution of cannabinoid receptors in placenta were observed by immunohistochemical (IHC) staining. Cell migration in response to THC was measured by transwell assays. The levels of cannabinoid receptors and Signal Transducer and Activator of Transcription 3 (STAT3) were detected by western blot. We found the placenta expressed two main cannabinoid receptors, suggesting that THC induced biological responses in placental cells. Supporting this hypothesis, we observed dramatic alterations of placental morphology in marijuana users. Using THC and inhibitors of cannabinoid receptors, we demonstrated that THC impaired trophoblast cell migration and invasion partly via cannabinoid receptors. Additionally, pregnant mice injected with THC showed adverse reproductive events including reduced number of fetuses, lower maternal and placental weights. Mechanistically, STAT3 signaling pathway was involved in the THC-induced suppression of trophoblast cell motility and pregnancy outcomes. Our study indicates that the STAT3 signaling pathway plays a critical role in THC-induced trophoblast dysfunction. © 2017 The Author(s). Published by S. Karger AG, Basel.

  3. Synthesis and release of fatty acids by human trophoblast cells in culture

    International Nuclear Information System (INIS)

    Coleman, R.A.; Haynes, E.B.

    1987-01-01

    In order to determine whether placental cells can synthesize and release fatty acids, trophoblast cells from term human placentas were established in monolayer culture. The cells continued to secrete placental lactogen and progesterone and maintained specific activities of critical enzymes of triacylglycerol and phosphatidylcholine biosynthesis for 24 to 72 hr in culture. Fatty acid was rapidly synthesized from [ 14 C]acetate and released by the cells. Palmitoleic, palmitic, and oleic acids were the major fatty acids synthesized from [ 14 C]acetate and released. Small amounts of lauric, myristic, and stearic acids were also identified. [ 14 C]acetate was also incorporated into cellular triacylglycerol, phospholipid, and cholesterol, but radiolabeled free fatty acid did not accumulate intracellularly. In a pulse-chase experiment, cellular glycerolipids were labeled with [1- 14 C]oleate; trophoblast cells then released 14 C-labeled fatty acid into the media as the cellular content of labeled phospholipid and triacylglycerol decreased without intracellular accumulation of free fatty acid. Twenty percent of the 14 C-label lost from cellular glycerolipid could not be recovered as a chloroform-extractable product, suggesting that some of the hydrolyzed fatty acid had been oxidized. These data indicate that cultured placenta trophoblast cells can release fatty acids that have either been synthesized de novo or that have been hydrolyzed from cellular glycerolipids. Trophoblast cells in monolayer culture should provide an excellent model for molecular studies of placental fatty acid metabolism and release

  4. Development of Non-Viral, Trophoblast-Specific Gene Delivery for Placental Therapy.

    Directory of Open Access Journals (Sweden)

    Noura Abd Ellah

    Full Text Available Low birth weight is associated with both short term problems and the fetal programming of adult onset diseases, including an increased risk of obesity, diabetes and cardiovascular disease. Placental insufficiency leading to intrauterine growth restriction (IUGR contributes to the prevalence of diseases with developmental origins. Currently there are no therapies for IUGR or placental insufficiency. To address this and move towards development of an in utero therapy, we employ a nanostructure delivery system complexed with the IGF-1 gene to treat the placenta. IGF-1 is a growth factor critical to achieving appropriate placental and fetal growth. Delivery of genes to a model of human trophoblast and mouse placenta was achieved using a diblock copolymer (pHPMA-b-pDMAEMA complexed to hIGF-1 plasmid DNA under the control of trophoblast-specific promoters (Cyp19a or PLAC1. Transfection efficiency of pEGFP-C1-containing nanocarriers in BeWo cells and non-trophoblast cells was visually assessed via fluorescence microscopy. In vivo transfection and functionality was assessed by direct placental-injection into a mouse model of IUGR. Complexes formed using pHPMA-b-pDMAEMA and CYP19a-923 or PLAC1-modified plasmids induce trophoblast-selective transgene expression in vitro, and placental injection of PLAC1-hIGF-1 produces measurable RNA expression and alleviates IUGR in our mouse model, consequently representing innovative building blocks towards human placental gene therapies.

  5. The curative effect of a second curettage in persistent trophoblastic disease: a retrospective cohort survey.

    NARCIS (Netherlands)

    Trommel, N.E. van; Massuger, L.F.A.G.; Verheijen, R.; Sweep, C.G.J.; Thomas, C.M.G.

    2005-01-01

    OBJECTIVE: To assess the curative effect of a second curettage in patients with low-risk Persistent Trophoblastic Disease (PTD) after molar pregnancy. METHODS: A retrospective cohort survey was performed on 2122 patients registered with the Dutch Central Registry for Hydatidiform Moles between 1987

  6. Pre-evacuation hCG glycoforms in uneventful complete hydatidiform mole and persistent trophoblastic disease.

    NARCIS (Netherlands)

    Thomas, C.M.G.; Kerkmeijer, L.G.W.; Ariaens, H.J.; Steen, R. van der; Massuger, L.F.A.G.; Sweep, F.C.

    2010-01-01

    OBJECTIVE: To investigate whether the glycoform distribution patterns of human chorionic gonadotropin (hCG) obtained by chromatofocusing in pre-evacuation serum are different for patients who will eventually develop into persistent trophoblastic disease in case of complete hydatidiform mole

  7. Oxygen Modulates Human Decidual Natural Killer Cell Surface Receptor Expression and Interactions with Trophoblasts1

    Science.gov (United States)

    Wallace, Alison E.; Goulwara, Sonu S.; Whitley, Guy S.; Cartwright, Judith E.

    2014-01-01

    Decidual natural killer (dNK) cells have been shown to both promote and inhibit trophoblast behavior important for decidual remodeling in pregnancy and have a distinct phenotype compared to peripheral blood NK cells. We investigated whether different levels of oxygen tension, mimicking the physiological conditions of the decidua in early pregnancy, altered cell surface receptor expression and activity of dNK cells and their interactions with trophoblast. dNK cells were isolated from terminated first-trimester pregnancies and cultured in oxygen tensions of 3%, 10%, and 21% for 24 h. Cell surface receptor expression was examined by flow cytometry, and the effects of secreted factors in conditioned medium (CM) on the trophoblast cell line SGHPL-4 were assessed in vitro. SGHPL-4 cells treated with dNK cell CM incubated in oxygen tensions of 10% were significantly more invasive (P cells treated with dNK cell CM incubated in oxygen tensions of 3% or 21%. After 24 h, a lower percentage of dNK cells expressed CD56 at 21% oxygen (P cells expressed NKG2D at 10% oxygen (P oxygen tensions, with large patient variation. This study demonstrates dNK cell phenotype and secreted factors are modulated by oxygen tension, which induces changes in trophoblast invasion and endovascular-like differentiation. Alterations in dNK cell surface receptor expression and secreted factors at different oxygen tensions may represent regulation of function within the decidua during the first trimester of pregnancy. PMID:25232021

  8. Formaldehyde Crosses the Human Placenta and Affects Human Trophoblast Differentiation and Hormonal Functions.

    Directory of Open Access Journals (Sweden)

    Guillaume Pidoux

    Full Text Available The chorionic villus of the human placenta is the source of specific endocrine functions and nutrient exchanges. These activities are ensured by the syncytiotrophobast (ST, which bathes in maternal blood. The ST arises and regenerates throughout pregnancy by fusion of underlying cytotrophoblasts (CT. Any anomaly of ST formation or regeneration can affect pregnancy outcome and fetal growth. Because of its direct interaction with maternal blood, the ST is sensitive to drugs, pollutants and xenohormones. Ex vivo assays of perfused cotyledon show that formaldehyde, a common pollutant present in furniture, paint and plastics, can accumulate in the human placenta and cross to the fetal compartment. By means of RT-qPCR, immunoblot and immunocytochemistry experiments, we demonstrate in vitro that formaldehyde exerts endocrine toxicity on human trophoblasts, including a decrease in the production of protein hormones of pregnancy. In addition, formaldehyde exposure triggered human trophoblast fusion by upregulating syncitin-1 receptor expression (ASC-type amino-acid transporter 2: ASCT2. Moreover, we show that formaldehyde-exposed trophoblasts present an altered redox status associated with oxidative stress, and an increase in ASCT2 expression intended to compensate for this stress. Finally, we demonstrate that the adverse effects of formaldehyde on trophoblast differentiation and fusion are reversed by N-acetyl-L-cysteine (Nac, an antioxidant.

  9. Oxygen concentration modulates cellular senescence and autophagy in human trophoblast cells.

    Science.gov (United States)

    Seno, Kotomi; Tanikawa, Nao; Takahashi, Hironori; Ohkuchi, Akihide; Suzuki, Hirotada; Matsubara, Shigeki; Iwata, Hisataka; Kuwayama, Takehito; Shirasuna, Koumei

    2018-02-15

    We investigated the effect of oxygen concentrations on cellular senescence and autophagy and examined the role of autophagy in human trophoblast cells. Human first-trimester trophoblast cells (Sw.71) were incubated under 21%, 5%, or 1% O 2 concentrations for 24 hours. We examined the extent of senescence caused using senescence-associated β-galactosidase (SA-β-Gal) and senescence-associated secretory phenotype (SASP) as markers. Moreover, we examined the role of autophagy in causing cellular senescence using an autophagy inhibitor (3-methyladenine, 3MA). Physiological normoxia (5% O 2 ) decreased SA-β-Gal-positive cells and SASP including interleukin-6 (IL-6) and IL-8 compared with cultured cells in 21% O 2 . Pathophysiological hypoxia (1% O 2 ) caused cytotoxicity, including extracellular release of ATP and lactate dehydrogenase, and decreased senescence phenotypes. 3MA-treated trophoblast cells significantly suppressed senescence markers (SA-β-Gal-positive cells and SASP secretion) in O 2 -independent manner. We conclude that O 2 concentration modulates cellular senescence phenotypes regulating autophagy in the human trophoblast cells. Moreover, inhibiting autophagy suppresses cellular senescence, suggesting that autophagy contributes to oxygen stress-induced cellular senescence. © 2018 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  10. Suppression of STAT3 Signaling by Δ9-Tetrahydrocannabinol (THC Induces Trophoblast Dysfunction

    Directory of Open Access Journals (Sweden)

    Xinwen Chang

    2017-06-01

    Full Text Available Aims: Marijuana is a widely used illicit drug and its consumption during pregnancy has been associated with adverse reproductive outcomes. The purpose of this study was to determine the effects of chronic intake of Δ9-tetrahydrocannabinol (THC, the major component of marijuana, on trophoblast function, placental development, and birth outcomes. Methods: The pathological characteristics and distribution of cannabinoid receptors in placenta were observed by immunohistochemical (IHC staining. Cell migration in response to THC was measured by transwell assays. The levels of cannabinoid receptors and Signal Transducer and Activator of Transcription 3 (STAT3 were detected by western blot. Results: We found the placenta expressed two main cannabinoid receptors, suggesting that THC induced biological responses in placental cells. Supporting this hypothesis, we observed dramatic alterations of placental morphology in marijuana users. Using THC and inhibitors of cannabinoid receptors, we demonstrated that THC impaired trophoblast cell migration and invasion partly via cannabinoid receptors. Additionally, pregnant mice injected with THC showed adverse reproductive events including reduced number of fetuses, lower maternal and placental weights. Mechanistically, STAT3 signaling pathway was involved in the THC-induced suppression of trophoblast cell motility and pregnancy outcomes. Conclusion: Our study indicates that the STAT3 signaling pathway plays a critical role in THC-induced trophoblast dysfunction.

  11. Application of monoclonal antibodies against trophoblastic cells to study female infertility

    Czech Academy of Sciences Publication Activity Database

    Sedláková, Alena; Elzeinová, Fatima; Bukovský, A.; Madar, J.; Ulčová-Gallová, Z.; Pěknicová, Jana

    2004-01-01

    Roč. 51, č. 6 (2004), s. 482-483 ISSN 1046-7408. [European congress of reproductive immunology. Plzeň, 30.06.2004-03.07.2004] R&D Projects: GA MŠk LN00B030 Keywords : trophoblast * monoclonal antibody * ELISA Subject RIV: EC - Immunology Impact factor: 1.808, year: 2004

  12. Oxygen tension regulates the miRNA profile and bioactivity of exosomes released from extravillous trophoblast cells - Liquid biopsies for monitoring complications of pregnancy.

    Directory of Open Access Journals (Sweden)

    Grace Truong

    Full Text Available Our understanding of how cells communicate has undergone a paradigm shift since the recent recognition of the role of exosomes in intercellular signaling. In this study, we investigated whether oxygen tension alters the exosome release and miRNA profile from extravillous trophoblast (EVT cells, modifying their bioactivity on endothelial cells (EC. Furthermore, we have established the exosomal miRNA profile at early gestation in women who develop pre-eclampsia (PE and spontaneous preterm birth (SPTB. HTR-8/SVneo cells were used as an EVT model. The effect of oxygen tension (i.e. 8% and 1% oxygen on exosome release was quantified using nanocrystals (Qdot® coupled to CD63 by fluorescence NTA. A real-time, live-cell imaging system (Incucyte™ was used to establish the effect of exosomes on EC. Plasma samples were obtained at early gestation (<18 weeks and classified according to pregnancy outcomes. An Illumina TrueSeq Small RNA kit was used to construct a small RNA library from exosomal RNA obtained from EVT and plasma samples. The number of exosomes was significantly higher in EVT cultured under 1% compared to 8% oxygen. In total, 741 miRNA were identified in exosomes from EVT. Bioinformatic analysis revealed that these miRNA were associated with cell migration and cytokine production. Interestingly, exosomes isolated from EVT cultured at 8% oxygen increased EC migration, whilst exosomes cultured at 1% oxygen decreased EC migration. These changes were inversely proportional to TNF-α released from EC. Finally, we have identified a set of unique miRNAs in exosomes from EVT cultured at 1% oxygen and exosomes isolated from the circulation of mothers at early gestation, who later developed PE and SPTB. We suggest that aberrant exosomal signalling by placental cells is a common aetiological factor in pregnancy complications characterised by incomplete SpA remodeling and is therefore a clinically relevant biomarker of pregnancy complications.

  13. Hypoxic stress induces, but cannot sustain trophoblast stem cell differentiation to labyrinthine placenta due to mitochondrial insufficiency

    Directory of Open Access Journals (Sweden)

    Yufen Xie

    2014-11-01

    Full Text Available Dysfunctional stem cell differentiation into placental lineages is associated with gestational diseases. Of the differentiated lineages available to trophoblast stem cells (TSC, elevated O2 and mitochondrial function are necessary to placental lineages at the maternal–placental surface and important in the etiology of preeclampsia. TSC lineage imbalance leads to embryonic failure during uterine implantation. Stress at implantation exacerbates stem cell depletion by decreasing proliferation and increasing differentiation. In an implantation site O2 is normally ~2%. In culture, exposure to 2% O2 and fibroblast growth factor 4 (FGF4 enabled the highest mouse TSC multipotency and proliferation. In contrast, hypoxic stress (0.5% O2 initiated the most TSC differentiation after 24 h despite exposure to FGF4. However, hypoxic stress supported differentiation poorly after 4–7 days, despite FGF4 removal. At all tested O2 levels, FGF4 maintained Warburg metabolism; mitochondrial inactivity and aerobic glycolysis. However, hypoxic stress suppressed mitochondrial membrane potential and maintained low mitochondrial cytochrome c oxidase (oxidative phosphorylation/OxPhos, and high pyruvate kinase M2 (glycolysis despite FGF4 removal. Inhibiting OxPhos inhibited optimum differentiation at 20% O2. Moreover, adding differentiation-inducing hyperosmolar stress failed to induce differentiation during hypoxia. Thus, differentiation depended on OxPhos at 20% O2; hypoxic and hyperosmolar stresses did not induce differentiation at 0.5% O2. Hypoxia-limited differentiation and mitochondrial inhibition and activation suggest that differentiation into two lineages of the labyrinthine placenta requires O2 > 0.5–2% and mitochondrial function. Stress-activated protein kinase increases an early lineage and suppresses later lineages in proportion to the deviation from optimal O2 for multipotency, thus it is the first enzyme reported to prioritize differentiation.

  14. Early expression of pregnancy-specific glycoprotein 22 (PSG22) by trophoblast cells modulates angiogenesis in mice.

    Science.gov (United States)

    Blois, Sandra M; Tirado-González, Irene; Wu, Julie; Barrientos, Gabriela; Johnson, Briana; Warren, James; Freitag, Nancy; Klapp, Burghard F; Irmak, Ster; Ergun, Suleyman; Dveskler, Gabriela S

    2012-06-01

    Mouse and human pregnancy-specific glycoproteins (PSG) are known to exert immunomodulatory functions during pregnancy by inducing maternal leukocytes to secrete anti-inflammatory cytokines that promote a tolerogenic decidual microenvironment. Many such anti-inflammatory mediators also function as proangiogenic factors, which, along with the reported association of murine PSG with the uterine vasculature, suggest that PSG may contribute to the vascular adaptations necessary for successful implantation and placental development. We observed that PSG22 is strongly expressed around the embryonic crypt on Gestation Day 5.5, indicating that trophoblast giant cells are the main source of PSG22 during the early stages of pregnancy. PSG22 treatment up-regulated the secretion of transforming growth factor beta 1 and vascular endothelial growth factor A (VEGFA) in murine macrophages, uterine dendritic cells, and natural killer cells. A possible role of PSGs in uteroplacental angiogenesis is further supported by the finding that incubation of endothelial cells with PSG22 resulted in the formation of tubes in the presence and absence of VEGFA. We determined that PSG22, like human PSG1 and murine PSG17 and PSG23, binds to the heparan sulfate chains in syndecans. Therefore, our findings indicate that despite the independent evolution and expansion of human and rodent PSG, members in both families have conserved functions that include their ability to induce anti-inflammatory cytokines and proangiogenic factors as well as to induce the formation of capillary structures by endothelial cells. In summary, our results indicate that PSG22, the most abundant PSG expressed during mouse early pregnancy, is likely a major contributor to the establishment of a successful pregnancy.

  15. Genetic influence on prolonged gestation

    DEFF Research Database (Denmark)

    Laursen, Maja; Bille, Camilla; Olesen, Annette Wind

    2004-01-01

    OBJECTIVE: The purpose of this study was to test a possible genetic component to prolonged gestation. STUDY DESIGN: The gestational duration of single, first pregnancies by both female and male twins was obtained by linking the Danish Twin Registry, The Danish Civil Registration System, and the D...... factors. CONCLUSION: Maternal genes influence prolonged gestation. However, a substantial paternal genetic influence through the fetus was not found....

  16. Can the Ni classification of vessels predict neoplasia?

    DEFF Research Database (Denmark)

    Mehlum, Camilla Slot; Rosenberg, Tine; Dyrvig, Anne-Kirstine

    2018-01-01

    OBJECTIVES: The Ni classification of vascular change from 2011 is well documented for evaluating pharyngeal and laryngeal lesions, primarily focusing on cancer. In the planning of surgery it may be more relevant to differentiate neoplasia from non-neoplasia. We aimed to evaluate the ability...... of the Ni classification to predict laryngeal or hypopharyngeal neoplasia and to investigate if a changed cutoff value would support the recent European Laryngological Society (ELS) proposal of perpendicular vascular changes as indicative of neoplasia. DATA SOURCES: PubMed, Embase, Cochrane, and Scopus....... The pooled sensitivity and specificity of the Ni classification with two different cutoffs were calculated, and bubble and summary receiver operating characteristics plots were created. RESULTS: The combined sensitivity of five studies (n = 687) with Ni type IV-V defined as test-positive was 0.89 (95...

  17. Inmunología tumoral y neoplasias del sistema inmune

    OpenAIRE

    Sen Fernández, María Luz de la; Sempere Ortells, José Miguel; Marco, Francisco M.; Vázquez Araujo, Begoña

    2012-01-01

    Inmunología tumoral: vigilancia inmunológica, antígenos tumorales, respuesta inmune antitumoral, escape tumoral. Inmunología y diagnóstico. Inmunoterapia. Neoplasias del sistema inmune: leucemias y linfomas.

  18. Gestational surrogacy: Psychosocial aspects

    Directory of Open Access Journals (Sweden)

    Nicolás Ruiz-Robledillo

    2016-12-01

    Full Text Available Innovation in assisted reproductive technologies together with increased infertility and new family structures are increasing the use of gestational surrogacy as a means to have children. Before, during and after the process, it is necessary to study the psychosocial characteristics of triad members: the gestational surrogate, intended parents, and offspring. Research has indicated positive adaptation to the process and benefits for all members of the triad. Altruism is the main motivation of surrogates. Notably, psychological well-being has been found to be higher in individuals who have become parents through surrogacy than in those who have used egg donation or have followed a natural process of conception. Moreover, no differences in psychosocial characteristics have been observed in the offspring, compared with children born through natural conception or egg donation. Results highlight the positive aspects of surrogacy. Future research should investigate psychosocial factors that modulate the process, acting as risk and protective factors for well-being of the triad members, and identify the optimal profiles of surrogates for the process to be a success.

  19. Indomethacin inhibits the uptake of 22sodium by ovine trophoblastic tissue in vitro

    International Nuclear Information System (INIS)

    Lewis, G.S.

    1986-01-01

    Blastocysts from several species synthesize prostaglandins in vitro, but the exact functions of the prostaglandins are unknown. The purpose of this study was to determine if indomethacin, an inhibitor of prostaglandin synthesis, would inhibit the uptake of 22sodium ([22Na]) by ovine trophoblastic tissue. To determine the concentration of indomethacin that would inhibit the synthesis of PGF2 alpha and 13,14-dihydro-15-keto-PGF2 alpha (PGFM) by blastocysts, blastocysts were collected from ewes 16 days after mating, sliced into pieces approximately 2 mm in length and incubated for 48 h at 37 degrees C in 2 ml of medium containing either 0, 0.2, 0.4, 0.8 or 1.6 mM of indomethacin. Concentrations of indomethacin greater than or equal to 0.2 mM reduced (P less than .01) trophoblastic release (ng/micrograms DNA) of PGF2 alpha from 205 +/- 71.2 to less than or equal to 3.3 +/- 0.2, reduced PGFM from 0.7 +/- 0.1 to less than or equal to 0.17 +/- 0.01, and inhibited formation of trophoblastic vesicles. In a second experiment, blastocysts were recovered from ewes 16 days after mating and pieces of trophoblast were incubated with [22Na] and either 0 or 0.4 mM of indomethacin. Indomethacin reduced the uptake of [22Na], which is an indirect measure of the transport of water across epithelia, from 3680 +/- 1118 to 934 +/- 248 cpm/micrograms DNA (P less than .03) and prevented formation of trophoblastic vesicles. Prostaglandins produced by ovine blastocysts might be involved in controlling uptake of water, which is essential for expansion of blastocysts

  20. Vitamin D attenuates sphingosine-1-phosphate (S1P)-mediated inhibition of extravillous trophoblast migration.

    Science.gov (United States)

    Westwood, Melissa; Al-Saghir, Khiria; Finn-Sell, Sarah; Tan, Cherlyn; Cowley, Elizabeth; Berneau, Stéphane; Adlam, Daman; Johnstone, Edward D

    2017-12-01

    Failure of trophoblast invasion and remodelling of maternal blood vessels leads to the pregnancy complication pre-eclampsia (PE). In other systems, the sphingolipid, sphingosine-1-phosphate (S1P), controls cell migration therefore this study determined its effect on extravillous trophoblast (EVT) function. A transwell migration system was used to assess the behaviour of three trophoblast cell lines, Swan-71, SGHPL-4, and JEG3, and primary human trophoblasts in the presence or absence of S1P, S1P pathway inhibitors and 1,25(OH) 2 D 3 . QPCR and immunolocalisation were used to demonstrate EVT S1P receptor expression. EVTs express S1P receptors 1, 2 and 3. S1P inhibited EVT migration. This effect was abolished in the presence of the specific S1PR2 inhibitor, JTE-013 (p S1P alone) whereas treatment with the S1R1/3 inhibitor, FTY720, had no effect. In other cell types S1PR2 is regulated by vitamin D; here we found that treatment with 1,25(OH) 2 D 3 for 48 or 72 h reduces S1PR2 (4-fold; S1P did not inhibit the migration of cells exposed to 1,25(OH) 2 D 3 (p S1P receptor isoforms, S1P predominantly signals through S1PR2/Gα 12/13 to activate Rho and thereby acts as potent inhibitor of EVT migration. Importantly, expression of S1PR2, and therefore S1P function, can be down-regulated by vitamin D. Our data suggest that vitamin D deficiency, which is known to be associated with PE, may contribute to the impaired trophoblast migration that underlies this condition. Copyright © 2017 Elsevier Ltd. All rights reserved.

  1. Molecular biological factors in the diagnosis of cervical intraepithelial neoplasias

    Directory of Open Access Journals (Sweden)

    Yu. N. Ponomareva

    2010-01-01

    Full Text Available The authors have made a complex analysis of the molecular biological factors associated with cervical intraepithelial neoplasia. They have revealed that infection by oncogenic human papillomavirus types is associated with suppressed apoptosis and enhanced cellular proliferative activity, which can be effectively used in the diagnosis and prediction of cervical neoplasias to optimize management tac- tics and to improve the results of treatment.

  2. Progranulin shows cytoprotective effects on trophoblast cells in vitro but does not antagonize TNF-α-induced apoptosis.

    Science.gov (United States)

    Stubert, Johannes; Waldmann, Kathrin; Dieterich, Max; Richter, Dagmar-Ulrike; Briese, Volker

    2014-11-01

    The glycoprotein progranulin directly binds to TNF-receptors and thereby can antagonize the inflammatory effects of TNF-α. Here we analyzed the impact of both cytokines on cytotoxicity and viability of trophoblast cells. Isolated villous first trimester human trophoblast cells and the human choriocarcinoma cell line BeWo were treated with recombinant human progranulin and TNF-α. Analyses were performed by LDH- and MTT-assay and measurement of caspase-8-activity. Progranulin treatment showed some cytoprotective effects on isolated trophoblast cells. However, TNF-α-induced apoptosis was not antagonized by addition of progranulin. Effects were similar, but more pronounced in BeWo cells. The cytoprotective activity of progranulin on trophoblast cells in vitro was only weak and of doubtful biologic relevance. It was not able to antagonize TNF-α. Future studies should focus on possible paracrine activities of progranulin.

  3. Gestational diabetes: A clinical update

    DEFF Research Database (Denmark)

    Kampmann, Ulla; Madsen, Lene Ring; Skajaa, Gitte Oeskov

    2015-01-01

    Gestational diabetes mellitus (GDM) is increasing in prevalence in tandem with the dramatic increase in the prevalence of overweight and obesity in women of childbearing age. Much controversy surrounds the diagnosis and management of gestational diabetes, emphasizing the importance and relevance...

  4. Screening for gestational diabetes mellitus

    NARCIS (Netherlands)

    van Leeuwen, M.

    2012-01-01

    Gestational diabetes mellitus is associated with increased risk of complications for mother and child. Along with the growing epidemic of obesity and type 2 diabetes, the prevalence of gestational diabetes is expected to rise. With adequate and timely treatment, the risk of complications is reduced.

  5. Controversies in gestational diabetes.

    Science.gov (United States)

    Nolan, Christopher J

    2011-02-01

    Gestational diabetes mellitus (GDM) and controversy are old friends. However, several major studies in the field have clarified some of the main issues. There is now no doubt that hyperglycaemia, at levels less than those that occur in overt diabetes, is associated with adverse pregnancy outcomes, such as large-for-gestational age infants, neonatal hyperinsulinism, neonatal hypoglycaemia and pre-eclampsia. We also have evidence now that a standard approach to GDM with diagnosis at 24-28 weeks, dietary advice, self-monitoring of blood glucose and insulin therapy as needed reduces these adverse perinatal outcomes. Unknown, however, is if this same approach is effective at reducing long-term risks of metabolic syndrome, type 2 diabetes and cardiovascular disease in both the mothers and babies. For example, could our management strategies miss critical time points of fuel-mediated injury to the foetus important for the baby's long-term metabolic health? The implications of a recent international consensus statement on new diagnostic criteria for GDM are discussed, as well as issues relating to the timing of diagnosis. The potential place for a risk calculator for adverse outcomes in GDM pregnancy that takes into account glycaemic and non-glycaemic risk factors is considered. Such a tool could help stratify GDM women to different levels of care. Ongoing issues relating to maternal glycaemic and foetal growth targets, and the use of oral hypoglycaemic agents in GDM are discussed. To resolve some of the remaining controversies, further carefully designed randomised controlled trials in GDM with long-term follow-up of both mothers and babies are necessary. Copyright © 2010 Elsevier Ltd. All rights reserved.

  6. Lobular neoplasia: frequency and association with other breast lesions

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    Gobbi Helenice

    2011-08-01

    Full Text Available Abstract Background Using new molecular biology techniques, recent studies have implicated a common evolutionary pathway between lobular neoplasia, lobular carcinomas, and columnar cell lesions. Our aims were to assess the frequency of lobular neoplasia in a series of breast biopsies that were performed and examined in the same institution and to analyze the association between subtypes of lobular neoplasia and benign and malignant breast lesions. Methods Cases were selected after reviewing archived pathological reports in the Breast Pathology Laboratory, School of Medicine of Federal University of Minas Gerais (1999-2008. Cases of lobular neoplasia were reviewed and classified as atypical lobular hyperplasia, ductal involvement by cells of atypical lobular hyperplasia, lobular carcinoma in situ, and pleomorphic lobular carcinoma in situ. Coexistence of lobular neoplasia with other breast lesions, including columnar cell lesions, invasive ductal carcinoma and invasive lobular carcinoma, was evaluated. The association between lobular neoplasia and breast lesions was analyzed by Fisher's exact test and chi-square test for linear trend. Results We analyzed 5650 breast specimens, selecting 135 breast specimens (2.4% that had a diagnosis of lobular neoplasia, corresponding to 106 patients. Hematoxylin and eosin-stained slides were available for 84 cases, 5 of which were excluded because they contained only "indeterminate" in situ lesions. Of the 79 remaining cases, columnar cell lesions were present in 78.5%, primarily with columnar cell changes without atypia (67.7%. Invasive carcinoma was present in 45.6% of cases of lobular neoplasia--a similar frequency (47.2% as invasive ductal carcinoma and invasive lobular carcinoma. We noted a significant linear trend (p in situ compared with atypical lobular hyperplasia. Invasive lobular carcinomas were associated with lobular carcinoma in situ in 33% of cases, compared with 2.8% of atypical lobular

  7. Anal intraepitelial neoplasia: a narrative review

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    Garazi Elorza

    2016-01-01

    Full Text Available Anal intraepitelial neoplasia (AIN constitutes a major health problem in certain risk groups, such as patients with immunosuppression of varied origin, males who have sexual relations with other males, and females with a previous history of vaginal or cervical abnormalities in cytology. Its relationship with the human papillomavirus (HPV infection has been well documented; however, many of the factors involved in the progression and regression of the viral infection to dysplasia and anal carcinoma are unknown. AIN can be diagnosed through cytology of the anal canal or biopsy guided by high-resolution anoscopy. However, the need for these techniques in high-risk groups remains controversial. Treatment depends on the risk factors and given the high morbidity and high recurrence rates the utility of the different local treatments is still a subject of debate. Surgical biopsy is justified only in the case of progression suggesting lesions. The role of the vaccination in high-risk patients as primary prevention has been debated by different groups. However, there is no general consensus on its use or on the need for screening this population.

  8. Radiogenic neoplasia in thyroid and mammary clonogens

    International Nuclear Information System (INIS)

    Clifton, K.H.

    1993-01-01

    The induction of cancer by ionizing radiation is a matter of great practical importance to the nuclear industry, to national defense, to radiological medicine and to the general public. It is increasingly apparent that carcinogenesis is one of the leading dose-limiting effects of radiation exposure (Co90). Quantitative information at the cellular level is essential to an understanding of the mechanisms of radiogenic neoplastic initiation and the stages of promotion and progression to overt neoplasia. We have developed two experimental models, the rat thyroid and rat mammary clonogen transplant systems, for the quantitative study of radiation carcinogenesis at the cellular level in vivo (C185). The most important steps taken or completed during the current grant year include: (a) demonstration of the high age-dependent radiosensitivity of prepubertal rat mammary clonogens to radiogenic damage which may influence their susceptibility to neoplastic initiation, and (b) demonstration of the feasibility of using a molecular test for clonogenicity in which Simple Sequence Repeats in the DNA serve as identifying signals of the genotypic origin of the cells. We have also (c) set up a large carcinogenesis experiment to test the effect of close intercellular contact in thyroid glands in situ on promotion-progression of radiogenically initiated clonogens, (d) achieved considerable further concentration of thyroid clonogens, and (e) begun to explore whether thyroid cells can be induced to give rise to three dimensional multicellular structures in culture in reconstituted basement membrane. These are discussed in this report

  9. Y-27632 enhances differentiation of blastocyst like cystic human embryoid bodies to endocrinologically active trophoblast cells on a biomimetic platform

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    Totey Satish M

    2009-09-01

    Full Text Available Abstract Trophoblast differentiation and formation of the placenta are important events linked to post-implantation embryonic development. Models mimicking the biology of trophoblast differentiation in a post-implantation maternal microenvironment are needed for understanding disorders like placental-ischemia or for applications in drug-screening, and would help in overcoming the ethical impasse on using human embryos for such research. Here we attempt to create such a model by using embryoid bodies (EBs and a biomimetic platform composed of a bilayer of fibronectin and gelatin on top of low-melting agarose. Using this model we test the hypothesis that cystic-EBs (day 30 that resemble blastocysts morphologically, are better sources as compared to noncytic EBs (day 10, for functional trophoblast differentiation; and that the Rho kinases inhibitor Y27632 can enhance this differentiation. Non/cytic EBs with/out Y27632 were grown on this platform for 28 days, and screened from secretion and expression of trophoblast and other lineage markers using ECLIA, RT-PCR, and Immunofluorescence. All EBs attached on this surface and rapidly proliferated into hCG and progesterone (P2 secreting functional trophoblast cells. However, the cells derived from cytic-EBs and cytic-EBs+ Y27632 showed the maximum secretion of these hormones and expressed IGF2, supporting our hypothesis. Also Y27632 reduced extraembryonic endoderm and trophoblast lineage differentiation from early noncystic-EBs, whereas, it specifically enhanced the induction of trophoblast and multinucleated syncitiotrophoblast differentiation from late cystic-EBs. In vivo trophoblast differentiation can be replicated in fibronectin based biomaterials, using cytic-EBs and by maneuvering the Rho-ROCK pathways. Response of EBs to a compound may vary temporally, and determination of their right stage is crucial for applications in directed-differentiation or drug-screening.

  10. Decreased IL-33 Production Contributes to Trophoblast Cell Dysfunction in Pregnancies with Preeclampsia

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    Hong Chen

    2018-01-01

    Full Text Available Preeclampsia (PE is a life-threatening pregnancy complication which is related to aggradation of risk regarding fetal and maternal morbidity and mortality. Dysregulation of systemic inflammatory response and dysfunction of trophoblast cells have been proposed to be involved in the development and progression of PE. Some studies have demonstrated that interleukin-33 (IL-33 is an immunomodulatory cytokine that is associated with the immune regulation of tumor cells. However, little is known whether IL-33 and its receptor ST2/IL-1 R4 could regulate trophoblast cells, which are associated with the pathogenesis of PE. In this study, our target is to explore the impact of IL-33 on trophoblast cells and elucidate its underlying pathophysiological mechanisms. Placental tissues from the severe PE group (n=11 and the normotensive pregnant women’s group (n=11 were collected for the protein expression and distribution of IL-33 along with its receptor ST2/IL-1 R4 via Western blot analysis and immunohistochemistry, respectively. We discovered that the level of IL-33 was decreased in placental tissues of pregnant women with PE, while no distinction was observed in the expression of ST2/IL-1 R4. These results were further verified in villous explants which were treated with sodium nitroprusside with different concentrations, to simulate the pathological environment of PE. To investigate IL-33 effects on trophoblast cells separately, IL-33 shRNA was introduced into HTR8/SVneo cells and villi. IL-33 shRNA weakened the proliferation, migration, and invasion capacity of HTR8/SVneo cells. The migration distance of villous explants was also markedly decreased. The reduced invasion of trophoblast cells is a result of IL-33 knockdown which could be related to the decline of MMP2/9 activity and the increased utterance of TIMP1/2. Overall, our findings demonstrated that the reduction of IL-33 production was connected with the reduced functional capability of

  11. Effects of phytoestrogens genistein and daidzein on progesterone and estrogen (estradiol) production of human term trophoblast cells in vitro.

    Science.gov (United States)

    Richter, Dagmar Ulrike; Mylonas, Ioannis; Toth, Bettina; Scholz, Christoph; Briese, Volker; Friese, Klaus; Jeschke, Udo

    2009-01-01

    Phytoestrogens are a diverse group of nonsteroidal plant compounds that occur naturally in many plants. Because they possess a ring system similar to estrogens they are able to bind on estrogen receptors alpha and beta in humans. The effects of the phytoestrogens genistein and daidzein on the production of progesterone and estrogen in isolated human term trophoblast cells in vitro were tested in this study. Cytotrophoblast cells were isolated from human term placentas. Phytoestrogens genistein and daidzein were incubated in different concentrations with trophoblast cells. Untreated cells were used as controls. After 24 h aliquots were removed and tested for progesterone and estrogen production. The production of the steroid hormones progesterone and estrogen are influenced by phytoestrogens genistein and daidzein in human term trophoblast cells. A strong inhibition effect of both phytoestrogens tested in the production of progesterone was demonstrated. In addition, a significant stimulating effect on estrogen production by genistein and daidzein was observed. Results obtained with this study show that phytoestrogens (genistein and daidzein) sufficiently reduce progesterone production in human term trophoblast cells. Because blockade of progesterone is a possible mechanism involved in initiation of labor, we may speculate that high doses of phytoestrogens at the feto-maternal interphase could play a negative role in maintenance of pregnancy. Stimulation of estrogen production by genistein and daidzein in trophoblast cells is probably due to estrogen receptor blocking effects of both phytoestrogens. Trophoblast cells seem to compensate blocking of its estrogen receptors by higher estrogen production.

  12. [Heredity in renal and prostatic neoplasia].

    Science.gov (United States)

    Prayer Galetti, T; D'Arrigo, L; De Zorzi, L; Patarnello, T

    1997-09-01

    There is an ever growing report of data supporting the evidence that accumulated genetic changes underlie the development of neoplasia. The paradigma of this multistep process is colon cancer were cancer onset is associated, over decades, with at least seven genetic events. The number of genetic alterations increases moving from adenomatous lesions to colon cancer and, although the genetic alterations occur according to a preferred sequence, the total accumulation of changes rather than their sequential order is responsible of tumor biological behavior. It is noteworthy that, at least for this neoplasia, carcinogenesis appears to arise as a result of the mutational activation of oncogenes coupled with the mutational inactivation of tumor suppressor genes. In some cases mutant suppressor genes appear to exert a phenotypic effect even when present in the heterozygous state thus been non "recessive" at the cellular level. The general features of this model may apply also to renal cell cancer (RCC) and prostate cancer (CaP). Extensive literature exists on the cytogenetic and molecular findings in RCC. Only 2% of RCC are familiar, but molecular genetic studies of these cancers have provided important informations on RCC pathogenesis. As with other cancers, familiar RCC is characterized by an early age of onset and frequent multicentricity. A pathological classification useful in studying these patients subdivide renal cancers in papillary (pRCC) and non papillary (RCC) neoplasms. The most common cause of inherited RCC is the Von Hippel Lindau disease (VHL) a dominantly inherited multisystem disorder characterized by retinal and cerebellar hemangioblastomas, pheochromocytomas, pancreatic cysts and RCC. Over 70% of these patients will develop an RCC by their sixth decade. In 1993 the isolation of the tumor suppressor gene in VHL disease at the level of chromosome 3p25-p26 have lead to a better understanding of RCC. Most missense mutations are associated with high risk of

  13. DCLK1 immunoreactivity in colorectal neoplasia

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    Bellows CF

    2012-04-01

    Full Text Available Giuseppe Gagliardi1, Monica Goswami1, Roberto Passera2, Charles F Bellows11Department of Surgery and Pathology, Tulane University, New Orleans, LA, USA; 2Division of Nuclear Medicine Azienda Ospedaliero-Universitaria San Giovanni Battista, Turin, ItalyIntroduction: Microtubule-associated doublecortin and CaM kinase-like-1 (DCLK1 is a novel candidate marker for intestinal stem cells. The aim of our study was to assess DCLK1 immunoreactivity in colorectal carcinogenesis and its correlation with prognosis.Methods: DCLK1 immunostaining was performed in colorectal tissue from 71 patients, including 18 adenomatous polyps, 40 primary adenocarcinomas, and 14 metastatic lesions. Each case was evaluated by a combined scoring method based on the intensity of staining (score 0–3 and the percentage of tissue staining positive (score 0–3. Immunoexpression for DCLK1 was considered as positive when the combined score was 2–6 and negative with a score of 0–1.Results: Overall, 14/18 (78% of polyps, 30/40 (75% of primary adenocarcinomas, and 7/14 (50% of distant metastases were positive for DCLK1. In adenomatous polyps and primary cancer there was no association between DCLK1 staining score and tumor pathology. However, after curative colorectal cancer resection, patients whose tumor had a high (≥5 combined staining score had increased cancer-specific mortality compared to patients with low (0–4 staining score (hazard ratio 5.89; 95% confidence interval: 1.22–28.47; P = 0.027.Conclusion: We found that DCLK1 is frequently expressed in colorectal neoplasia and may be associated with poor prognosis. Further studies are necessary to validate the use of DCLK1 as a prognostic marker.Keywords: DCLK1, DCAMKL-1, gastrointestinal stem cell, cancer stem cell, adenomatous polyps, liver metastasis, immunohistochemistry

  14. Radiogenic neoplasia in thyroid and mammary clonogens

    International Nuclear Information System (INIS)

    Clifton, K.H.

    1992-01-01

    We have developed rat thyroid and mammary clonogen transplantation systems for the study of radiogenic cancer induction at the target cell level in vivo. The epithelial cell populations of both glands contain small subpopulations of cells which are capable of giving rise to monoclonal glandular structures when transplanted and stimulated with appropriate hormones. Previous results indicated that these clonogens are the precursor cells of radiogenic cancer, and that initiation, is common event at the clonegenic cell level. Detailed information on the physiologic control of clonogen proliferation, differentiation, and total numbers is thus essential to an understanding of the carcinogenic process. We report here studies on investigations on the relationships between grafted thyroid cell number and the rapidity and degree of reestablishment of the thyroid-hypothalamus-pituitary feedback axis in thyroidectomized rats maintained on a normal diet or an iodine deficient diet; studies of the persistence of, and the differentiation potential and functional characteristics of, the TSH-(thyrotropin-) responsive sub- population of clonogens during goitrogenesis, the plateau-phase of goiter growth, and goiter involution; studies of changes in the size of the clonogen sub-population during goitrogenesis, goiter involution and the response to goitrogen rechallenge; and a large carcinogenesis experiment on the nature of the grafted thyroid cell number-dependent suppression of promotion/progression to neoplasia in grafts of radiation-initiated thyroid cells. Data from these studies will be used in the design of future carcinogenesis experiments on neoplastic initiation by high and low LET radiations and on cell interactions during the neoplastic process

  15. Cutaneous neoplasia following PUVA therapy for psoriasis

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    McKenna, K.E.; Handley, J.; McGinn, S.; Allen, G. [Belfast City Hospital (United Kingdom). Dept. of Dermatology; Patterson, C.C. [Queen`s Univ., Belfast, Northern Ireland (United Kingdom)

    1996-04-01

    To determine the risk of cutaneous neoplasia following photochemotherapy (PUVA), we reviewed patients with psoriasis treated at out unit between 1979 and 1991. Two hundred and forty-five patients were assessed, with a median duration of follow-up of 9.5 years. Fifty-nine per cent were male, and 41% female. The median number of exposures was 59, and the median total dose was 133J/cm{sup 2} for the group as a whole. Non-melanoma skin cancers (NMSC) occurred in six individuals (2.4%), basal cell carcinoma occurred in all six and one individual also developed four squamous cell carcinomas and Bowen`s disease of the penis. No cases of malignant melanoma were recorded. Patients who developed NMSC received a median number of 225 exposures and a median cumulative dose of 654J/cm{sup 2}. Compared with a control study population in West Glamorgan, Wales, there was a 1.4 (95% confidence limits (CL) 0.5 and 3.1) times increased risk of NMSC. A statistically significant increased incidence of NMSC was found for patients who had received 100 or more exposures, and 250 or more J/cm{sup 2}, with risks of 3.7 (95% CL 1.0 and 9.5), and 4.0 (95% CL 1.1 and 10), respectively. A PUVA dose of < 250 J/cm{sup 2} or < 100 exposures conferred a minimal increase in risk of NMSC in our study population. (author).

  16. Radiogenic neoplasia in thyroid and mammary clonogens

    International Nuclear Information System (INIS)

    Clifton, K.H.

    1991-01-01

    We have developed rat thyroid and mammary clonogen transplantation systems for the study of radiogenic cancer induction at the target cell level in vivo. The epithelial cell populations of both glands contain small subpopulations of cells which are capable of giving rise to monoclonal glandular structures when transplanted and stimulated with appropriate hormones. During the end of the last grant year and the first half of the current grant year, we have completed analyses and summarized for publication: investigations on the relationship between grafted thyroid cell number and the rapidity and degree of reestablishment of the thyroid-hypothalamicpituitary axis in thyroidectomized rats maintained on a normal diet or an iodine deficient diet; studies of the persistence of, and the differentiation potential and functional characteristics of, the TSH- (thyrotropin-) responsive sub-population of clonogens during goitrogenesis, the plateau-phase of goiter growth, and goiter involution; studies of changes in the size of the clonogen sub-population during goitrogenesis, goiter involution and the response to goitrogen rechallenge; and the results of the large carcinogenesis experiment on the nature of the grafted thyroid cell number-dependent suppression of promotion/progression to neoplasia in grafts of radiation-initiated thyroid cells. We are testing new techniques for the culture, cytofluorescent analysis and characterization mammary epithelial cells and of clonogens in a parallel project, and plan to apply similar technology to the thyroid epithelial cells and clonogen population. Data from these studies will be used in the design of future carcinogenesis experiments on neoplastic initiation by high and low LET radiations and on cells interactions during the neoplastic process

  17. Neoplasias malignas: caracterización

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    Freddie Hernández Cisneros

    1997-02-01

    Full Text Available Se realizó un estudio transversal con el objetivo de caracterizar a los pacientes con neoplasias malignas en un área de salud desde marzo de 1994 hasta agosto del mismo año; el universo de estudio estuvo representado por 75 pacientes diagnosticados con algún tipo de afección maligna y el registro primario de los datos, por una encuesta con variables seleccionadas; se procesó la información de una forma computadorizada. Se encontraron como resultados más importantes: una mayor incidencia en el grupo de edad de 50 años y más; un 56 % fumaba y un 17,33 % ingería bebidas alcohólicas; las 3 localizaciones más frecuentes fueron: mama, cuello del útero y piel, y se detectaron deficiencias llamativas en la promoción y la prevención de estas enfermedades.: A cross-sectional study was carried out, with the aim of characterizing the patients with malignant neoplasms in a health area, from March 1994 to August of the same year; the universe of study was represented by 75 patients diagnosed with some kind of malignant disease, and the primary score of the data, by means of a survey with selected variables; information was processed in a computed way. The most important results found, were: the highest incidence in the 50 years old or more age group; the 56 % smoked, and the 17.33 % drank alcoholic beverages; the three most frequent sites, were: breast, cervix uteri and skin, and also outstanding defficiencies were detected in the promotion and prevention of these diseases.

  18. In vitro effects of triiodothyronine on gene expression in mouse trophoblast cells.

    Science.gov (United States)

    Silva, J F; Ocarino, N M; Serakides, R

    2015-01-01

    The objective of the present study was to evaluate the effects of different doses of T3 (10(-4) M, 10(-7) M, 10(-9) M) on the in vitro gene expression of Tpbp, Prl3b1, VEGF, PGF, PL-1, and INFy in mouse trophoblast cells by real-time RT-PCR. Doses of 10(-7) and 10(-9) M T3 increased the mRNA levels of Tpbp, Pl3b1, VEGF, PGF, INFy and PL-1. In contrast, the dose of 10(-4) M reduced the gene expression of PL-1 and VEGF. T3 affected the gene expression of differentiation, hormonal, immune and angiogenic factors in mouse trophoblast cells. Copyright © 2014 Elsevier Ltd. All rights reserved.

  19. The risk of persistent trophoblastic disease after hydatidiform mole classified by morphology and ploidy

    DEFF Research Database (Denmark)

    Niemann, Isa; Hansen, Estrid S; Sunde, Lone

    2007-01-01

    classifications, and compared the ability of the two classifications to discriminate between patients with and without a substantial risk of persistent trophoblastic disease. METHODS: 294 cases of consecutively collected hydropic placentas clinically suspected of hydatidiform mole made the basis......OBJECTIVE: Hydatidiform mole can be classified by histopathologic characteristics and by genetic constitutions and most complete moles are diploid, whereas most partial moles are triploid. We investigated the concordance between these two classifications, characterized moles with conflicting......-molar miscarriage, 20 were triploids, 2 were diploid androgenetic and 2 were diploid biparental. In 23% of the conceptuses, the histopathologic and genetic classifications were conflicting. 5% of the patients with hydropic placentas classified as partial mole encountered persistent trophoblastic disease; however...

  20. Defective trophoblast invasion underlies fetal growth restriction and preeclampsia-like symptoms in the stroke-prone spontaneously hypertensive rat.

    Science.gov (United States)

    Barrientos, G; Pussetto, M; Rose, M; Staff, A C; Blois, S M; Toblli, J E

    2017-07-01

    What is the impact of chronic hypertension on placental development, fetal growth and maternal outcome in the stroke-prone spontaneously hypertensive rat (SHRSP)? SHRSP showed an impaired remodeling of the spiral arteries and abnormal pattern of trophoblast invasion during placentation, which were associated with subsequent maternal glomerular injury and increased baseline hypertension as well as placental insufficiency and asymmetric fetal growth restriction (FGR). A hallmark in the pathogenesis of preeclampsia (PE) is abnormal placentation with defective remodeling of the spiral arteries preceding the onset of the maternal syndrome. Pregnancies affected by chronic hypertension display an increased risk for PE, often associated with poor maternal and fetal outcomes. However, the impact of chronic hypertension on the placentation process as well as the nature of the factors promoting the development of PE in pregnant hypertensive women remain elusive. Timed pregnancies [n = 5] were established by mating 10-12-week-old SHRSP and Wistar Kyoto (WKY, normotensive controls) females with congenic males. Maternal systolic blood pressures (SBPs) were recorded pre-mating, throughout pregnancy (GD1-19) and post-partum by the tail-cuff method. On selected dates, 24 h urine- and blood samples were collected, and animals were euthanized for isolation of implantation sites and kidneys for morphometrical analyses. The 24 h proteinuria and the albumin:creatinine ratio were used for evaluation of maternal renal function. Renal injury was assessed on periodic acid Schiff, Masson's trichrome and Sirius red stainings. Placental and fetal weights were recorded on gestation day (GD)18 and GD20, followed by determination of fetal cephalization indexes and developmental stage, according to the Witschi scale. Morphometric analyses of placental development were conducted on hematoxylin-eosin stained tissue sections collected on GD14 and GD18, and complemented with immunohistochemical

  1. Gestational Day-Dependent Expression of Interleukin-10 and Tumor Necrosis Factor-alpha in Porphyromonas gingivalis-infected Pregnant Rats

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    Banun Kusumawardani

    2014-04-01

    Full Text Available Normal 0 false false false IN X-NONE X-NONE MicrosoftInternetExplorer4 Fetal growth restriction remains a major cause of neonatal morbidity and mortality. Porphyromonas gingivaliscan induce placental inflammatory response resulting in fetal growth restriction. Objective: This study aimed to evaluate the potential utility of the pro-inflammatory cytokine TNF-α and anti-inflammatory cytokine IL-10 in rat placental tissues to understand whether these events were causally related. Methods: Female rats were infected with live-Porphyromonas gingivalis at concentration of 2x109 cells/ml into subgingival sulcus area of the maxillary first molar before and/or during pregnancy. They were sacrificed on gestational day (GD-14 and GD20. The expression of TNF-α and IL-10 in macrophages and trophoblast cells were detected by immunohistochemistry. Results: A higher expression of TNF-α was found in spongiotrophoblast of the Pg-BD group on GD14 (6.30±1.16, and in trophoblastic giant cells of Pg-D group on GD20 (5.50±1.35. Furthermore, a higher expression of IL-10 was found in trophoblastic giant cells of the Pg-BD group on GD14 (4.50±1.51 and in syncytiotrophoblasts of Pg-BD group on GD20 (8.70±2.67. Conclusion: The expression of TNF-α on GD14 and GD20 were accompanied by increased expression of IL-10. The placental pathologic conditions induced by Porphyromonas gingivalis can be inhibited by elevated expression of IL-10 in macrophages and trophoblast cells.DOI: 10.14693/jdi.v20i3.199

  2. Trophoblast cell fusion and differentiation are mediated by both the protein kinase C and a pathways.

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    Waka Omata

    Full Text Available The syncytiotrophoblast of the human placenta is an epithelial barrier that interacts with maternal blood and is a key for the transfer of nutrients and other solutes to the developing fetus. The syncytiotrophoblast is a true syncytium and fusion of progenitor cytotrophoblasts is the cardinal event leading to the formation of this layer. BeWo cells are often used as a surrogate for cytotrophoblasts, since they can be induced to fuse, and then express certain differentiation markers associated with trophoblast syncytialization. Dysferlin, a syncytiotrophoblast membrane repair protein, is up-regulated in BeWo cells induced to fuse by treatment with forskolin; this fusion is thought to occur through cAMP/protein kinase A-dependent mechanisms. We hypothesized that dysferlin may also be up-regulated in response to fusion through other pathways. Here, we show that BeWo cells can also be induced to fuse by treatment with an activator of protein kinase C, and that this fusion is accompanied by increased expression of dysferlin. Moreover, a dramatic synergistic increase in dysferlin expression is observed when both the protein kinase A and protein kinase C pathways are activated in BeWo cells. This synergy in fusion is also accompanied by dramatic increases in mRNA for the placental fusion proteins syncytin 1, syncytin 2, as well as dysferlin. Dysferlin, however, was shown to be dispensable for stimulus-induced BeWo cell syncytialization, since dysferlin knockdown lines fused to the same extent as control cells. The classical trophoblast differentiation marker human chorionic gonadotropin was also monitored and changes in the expression closely parallel that of dysferlin in all of the experimental conditions employed. Thus different biochemical markers of trophoblast fusion behave in concert supporting the hypothesis that activation of both protein kinase C and A pathways lead to trophoblastic differentiation.

  3. HCG-Activated Human Peripheral Blood Mononuclear Cells (PBMC Promote Trophoblast Cell Invasion.

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    Nan Yu

    Full Text Available Successful embryo implantation and placentation depend on appropriate trophoblast invasion into the maternal endometrial stroma. Human chorionic gonadotropin (hCG is one of the earliest embryo-derived secreted signals in the peripheral blood mononuclear cells (PBMC that abundantly expresses hCG receptors. The aims of this study were to estimate the effect of human embryo-secreted hCG on PBMC function and investigate the role and underlying mechanisms of activated PBMC in trophoblast invasion. Blood samples were collected from women undergoing benign gynecological surgery during the mid-secretory phase. PBMC were isolated and stimulated with or without hCG for 0 or 24 h. Interleukin-1β (IL-1β and leukemia inhibitory factor (LIF expressions in PBMC were detected by enzyme-linked immunosorbent assay and real-time polymerase chain reaction (PCR. The JAR cell line served as a model for trophoblast cells and was divided into four groups: control, hCG only, PBMC only, and PBMC with hCG. JAR cell invasive and proliferative abilities were detected by trans-well and CCK8 assays and matrix metalloproteinase (MMP-2 (MMP-2, MMP-9, vascular endothelial growth factor (VEGF, tissue inhibitor of metalloproteinase (TIMP-1, and TIMP-2 expressions in JAR cells were detected by western blotting and real-time PCR analysis. We found that hCG can remarkably promote IL-1β and LIF promotion in PBMC after 24-h culture. PBMC activated by hCG significantly increased the number of invasive JAR cells in an invasion assay without affecting proliferation, and hCG-activated PBMC significantly increased MMP-2, MMP-9, and VEGF and decreased TIMP-1 and TIMP-2 expressions in JAR cells in a dose-dependent manner. This study demonstrated that hCG stimulates cytokine secretion in human PBMC and could stimulate trophoblast invasion.

  4. Downregulation of SPARC expression inhibits the invasion of human trophoblast cells in vitro.

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    Yahong Jiang

    Full Text Available Successful pregnancy depends on the precise regulation of extravilloustrophoblast (EVT invasion into the uterine decidua. SPARC (secreted protein acidic and rich in cysteine is a matricellular glycoprotein that plays critical roles in the pathologies associated with obesity and diabetes, as well as tumorigenesis. The objective of this study was to investigate the role of SPARC in the process of trophoblast invasion which shares many similarities with tumor cell invasion. By Western blot, higher expression of SPARC was observed in mouse brain, ovary and uterus compared to other mouse tissues. Immunohistochemistry analysis revealed a spatio-temporal expression of SPARC in mouse uterus in the periimplantation period. At the implantation site of d8 pregnancy, SPARC mainly accumulated in the secondary decidua zone (SDZ, trophoblast cells and blastocyst. The expression of SPARC was also detected in human placental villi and trophoblast cell lines. In a Matrigel invasion assay, we found SPARC-specific RNA interference significantly reduced the invasion of human extravilloustrophoblast HTR8/SVneo cells. Microarray analysis revealed that SPARC depletion upregulated the expression of interleukin 11 (IL11, KISS1, insulin-like growth factor binding protein 4 (IGFBP4, collagen type I alpha 1 (COLIA1, matrix metallopeptidase 9 (MMP9, and downregulated the expression of the alpha polypeptide of chorionic gonadotropin (CGA, MMP1, gap junction protein alpha 1 (GJA1, et al. The gene array result was further validated by qRT-PCR and Western blot. The present data indicate that SPARC may play an important role in the regulation of normal placentation by promoting the invasion of trophoblast cells into the uterine decidua.

  5. Gender-Dependent Survival of Allogeneic Trophoblast Stem Cells in Liver

    Science.gov (United States)

    Epple-Farmer, Jessica; Debeb, Bisrat G.; Smithies, Oliver; Binas, Bert

    2012-01-01

    In view of the well-known phenomenon of trophoblast immune privilege, trophoblast stem cells (TSCs) might be expected to be immune privileged, which could be of interest for cell or gene therapies. Yet in the ectopic sites tested so far, TSC transplants fail to show noticeable immune privilege and seem to lack physiological support. However, we show here that after portal venous injection, green fluorescent protein (GFP)-labeled TSCs survive for several months in the livers of allogeneic female but not male mice. Gonadectomy experiments revealed that this survival does not require the presence of ovarian hormones but does require the absence of testicular factors. By contrast, GFP-labeled allogeneic embryonic stem cells (ESCs) are reliably rejected; however, these same ESCs survive when mixed with unlabeled TSCs. The protective effect does not require immunological compatibility between ESCs and TSCs. Tumors were not observed in animals with either successfully engrafted TSCs or coinjected ESCs. We conclude that in a suitable hormonal context and location, ectopic TSCs can exhibit and confer immune privilege. These findings suggest applications in cell and gene therapy as well as a new model for studying trophoblast immunology and physiology. PMID:19523327

  6. Primary Human Placental Trophoblasts are Permissive for Zika Virus (ZIKV) Replication.

    Science.gov (United States)

    Aagaard, Kjersti M; Lahon, Anismrita; Suter, Melissa A; Arya, Ravi P; Seferovic, Maxim D; Vogt, Megan B; Hu, Min; Stossi, Fabio; Mancini, Michael A; Harris, R Alan; Kahr, Maike; Eppes, Catherine; Rac, Martha; Belfort, Michael A; Park, Chun Shik; Lacorazza, Daniel; Rico-Hesse, Rebecca

    2017-01-27

    Zika virus (ZIKV) is an emerging mosquito-borne (Aedes genus) arbovirus of the Flaviviridae family. Although ZIKV has been predominately associated with a mild or asymptomatic dengue-like disease, its appearance in the Americas has been accompanied by a multi-fold increase in reported incidence of fetal microcephaly and brain malformations. The source and mode of vertical transmission from mother to fetus is presumptively transplacental, although a causal link explaining the interval delay between maternal symptoms and observed fetal malformations following infection has been missing. In this study, we show that primary human placental trophoblasts from non-exposed donors (n = 20) can be infected by primary passage ZIKV-FLR isolate, and uniquely allowed for ZIKV viral RNA replication when compared to dengue virus (DENV). Consistent with their being permissive for ZIKV infection, primary trophoblasts expressed multiple putative ZIKV cell entry receptors, and cellular function and differentiation were preserved. These findings suggest that ZIKV-FLR strain can replicate in human placental trophoblasts without host cell destruction, thereby serving as a likely permissive reservoir and portal of fetal transmission with risk of latent microcephaly and malformations.

  7. Feeder Cell Type Affects the Growth of In Vitro Cultured Bovine Trophoblast Cells

    Directory of Open Access Journals (Sweden)

    Islam M. Saadeldin

    2017-01-01

    Full Text Available Trophectoderm cells are the foremost embryonic cells to differentiate with prospective stem-cell properties. In the current study, we aimed at improving the current approach for trophoblast culture by using granulosa cells as feeders. Porcine granulosa cells (PGCs compared to the conventional mouse embryonic fibroblasts (MEFs were used to grow trophectoderm cells from hatched bovine blastocysts. Isolated trophectoderm cells were monitored and displayed characteristic epithelial/cuboidal morphology. The isolated trophectoderm cells expressed mRNA of homeobox protein (CDX2, cytokeratin-8 (KRT8, and interferon tau (IFNT. The expression level was higher on PGCs compared to MEFs throughout the study. In addition, primary trophectoderm cell colonies grew faster on PGCs, with a doubling time of approximately 48 hrs, compared to MEFs. PGCs feeders produced a fair amount of 17β-estradiol and progesterone. We speculated that the supplementation of sex steroids and still-unknown factors during the trophoblasts coculture on PGCs have helped to have better trophectoderm cell’s growth than on MEFs. This is the first time to use PGCs as feeders to culture trophectoderm cells and it proved superior to MEFs. We propose PGCs as alternative feeders for long-term culture of bovine trophectoderm cells. This model will potentially benefit studies on the early trophoblast and embryonic development in bovines.

  8. Morphologic and proteomic characterization of exosomes released by cultured extravillous trophoblast cells

    International Nuclear Information System (INIS)

    Atay, Safinur; Gercel-Taylor, Cicek; Kesimer, Mehmet; Taylor, Douglas D.

    2011-01-01

    Exosomes represent an important intercellular communication vehicle, mediating events essential for the decidual microenvironment. While we have demonstrated exosome induction of pro-inflammatory cytokines, to date, no extensive characterization of trophoblast-derived exosomes has been provided. Our objective was to provide a morphologic and proteomic characterization of these exosomes. Exosomes were isolated from the conditioned media of Swan71 human trophoblast cells by ultrafiltration and ultracentrifugation. These were analyzed for density (sucrose density gradient centrifugation), morphology (electron microscopy), size (dynamic light scattering) and protein composition (Ion Trap mass spectrometry and western immunoblotting). Based on density gradient centrifugation, microvesicles from Sw71 cells exhibit a density between 1.134 and 1.173 g/ml. Electron microscopy demonstrated that microvesicles from Sw71 cells exhibit the characteristic cup-shaped morphology of exosomes. Dynamic light scattering showed a bell-shaped curve, indicating a homogeneous population with a mean size of 165 nm ± 0.5 nm. Ion Trap mass spectrometry demonstrated the presence of exosome marker proteins (including CD81, Alix, cytoskeleton related proteins, and Rab family). The MS results were confirmed by western immunoblotting. Based on morphology, density, size and protein composition, we defined the release of exosomes from extravillous trophoblast cells and provide their first extensive characterization. This characterization is essential in furthering our understanding of 'normal' early pregnancy.

  9. Sildenafil Prevents Apoptosis of Human First-Trimester Trophoblast Cells Exposed to Oxidative Stress

    Science.gov (United States)

    Bolnick, Jay M.; Kilburn, Brian A.; Bolnick, Alan D.; Diamond, Michael P.; Singh, Manvinder; Hertz, Michael; Dai, Jing

    2015-01-01

    Human first-trimester trophoblast cells proliferate at low O2, but survival is compromised by oxidative stress, leading to uteroplacental insufficiency. The vasoactive drug, sildenafil citrate (Viagra, Sigma, St Louis, Missouri), has proven useful in reducing adverse pregnancy outcomes. An important biological function of this pharmaceutical is its action as an inhibitor of cyclic guanosine monophosphate (cGMP) phosphodiesterase type 5 activity, which suggests that it could have beneficial effects on trophoblast survival. To investigate whether sildenafil can prevent trophoblast cell death, human first-trimester villous explants and the HTR-8/SVneo cytotrophoblast cell line were exposed to hypoxia and reoxygenation (H/R) to generate oxidative stress, which induces apoptosis. Apoptosis was optimally inhibited during H/R by 350 ng/mL sildenafil. Sildenafil-mediated survival was reversed by l-NG-nitro-l-arginine methyl ester hydrochloride or cGMP antagonist, indicating a dependence on both nitric oxide (NO) and cGMP. Indeed, either a cGMP agonist or an NO generator was cytoprotective independent of sildenafil. These findings suggest a novel intervention route for patients with recurrent pregnancy loss or obstetrical placental disorders. PMID:25431453

  10. Morphologic and proteomic characterization of exosomes released by cultured extravillous trophoblast cells

    Energy Technology Data Exchange (ETDEWEB)

    Atay, Safinur [Department of Microbiology and Immunology, University of Louisville School of Medicine, Louisville, KY (United States); Gercel-Taylor, Cicek [Obstetrics, Gynecology and Women' s Health, University of Louisville School of Medicine, Louisville, KY (United States); Kesimer, Mehmet [Department of Biochemistry and Biophysics, University of North Carolina at Chapel Hill, Chapel Hill, NC (United States); Taylor, Douglas D., E-mail: ddtaylor@louisville.edu [Department of Microbiology and Immunology, University of Louisville School of Medicine, Louisville, KY (United States); Obstetrics, Gynecology and Women' s Health, University of Louisville School of Medicine, Louisville, KY (United States)

    2011-05-01

    Exosomes represent an important intercellular communication vehicle, mediating events essential for the decidual microenvironment. While we have demonstrated exosome induction of pro-inflammatory cytokines, to date, no extensive characterization of trophoblast-derived exosomes has been provided. Our objective was to provide a morphologic and proteomic characterization of these exosomes. Exosomes were isolated from the conditioned media of Swan71 human trophoblast cells by ultrafiltration and ultracentrifugation. These were analyzed for density (sucrose density gradient centrifugation), morphology (electron microscopy), size (dynamic light scattering) and protein composition (Ion Trap mass spectrometry and western immunoblotting). Based on density gradient centrifugation, microvesicles from Sw71 cells exhibit a density between 1.134 and 1.173 g/ml. Electron microscopy demonstrated that microvesicles from Sw71 cells exhibit the characteristic cup-shaped morphology of exosomes. Dynamic light scattering showed a bell-shaped curve, indicating a homogeneous population with a mean size of 165 nm {+-} 0.5 nm. Ion Trap mass spectrometry demonstrated the presence of exosome marker proteins (including CD81, Alix, cytoskeleton related proteins, and Rab family). The MS results were confirmed by western immunoblotting. Based on morphology, density, size and protein composition, we defined the release of exosomes from extravillous trophoblast cells and provide their first extensive characterization. This characterization is essential in furthering our understanding of 'normal' early pregnancy.

  11. p53 tumor suppressor gene: significance in neoplasia - a review

    International Nuclear Information System (INIS)

    Alam, J.M.

    2000-01-01

    p53 is a tumor suppressor gene located on chromosome 17p13.1. Its function includes cell cycle control and apoptosis. Loss of p53 function, either due to decreased level or genetic transformation, is associated with loss of cell cycle control, decrease, apoptosis and genomic modification, such mutation of p53 gene is now assessed and the indicator of neoplasia of cancer of several organs and cell types, p53 has demonstrated to have critical role in defining various progressive stages of neoplasia, therapeutic strategies and clinical application. The present review briefly describes function of p53 in addition to its diagnostic and prognostic significance in detecting several types of neoplasia. (author)

  12. Neoplasia intraepitelial vulvar: um problema atual Vulvar intraepithelial neoplasia: a current problem

    Directory of Open Access Journals (Sweden)

    José Alberto Fonseca-Moutinho

    2008-08-01

    Full Text Available A neoplasia intraepitelial da vulva (VIN é uma denominação que foi introduzida incialmente pela International Society for Study of Vulvo-vaginal Diseases (ISSVD e reconhecida posteriormente pela International Society of Gynaecological Pathology (ISGYP e Organização Mundial da Saúde. É uma entidade patológica a que correspondem as VIN de tipo usual (verrucoso, basalióide e misto e as VIN de tipo diferenciado. A incidência das lesões de VIN tem aumentado progressivamente, principalmente em mulheres jovens. A infecção pelo papilomavírus humano (HPV de alto risco, pelo vírus da imunodeficiência humana (HIV, o tabagismo e a neoplasia intraepitelial do colo do útero, da vagina e região anal são factores de risco estabelecidos para as VIN. Não existem sintomas e sinais característicos das VIN, mas a doença se traduz sempre por lesões clinicamente identificáveis. A biópsia com o auxílio do colposcópio permite o diagnóstico. O tratamento da doença está sempre justificado pelo elevado risco de progressão para cancro invasivo. A excisão alargada das lesões ou a sua destruição com laser CO2 têm sido os métodos mais populares de tratamento. Independentemente do método terapêutico utilizado, as taxas de recidiva são elevadas, pelo que está aconselhada a vigilância apertada das doentes após tratamento. A terapêutica tópica com imiquimod se afigura promissora no tratamento das VIN. As vacinas profiláticas contra os tipos de HPV de alto risco prometem se tornar armas poderosas na prevenção primária da doença.Vulvar intraepithelial neoplasia (VIN is a pathological denomination coined by the International Society for Study of Vulvo-vaginal Diseases (ISSVD and adopted by the International Society of Gynaecological Pathology (ISGYP and by the World Health Organization. VIN is a heterogeneous pathological entity with a usual type (warty, basaloid and mixed and a differentiated type. The incidence of the disease is

  13. Establishment and characterization of a spontaneously immortalized trophoblast cell line (HPT-8) and its hepatitis B virus-expressing clone.

    Science.gov (United States)

    Zhang, Lei; Zhang, Weilu; Shao, Chen; Zhang, Jingxia; Men, Ke; Shao, Zhongjun; Yan, Yongping; Xu, Dezhong

    2011-08-01

    Most trophoblast cell lines currently available to study vertical transmission of hepatitis B virus (HBV) are immortalized by viral transformation. Our goal was to establish and characterize a spontaneously immortalized human first-trimester trophoblast cell line and its HBV-expressing clone. Chorionic villi of Asian human first-trimester placentae were digested with trypsin and collagenase I to obtain the primary trophoblast cell culture. A spontaneously immortalized trophoblast cell line (HPT-8) was analyzed by scanning and transmission electron microscopy, cell cycle analysis, immunohistochemistry and immunofluorescence. HPT-8 cells were stably transfected with the adr subtype of HBV (HPT-8-HBV) and characterized by PCR and enzyme-linked immunosorbent assay. We obtained a clonal derivative of a spontaneously immortalized primary cell clone (HPT-8). HPT-8 cells were epithelioid and polygonal, and formed multinucleate, giant cells. They exhibited microvilli, distinct desmosomes between adjacent cells, abundant endoplasm, lipid inclusions and glycogen granules, which are all characteristic of cytotrophoblasts. HPT-8 cells expressed cytokeratin 7, cytokeratin 18, vimentin, cluster of differentiation antigen 9, epidermal growth factor receptor, stromal cell-derived factor 1 and placental alkaline phosphatase. They secreted prolactin, estradiol, progesterone and hCG, and were positive for HLA-G, a marker of extravillous trophoblasts. HPT-8-HBV cells were positive for HBV relaxed-circular, covalently closed circular DNA and pre-S sequence. HPT-8-HBV cells also produced and secreted HBV surface antigen and HBV e antigen. We established a trophoblast cell line, HPT-8 and its HBV-expressing clone which could be valuable in exploring the mechanism of HBV viral integration in human trophoblasts during intrauterine infection.

  14. The management of gestational diabetes

    Directory of Open Access Journals (Sweden)

    N Wah Cheung

    2009-01-01

    Full Text Available N Wah CheungCentre for Diabetes and Endocrinology Research, Westmead Hospital, and University of Sydney, NSW, AustraliaAbstract: The incidence of gestational diabetes is increasing. As gestational diabetes is associated with adverse pregnancy outcomes, and has long-term implications for both mother and child, it is important that it is recognized and appropriately managed. This review will examine the pharmacological options for the management of gestational diabetes, as well as the evidence for blood glucose monitoring, dietary and exercise therapy. The medical management of gestational diabetes is still evolving, and recent randomized controlled trials have added considerably to our knowledge in this area. As insulin therapy is effective and safe, it is considered the gold standard of pharmacotherapy for gestational diabetes, against which other treatments have been compared. The current experience is that the short acting insulin analogs lispro and aspart are safe, but there are only limited data to support the use of long acting insulin analogs. There are randomized controlled trials which have demonstrated efficacy of the oral agents glyburide and metformin. Whilst short-term data have not demonstrated adverse effects of glyburide and metformin on the fetus, and they are increasingly being used in pregnancy, there remain long-term concerns regarding their potential for harm.Keywords: gestational diabetes, insulin, oral antidiabetic agents, pregnancy, type 2 diabetes

  15. Use of mammary epithelial antigens as markers in mammary neoplasia

    International Nuclear Information System (INIS)

    Ceriani, R.L.; Peterson, J.A.; Blank, E.W.

    1979-01-01

    Cell-type specific antigens of the mammary epithelial cells can be used as markers of breast neoplasia. Methods are proposed for the detection of metastatic mammary tissue in vivo by injection of [ 125 I]-labeled antibodies against the mammary epithelial antigens. In addition, the reduced expression of mammary epithelial cell antigens in neoplastic breast cells, quantitated here on a cell per cell basis by flow cytofluorimetry, is a marker of neoplasia and an indication of a deletion accompanying the neoplastic transformation of these cells. (Auth.)

  16. Lobular intraepithelial neoplasia arising within breast fibroadenoma

    Science.gov (United States)

    2013-01-01

    Background Fibroadenomas are the second most common breast pathology occurring in young women under the age of 35 years old. Fibroadenomas can be classified as simple or complex according to histological features. Complex fibroadenomas differ from simple fibroadenomas because of the presence of cysts (3 mm), sclerosing adenosis, epithelial calcifications, or papillary apocrine changes. Most fibroadenomas are clinically identifiable. In 25% of cases, fibroadenomas are non-palpable and are diagnosed with mammography and ultrasound. Differential diagnosis with well differentiated breast cancer is often necessary, particularly with medullary or mucinous tumors. Calcification findings within fibroadenomas by mammogram have to be investigated. The age of a lump is usually reflected by calcifications. Microcalcification can hide foci of carcinoma in situ when they are small, branching type, and heterogeneous. However, many morphological possibilities may not be reliable for deciding whether a certain calcification is the product of a malignant or a benign process. From a radiological point of view, fibroadenomas containing foci of carcinoma in situ can be indistinguishable from benign lesions, even if the incidence of carcinoma within fibroadenomas is estimated as 0.1–0.3%, and it could be a long-term risk factor for invasive breast cancer. Case presentation A 44-year-old woman presented with a 1.5-cm palpable, smooth, mobile lump in the lower-inner quadrant of her right breast. Standard mediolateral oblique and craniocaudal mammograms showed a cluster of eccentric popcorn-like calcifications within the fibroadenoma. After lumpectomy, a definitive histological examination confirmed the intra-operative diagnosis of a benign mass. However, lobular intraepithelial neoplasia foci were found, surrounded by atypical lobular hyperplasia. Conclusions The possibility of an old benign breast lump might be supported by fine needle aspiration biopsy or core biopsy before initiating

  17. The Danish National Chronic Myeloid Neoplasia Registry

    Directory of Open Access Journals (Sweden)

    Bak M

    2016-10-01

    Full Text Available Marie Bak,1 Else Helene Ibfelt,2 Thomas Stauffer Larsen,3 Dorthe Rønnov-Jessen,4 Niels Pallisgaard,5 Ann Madelung,6 Lene Udby,1 Hans Carl Hasselbalch,1 Ole Weis Bjerrum,7 Christen Lykkegaard Andersen1,7 1Department of Hematology, Zealand University Hospital, University of Copenhagen, Roskilde, 2Research Centre for Prevention and Health, Rigshospitalet Glostrup, University of Copenhagen, Glostrup, 3Department of Hematology, Odense University Hospital, Odense, 4Department of Hematology, Vejle Hospital, Vejle, 5Department of Surgical Pathology, Zealand University Hospital, University of Copenhagen, Roskilde, 6Department of Surgical Pathology, Zealand University Hospital, University of Copenhagen, Næstved, 7Department of Hematology, Rigshospitalet, University of Copenhagen, Copenhagen, Denmark Aim: The Danish National Chronic Myeloid Neoplasia Registry (DCMR is a population-based clinical quality database, introduced to evaluate diagnosis and treatment of patients with chronic myeloid malignancies. The aim is to monitor the clinical quality at the national, regional, and hospital departmental levels and serve as a platform for research. Study population: The DCMR has nationwide coverage and contains information on patients diagnosed at hematology departments from January 2010 onward, including patients with essential thrombocythemia, polycythemia vera, myelofibrosis, unclassifiable myeloproliferative neoplasms, chronic myelomonocytic leukemia, and chronic myeloid leukemia. Main variables: Data are collected using standardized registration forms (so far up to four forms per patient, which are consecutively filled out online at time of diagnosis, after 2-year and 5-year follow-ups, and at end of follow-up. The forms include variables that describe clinical/paraclinical assessments, treatment, disease progression, and survival – disease-specific variables – as well as variables that are identical for all chronic myeloid malignancies. Descriptive

  18. Identification of CD147 (basigin) as a mediator of trophoblast functions.

    Science.gov (United States)

    Lee, Cheuk-Lun; Lam, Maggie P Y; Lam, Kevin K W; Leung, Carmen O N; Pang, Ronald T K; Chu, Ivan K; Wan, Tiffany H L; Chai, Joyce; Yeung, William S B; Chiu, Philip C N

    2013-11-01

    Does CD147 regulate trophoblast functions in vitro? CD147 exists as a receptor complex on human trophoblast and regulates the implantation, invasion and differentiation of trophoblast. CD147 is a membrane protein implicated in a variety of physiological and pathological conditions due to its regulation of cell-cell recognition, cell differentiation and tissue remodeling. Reduced placental CD147 expression is associated with pre-eclampsia, but the mechanism of actions remains unclear. A loss of function approach or functional blocking antibody was used to study the function of CD147 in primary human cytotrophoblasts isolated from first trimester termination of pregnancy and/or in the BeWo cell line, which possesses characteristics of human cytotrophoblasts. CD147 expression was analyzed by immunofluorescence staining and western blotting. CD147-associated protein complex on plasma membrane were separated by blue native gel electrophoresis and identified by reversed-phase liquid chromatography coupled with quadrupole time-of-flight hybrid mass spectrometer. Cell proliferation and invasion were determined by fluorometric cell proliferation assays and transwell invasion assays, respectively. Matrix metalloproteinases (MMPs) and urokinase plasminogen activator (uPA) activities were measured by gelatin gel zymography and uPA assay kits, respectively. Cell migration was determined by wound-healing assays. Cell fusion was analyzed by immunocytochemistry staining of E-cadherin and 4',6-diamidino-2-phenylindole. The transcripts of matrix proteinases and trophoblast lineage markers were measured by quantitative PCR. Extracellular signal-regulated kinase (ERK) activation was analyzed by western blot using antibodies against ERKs. CD147 exists as protein complexes on the plasma membrane of primary human cytotrophoblasts and BeWo cells. Several known CD147-interacting partners, including integrin β1 and monocarboxylate transporter-1, were identified. Suppression of CD147 by si

  19. Human trophoblast-derived hydrogen sulfide stimulates placental artery endothelial cell angiogenesis.

    Science.gov (United States)

    Chen, Dong-Bao; Feng, Lin; Hodges, Jennifer K; Lechuga, Thomas J; Zhang, Honghai

    2017-09-01

    Endogenous hydrogen sulfide (H2S), mainly synthesized by cystathionine β-synthase (CBS) and cystathionine γ-lyase (CTH), has been implicated in regulating placental angiogenesis; however, the underlying mechanisms are unknown. This study was to test a hypothesis that trophoblasts synthesize H2S to promote placental angiogenesis. Human choriocarcinoma-derived BeWo cells expressed both CBS and CTH proteins, while the first trimester villous trophoblast-originated HTR-8/SVneo cells expressed CTH protein only. The H2S producing ability of BeWo cells was significantly inhibited by either inhibitors of CBS (carboxymethyl hydroxylamine hemihydrochloride, CHH) or CTH (β-cyano-L-alanine, BCA) and that in HTR-8/SVneo cells was inhibited by CHH only. H2S donors stimulated cell proliferation, migration, and tube formation in ovine placental artery endothelial cells (oFPAECs) as effectively as vascular endothelial growth factor. Co-culture with BeWo and HTR-8/SVneo cells stimulated oFPAEC migration, which was inhibited by CHH or BCA in BeWo but CHH only in HTR-8/SVneo cells. Primary human villous trophoblasts (HVT) were more potent than trophoblast cell lines in stimulating oFPAEC migration that was inhibited by CHH and CHH/BCA combination in accordance with its H2S synthesizing activity linked to CBS and CTH expression patterns. H2S donors activated endothelial nitric oxide synthase (NOS3), v-AKT murine thymoma viral oncogene homolog 1 (AKT1), and extracellular signal-activated kinase 1/2 (mitogen-activated protein kinase 3/1, MAPK3/1) in oFPAECs. H2S donor-induced NOS3 activation was blocked by AKT1 but not MAPK3/1 inhibition. In keeping with our previous studies showing a crucial role of AKT1, MAPK3/1, and NOS3/NO in placental angiogenesis, these data show that trophoblast-derived endogenous H2S stimulates placental angiogenesis, involving activation of AKT1, NOS3/NO, and MAPK3/1. © The Authors 2017. Published by Oxford University Press on behalf of Society for the Study

  20. Co-expression of cytokeratins and vimentin by highly invasive trophoblast in the white-winged vampire bat, Diaemus youngi, and the black mastiff bat, Molossus ater, with observations on intermediate filament proteins in the decidua and intraplacental trophoblast.

    Science.gov (United States)

    Badwaik, N K; Rasweiler, J J; Muradali, F

    1998-11-01

    Histological and immunocytochemical studies of gravid reproductive tracts obtained from the white-winged vampire bat (Diaemus youngi) and the black mastiff bat (Molossus ater) have established that both species develop unusually invasive trophoblast. This is released by the developing discoidal haemochorial placenta, expresses both cytokeratins and vimentin, and invades the myometrium and adjacent tissues (including the ovaries) via interstitial migration within the walls of maternal blood vessels. Hence, this trophoblast is noteworthy for the extent to which it undergoes an epithelial-mesenchymal transformation. In Molossus, it originates from the cytotrophoblastic shell running along the base of the placenta, is mononuclear, and preferentially invades maternal arterial vessels serving the discoidal placenta. This trophoblast may have a role in dilatation of these vessels when the discoidal placenta becomes functional. In Diaemus, the highly invasive trophoblast appears to originate instead from a layer of syncytiotrophoblast on the periphery of the placenta is multinucleated, and vigorously invades both arterial and venous vessels. During late pregnancy, it becomes extensively branched and sends attenuated processes around many of the myometrial smooth muscle fibres. In view of its distribution, this trophoblast could have important influences upon myometrial contractility and the function of blood vessels serving the gravid tract. Other aspects of intermediate filament expression in the uteri and placentae of these bats are also noteworthy. Many of the decidual giant cells in Molossus co-express cytokeratins and vimentin, while the syncytiotrophoblast lining the placental labyrinth in Diaemus late in pregnancy expresses little cytokeratin.

  1. Gestational hypoxia induces preeclampsia-like symptoms via heightened endothelin-1 signaling in pregnant rats.

    Science.gov (United States)

    Zhou, Jianjun; Xiao, Daliao; Hu, Yali; Wang, Zhiqun; Paradis, Alexandra; Mata-Greenwood, Eugenia; Zhang, Lubo

    2013-09-01

    Preeclampsia is a life-threatening pregnancy disorder. However, its pathogenesis remains unclear. We tested the hypothesis that gestational hypoxia induces preeclampsia-like symptoms via heightened endothelin-1 (ET-1) signaling. Time-dated pregnant and nonpregnant rats were divided into normoxic and hypoxic (10.5% O2 from the gestational day 6-21) groups. Chronic hypoxia had no significant effect on blood pressure or proteinuria in nonpregnant rats but significantly increased blood pressure on day 12 (systolic blood pressure, 111.7 ± 6.1 versus 138.5 ± 3.5 mm Hg; P=0.004) and day 20 (systolic blood pressure, 103.4 ± 4.6 versus 125.1 ± 6.1 mm Hg; P=0.02) in pregnant rats and urine protein (μg/μL)/creatinine (nmol/μL) ratio on day 20 (0.10 ± 0.01 versus 0.20 ± 0.04; P=0.04), as compared with the normoxic control group. This was accompanied with asymmetrical fetal growth restriction. Hypoxia resulted in impaired trophoblast invasion and uteroplacental vascular remodeling. In addition, plasma ET-1 levels, as well as the abundance of prepro-ET-1 mRNA, ET-1 type A receptor and angiotensin II type 1 receptor protein in the kidney and placenta were significantly increased in the chronic hypoxic group, as compared with the control animals. Treatment with the ET-1 type A receptor antagonist, BQ123, during the course of hypoxia exposure significantly attenuated the hypoxia-induced hypertension and other preeclampsia-like features. The results demonstrate that chronic hypoxia during gestation induces preeclamptic symptoms in pregnant rats via heightened ET-1 and ET-1 type A receptor-mediated signaling, providing a molecular mechanism linking gestational hypoxia and increased risk of preeclampsia.

  2. Ethical issues in gestational surrogacy.

    Science.gov (United States)

    Ber, R

    2000-01-01

    The introduction of contraceptive technologies has resulted in the separation of sex and procreation. The introduction of new reproductive technologies (mainly IVF and embryo transfer) has led not only to the separation of procreation and sex, but also to the redefinition of the terms mother and family. For the purpose of this essay, I will distinguish between: 1. the genetic mother--the donor of the egg; 2. the gestational mother--she who bears and gives birth to the baby; 3. the social mother--the woman who raises the child. This essay will deal only with the form of gestational surrogacy in which the genetic parents intend to be the social parents, and the surrogate mother has no genetic relationship to the child she bears and delivers. I will raise questions regarding medical ethical aspects of surrogacy and the obligation(s) of the physician(s) to the parties involved. I will argue that the gestational surrogate is "a womb to rent," that there is great similarity between gestational commercial surrogacy and organ transplant marketing. Furthermore, despite claims to freedom of choice and free marketing, I will claim that gestational surrogacy is a form of prostitution and slavery, exploitation of the poor and needy by those who are better off. The right to be a parent, although not constitutional, is intuitive and deeply rooted. However, the issue remains whether this right overrules all other rights, and at what price to the parties involved. I will finally raise the following provocative question to society: In the interim period between today's limited technology and tomorrow's extra-corporeal gestation technology (ectogenesis), should utilizing females in PVS (persistent vehetative state) for gestational surrogacy be socially acceptable/permissible--provided they have left permission in writing?

  3. Chlamydia trachomatis infection and risk of cervical intraepithelial neoplasia

    DEFF Research Database (Denmark)

    Lehtinen, Matti; Ault, Kevin A; Lyytikainen, Erika

    2011-01-01

    High-risk human papillomavirus (hrHPV) is the primary cause of cervical cancer. As Chlamydia trachomatis is also linked to cervical cancer, its role as a potential co-factor in the development of cervical intraepithelial neoplasia (CIN) grade 2 or higher was examined....

  4. Cold-knife and laser conization for cervical intraepithelial neoplasia

    DEFF Research Database (Denmark)

    Tabor, A; Berget, A

    1990-01-01

    In a 5-year study, 425 women had conization performed for cervical intraepithelial neoplasia (CIN) I, II or III. Conization was performed only in cases of positive endocervical curettage or when colposcopy was inconclusive. In all other cases, local destruction was the operation of choice...

  5. Imaging Finding of Multiple Endocrine Neoplasia Type 1: Case Report

    International Nuclear Information System (INIS)

    Yum, Tae Jun; Cho, Hee Woo

    2012-01-01

    Multiple endocrine neoplasia type 1 (MEN1) is an autosomal dominant inherited syndrome with characteristic clinical and radiological manifestations. Many reports on MEN1 have been published; however, no cases of radiologically diagnosed MEN1 have been reported. Therefore, we report on a radiologically diagnosed case of MEN1 with clinical symptoms of gastroduodenal ulcer.

  6. Nuclear Receptors and Multiple Endocrine Neoplasia type 1 (MEN1)

    NARCIS (Netherlands)

    Dreijerink, K.M.A.

    2009-01-01

    Multiple Endocrine Neoplasia type 1 (MEN1) is an inherited syndrome that is characterized by the occurrence of tumours of the parathyroid glands, gastroenteropancreatic tumours, pitui-tary gland adenomas, as well as adrenal adenomas and neuro-endocrine tumours, often at a young age. MEN1 tumours can

  7. Manejo dos portadores das neoplasias intraepiteliais anais Managment of anal intra-epithelial neoplasia patients

    Directory of Open Access Journals (Sweden)

    Sidney Roberto Nadal

    2008-12-01

    Full Text Available Acredita-se que a neoplasia intraepitelial anal (NIA, provocada pelo HPV, seja a lesão precursora do carcinoma anal. Segundo a literatura, são encontradas entre 11% e 52% dos homens infectados pelo HIV, entre 6% a 20% dos homens e 1% a 2,8% das mulheres sem essa infecção. Entre 8,5% e 13% das NIA de alto grau evoluirão para carcinoma invasivo, indicando a necessidade do rastreamento e do seguimento desses doentes para prevenção. Não há tratamento satisfatório com baixos índices de morbidez e a recidiva é comum. Em geral, as formas de tratamento podem de ser divididas em tópicas, entre elas, ácido tricloroacético, podofilina, podofilotoxina, imiquimod, terapia fotodinâmica, e ablativas, ou seja, excisão cirúrgica, ablação pelo LASER, coagulação pelo infravermelho e eletrofulguração. Há, ainda, os que consideram aceitável a conduta expectante. O tratamento tópico se justifica pelo caráter multifocal da lesão e os ablativos têm taxas de complicação e recidiva muito semelhantes. De qualquer forma, doentes com qualquer anormalidade histológica necessitam de seguimento adequado, principalmente com colposcopia e citologia anal.Anal intra-epithelial neoplasia (AIN, provoked by HPV, is considered as an anal cancer precursor. Some articles noticed that it occurred among 11% and 52% of men who have sex with men (MSM infected with HIV and, among seronegatives, from 6% to 20% of men and from 1% to 2.8% of women. From 8.5% to 13% of high grade AIN will evolve to invasive carcinoma, needing follow-up and screening for prevention. There is no satisfactory treatment with low morbidity and recurrence is frequent. There are two main forms of treatment: topics (trichloroacetic acid, podophylin, podophylotoxin, imiquimod, photodynamic therapy and ablatives (chirurgical excision, LASER, infrared, eletrocautery. Others consider acceptable an expectant management. Topical therapy is justified because of multifocal presentation of HPV

  8. The food processing contaminant glyoxal promotes tumour growth in the multiple intestinal neoplasia (Min) mouse model.

    Science.gov (United States)

    Svendsen, Camilla; Høie, Anja Hortemo; Alexander, Jan; Murkovic, Michael; Husøy, Trine

    2016-08-01

    Glyoxal is formed endogenously and at a higher rate in the case of hyperglycemia. Glyoxal is also a food processing contaminant and has been shown to be mutagenic and genotoxic in vitro. The tumourigenic potential of glyoxal was investigated using the multiple intestinal neoplasia (Min) mouse model, which spontaneously develops intestinal tumours and is susceptible to intestinal carcinogens. C57BL/6J females were mated with Min males. Four days after mating and throughout gestation and lactation, the pregnant dams were exposed to glyoxal through drinking water (0.0125%, 0.025%, 0.05%, 0.1%) or regular tap water. Female and male offspring were housed separately from PND21 and continued with the same treatment. One group were only exposed to 0.1% glyoxal from postnatal day (PND) 21. There was no difference in the number of intestinal tumours between control and treatment groups. However, exposure to 0.1% glyoxal starting in utero and at PND21 caused a significant increase in tumour size in the small intestine for male and female mice in comparison with respective control groups. This study suggests that glyoxal has tumour growth promoting properties in the small intestine in Min mice. Copyright © 2016 Norwegian Institute of Public Health. Published by Elsevier Ltd.. All rights reserved.

  9. Clinical diagnosis of gestational diabetes.

    Science.gov (United States)

    Ryan, Edmond A

    2013-12-01

    Gestational diabetes mellitus (GDM) diagnosis remains controversial. ACOG criteria are based on the long-term risk of maternal diabetes. ADA recently suggested diagnosing GDM with 1 elevated value on an oral glucose tolerance test based on a 1.75-fold risk of large-for-gestational age infants resulting in a 17.8% rate of GDM. Given the lack of neonatal-based outcomes for the traditional position and problems of reproducibility and benefit/harm balance of the ADA approach, an alternative is presented herein based on a 2-fold risk of a large-for-gestational age baby, requiring 2 separate abnormalities to reduce false positives giving a more balanced benefit/harm ratio (10% GDM rate).

  10. Enhancement of trophoblast differentiation and survival by low molecular weight heparin requires heparin-binding EGF-like growth factor.

    Science.gov (United States)

    Bolnick, Alan D; Bolnick, Jay M; Kohan-Ghadr, Hamid-Reza; Kilburn, Brian A; Pasalodos, Omar J; Singhal, Pankaj K; Dai, Jing; Diamond, Michael P; Armant, D Randall; Drewlo, Sascha

    2017-06-01

    Does low molecular weight heparin (LMWH) require heparin-binding epidermal growth factor (EGF)-like growth factor (HBEGF) signaling to induce extravillous trophoblast differentiation and decrease apoptosis during oxidative stress? LMWH increased HBEGF expression and secretion, and HBEGF signaling was required to stimulate trophoblast extravillous differentiation, increase invasion in vitro and reduce trophoblast apoptosis during oxidative stress. Abnormal trophoblast differentiation and survival contribute to placental insufficiency syndromes, including preeclampsia and intrauterine growth restriction. Preeclampsia often manifests as a pro-thrombotic state, with unsuccessful transformation of the spiral arteries that reduces oxygen supply and can produce placental infarction. LMWH improves placental function by increasing blood flow. Recent data suggest that the actions of LMWH transcend its anti-coagulative properties, but the molecular mechanism is unknown. There is evidence that LMWH alters the expression of human HBEGF in trophoblast cells, which regulates human trophoblast pathophysiology. HBEGF, itself, is capable of increasing trophoblast survival and invasiveness. First-trimester placental explants and the HTR-8/SVneo cell line, established using extravillous trophoblast outgrowths from first-trimester villous explants, were treated in vitro with LMWH to examine the effects on HBEGF signaling and trophoblast function under normal physiological and pathological conditions. A highly specific antagonist of HBEGF and other inhibitors of HBEGF downstream signaling were used to determine the relationship between LMWH treatment and HBEGF. Placental tissues (n = 5) were obtained with IRB approval and patient consent from first-trimester terminations. Placental explants and HTR-8/SVneo cells were cultured on plastic or Matrigel™ and treated with a therapeutic dose of LMWH (Enoxaparin; 10 IU/ml), with or without CRM197, pan Erb-B2 Receptor Tyrosine Kinase (ERBB

  11. Ets-2 and p53 mediate cAMP-induced MMP-2 expression, activity and trophoblast invasion

    Directory of Open Access Journals (Sweden)

    Goldman Shlomit

    2009-11-01

    Full Text Available Abstract Background We have previously shown that Matrix metalloproteinase (MMP -2 is a key-enzyme in early trophoblast invasion and that Protein Kinase A (PKA increases MMP-2 expression and trophoblast invasion. The aim of this study was to examine MMP -2 regulation by PKA in invasive trophoblasts: JAR choriocarcinoma cell-line and 6-8 w first trimester trophoblasts. Methods The effect of Forskolin (PKA on MMP-2 expression was assessed by Northern Blot and RT-PCR. Possible transcription factors binding to consensus MMP-2 promoter sequences in response to Forskolin, were detected by EMSA binding assay and their expression assessed by western blot analysis. Antisense transfection of relevant transcription factors was performed and the inhibitory effect assessed on MMP-2 expression (RT-PCR, secretion (zymography and trophoblast invasiveness (transwell migration assay. Results We found that Forskolin increased MMP-2 mRNA in JAR cells within 24 hours, and induced binding to p53, Ets, C/EBP and AP-2. Transcription factors Ets-2, phospho- p53, C/EBP epsilon, C/EBP lambda and AP-2 alpha bound to their respective binding sequences in response to Forskolin and the expressions of these transcription factors were all elevated in Forskolin- treated cells. Inhibition of Ets-2 and p53 reduced MMP-2 expression, secretion and invasiveness of Forskolin treated cells. Conclusion MMP-2 is regulated by PKA through several binding sites and transcription factors including Ets-2, p53, C/EBP, C/EBP lambda and AP-2 alpha. Ets-2 and p53 mediate cAMP- induced trophoblast invasiveness, through regulation of MMP-2.

  12. A Critical Role of TET1/2 Proteins in Cell-Cycle Progression of Trophoblast Stem Cells

    Directory of Open Access Journals (Sweden)

    Stephanie Chrysanthou

    2018-04-01

    Full Text Available Summary: The ten-eleven translocation (TET proteins are well known for their role in maintaining naive pluripotency of embryonic stem cells. Here, we demonstrate that, jointly, TET1 and TET2 also safeguard the self-renewal potential of trophoblast stem cells (TSCs and have partially redundant roles in maintaining the epithelial integrity of TSCs. For the more abundantly expressed TET1, we show that this is achieved by binding to critical epithelial genes, notably E-cadherin, which becomes hyper-methylated and downregulated in the absence of TET1. The epithelial-to-mesenchymal transition phenotype of mutant TSCs is accompanied by centrosome duplication and separation defects. Moreover, we identify a role of TET1 in maintaining cyclin B1 stability, thereby acting as facilitator of mitotic cell-cycle progression. As a result, Tet1/2 mutant TSCs are prone to undergo endoreduplicative cell cycles leading to the formation of polyploid trophoblast giant cells. Taken together, our data reveal essential functions of TET proteins in the trophoblast lineage. : TET proteins are well known for their role in pluripotency. Here, Hemberger and colleagues show that TET1 and TET2 are also critical for maintaining the epithelial integrity of trophoblast stem cells. TET1/2 ensure mitotic cell-cycle progression by stabilizing cyclin B1 and by regulating centrosome organization. These insights reveal the importance of TET proteins beyond their role in epigenome remodeling. Keywords: TET proteins, trophoblast stem cells, cell cycle, endoreduplication, self-renewal, mitosis, trophoblast giant cells, differentiation

  13. Administration of angiotensin II and a bradykinin B2 receptor blocker in midpregnancy impairs gestational outcome in guinea pigs.

    Science.gov (United States)

    Valdés, Gloria; Schneider, Daniela; Corthorn, Jenny; Ortíz, Rita; Acuña, Stephanie; Padilla, Oslando

    2014-06-04

    The opposing renin-angiotensin system (RAS) and kallikrein-kinin system (KKS) are upregulated in pregnancy and localize in the utero-placental unit. To test their participation as counter-regulators, circulating angiotensin II (AII) was exogenously elevated and the bradykinin B2 receptor (B2R) was antagonized in pregnant guinea-pigs. We hypothesized that disrupting the RAS/KKS balance during the period of maximal trophoblast invasion and placental development would provoke increased blood pressure, defective trophoblast invasion and a preeclampsia-like syndrome. Pregnant guinea-pigs received subcutaneous infusions of AII (200 μg/kg/day), the B2R antagonist Bradyzide (BDZ; 62.5 microg/kg/day), or both (AII + BDZ) from gestational day 20 to 34. Non-pregnant cycling animals were included in a control group (C NP) or received AII + BDZ (AII + BDZ NP) during 14 days. Systolic blood pressure was determined during cycle in C NP, and on the last day of infusion, and 6 and 26 days thereafter in the remaining groups. Twenty six days after the infusions blood and urine were extracted, fetuses, placentas and kidneys were weighed, and trophoblast invasion of spiral arteries was defined in the utero-placental units by immunocytochemistry. Systolic blood pressure transiently rose in a subgroup of the pregnant females while receiving AII + BDZ infusion, but not in AII + BDZ NP. Plasma creatinine was higher in AII- and BDZ-treated dams, but no proteinuria or hyperuricemia were observed. Kidney weight increased in AII + BDZ-treated pregnant and non-pregnant females. Aborted and dead fetuses were increased in dams that received AII and AII + BDZ. The fetal/placental weight ratio was reduced in litters of AII + BDZ-treated mothers. All groups that received interventions during pregnancy showed reduced replacement of endothelial cells by extravillous trophoblasts in lateral and myometrial spiral arteries. The acute effects on fetal viability, and the persistently impaired renal

  14. Role of HLA-G1 in trophoblast cell proliferation, adhesion and invasion

    Energy Technology Data Exchange (ETDEWEB)

    Jiang, Feng, E-mail: jiangfeng1161@163.com [Department of Gynecology and Obstetrics, Tangdu Hospital, The Fourth Military Medical University, 569 Xinsi Road, Baqiao District, Xi' an 710038 (China); Zhao, Hongxi [Department of Gynecology and Obstetrics, Tangdu Hospital, The Fourth Military Medical University, 569 Xinsi Road, Baqiao District, Xi' an 710038 (China); Wang, Li [Department of Gynecology and Obstetrics, The Chinese PLA General Hospital, 28 Fuxing Road, Haidian District, Beijing 100853 (China); Guo, Xinyu [Assisted Reproductive Center, General Hospital of Guangzhou Military Command, Guangzhou 510010 (China); Wang, Xiaohong; Yin, Guowu [Department of Gynecology and Obstetrics, Tangdu Hospital, The Fourth Military Medical University, 569 Xinsi Road, Baqiao District, Xi' an 710038 (China); Hu, Yunsheng [Department of Orthopedics, Tangdu Hospital, The Fourth Military Medical University, Xi' an 710038 (China); Li, Yi [Department of Gynecology and Obstetrics, Tangdu Hospital, The Fourth Military Medical University, 569 Xinsi Road, Baqiao District, Xi' an 710038 (China); Yao, Yuanqing, E-mail: yuanqingyaoxa@163.com [Department of Gynecology and Obstetrics, The Chinese PLA General Hospital, 28 Fuxing Road, Haidian District, Beijing 100853 (China)

    2015-02-27

    Trophoblast cells are important in embryo implantation and fetomaternal tolerance. HLA-G is specifically expressed at the maternal–fetal interface and is a regulator in pregnancy. The aim of the present study was to detect the effect of HLA-G1 on trophoblast cell proliferation, adhesion, and invasion. Human trophoblast cell lines (JAR and HTR-8/SVneo cells) were infected with HLA-G1-expressing lentivirus. After infection, HLA-G1 expression of the cells was detected by western blotting. Cell proliferation was detected by the BrdU assay. The cell cycle and apoptosis of JAR and HTR-8/SVneo cells was measured by flow cytometry (FCM). The invasion of the cells under different conditions was detected by the transwell invasion chamber assay. HLA-G1 didn't show any significant influence on the proliferation, apoptosis, adhesion, and invasion of trophocytes in normal culture conditions. However, HLA-G1 inhibited JAR and HTR-8/SVneo cells invasion induced by hepatocyte growth factor (HGF) under normal oxygen conditions. In conditions of hypoxia, HLA-G1 couldn't inhibit the induction of cell invasion by HGF. HLA-G1 is not an independent factor for regulating the trophocytes. It may play an indirect role in embryo implantation and formation of the placenta. - Highlights: • HLA-G1 could not influence trophocytes under normal conditions. • HLA-G1 inhibited cell invasion induced by HGF under normal oxygen condition. • HLA-G1 could not influence cell invasion under hypoxia conditions.

  15. Waddlia chondrophila infects and multiplies in ovine trophoblast cells stimulating an inflammatory immune response.

    Directory of Open Access Journals (Sweden)

    Nick Wheelhouse

    Full Text Available Waddlia chondrophila (W. chondrophila is an emerging abortifacient organism which has been identified in the placentae of humans and cattle. The organism is a member of the order Chlamydiales, and shares many similarities at the genome level and in growth studies with other well-characterised zoonotic chlamydial abortifacients, such as Chlamydia abortus (C. abortus. This study investigates the growth of the organism and its effects upon pro-inflammatory cytokine expression in a ruminant placental cell line which we have previously utilised in a model of C. abortus pathogenicity.Using qPCR, fluorescent immunocytochemistry and electron microscopy, we characterised the infection and growth of W. chondrophila within the ovine trophoblast AH-1 cell line. Inclusions were visible from 6 h post-infection (p.i. and exponential growth of the organism could be observed over a 60 h time-course, with significant levels of host cell lysis being observed only after 36 h p.i. Expression of CXCL8, TNF-α, IL-1α and IL-1β were determined 24 h p.i. A statistically significant response in the expression of CXCL8, TNF-α and IL-1β could be observed following active infection with W. chondrophila. However a significant increase in IL-1β expression was also observed following the exposure of cells to UV-killed organisms, indicating the stimulation of multiple innate recognition pathways.W. chondrophila infects and grows in the ruminant trophoblast AH-1 cell line exhibiting a complete chlamydial replicative cycle. Infection of the trophoblasts resulted in the expression of pro-inflammatory cytokines in a dose-dependent manner similar to that observed with C. abortus in previous studies, suggesting similarities in the pathogenesis of infection between the two organisms.

  16. Waddlia chondrophila infects and multiplies in ovine trophoblast cells stimulating an inflammatory immune response.

    Science.gov (United States)

    Wheelhouse, Nick; Coyle, Christopher; Barlow, Peter G; Mitchell, Stephen; Greub, Gilbert; Baszler, Tim; Rae, Mick T; Longbottom, David

    2014-01-01

    Waddlia chondrophila (W. chondrophila) is an emerging abortifacient organism which has been identified in the placentae of humans and cattle. The organism is a member of the order Chlamydiales, and shares many similarities at the genome level and in growth studies with other well-characterised zoonotic chlamydial abortifacients, such as Chlamydia abortus (C. abortus). This study investigates the growth of the organism and its effects upon pro-inflammatory cytokine expression in a ruminant placental cell line which we have previously utilised in a model of C. abortus pathogenicity. Using qPCR, fluorescent immunocytochemistry and electron microscopy, we characterised the infection and growth of W. chondrophila within the ovine trophoblast AH-1 cell line. Inclusions were visible from 6 h post-infection (p.i.) and exponential growth of the organism could be observed over a 60 h time-course, with significant levels of host cell lysis being observed only after 36 h p.i. Expression of CXCL8, TNF-α, IL-1α and IL-1β were determined 24 h p.i. A statistically significant response in the expression of CXCL8, TNF-α and IL-1β could be observed following active infection with W. chondrophila. However a significant increase in IL-1β expression was also observed following the exposure of cells to UV-killed organisms, indicating the stimulation of multiple innate recognition pathways. W. chondrophila infects and grows in the ruminant trophoblast AH-1 cell line exhibiting a complete chlamydial replicative cycle. Infection of the trophoblasts resulted in the expression of pro-inflammatory cytokines in a dose-dependent manner similar to that observed with C. abortus in previous studies, suggesting similarities in the pathogenesis of infection between the two organisms.

  17. Knockdown of Heparanase Suppresses Invasion of Human Trophoblasts by Activating p38 MAPK Signaling Pathway

    Directory of Open Access Journals (Sweden)

    Guanglu Che

    2018-01-01

    Full Text Available Preeclampsia is a pregnancy-related disease with increasing maternal and perinatal morbidity and mortality worldwide. Defective trophoblast invasion is considered to be a major factor in the pathophysiological mechanism of preeclampsia. Heparanase, the only endo-β-glucuronidase in mammalian cells, has been shown to be abnormally expressed in the placenta of preeclampsia patients in our previous study. The biological role and potential mechanism of heparanase in trophoblasts remain unclear. In the present study, stably transfected HTR8/SVneo cell lines with heparanase overexpression or knockdown were constructed. The effect of heparanase on cellular proliferation, apoptosis, invasion, tube formation, and potential pathways in trophoblasts was explored. Our results showed that overexpression of heparanase promoted proliferation and invasion. Knockdown of heparanase suppressed proliferation, invasion, and tube formation but induced apoptosis. These findings reveal that downregulation of heparanase may contribute to defective placentation and plays a crucial role in the pathogenesis of preeclampsia. Furthermore, increased activation of p38 MAPK in heparanase-knockdown HTR8/SVneo cell was shown by MAPK pathway phosphorylation array and Western blotting assay. After pretreatment with 3 specific p38 MAPK inhibitors (BMS582949, SB203580, or BIRB796, inadequate invasion in heparanase-knockdown HTR8/SVneo cell was rescued. That indicates that knockdown of heparanase decreases HTR8/SVneo cell invasion through excessive activation of the p38 MAPK signaling pathway. Our study suggests that heparanase can be a potential predictive biomarker for preeclampsia at an early stage of pregnancy and represents a promising therapeutic target for the treatment of preeclampsia.

  18. Role of HLA-G1 in trophoblast cell proliferation, adhesion and invasion

    International Nuclear Information System (INIS)

    Jiang, Feng; Zhao, Hongxi; Wang, Li; Guo, Xinyu; Wang, Xiaohong; Yin, Guowu; Hu, Yunsheng; Li, Yi; Yao, Yuanqing

    2015-01-01

    Trophoblast cells are important in embryo implantation and fetomaternal tolerance. HLA-G is specifically expressed at the maternal–fetal interface and is a regulator in pregnancy. The aim of the present study was to detect the effect of HLA-G1 on trophoblast cell proliferation, adhesion, and invasion. Human trophoblast cell lines (JAR and HTR-8/SVneo cells) were infected with HLA-G1-expressing lentivirus. After infection, HLA-G1 expression of the cells was detected by western blotting. Cell proliferation was detected by the BrdU assay. The cell cycle and apoptosis of JAR and HTR-8/SVneo cells was measured by flow cytometry (FCM). The invasion of the cells under different conditions was detected by the transwell invasion chamber assay. HLA-G1 didn't show any significant influence on the proliferation, apoptosis, adhesion, and invasion of trophocytes in normal culture conditions. However, HLA-G1 inhibited JAR and HTR-8/SVneo cells invasion induced by hepatocyte growth factor (HGF) under normal oxygen conditions. In conditions of hypoxia, HLA-G1 couldn't inhibit the induction of cell invasion by HGF. HLA-G1 is not an independent factor for regulating the trophocytes. It may play an indirect role in embryo implantation and formation of the placenta. - Highlights: • HLA-G1 could not influence trophocytes under normal conditions. • HLA-G1 inhibited cell invasion induced by HGF under normal oxygen condition. • HLA-G1 could not influence cell invasion under hypoxia conditions

  19. Rare Presentation of Metastatic Cystic Trophoblastic Tumor in a Patient Without Prior Chemotherapy

    Directory of Open Access Journals (Sweden)

    Michael L. Wang

    2017-07-01

    Full Text Available Cystic trophoblastic tumor (CTT is a rare testicular germ cell tumor (GCT predominantly seen in post-chemotherapy patients. It is prognostically similar to teratoma and requires no additional chemotherapy in the absence of a nonteratomatous GCT component. We report a case of metastatic CTT in a patient with primary testicular teratoma without prior chemotherapy. Retroperitoneal lymph node metastases contained teratoma, embryonal carcinoma, and CTT. The CTT was β-hCG positive and SALL4 negative by immunohistochemistry (IHC. CTT can arise in metastatic testicular GCT in treatment naïve patients. An important differential diagnosis is choriocarcinoma due to treatment implications, and SALL4 IHC may help.

  20. Gestational diabetes insipidus. Case Report.

    Science.gov (United States)

    Ejmocka-Ambroziak, Anna; Grzechocińska, Barbara; Jastrzebska, Helena; Kochman, Magdalena; Cyganek, Anna; Wielgoś, Mirosław; Zgliczyński, Wojciech

    2015-01-01

    Gestational diabetes insipidus is a very rare complication. However, undiagnosed and untreated may lead to serious complications in both mother and fetus. In this study, a case of 34-year-old female patient with diabetes insipidus associated with pregnancy was reported. We discussed process of diagnosis and treatment with particular emphasis on the monitoring of water-electrolyte imbalance during labor.

  1. Gestational diabetes mellitus in Greenland

    DEFF Research Database (Denmark)

    Pedersen, Michael Lynge; Olesen, Jesper; Jørgensen, M. E.

    2016-01-01

    Background. Within the last 20 years, the prevalence of gestational diabetes mellitus (GDM) has been reported to be increasing worldwide in correlation with ethnic and geographic variations. The actual prevalence of GDM throughout all of Greenland remains unknown. Objective. The aim of this study...

  2. Large for Gestational Age (LGA)

    Science.gov (United States)

    ... mother Other risk factors for having large-for-gestational-age newborns include Maternal obesity Having had previous LGA babies Genetic abnormalities or syndromes (for example, Beckwith-Wiedemann syndrome or Sotos syndrome) Excessive weight gain during pregnancy (the fetus gets more calories as ...

  3. EAMJ Feb. gestation.indd

    African Journals Online (AJOL)

    2009-02-02

    Feb 2, 2009 ... Majority of the women studied were at a gestation of 8 to 11 weeks (38.9%). Most patients ... foetal risks, and management and follow-up of both entities are .... thyrotoxicosis in Asian women in Singapore and found-out that the ...

  4. OS041. Apolipoprotein A-I protects normal integration of the trophoblast into endothelial cellular networks in an in vitro model of preeclampsia.

    Science.gov (United States)

    Charlton, F; Xu, B; Makris, A; Hennessy, A; Rye, K-A

    2012-07-01

    Failure of the trophoblast to appropriately invade uterine spiral arteries is thought to be an initiating event in preeclampsia, a disorder associated with endothelial dysfunction. A dyslipidemia characterised by low plasma levels of high density lipoproteins (HDL) and elevated triglycerides has also been described in preeclampsia. The pro-inflammatory cytokine TNF-α inhibits trophoblast invasion of uterine endothelial cells. Previous work using an in vitro JEG-3 cell/Uterine endothelial cell co-culture model investigated the effect of apoliopoprotein A-I, the main apolipoprotein component of HDL, on trophoblast incorporation into endothelial tubules in the presence and absence of TNF-α. These effects are now investigated using the human invasive trophoblast cell line HTR-8/SVneo. This study asks if apoA-I, which has established anti-inflammatory properties, can protect against the deleterious effect of TNF-α on trophoblast-endothelial cell interactions. The in vitro trophoblast-uterine endothelial cell co-culture model was used to investigate the effect of apoA-I on trophoblast incorporation into endothelial tubules in the presence and absence of TNF-α. Uterine endothelial cells were pre-incubated with lipid free apoA-I (final apoA-I concentration 1 mg/mL) for 16h prior to seeding on matrigel coated plates. Tubules formed within 4h. Fluorescence-labelled HTR-8/SVneo trophoblast cells were then co-cultured with the endothelial cells±TNF-α (final concentration of 0.2ng/mL). Bright field and fluorescent images were captured after 24h. The effect of TNF-α on HTR-8/SVneo cell invasion was quantified with Image J software. Integration of HTR-8/SVneo trophoblast cells into uterine endothelial tubular networks was also imaged using live cell imaging techniques (Zeiss Axiovert). TNF-α inhibited HTR-8/SVneo (trophoblast) cell integration into endothelial tubular structures by 24.1±3.7% pintegration of trophoblast into endothelial tubular structures in the presence

  5. Am I at Risk for Gestational Diabetes?

    Science.gov (United States)

    ... they control their blood sugar levels. Babies whose mothers had gestational diabetes are at higher risk for certain health ... best way to improve outcomes for babies whose mothers have gestational diabetes. Later in Life Babies whose mothers had ...

  6. Testicular neoplasia in undescended testes of cryptorchid boys-does surgical strategy have an impact on the risk of invasive testicular neoplasia?

    DEFF Research Database (Denmark)

    Cortes, Dina; Thorup, Jørgen Mogens; Petersen, Bodil Laub

    2004-01-01

    We investigated whether or not surgical strategy has an impact on the risk of invasive testicular neoplasia in cases of cryptorchidism. We made a database study of the incidence of testicular neoplasia at surgery for cryptorchidism in childhood, and evaluated if such abnormalities were found......, p placed...

  7. Germ cell neoplasia in situ (GCNIS)

    DEFF Research Database (Denmark)

    Berney, Daniel M; Looijenga, Leendert H J; Idrees, Muhammad

    2016-01-01

    The pre-invasive lesion associated with post-pubertal malignant germ cell tumours of the testis was first recognized in the early 1970s and confirmed by a number of observational and follow-up studies. Until this year, this scientific story has been confused by resistance to the entity and disagr......The pre-invasive lesion associated with post-pubertal malignant germ cell tumours of the testis was first recognized in the early 1970s and confirmed by a number of observational and follow-up studies. Until this year, this scientific story has been confused by resistance to the entity...... and disagreement on its name. Initially termed 'carcinoma in situ' (CIS), it has also been known as 'intratubular germ cell neoplasia, unclassified' (IGCNU) and 'testicular intraepithelial neoplasia' (TIN). In this paper, we review the history of discovery and controversy concerning these names and introduce...

  8. Molecular events leading to HPV-induced high grade neoplasia

    Directory of Open Access Journals (Sweden)

    Saskia M. Wilting

    2016-12-01

    Full Text Available Cervical cancer is initiated by high-risk types of the human papillomavirus (hrHPV and develops via precursor stages, called cervical intraepithelial neoplasia (CIN. High-grade CIN lesions are considered true precancerous lesions when the viral oncogenes E6 and E7 are aberrantly expressed in the dividing cells. This results in abolishment of normal cell cycle control via p53 and pRb degradation. However, it has become clear that these viral oncogenes possess additional oncogenic properties, including interference with the DNA methylation machinery and mitotic checkpoints. Identification of the resulting molecular events leading to high-grade neoplasia will 1 increase our understanding of cervical carcinogenesis, 2 yield biomarkers for early diagnosis, and 3 identify therapeutic targets for HPV-induced (pre cancerous lesions.This review will briefly summarise current advances in our understanding of the molecular alterations in the host cell genome that occur during HPV-induced carcinogenesis.

  9. Tobacco, alcohol, and p53 overexpression in early colorectal neoplasia

    International Nuclear Information System (INIS)

    Terry, Mary Beth; Neugut, Alfred I; Mansukhani, Mahesh; Waye, Jerome; Harpaz, Noam; Hibshoosh, Hanina

    2003-01-01

    The p53 tumor suppressor gene is commonly mutated in colorectal cancer. While the effect of p53 mutations on colorectal cancer prognosis has been heavily studied, less is known about how epidemiologic risk factors relate to p53 status, particularly in early colorectal neoplasia prior to clinically invasive colorectal cancer (including adenomas, carcinoma in situ (CIS), and intramucosal carcinoma). We examined p53 status, as measured by protein overexpression, in 157 cases with early colorectal neoplasia selected from three New York City colonoscopy clinics. After collecting paraffin-embedded tissue blocks, immunohistochemistry was performed using an anti-p53 monoclonal mouse IgG 2 a [BP53-12-1] antibody. We analyzed whether p53 status was different for risk factors for colorectal neoplasia relative to a polyp-free control group (n = 508). p53 overexpression was found in 10.3%, 21.7%, and 34.9%, of adenomatous polyps, CIS, and intramucosal cases, respectively. Over 90% of the tumors with p53 overexpression were located in the distal colon and rectum. Heavy cigarette smoking (30+ years) was associated with cases not overexpressing p53 (OR = 1.8, 95% CI = 1.1–2.9) but not with those cases overexpressing p53 (OR = 1.0, 95% CI = 0.4–2.6). Heavy beer consumption (8+ bottles per week) was associated with cases overexpressing p53 (OR = 4.0, 95% CI = 1.3–12.0) but not with cases without p53 overexpression (OR = 1.6, 95% CI = 0.7–3.7). Our findings that p53 overexpression in early colorectal neoplasia may be positively associated with alcohol intake and inversely associated with cigarette smoking are consistent with those of several studies of p53 expression and invasive cancer, and suggest that there may be relationships of smoking and alcohol with p53 early in the adenoma to carcinoma sequence

  10. Multiple endocrine neoplasia type 2: achievements and current challenges

    Directory of Open Access Journals (Sweden)

    Andreas Machens

    2012-01-01

    Full Text Available Incremental advances in medical technology, such as the development of sensitive hormonal assays for routine clinical care, are the drivers of medical progress. This principle is exemplified by the creation of the concept of multiple endocrine neoplasia type 2, encompassing medullary thyroid cancer, pheochromocytoma, and primary hyperparathyroidism, which did not emerge before the early 1960s. This review sets out to highlight key achievements, such as joint biochemical and DNA-based screening of individuals at risk of developing multiple endocrine neoplasia type 2, before casting a spotlight on current challenges which include: (i ill-defined upper limits of calcitonin assays for infants and young children, rendering it difficult to implement the biochemical part of the integrated DNA-based/biochemical concept; (ii our increasingly mobile society in which different service providers are caring for one individual at various stages in the disease process. With familial relationships disintegrating as a result of geographic dispersion, information about the history of the origin family may become sketchy or just unavailable. This is when DNA-based gene tests come into play, confirming or excluding an individual's genetic predisposition to multiple endocrine neoplasia type 2 even before there is any biochemical or clinical evidence of the disease. However, the unrivaled molecular genetic progress in multiple endocrine neoplasia type 2 does not come without a price. Screening may uncover unknown gene sequence variants representing either harmless polymorphisms or pathogenic mutations. In this setting, functional characterization of mutant cells in vitro may generate helpful ancillary evidence with regard to the pathogenicity of gene variants in comparison with established mutations.

  11. EXPRESSION OF HPV 16 AND 18 IN CERVICAL INTRAEPITHELIAL NEOPLASIA

    OpenAIRE

    Kodali Venkataramana; Prasad Usha

    2017-01-01

    BACKGROUND Cervical cancer is by far the most common human papilloma virus related disease. Nearly, all cases of cervical cancer can be attributable to human papilloma virus infection. Infection with the human papilloma virus is the main risk factors for cervical intraepithelial neoplasia and cervical cancer especially the high-risk types. The aim of the study is to study the prevalence of high-risk human papilloma virus 16 and 18 in various grades of cervical intraepithelia...

  12. miR-210 inhibits trophoblast invasion and is a serum biomarker for preeclampsia.

    Science.gov (United States)

    Anton, Lauren; Olarerin-George, Anthony O; Schwartz, Nadav; Srinivas, Sindhu; Bastek, Jamie; Hogenesch, John B; Elovitz, Michal A

    2013-11-01

    Preeclampsia is characterized by hypertension and proteinuria in pregnant women. Its exact cause is unknown. Preeclampsia increases the risk of maternal and fetal morbidity and mortality. Although delivery, often premature, is the only known cure, early targeted interventions may improve maternal and fetal outcomes. Successful intervention requires a better understanding of the molecular etiology of preeclampsia and the development of accurate methods to predict women at risk. To this end, we tested the role of miR-210, a miRNA up-regulated in preeclamptic placentas, in first-trimester extravillous trophoblasts. miR-210 overexpression reduced trophoblast invasion, a process necessary for uteroplacental perfusion, in an extracellular signal-regulated kinase/mitogen-activated protein kinase-dependent manner. Conversely, miR-210 inhibition promoted invasion. Furthermore, given that the placenta secretes miRNAs into the maternal circulation, we tested if serum expression of miR-210 was associated with the disease. We measured miR-210 expression in two clinical studies: a case-control study and a prospective cohort study. Serum miR-210 expression was significantly associated with a diagnosis of preeclampsia (P = 0.007, area under the receiver operator curves = 0.81) and was predictive of the disease, even months before clinical diagnosis (P preeclampsia that can help in identifying at-risk women for monitoring and treatment. Copyright © 2013 American Society for Investigative Pathology. Published by Elsevier Inc. All rights reserved.

  13. Permissive cytomegalovirus infection of primary villous term and first trimester trophoblasts.

    Science.gov (United States)

    Hemmings, D G; Kilani, R; Nykiforuk, C; Preiksaitis, J; Guilbert, L J

    1998-06-01

    Forty percent of women with primary cytomegalovirus (CMV) infections during pregnancy infect their fetuses with complications for the baby varying from mild to severe. How CMV crosses the syncytiotrophoblast, the barrier between maternal blood and fetal tissue in the villous placenta, is unknown. Virus may cross by infection of maternal cells that pass through physical breaches in the syncytiotrophoblast or by direct infection of the syncytiotrophoblast, with subsequent transmission to underlying fetal placental cells. In this study, we show that pure (>99.99%), long-term and healthy (>3 weeks) cultures of syncytiotrophoblasts are permissively infected with CMV. Greater than 99% of infectious progeny virus remained cell associated throughout culture periods up to 3 weeks. Infection of term trophoblasts required a higher virus inoculum, was less efficient, and progressed more slowly than parallel infections of placental and human embryonic lung fibroblasts. Three laboratory strains (AD169, Towne, and Davis) and a clinical isolate from a congenitally infected infant all permissively infected trophoblasts, although infection efficiencies varied. The infection of first trimester syncytiotrophoblasts with strain AD169 occurred at higher frequency and progressed more rapidly than infection of term cells but less efficiently and rapidly than infection of fibroblasts. These results show that villous syncytiotrophoblasts can be permissively infected by CMV but that the infection requires high virus titers and proceeds slowly and that progeny virus remains predominantly cell associated.

  14. Adiponectin inhibits insulin function in primary trophoblasts by PPARα-mediated ceramide synthesis.

    Science.gov (United States)

    Aye, Irving L M H; Gao, Xiaoli; Weintraub, Susan T; Jansson, Thomas; Powell, Theresa L

    2014-04-01

    Maternal adiponectin (ADN) levels are inversely correlated with birth weight, and ADN infusion in pregnant mice down-regulates placental nutrient transporters and decreases fetal growth. In contrast to the insulin-sensitizing effects in adipose tissue and muscle, ADN inhibits insulin signaling in the placenta. However, the molecular mechanisms involved are unknown. We hypothesized that ADN inhibits insulin signaling and insulin-stimulated amino acid transport in primary human trophoblasts by peroxisome proliferator-activated receptor-α (PPARα)-mediated ceramide synthesis. Primary human term trophoblast cells were treated with ADN and/or insulin. ADN increased the phosphorylation of p38 MAPK and PPARα. ADN inhibited insulin signaling and insulin-stimulated amino acid transport. This effect was dependent on PPARα, because activation of PPARα with an agonist (GW7647) inhibited insulin signaling and function, whereas PPARα-small interfering RNA reversed the effects of ADN on the insulin response. ADN increased ceramide synthase expression and stimulated ceramide production. C2-ceramide inhibited insulin signaling and function, whereas inhibition of ceramide synthase (with Fumonisin B1) reversed the effects of ADN on insulin signaling and amino acid transport. These findings are consistent with the model that maternal ADN limits fetal growth mediated by activation of placental PPARα and ceramide synthesis, which inhibits placental insulin signaling and amino acid transport, resulting in reduced fetal nutrient availability.

  15. miR-520 promotes DNA-damage-induced trophoblast cell apoptosis by targeting PARP1 in recurrent spontaneous abortion (RSA).

    Science.gov (United States)

    Dong, Xiujuan; Yang, Long; Wang, Hui

    2017-04-01

    The establishment and maintenance of successful pregnancy mainly depends on trophoblast cells. Their dysfunction has been implicated in recurrent spontaneous abortion (RSA), a major complication of pregnancy. However, the underlying mechanisms of trophoblasts dysfunction remain unclear. DNA-damage-induced cell apoptosis has been reported to play a vital role in cell death. In this study, we identified a novel microRNA (miR-520) in RSA progression via regulating trophoblast cell apoptosis. Microarray analysis showed that miR-520 was highly expressed in villus of RSA patients. By using flow cytometry analysis, we observed miR-520 expression was correlated with human trophoblast cell apoptosis in vitro, along with decreased poly (ADP-ribose) polymerase-1 (PARP1) expression. With the analysis of clinic samples, we observed that miR-520 level was negatively correlated with PARP1 level in RSA villus. In addition, overexpression of PARP1 restored the miR-520-induced trophoblast cell apoptosis in vitro. The status of chromosome in trophoblast implied that miR-520-promoted DNA-damage-induced cell apoptosis to regulate RSA progression. These results indicated that the level of miR-520 might associate with RSA by prompting trophoblast cell apoptosis via PARP1 dependent DNA-damage pathway.

  16. Piroxicam decreases postirradiation colonic neoplasia in the rat.

    Science.gov (United States)

    Northway, M G; Scobey, M W; Cassidy, K T; Geisinger, K R

    1990-12-01

    This study evaluated the effects of the nonsteroidal antiinflammatory agent piroxicam on chronic radiation proctitis in the rat. Forty female Wistar rats received a 2250-cGy dose of irradiation to the distal 2 cm of the colon. Twenty received piroxicam 8.0 mg/kg orally 30 minutes before exposure and 24 hours after exposure; 20 rats served as irradiated controls. All animals were evaluated by colonoscopy 1 and 3 weeks postexposure and every third week until death or killing at 1 year. At killing, colons were removed for light microscopic examination. One year postirradiation results showed no differences in mortality, vascular changes, acute inflammation, colitis cystica profunda, or rectal stricture between the control and piroxicam-treated groups. However, at 1 year postirradiation the control group demonstrated neoplasia in 15 of 19 animals compared with eight of 20 animals in the piroxicam-treated group. The first endoscopic appearance of colonic neoplasm occurred at 15 weeks postirradiation in one control irradiated rat whereas the first evidence of endoscopic neoplasm in the piroxicam-treated group did not occur until 36 weeks postirradiation. Histologic examination documented a tendency toward a greater presence of adenocarcinomas in the control group compared with the piroxicam-treated group. The authors conclude that piroxicam treatment significantly decreased the incidence of colonic neoplasia in general as well as delayed the endoscopic appearance of colonic neoplasia in rats after pelvic irradiation.

  17. Piroxicam decreases postirradiation colonic neoplasia in the rat

    International Nuclear Information System (INIS)

    Northway, M.G.; Scobey, M.W.; Cassidy, K.T.; Geisinger, K.R.

    1990-01-01

    This study evaluated the effects of the nonsteroidal antiinflammatory agent piroxicam on chronic radiation proctitis in the rat. Forty female Wistar rats received a 2250-cGy dose of irradiation to the distal 2 cm of the colon. Twenty received piroxicam 8.0 mg/kg orally 30 minutes before exposure and 24 hours after exposure; 20 rats served as irradiated controls. All animals were evaluated by colonoscopy 1 and 3 weeks postexposure and every third week until death or killing at 1 year. At killing, colons were removed for light microscopic examination. One year postirradiation results showed no differences in mortality, vascular changes, acute inflammation, colitis cystica profunda, or rectal stricture between the control and piroxicam-treated groups. However, at 1 year postirradiation the control group demonstrated neoplasia in 15 of 19 animals compared with eight of 20 animals in the piroxicam-treated group. The first endoscopic appearance of colonic neoplasm occurred at 15 weeks postirradiation in one control irradiated rat whereas the first evidence of endoscopic neoplasm in the piroxicam-treated group did not occur until 36 weeks postirradiation. Histologic examination documented a tendency toward a greater presence of adenocarcinomas in the control group compared with the piroxicam-treated group. The authors conclude that piroxicam treatment significantly decreased the incidence of colonic neoplasia in general as well as delayed the endoscopic appearance of colonic neoplasia in rats after pelvic irradiation. 41 references

  18. Piroxicam decreases postirradiation colonic neoplasia in the rat

    Energy Technology Data Exchange (ETDEWEB)

    Northway, M.G.; Scobey, M.W.; Cassidy, K.T.; Geisinger, K.R. (Wake Forest Univ., Winston Salem, NC (USA))

    1990-12-01

    This study evaluated the effects of the nonsteroidal antiinflammatory agent piroxicam on chronic radiation proctitis in the rat. Forty female Wistar rats received a 2250-cGy dose of irradiation to the distal 2 cm of the colon. Twenty received piroxicam 8.0 mg/kg orally 30 minutes before exposure and 24 hours after exposure; 20 rats served as irradiated controls. All animals were evaluated by colonoscopy 1 and 3 weeks postexposure and every third week until death or killing at 1 year. At killing, colons were removed for light microscopic examination. One year postirradiation results showed no differences in mortality, vascular changes, acute inflammation, colitis cystica profunda, or rectal stricture between the control and piroxicam-treated groups. However, at 1 year postirradiation the control group demonstrated neoplasia in 15 of 19 animals compared with eight of 20 animals in the piroxicam-treated group. The first endoscopic appearance of colonic neoplasm occurred at 15 weeks postirradiation in one control irradiated rat whereas the first evidence of endoscopic neoplasm in the piroxicam-treated group did not occur until 36 weeks postirradiation. Histologic examination documented a tendency toward a greater presence of adenocarcinomas in the control group compared with the piroxicam-treated group. The authors conclude that piroxicam treatment significantly decreased the incidence of colonic neoplasia in general as well as delayed the endoscopic appearance of colonic neoplasia in rats after pelvic irradiation. 41 references.

  19. EXPRESSION OF HPV 16 AND 18 IN CERVICAL INTRAEPITHELIAL NEOPLASIA

    Directory of Open Access Journals (Sweden)

    Kodali Venkataramana

    2017-03-01

    Full Text Available BACKGROUND Cervical cancer is by far the most common human papilloma virus related disease. Nearly, all cases of cervical cancer can be attributable to human papilloma virus infection. Infection with the human papilloma virus is the main risk factors for cervical intraepithelial neoplasia and cervical cancer especially the high-risk types. The aim of the study is to study the prevalence of high-risk human papilloma virus 16 and 18 in various grades of cervical intraepithelial neoplasia. MATERIALS AND METHODS It is a prospective study for a period of two years. 50 cases of cervical intraepithelial neoplasia of various grades on histopathology were included in the study. Polymerase chain reaction DNA sequencing was done in all the cases. The patients were followed up for 1 year with Pap smears and results tabulated. RESULTS 77.77% of cases were human papilloma virus 16 positive and 22.22% for human papilloma virus 18. High-risk human papilloma virus was positive in 66.66% of cases beyond 30 years of age. In cases with positive HPV 16 or 18, 62.5% of CIN 1 cases progressed to CIN 2 on follow up for one year,all the CIN2 cases progressed to CIN 3 and CIN 3 cases persisted in the same phase. CONCLUSION High-risk human papilloma virus testing beyond 30 years should be included in the screening test along with Pap smears.

  20. Quantitative investigation of reproduction of gonosomal condensed chromatin during trophoblast cell polyploidization and endoreduplication in the east-european field vole Microtus rossiaemeridionalis

    Directory of Open Access Journals (Sweden)

    Bogdanova Margarita S

    2003-04-01

    Full Text Available Abstract Simultaneous determinations of DNA content in cell nuclei and condensed chromatin bodies formed by heterochromatized regions of sex chromosomes (gonosomal chromatin bodies, GCB have been performed in two trophoblast cell populations of the East-European field vole Microtus rossiaemeridionalis: in the proliferative population of trophoblast cells of the junctional zone of placenta and in the secondary giant trophoblast cells. One or two GCBs have been observed in trophoblast cell nuclei of all embryos studied (perhaps both male and female. In the proliferative trophoblast cell population characterized by low ploidy levels (2–16c and in the highly polyploid population of secondary giant trophoblast cells (32–256c the total DNA content in GCB increased proportionally to the ploidy level. In individual GCBs the DNA content also rose proportionally to the ploidy level in nuclei both with one and with two GCBs in both trophoblast cell populations. Some increase in percentage of nuclei with 2–3 GCBs was shown in nuclei of the placenta junctional zone; this may be accounted for by genome multiplication via uncompleted mitoses. In nuclei of the secondary giant trophoblast cells (16–256c the number of GCBs did not exceed 2, and the fraction of nuclei with two GCBs did not increase, which suggests the polytene nature of sex chromosomes in these cells. In all classes of ploidy the DNA content in trophoblast cell nuclei with the single GCB was lower than in nuclei with two and more GCBs. This can indicate that the single GCB in many cases does not derive from fusion of two GCBs. The measurements in individual GCBs suggest that different heterochromatized regions of the X- and Y-chromosome may contribute in GCB formation.

  1. IL-27 Activates Human Trophoblasts to Express IP-10 and IL-6: Implications in the Immunopathophysiology of Preeclampsia

    Directory of Open Access Journals (Sweden)

    Nanlin Yin

    2014-01-01

    Full Text Available Purpose. To investigate the effects of IL-27 on human trophoblasts and the underlying regulatory signaling mechanisms in preeclampsia. Methods. The expression of IL-27 and IL-27 receptor (WSX-1 was studied in the placenta or sera from patients with preeclampsia. In vitro, we investigated the effects of IL-27 alone or in combination with inflammatory cytokine tumor necrosis factor (TNF-α on the proinflammatory activation of human trophoblast cells (HTR-8/SVneo and the underlying intracellular signaling molecules. Results. The expression of IL-27 and IL-27 receptor α (WSX-1 was significantly elevated in the trophoblastic cells from the placenta of patients with preeclampsia compared with control specimens. In vitro, IL-27 could induce the expression of inflammatory factors IFN-γ-inducible protein 10 (CXCL10/IP-10 and IL-6 in trophoblasts, and a synergistic effect was observed in the combined treatment of IL-27 and TNF-α on the release of IP-10 and IL-6. Furthermore, the production of IP-10 and IL-6 stimulated by IL-27 was differentially regulated by intracellular activation of phosphatidylinositol 3-OH kinase-AKT, p38MAPK, and JAK/STAT pathways. Conclusions. These results provide a new insight into the IL-27-activated immunopathological effects mediated by distinct intracellular signal transduction molecules in preeclampsia.

  2. Allelic imbalance modulates surface expression of the tolerance-inducing HLA-G molecule on primary trophoblast cells

    DEFF Research Database (Denmark)

    Djurisic, S; Teiblum, S; Tolstrup, C K

    2015-01-01

    The HLA-G molecule is expressed on trophoblast cells at the feto-maternal interface, where it interacts with local immune cells, and upholds tolerance against the semi-allogeneic fetus. Aberrant HLA-G expression in the placenta and reduced soluble HLA-G levels are observed in pregnancy complicati...

  3. Human Primary Trophoblast Cell Culture Model to Study the Protective Effects of Melatonin Against Hypoxia/reoxygenation-induced Disruption.

    Science.gov (United States)

    Sagrillo-Fagundes, Lucas; Clabault, Hélène; Laurent, Laetitia; Hudon-Thibeault, Andrée-Anne; Salustiano, Eugênia Maria Assunção; Fortier, Marlène; Bienvenue-Pariseault, Josianne; Wong Yen, Philippe; Sanderson, J Thomas; Vaillancourt, Cathy

    2016-07-30

    This protocol describes how villous cytotrophoblast cells are isolated from placentas at term by successive enzymatic digestions, followed by density centrifugation, media gradient isolation and immunomagnetic purification. As observed in vivo, mononucleated villous cytotrophoblast cells in primary culture differentiate into multinucleated syncytiotrophoblast cells after 72 hr. Compared to normoxia (8% O2), villous cytotrophoblast cells that undergo hypoxia/reoxygenation (0.5% / 8% O2) undergo increased oxidative stress and intrinsic apoptosis, similar to that observed in vivo in pregnancy complications such as preeclampsia, preterm birth, and intrauterine growth restriction. In this context, primary villous trophoblasts cultured under hypoxia/reoxygenation conditions represent a unique experimental system to better understand the mechanisms and signalling pathways that are altered in human placenta and facilitate the search for effective drugs that protect against certain pregnancy disorders. Human villous trophoblasts produce melatonin and express its synthesizing enzymes and receptors. Melatonin has been suggested as a treatment for preeclampsia and intrauterine growth restriction because of its protective antioxidant effects. In the primary villous cytotrophoblast cell model described in this paper, melatonin has no effect on trophoblast cells in normoxic state but restores the redox balance of syncytiotrophoblast cells disrupted by hypoxia/reoxygenation. Thus, human villous trophoblast cells in primary culture are an excellent approach to study the mechanisms behind the protective effects of melatonin on placental function during hypoxia/reoxygenation.

  4. Localization of chondromodulin-I at the feto-maternal interface and its inhibitory actions on trophoblast invasion in vitro

    Directory of Open Access Journals (Sweden)

    Kondo Jun

    2011-08-01

    Full Text Available Abstract Background Chondromodulin-I (ChM-I is an anti-angiogenic glycoprotein that is specifically localized at the extracellular matrix of the avascular mesenchyme including cartilage and cardiac valves. In this study, we characterized the expression pattern of ChM-I during early pregnancy in mice in vivo and its effect on invasion of trophoblastic cells into Matrigel in vitro. Results Northern blot analysis clearly indicated that ChM-I transcripts were expressed in the pregnant mouse uterus at 6.5-9.5 days post coitum. In situ hybridization and immunohistochemistry revealed that ChM-I was localized to the mature decidua surrounding the matrix metalloproteinase-9 (MMP-9-expressing trophoblasts. Consistent with this observation, the expression of ChM-I mRNA was induced in decidualizing endometrial stromal cells in vitro, in response to estradiol and progesterone. Recombinant human ChM-I (rhChM-I markedly inhibited the invasion through Matrigel as well as the chemotactic migration of rat Rcho-1 trophoblast cells in a manner independent of MMP activation. Conclusions This study demonstrates the inhibitory action of ChM-I on trophoblast migration and invasion, implying the potential role of the ChM-I expression in decidual cells for the regulated tissue remodeling and angiogenesis at feto-maternal interface.

  5. Human monocytes undergo functional re-programming during differentiation to dendritic cell mediated by human extravillous trophoblasts.

    Science.gov (United States)

    Zhao, Lei; Shao, Qianqian; Zhang, Yun; Zhang, Lin; He, Ying; Wang, Lijie; Kong, Beihua; Qu, Xun

    2016-02-09

    Maternal immune adaptation is required for a successful pregnancy to avoid rejection of the fetal-placental unit. Dendritic cells within the decidual microenvironment lock in a tolerogenic profile. However, how these tolerogenic DCs are induced and the underlying mechanisms are largely unknown. In this study, we show that human extravillous trophoblasts redirect the monocyte-to-DC transition and induce regulatory dendritic cells. DCs differentiated from blood monocytes in the presence of human extravillous trophoblast cell line HTR-8/SVneo displayed a DC-SIGN(+)CD14(+)CD1a(-) phenotype, similar with decidual DCs. HTR8-conditioned DCs were unable to develop a fully mature phenotype in response to LPS, and altered the cytokine secretory profile significantly. Functionally, conditioned DCs poorly induced the proliferation and activation of allogeneic T cells, whereas promoted CD4(+)CD25(+)Foxp3(+) Treg cells generation. Furthermore, the supernatant from DC and HTR-8/SVneo coculture system contained significant high amount of M-CSF and MCP-1. Using neutralizing antibodies, we discussed the role of M-CSF and MCP-1 during monocyte-to-DCs differentiation mediated by extravillous trophoblasts. Our data indicate that human extravillous trophoblasts play an important role in modulating the monocyte-to-DC differentiation through M-CSF and MCP-1, which facilitate the establishment of a tolerogenic microenvironment at the maternal-fetal interface.

  6. PP042. Anti-hypertensive drugs hydralazine, clonidine and labetalol improve trophoblast integration into endothelial cellular networks in vitro.

    Science.gov (United States)

    Xu, B; Charlton, F; Makris, A; Hennessy, A

    2012-07-01

    Preeclampsia is an exaggerated maternal inflammatory state with over-expression of placental soluble fms-like tyrosine kinase 1 (sFlt-1). It is also associated with shallow trophoblast invasion and inadequate transformation of uterine spiral arteries. Antihypertensive drugs administrated in preeclampsia to control blood pressure have been reported to regulate placental and circulating cytokine production from women with preeclampsia. Whether they could modulate the interaction between trophoblast and endothelial cells are not investigated. This study is to examine the effect of pharmacological dose of anti-hypertensive hydralazine, clonidine and labetalol on trophoblast cell integration into inflammatory TNF-a pre-exposed endothelial cellular networks. Human uterine myometrial microvascular endothelial cells (UtMVECs) were pre-incubated with (or without) low dose (0.5ng/ml) inflammatory TNF-a or TNF-a plus sFlt-1 (100ng/ml) for 24hours. These cells were labelled with red fluorescence and seeded on a 24-well culture plate coated with Matrigel. Endothelial tubular structures appeared within 4hours. Green fluorescent-labelled HTR-8/SVneo trophoblast cells were then co-cultured with endothelial cells, with (or without) hydralazine (10μg/ml), clonidine (1.0μg/ml) or labetalol (0.5μg/ml). Red and green fluorescent images were captured after 24hours. Drug effect on HTR-8 cells integration into endothelial cellular networks was quantified by Image Analysis software. The conditioned media were also collected to measure concentrations of free VEGF, PLGF and sFlt-1 by ELISA. When HTR-8/SVneo trophoblast cells were co-cultured with TNF-a pre-incubated endothelial cells, hydralazine and clonidine can significantly increase the trophoblast integration into endothelial cellular networks. This increase was not seen if co-cultured with normal endothelial cells (without TNF-a pre-incubation) or with TNF-a plus sFlt-1 treated endothelial cells. Labetalol could increase the HTR-8

  7. Gestational Hyperandrogenism in Developmental Programming

    Science.gov (United States)

    Hakim, Christopher; Padmanabhan, Vasantha

    2017-01-01

    Androgen excess (hyperandrogenism) is a common endocrine disorder affecting women of reproductive age. The potential causes of androgen excess in women include polycystic ovary syndrome, congenital adrenal hyperplasia (CAH), adrenal tumors, and racial disparity among many others. During pregnancy, luteoma, placental aromatase deficiency, and fetal CAH are additional causes of gestational hyperandrogenism. The present report reviews the various phenotypes of hyperandrogenism during pregnancy and its origin, pathophysiology, and the effect of hyperandrogenism on the fetal developmental trajectory and offspring consequences. PMID:27967205

  8. Diabetes and Pregnancy: Gestational Diabetes

    Centers for Disease Control (CDC) Podcasts

    2007-11-14

    Gestational diabetes happens in a woman who develops diabetes during pregnancy. This podcast discusses its potential effects and action steps to avoid complications.  Created: 11/14/2007 by National Center for Chronic Disease Prevention and Health Promotion (NCCDPHP), Division of Diabetes Translation (DDT) and National Center on Birth Defects and Developmental Disabilities (NCBDDD), Prevention Research Branch.   Date Released: 11/27/2007.

  9. Surgical treatment of pancreatic endocrine tumors in multiple endocrine neoplasia type 1

    Directory of Open Access Journals (Sweden)

    Marcel Cerqueira Cesar Machado

    Full Text Available Surgical approaches to pancreatic endocrine tumors associated with multiple endocrine neoplasia type 1 may differ greatly from those applied to sporadic pancreatic endocrine tumors. Presurgical diagnosis of multiple endocrine neoplasia type 1 is therefore crucial to plan a proper intervention. Of note, hyperparathyroidism/multiple endocrine neoplasia type 1 should be surgically treated before pancreatic endocrine tumors/multiple endocrine neoplasia type 1 resection, apart from insulinoma. Non-functioning pancreatic endocrine tumors/multiple endocrine neoplasia type 1 >1 cm have a high risk of malignancy and should be treated by a pancreatic resection associated with lymphadenectomy. The vast majority of patients with gastrinoma/multiple endocrine neoplasia type 1 present with tumor lesions at the duodenum, so the surgery of choice is subtotal or total pancreatoduodenectomy followed by regional lymphadenectomy. The usual surgical treatment for insulinoma/multiple endocrine neoplasia type 1 is distal pancreatectomy up to the mesenteric vein with or without spleen preservation, associated with enucleation of tumor lesions in the pancreatic head. Surgical procedures for glucagonomas, somatostatinomas, and vipomas/ multiple endocrine neoplasia type 1 are similar to those applied to sporadic pancreatic endocrine tumors. Some of these surgical strategies for pancreatic endocrine tumors/multiple endocrine neoplasia type 1 still remain controversial as to their proper extension and timing. Furthermore, surgical resection of single hepatic metastasis secondary to pancreatic endocrine tumors/multiple endocrine neoplasia type 1 may be curative and even in multiple liver metastases surgical resection is possible. Hepatic trans-arterial chemo-embolization is usually associated with surgical resection. Liver transplantation may be needed for select cases. Finally, pre-surgical clinical and genetic diagnosis of multiple endocrine neoplasia type 1 syndrome and

  10. Down-Regulation of Neuropathy Target Esterase in Preeclampsia Placenta Inhibits Human Trophoblast Cell Invasion via Modulating MMP-9 Levels

    Directory of Open Access Journals (Sweden)

    Ting Zhong

    2018-02-01

    Full Text Available Background/Aims: Neuropathy target esterase (NTE, also known as neurotoxic esterase is proven to deacylate phosphatidylcholine (PC to glycerophosphocholine as a phospholipase B. Recently; studies showed that artificial phosphatidylserine/PC microvesicles can induce preeclampsia (PE-like changes in pregnant mice. However, it is unclear whether NTE plays a key role in the pathology of PE, a pregnancy-related disease, which was characterized by deficient trophoblast invasion and reduced trophoblast-mediated remodeling of spiral arteries. The aim of this study was to investigate the expression pattern of NTE in the placenta from women with PE and normal pregnancy, and the molecular mechanism of NTE involved in the development of PE. Methods: NTE expression levels in placentas from 20 pregnant women with PE and 20 healthy pregnant women were detected using quantitative PCR and immunohistochemistry staining. The effect of NTE on trophoblast migration and invasion and the underlying mechanisms were examined in HTR-8/SVneo cell lines by transfection method. Results: NTE mRNA and protein expression levels were significantly decreased in preeclamptic placentas than normal control. Over-expression of NTE in HTR-8/SVneo cells significantly promoted trophoblast cells migration and invasion and was associated with increased MMP-9 levels. Conversely, shRNA-mediated down-regulation of NTE markedly inhibited the cell migration and invasion. In addition, silencing NTE reduced the MMP-9 activity and phosphorylated Erk1/2 and AKT levels. Conclusions: Our results suggest that the decreased NTE may contribute to the development of PE through impairing trophoblast invasion by down-regulating MMP-9 via the Erk1/2 and AKT signaling pathway.

  11. Early Diagnosis of Breast Cancer by Identifying Malignant Cells Within Neoplasias Histologically Classified as Benign

    National Research Council Canada - National Science Library

    Lelievre, Sophie A

    2005-01-01

    Current diagnostic tools permit the classification of breast neoplasias into categories that represent different relative risks of developing cancer, but they do not indicate which particular lesion...

  12. Saturated fatty acids enhance TLR4 immune pathways in human trophoblasts.

    Science.gov (United States)

    Yang, Xiaohua; Haghiac, Maricela; Glazebrook, Patricia; Minium, Judi; Catalano, Patrick M; Hauguel-de Mouzon, Sylvie

    2015-09-01

    What are the effects of fatty acids on placental inflammatory cytokine with respect to toll-like receptor-4/nuclear factor-kappa B (TLR4/NF-kB)? Exogenous fatty acids induce a pro-inflammatory cytokine response in human placental cells in vitro via activation of TLR4 signaling pathways. The placenta is exposed to changes in circulating maternal fatty acid concentrations throughout pregnancy. Fatty acids are master regulators of innate immune pathways through recruitment of toll-like receptors and activation of cytokine synthesis. Trophoblast cells isolated from 14 normal term human placentas were incubated with long chain fatty acids (FA) of different carbon length and degree of saturation. The expression and secretion of interleukin-6 (IL-6), IL-8 and tumor necrosis factor-alpha (TNF-α) were measured by reverse transcription-polymerase chain reaction and enzyme-linked immunosorbent assay. Antibodies against TLR4 ligand binding domain, downstream signaling and anti-p65 NFkB-inhibitor were used to characterize the pathways of FA action. General approach used primary human term trophoblast cell culture. Methods and end-points used real-time quantitative PCR, cytokine measurements, immunohistochemistry, western blots. The long chain saturated fatty acids, stearic and palmitic (PA), stimulated the synthesis as well as the release of TNF-α, IL-6 and IL-8 by trophoblast cells (2- to 6-fold, P acids did not modify cytokine expression significantly. Palmitate-induced inflammatory effects were mediated via TLR4 activation, NF-kB phosphorylation and nuclear translocation. TNF-α protein level was close to the limit of detection in the culture medium even when cells were cultured with PA. These mechanisms open the way to a better understanding of how changes in maternal lipid homeostasis may regulate placental inflammatory status. X.Y. was recipient of fellowship award from West China Second University Hospital, Sichuan University (NIH HD 22965-19). The authors have nothing

  13. The clinicopathological features of intermediate trophoblastic tumor in the pineal region

    Directory of Open Access Journals (Sweden)

    ZHANG Yun-xiang

    2012-08-01

    Full Text Available Objective To evaluate the clinicopathological features of intermediate trophoblastic tumor (ITT in the pineal region. Methods A retrospective study was performed to analyse the diagnostic and therapeutic process of 1 case with ITT in the pineal region. The specimen obtained from the surgery was dealt with common tissue processing mode and cut into slices. HE staining was performed to observe histophathological features. Immunohistochemical staining (SP two-step method was performed to analyse the expression of tumor markers. Related literatures were reviewed. Results A 6-year old boy with clinical manifestations of penis enlargement and rapid growth for more than one year, presented a mass in his pineal region through MRI. The tumor was surgically excised after it is refractory to 10 times experimental radiotherapy as germinoma. The level of β-human chorionic gonadotropin ( β-hCG in his postoperative blood was decreased to normal, but gradually increased, once again followed to normal after three times chemotherapy. Patient was normal almost postoperative 6 months later by follow -up. Pathological examination showed sheets necrosis with multiple calcification and scattered fresh blood cells, epithelioid tumor cells with solid growth pattern. The tumor cells were atypical mononuclear cells with relative uniform (between heterotypic cells and partially surrounding and invasing the vascular walls. The cytoplasm of tumor cells was eosinophilic or clear, the nucleus was round or irregular in shape and some with intranuclear pseudoinclusions, and its mitotic figures were rarely seen under light microscopy. The tumor cells showed strong positive for AE1/AE3, cell adhesion molecules 5.2 (CAM5.2, human placental lactogen (hPL, octamer-binding transcription factor 3/4 (Oct3/4, epidermal growth factor receptor (EGFR and E-cadherin. P53 was also expressed. The positive rate of Ki-67 was about 10%, and β-hCG was expressed in the extremely tumor cells. The

  14. Steroid hormones modulate galectin-1 in the trophoblast HTR-8/SVneocell line

    Directory of Open Access Journals (Sweden)

    Bojić-Trbojević Žanka

    2008-01-01

    Full Text Available The effects of steroids on galectin-1 (gal-1 were studied in HTR-8/SVneo cells by immunocytochemistry, cell-based ELISA, the MTT proliferation test and the Matrigel TM invasion test. Dexamethasone (DEX, progesterone (PRG, and mifepristone (RU486 were used. Gal-1 was modulated in a steroid- and dose-dependent manner by DEX, which mildly but significantly stimulated production at low concentrations (0.1-10 nM, and inhibited it at 100 nM, while the effects of PRG and RU486 were opposite. HTR-8/SVneo cell invasion of Matrigel was significantly decreased in the presence of DEX and lactose. The obtained data support the proposed regulatory role of steroids in trophoblast gal-1 production.

  15. Elsevier Trophoblast Research Award lecture: The multifaceted role of Nodal signaling during mammalian reproduction.

    Science.gov (United States)

    Park, C B; Dufort, D

    2011-03-01

    Nodal, a secreted signaling protein in the transforming growth factor-beta (TGF-β) superfamily, has established roles in vertebrate development. However, components of the Nodal signaling pathway are also expressed at the maternal-fetal interface and have been implicated in many processes of mammalian reproduction. Emerging evidence indicates that Nodal and its extracellular inhibitor Lefty are expressed in the uterus and complex interactions between the two proteins mediate menstruation, decidualization and embryo implantation. Furthermore, several studies have shown that Nodal from both fetal and maternal sources may regulate trophoblast cell fate and facilitate placentation as both embryonic and uterine-specific Nodal knockout mouse strains exhibit disrupted placenta morphology. Here we review the established and prospective roles of Nodal signaling in facilitating successful pregnancy, including recent evidence supporting a potential link to parturition and preterm birth. Copyright © 2011 Elsevier Ltd. All rights reserved.

  16. Investigating work-related neoplasia associated with solar radiation.

    Science.gov (United States)

    Turner, S; Forman, S D; McNamee, R; Wilkinson, S M; Agius, R

    2015-01-01

    Both solar and non-solar exposures associated with occupation and work tasks have been reported as skin carcinogens. In the UK, there are well-established surveillance schemes providing relevant information, including when exposures took place, occupation, location of work and dates of symptom onset and diagnosis. To add to the evidence on work-related skin neoplasia, including causal agents, geographical exposure and time lag between exposure and diagnosis. This study investigated incident case reports of occupational skin disease originating from clinical specialists in dermatology reporting to a UK-wide surveillance scheme (EPIDERM) by analysing case reports of skin neoplasia from 1996 to 2012 in terms of diagnosis, employment, suspected causal agent and symptom onset. The suspected causal agent was 'sun/sunlight/ultraviolet light' in 99% of the reported work-related skin neoplasia cases. Most cases reported (91%) were in males, and the majority (62%) were aged over 65 at the time of reporting. More detailed information on exposure was available for 42% of the cases, with the median time from exposure to symptom onset ranging from 44 (melanoma) to 57 (squamous cell carcinoma) years. Irrespective of diagnostic category, the median duration of exposure to 'sun/sunlight/ultraviolet light' appeared longer where exposures occurred in the UK (range 39-51 years) rather than outside the UK (range 2.5-6.5 years). It is important to provide effective information about skin protection to workers exposed to solar radiation, especially to outdoor workers based outside the UK. © The Author 2014. Published by Oxford University Press on behalf of the Society of Occupational Medicine. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

  17. Male pattern baldness and risk of colorectal neoplasia.

    Science.gov (United States)

    Keum, N; Cao, Y; Lee, D H; Park, S M; Rosner, B; Fuchs, C S; Wu, K; Giovannucci, E L

    2016-01-12

    Male pattern baldness is positively associated with androgens as well as insulin-like growth factor 1 (IGF-1) and insulin, all of which are implicated in pathogenesis of colorectal neoplasia. From 1992 through 2010, we prospectively followed participants in the Health Professionals Follow-Up Study. Hair pattern at age 45 years was assessed at baseline with five image categories (no baldness, frontal-only baldness, frontal-plus-mild-vertex baldness, frontal-plus-moderate-vertex baldness, and frontal-plus-severe-vertex baldness). Cancer analysis included 32 782 men and used Cox proportional hazards models to estimate hazard ratios (HRs) and 95% confidence intervals (CIs). Restricted to men who underwent at least one endoscopy over the study period, adenoma analysis included 29 770 men and used logistic regressions for clustered data to estimate odds ratios (ORs) and 95% CIs. Over the mean follow-up of 15.6 years, 710 cases of colorectal cancer (478 for colon, 152 for rectum, and 80 unknown site) developed. Significantly increased risks associated with frontal-only baldness and frontal-plus-mild-vertex baldness relative to no baldness were observed for colon cancer with respective HR being 1.29 (95% CI, 1.03-1.62) and 1.31 (95% CI, 1.01-1.70). Over the 19-year study period, 3526 cases of colorectal adenoma were detected. Evidence for an increased risk of colorectal adenoma relative to no baldness was significant with frontal-only baldness (OR, 1.16; 95% CI, 1.06-1.26) and borderline insignificant with frontal-plus-severe-vertex baldness (OR, 1.14; 95% CI, 0.98-1.33). Subtypes of male pattern baldness at age 45 years were positively associated with colorectal neoplasia. Future studies are warranted to confirm our results and to determine the predictive value of male pattern baldness to identify those at high risk for colorectal neoplasia.

  18. ECM-dependent HIF induction directs trophoblast stem cell fate via LIMK1-mediated cytoskeletal rearrangement.

    Directory of Open Access Journals (Sweden)

    Hwa J Choi

    Full Text Available The Hypoxia-inducible Factor (HIF family of transcriptional regulators coordinates the expression of dozens of genes in response to oxygen deprivation. Mammalian development occurs in a hypoxic environment and HIF-null mice therefore die in utero due to multiple embryonic and placental defects. Mouse embryonic stem cells do not differentiate into placental cells; therefore, trophoblast stem cells (TSCs are used to study mouse placental development. Consistent with a requirement for HIF activity during placental development in utero, TSCs derived from HIF-null mice exhibit severe differentiation defects and fail to form trophoblast giant cells (TGCs in vitro. Interestingly, differentiating TSCs induce HIF activity independent of oxygen tension via unclear mechanisms. Here, we show that altering the extracellular matrix (ECM composition upon which TSCs are cultured changes their differentiation potential from TGCs to multinucleated syncytiotropholasts (SynTs and blocks oxygen-independent HIF induction. We further find that modulation of Mitogen Activated Protein Kinase Kinase-1/2 (MAP2K1/2, MEK-1/2 signaling by ECM composition is responsible for this effect. In the absence of ECM-dependent cues, hypoxia-signaling pathways activate this MAPK cascade to drive HIF induction and redirect TSC fate along the TGC lineage. In addition, we show that integrity of the microtubule and actin cytoskeleton is critical for TGC fate determination. HIF-2α ensures TSC cytoskeletal integrity and promotes invasive TGC formation by interacting with c-MYC to induce non-canonical expression of Lim domain kinase 1-an enzyme that regulates microtubule and actin stability, as well as cell invasion. Thus, we find that HIF can integrate positional and metabolic cues from within the TSC niche to regulate placental development by modulating the cellular cytoskeleton via non-canonical gene expression.

  19. Placental melatonin system is present throughout pregnancy and regulates villous trophoblast differentiation.

    Science.gov (United States)

    Soliman, Ahmed; Lacasse, Andrée-Anne; Lanoix, Dave; Sagrillo-Fagundes, Lucas; Boulard, Véronique; Vaillancourt, Cathy

    2015-08-01

    Melatonin is highly produced in the placenta where it protects against molecular damage and cellular dysfunction arising from hypoxia/re-oxygenation-induced oxidative stress as observed in primary cultures of syncytiotrophoblast. However, little is known about melatonin and its receptors in the human placenta throughout pregnancy and their role in villous trophoblast development. The purpose of this study was to determine melatonin-synthesizing enzymes, arylalkylamine N-acetyltransferase (AANAT) and hydroxyindole O-methyltransferase (HIOMT), and melatonin receptors (MT1 and MT2) expression throughout pregnancy as well as the role of melatonin and its receptors in villous trophoblast syncytialization. Our data show that the melatonin generating system is expressed throughout pregnancy (from week 7 to term) in placental tissues. AANAT and HIOMT show maximal expression at the 3rd trimester of pregnancy. MT1 receptor expression is maximal at the 1st trimester compared to the 2nd and 3rd trimesters, while MT2 receptor expression does not change significantly during pregnancy. Moreover, during primary villous cytotrophoblast syncytialization, MT1 receptor expression increases, while MT2 receptor expression decreases. Treatment of primary villous cytotrophoblast with an increasing concentration of melatonin (10 pM-1 mM) increases the fusion index (syncytium formation; 21% augmentation at 1 mM melatonin vs. vehicle) and β-hCG secretion (121% augmentation at 1 mM melatonin vs. vehicle). This effect of melatonin appears to be mediated via its MT1 and MT2 receptors. In sum, melatonin machinery (synthetizing enzymes and receptors) is expressed in human placenta throughout pregnancy and promotes syncytium formation, suggesting an essential role of this indolamine in placental function and pregnancy well-being. © 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  20. Graded hyperthyroidism and serum human chorionic gonadotropin concentration in patients with trophoblastic disease

    International Nuclear Information System (INIS)

    Rajatanavin, R.

    1989-11-01

    Serum thyroid hormone and basal and post TRH stimulated levels of TSH were measured in 48 female subjects of mean age 29.3 ± 9.2 and mean gravida 2.9 ± 2.6 with trophoblastic disease (TD), both benign and malignant. Normal pregnant women (n=21) served as controls. Twenty-five patients showed a normal response to TRH (Group i) while the rest (Group ii) had subnormal response while thyroid hormone levels were increased. Two subgroups iiA and iiB were formed within Group ii on the basis of the free T 4 levels (measured by equilibrium dialysis) falling below or above the 25th percentile. hCG levels were higher in Group ii than in Group i and a stepwise significant increase in the mean level of this hormone was observed in Group i to iiA and iiB. Significant correlation between hCG levels and those of thyroxine, free thyroxine, and triiodothyronine were found in TD patients as a whole, but not within the different subgroups. Clinical signs were minimal, with proximal muscle weakness and fine finger tumours observed in 10 patients in Group iiB. The study shows that the incidence of biochemical hyperthyroidism is higher than was reported before sensitive methods for TSH measurement were available, and postulates that increased hCG concentrations in themselves and/or abnormal metabolic variants of hCG produced by trophoblastic tumours may act as thyroid stimulators in this condition. 64 refs, 5 figs, 4 tabs

  1. Vitamin D and gestational diabetes

    DEFF Research Database (Denmark)

    Joergensen, Jan S; Lamont, Ronald F; Torloni, Maria R

    2014-01-01

    PURPOSE OF REVIEW: Vitamin D status (which is involved in glucose homeostasis) is related to gestational diabetes mellitus (GDM). GDM is characterized by increased resistance to and impaired secretion of insulin and results in higher risk of adverse pregnancy outcomes including operative delivery......, macrosomia, shoulder dystocia and neonatal hypoglycemia. Women with GDM and their babies are at increased risk for developing type II diabetes. RECENT FINDINGS: International definitions of vitamin D deficiency and normality are inconsistent. Vitamin D deficiency is common in pregnant women particularly...

  2. Imaging of multiple endocrine neoplasia (MEN II A)

    International Nuclear Information System (INIS)

    Tanaka, Hiroko; Kohno, Atsushi; Nojiri, Yoko

    1995-01-01

    A retrospective review of diagnostic imaging findings of 20 cases of multiple endocrine neoplasia II A (MEN II A) was performed. The characteristic findings of thyroidal medullary carcinomas were relatively well-defined hypo- to isoechoic masses on US and coarse calcifications on plain X-ray. The pheochromocytomas were smaller in size and less enhancing than the sporadic ones, and they revealed marked high intensity on T2WI of MRI. We consider that these imaging findings were useful for the supplementary diagnosis of MEN II A. (author)

  3. Endoscopic submucosal dissection for early Barrett’s neoplasia

    Science.gov (United States)

    Barret, Maximilien; Cao, Dalhia Thao; Beuvon, Frédéric; Leblanc, Sarah; Terris, Benoit; Camus, Marine; Coriat, Romain; Chaussade, Stanislas

    2015-01-01

    Introduction The possible benefit of endoscopic submucosal dissection (ESD) for early neoplasia arising in Barrett’s esophagus remains controversial. We aimed to assess the efficacy and safety of ESD for the treatment of early Barrett’s neoplasia. Methods All consecutive patients undergoing ESD for the resection of a visible lesion in a Barrett’s esophagus, either suspicious of submucosal infiltration or exceeding 10 mm in size, between February 2012 and January 2015 were prospectively included. The primary endpoint was the rate of curative resection of carcinoma, defined as histologically complete resection of adenocarcinomas without poor histoprognostic factors. Results Thirty-five patients (36 lesions) with a mean age of 66.2 ± 12 years, a mean ASA score of 2.1 ± 0.7, and a mean C4M6 Barrett’s segment were included. The mean procedure time was 191 ± 79 mn, and the mean size of the resected specimen was 51.3 ± 23 mm. En bloc resection rate was 89%. Lesions were 12 ± 15 mm in size, and 81% (29/36) were invasive adenocarcinomas, six of which with submucosal invasion. Although R0 resection of carcinoma was 72.4%, the curative resection rate was 66% (19/29). After a mean follow-up of 12.9 ± 9 months, 16 (45.7%) patients had required additional treatment, among whom nine underwent surgical resection, and seven further endoscopic treatments. Metachronous lesions or recurrence of cancer developed during the follow-up period in 17.2% of the patients. The overall complication rate was 16.7%, including 8.3% perforations, all conservatively managed, and no bleeding. The 30-day mortality was 0%. Conclusion In this early experience, ESD yielded a moderate curative resection rate in Barrett’s neoplasia. At present, improvements are needed if ESD is to replace piecemeal endoscopic mucosal resection in the management of Barrett’s neoplasia. PMID:27087948

  4. Detection of fetal-specific DNA after enrichment for trophoblasts using the monoclonal antibody LK26 in model systems but failure to demonstrate fetal DNA in maternal peripheral blood

    DEFF Research Database (Denmark)

    Hviid, T V; Sørensen, S; Morling, N

    1999-01-01

    Trophoblast cells can be detected in maternal blood during normal human pregnancy and DNA from these cells may be used for non-invasive prenatal diagnosis of inherited diseases. The possibility of enriching trophoblast cells from maternal blood samples using a monoclonal antibody (LK26) against...... a folate-binding protein, which recognizes trophoblast in normal tissues, in conjunction with immunomagnetic cell sorting was investigated. Verification of the presence of fetal DNA in the sorted samples was done by detection of fetal/paternal-specific short tandem repeat (STR) alleles using polymerase...... on peripheral maternal blood samples. However, it was not possible to detect fetal DNA sequences in these samples, most probably due to the extremely low number of trophoblast cells. Positive identification and retrieval of trophoblast cells in suspension or trophoblast nuclear material prepared on microscope...

  5. Correlation of VCAM-1 expression in serum, cord blood, and placental tissue with gestational hypertension associated with fetal growth restriction in women from Xingtai Hebei, China.

    Science.gov (United States)

    Zhang, H G; Guo, W; Gu, H F; Chen, S B; Wang, J Q; Qiao, Z X; Ma, H S; Geng, S X

    2016-08-26

    The aim of this study was to investigate the expression of vascular adhesion molecule (VCAM)-1 in the maternal serum, cord blood, and placental tissue of pregnant women from Xingtai, Hebei, with gestational hypertension (GH) combined with fetal growth restriction (FGR). A total of 108 patients with GH combined with FGR (GH-FGR), 60 patients with GH alone (GH), and 50 healthy pregnant women (control) were recruited to this study. VCAM- 1 expression was detected in the maternal serum and cord blood by enzyme-linked immunosorbent assay, and in the placental tissue by immunohistochemistry. VCAM-1 expression was significantly higher in the maternal serum of patients with GH-FGR (164.38 ± 60.35) and GH alone (103.85 ± 54.47) than in the serum of the control population (46.70 ± 21.79; P 0.05). Moreover, the VCAM-1 expression rates were significantly higher and lower in the vascular endothelial and trophoblastic cells of the placenta of patients with GH-FGR (74.71 and 56.1%) and GH (72.98 and 55.36%), respectively, compared to those in the control subjects (46.48 and 95.11%). Therefore, we concluded that VCAM- 1 plays an important role in the development and generation of GH. Additionally, the low VCAM-1 expression in the trophoblastic cell could be correlated to the pathogenesis and progression of GH.

  6. Genetics of Endocrine and Neuroendocrine Neoplasias (PDQ®)—Health Professional Version

    Science.gov (United States)

    Genetics of Endocrine and Neuroendocrine Neoplasias discusses inherited syndromes multiple endocrine neoplasia types 1, 2, and 4 (MEN1, MEN2, MEN4), familial pheochromocytoma and paraganglioma, Carney-Stratakis syndrome, and familial nonmedullary thyroid cancer. Learn more in this clinician summary.

  7. Prostaglandin E2-induced colonic secretion in patients with and without colorectal neoplasia

    DEFF Research Database (Denmark)

    Kaltoft, Nicolai; Tilotta, Maria C; Witte, Anne-Barbara

    2010-01-01

    colorectal neoplasia. Patients without endoscopic findings of neoplasia served as controls. Biopsy specimens were obtained from normally appearing mucosa in the sigmoid part of colon. Biopsies were mounted in miniaturized modified Ussing air-suction chambers. Indomethacin (10 microM), various stimulators...

  8. Preliminary stop of the TOPical Imiquimod treatment of high-grade Cervical intraepithelial neoplasia (TOPIC) trial

    NARCIS (Netherlands)

    Koeneman, M. M.; Kruse, Arnold-Jan; Kooreman, L. F. S.; zur Hausen, Axel; Hopman, Anton H N; Sep, S. J. S.; Van Gorp, T.; Slangen, B. F. M.; van Beekhuizen, H. J.; de Sande, Michiel A. J. van; Gerestein, Cornelis G.; Nijman, H. W.; Kruitwagen, R. F. M. P.

    2017-01-01

    The "TOPical Imiquimod treatment of high-grade Cervical intraepithelial neoplasia" (TOPIC) trial was stopped preliminary, due to lagging inclusions. This study aimed to evaluate the treatment efficacy and clinical applicability of imiquimod 5% cream in high-grade cervical intraepithelial neoplasia

  9. Relationship between 17-hydroxyprogesterone caproate concentrations and gestational age at delivery in twin gestation.

    LENUS (Irish Health Repository)

    Caritis, Steve N

    2012-11-01

    We sought to evaluate in women with twin gestation the relationship between 17-hydroxyprogesterone caproate (17-OHPC) concentration and gestational age at delivery and select biomarkers of potential pathways of drug action.

  10. Neoplasia intra-epitelial cervical: diagnóstico e tratamento Cervical intraepithelial neoplasia: diagnosis and treatment

    Directory of Open Access Journals (Sweden)

    Sophie Françoise Mauricette Derchain

    2005-07-01

    Full Text Available O câncer do colo uterino é hoje doença passível de prevenção secundária. Os métodos de detecção das lesões precursoras e da infecção pelo papilomavírus humano, tais como a citologia oncológica e biologia molecular, são de uso mundialmente difundido. Entretanto, ainda há muita controvérsia em relação à aplicação destes métodos na prática ginecológica. Qual o melhor exame ou a melhor associação de exames que podem ser utilizados, com que intervalo e em quais mulheres permanecem questões que com freqüência geram ansiedade nos consultórios ou nas unidades de saúde. Por outro lado, uma vez detectada a infecção viral ou a neoplasia intra-epitelial cervical, o tratamento dessas mulheres ainda não é consensual e muitos fatores interferem na definição da conduta ótima. O tipo de infecção, gravidade da neoplasia intra-epitelial, tipo histológico encontrado, todos estes aspectos tendem a dificultar o planejamento terapêutico. Esta revisão tem como objetivo abordar, dentro do conhecimento atual e baseado nos consensos vigentes no país, vários aspectos relacionados ao rastreamento das lesões cervicais e as possíveis condutas terapêuticas vigentes.Cervical cancer is nowadays a disease amenable to secondary prevention. Methods for the detection of its precursor lesions and human papillomavirus infection, such as cervical cytology and molecular biology, achieved widespread use worldwide. However, there is still too much controversy regarding the use of these methods in gynecological practice. Which is the best examination or the best association of examinations, and the most adequate time intervals to proceed with screening, are still pending questions, generating anxiety in patients and doctors. On the other hand, the management of women who have been diagnosed with viral infection and/or cervical intraepithelial neoplasia is not yet consensual, and several factors may affect the clinical decision on how to

  11. Sera of patients with recurrent miscarriages containing anti-trophoblast antibodies (ATAB) reduce hCG and progesterone production in trophoblast cells in vitro.

    Science.gov (United States)

    von Schönfeldt, Viktoria; Rogenhofer, Nina; Ruf, Katharina; Thaler, Christian J; Jeschke, Udo

    2016-09-01

    Reproductive failure including RM has been suggested to correlate with antibodies that cross react with HLA-negative syncytiotrophoblasts and we have reported that 17% of women with 2 or more miscarriages and 34% of women with 3 or more miscarriages express anti-trophoblast antibodies (ATAB). Until now, the mechanism, how ATAB interfere with pregnancy success is not known. HCG and progesterone both play fundamental roles in supporting human pregnancy. Therefore we investigated the effects of sera of RM patients containing ATAB on the hCG and progesterone production of cells of the choriocarcinoma cell line JEG-3. In vitro study to investigate effects of patient sera with and without ATAB on hCG and progesterone secretion of JEG-3 cells. The presence of ATAB was detected as described earlier. Effects of sera from ATAB positive and ATAB negative RM patients on hCG and progesterone secretion by JEG-3 cells were analysed 12 and 24h after plating. Sera of women without pregnancy pathologies served as controls. Sera of ATAB-positive RM patients significantly inhibit hCG secretion of JEG-3 cells for 12h after plating compared to sera of healthy controls (p=0.019) and significantly reduce progesterone production for 12h (p=0.046) and 24h (p=0.027) of co-culture. Sera of ATAB-negative RM patient show no significant effect on progesterone secretion. Inhibition of hCG and progesterone production might point to a mechanism, how ATAB interfere with early pregnancies. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

  12. "COMPARISON OF MATERNAL AND FETAL/NEONATAL COMPLICATIONS IN GESTATIONAL AND PRE-GESTATIONAL DIABETES MELLITUS "

    OpenAIRE

    F. Akhlaghi A. B. Hamedi

    2005-01-01

    Presence of maternal diabetes mellitus (DM) during pregnancy has important consequences for both mother and child. To determine maternal and fetal/neonatal complications of gestational DM and compare them with pre-gestational DM, a prospective study was performed in 100 diabetic women delivered in our hospital from January 2001 to April 2002. Pregnancy outcome in 27 women with gestational DM and 73 women with pre-gestational DM and their offspring were studied and analyzed. The mean age of wo...

  13. Fractal dimension and image statistics of anal intraepithelial neoplasia

    International Nuclear Information System (INIS)

    Ahammer, H.; Kroepfl, J.M.; Hackl, Ch.; Sedivy, R.

    2011-01-01

    Research Highlights: → Human papillomaviruses cause anal intraepithelial neoplasia (AIN). → Digital image processing was carried out to classify the grades of AIN quantitatively. → The fractal dimension as well as grey value statistics was calculated. → Higher grades of AIN yielded higher values of the fractal dimension. → An automatic detection system is feasible. - Abstract: It is well known that human papillomaviruses (HPV) induce a variety of tumorous lesions of the skin. HPV-subtypes also cause premalignant lesions which are termed anal intraepithelial neoplasia (AIN). The clinical classification of AIN is of growing interest in clinical practice, due to increasing HPV infection rates throughout human population. The common classification approach is based on subjective inspections of histological slices of anal tissues with all the drawbacks of depending on the status and individual variances of the trained pathologists. Therefore, a nonlinear quantitative classification method including the calculation of the fractal dimension and first order as well as second order image statistical parameters was developed. The absolute values of these quantitative parameters reflected the distinct grades of AIN very well. The quantitative approach has the potential to decrease classification errors significantly and it could be used as a widely applied screening technique.

  14. Synchronous high-risk melanoma and lymphoid neoplasia.

    LENUS (Irish Health Repository)

    Cahill, R A

    2012-02-03

    Large population-based studies have shown a significant association between melanoma and lymphoid neoplasia, particularly non-Hodgkin\\'s lymphoma (NHL) and chronic lymphocytic leukaemia (CLL), that is independent of any treatment received for the initial tumour. This study examines the presentation, diagnosis, treatment and progress of three patients who developed advanced melanoma concurrently with a lymphoid neoplasm (one NHL, two CLLs), in order to illustrate their association, discuss common aetiological factors and examine possible therapeutic options. As it is the melanoma rather than the lymphoid neoplasm that represents the bigger threat to overall survival, initial treatment should be targeted towards this cancer. However, because of the interplay between the diseases and the possible side-effects of the various treatments, the choice of adjuvant therapy requires careful consideration. Immunosuppression associated with chemotherapy may permit a more aggressive course for the melanoma, while locoregional radiotherapy is contraindicated following lymph node dissections. As immunotherapy is of benefit in the treatment of melanoma and has also been recently shown to be effective in the management of lymphoid neoplasia, we instituted interferon-alpha as adjuvant therapy for these patients, thereby utilizing a single agent to treat the dual pathologies. The three patients have now been followed-up for 6 months without evidence of disease recurrence or progression.

  15. A Multiscale Model Evaluates Screening for Neoplasia in Barrett's Esophagus.

    Directory of Open Access Journals (Sweden)

    Kit Curtius

    2015-05-01

    Full Text Available Barrett's esophagus (BE patients are routinely screened for high grade dysplasia (HGD and esophageal adenocarcinoma (EAC through endoscopic screening, during which multiple esophageal tissue samples are removed for histological analysis. We propose a computational method called the multistage clonal expansion for EAC (MSCE-EAC screening model that is used for screening BE patients in silico to evaluate the effects of biopsy sampling, diagnostic sensitivity, and treatment on disease burden. Our framework seamlessly integrates relevant cell-level processes during EAC development with a spatial screening process to provide a clinically relevant model for detecting dysplastic and malignant clones within the crypt-structured BE tissue. With this computational approach, we retain spatio-temporal information about small, unobserved tissue lesions in BE that may remain undetected during biopsy-based screening but could be detected with high-resolution imaging. This allows evaluation of the efficacy and sensitivity of current screening protocols to detect neoplasia (dysplasia and early preclinical EAC in the esophageal lining. We demonstrate the clinical utility of this model by predicting three important clinical outcomes: (1 the probability that small cancers are missed during biopsy-based screening, (2 the potential gains in neoplasia detection probabilities if screening occurred via high-resolution tomographic imaging, and (3 the efficacy of ablative treatments that result in the curative depletion of metaplastic and neoplastic cell populations in BE in terms of the long-term impact on reducing EAC incidence.

  16. Levels of oxidative damage and lipid peroxidation in thyroid neoplasia.

    LENUS (Irish Health Repository)

    Young, Orla

    2012-02-01

    BACKGROUND: This study assessed the presence of oxidative damage and lipid peroxidation in thyroid neoplasia. METHODS: Using tissue microarrays and immunohistochemistry, we assessed levels of DNA damage (8-oxo-dG) and lipid peroxidation (4-HNE) in 71 follicular thyroid adenoma (FTA), 45 papillary thyroid carcinoma (PTC), and 17 follicular thyroid carcinoma (FTC) and matched normal thyroid tissue. RESULTS: Cytoplasmic 8-oxo-dG and 4-HNE expression was significantly higher in FTA, FTC, and PTC tissue compared to matched normal tissue (all p values < .001). Similarly, elevated nuclear levels of 8-oxo-dG were seen in all in FTA, FTC, and PTC tissue compared to matched normal (p values < .07, < .001, < .001, respectively). In contrast, a higher level of 4-HNE expression was detected in normal thyroid tissue compared with matched tumor tissue (p < .001 for all groups). Comparing all 3 groups, 4-HNE levels were higher than 8-oxo-dG levels (p < .001 for all groups) except that cytoplasmic levels of 8-oxo-dG were higher than 4-HNE in all (p < .001). These results were independent of proliferation status. CONCLUSION: High levels of DNA damage and lipid peroxidation in benign and malignant thyroid neoplasia indicates this damage is an early event that may influence disease progression.

  17. Scrotal neoplasia: would truck drivers be at greater risk?

    Directory of Open Access Journals (Sweden)

    Daniel Seabra

    2007-08-01

    Full Text Available OBJECTIVE: To analyze how scrotal neoplasias have been managed during the past decade and to question possible factors or professions associated to its presence. MATERIALS AND METHODS: We retrospectively evaluated every case reported from 1995 to 2005 at our hospital. We described the clinical scenario, complementary exams, treatments and outcomes. We also tried to verify if there was any risk, predisposing factors or professions that would explain the cancer origin. RESULTS: Six cases were reviewed. Out of these, three patients were truck drivers. Five of them showed restricted lesions without inguinal lymph nodes enlargement. Histologically, six patients presented squamous carcinoma, with two of them having the verrucous type. The median age of patients was 52 years old (31 to 89. The five patients who are still alive had their lesions completely removed with safety margin and primary closure. CONCLUSIONS: We have noticed that the scrotal carcinoma behavior is similar to that of the penis, where removal of the lesion and study of the regional lymph nodes help to increase the patient survival rate. The outstanding fact was that three out of six patients were truck drivers, raising the hypothesis that such profession, maybe due to the contact or attrition with the diesel exhaust expelled by the engine or to sexual promiscuity, would imply in a larger risk of developing this rare neoplasia.

  18. Dietary habits of colorectal neoplasia patients in comparison to their first-degree relatives.

    Science.gov (United States)

    Kajzrlikova, Ivana Mikoviny; Vitek, Petr; Chalupa, Josef; Dite, Petr

    2014-05-07

    To compare the dietary habits between colorectal neoplasia patients, their first-degree relatives, and unrelated controls. From July 2008 to April 2011, we collected epidemiological data relevant to colorectal cancer from patients with colorectal neoplasias, their first-degree relatives, and also from a control group consisting of people referred for colonoscopy with a negative family history of colorectal cancer and without evidence of neoplasia after colonoscopic examination. The first-degree relatives were divided into two groups following the colonoscopic examination: (1) patients with neoplasia or (2) patients without neoplasia. Dietary habits of all groups were compared. A χ (2) test was used to assess the association between two dichotomous categorical variables. The study groups consisted of 242 patients with colorectal neoplasias (143 men, 99 women; mean age: 64 ± 12 years) and 160 first-degree relatives (66 men, 94 women; mean age: 48 ± 11 years). Fifty-five of the first-degree relatives were found to have a neoplastic lesion upon colonoscopy, while the remaining 105 were without neoplasia. The control group contained 123 individuals with a negative family history for neoplastic lesions (66 men, 57 women; mean age: 54 ± 12 years). Two hypotheses were tested. In the first, the dietary habits of first-degree relatives with neoplasia were more similar to those of patients with neoplasia, while the dietary habits of first-degree relatives without neoplasia were similar to those of the control group. In the second, no sex-related differences in dietary habits were expected between the particular groups. Indeed, no significant differences were observed in the dietary habits between the groups of patients, controls and first-degree relatives with/without neoplastic lesions. Nevertheless, statistically significant sex-related differences were observed in all groups, wherein women had healthier dietary habits than men. In all groups examined, women had

  19. Ultrathin endoscopy versus high-resolution endoscopy for diagnosing superficial gastric neoplasia.

    Science.gov (United States)

    Toyoizumi, Hirobumi; Kaise, Mitsuru; Arakawa, Hiroshi; Yonezawa, Jin; Yoshida, Yukinaga; Kato, Masayuki; Yoshimura, Noboru; Goda, Ken-ichi; Tajiri, Hisao

    2009-08-01

    Ultrathin endoscopy (UTE) is an acceptable and cost-effective alternative to EGD with the patient under sedation, although the diagnostic accuracy of UTE is not well established. To compare the diagnostic accuracy of UTE and high-resolution endoscopy (HRE) for superficial gastric neoplasia. Prospective comparative study. Academic center. Patients with or without superficial gastric neoplasia underwent peroral UTE and HRE, back-to-back in a random order while under standard sedation. The procedures were performed by 2 endoscopists who were blinded to the clinical information. The rate of missed lesions and misdiagnosis, sensitivity, and specificity for the diagnosis of gastric neoplasia when using pathology as the reference standard. In total, 126 lesions (41 superficial gastric neoplasias, 85 nonneoplastic lesions) were recorded in 57 enrolled patients. For the diagnosis of gastric neoplasia, the sensitivity of UTE (58.5%) was significantly (P = .021) lower than that of HRE (78%), and the specificity of UTE (91.8%) was significantly (P = .014) lower than that of HRE (100%). The rate of missed lesions and misdiagnosis of gastric neoplasias when using UTE (41.5%) was significantly (P > .001) higher than that of HRE (22.0%). The corresponding rate of neoplasias at the proximal portion (fornix and corpus) when using UTE (29%) was significantly (P = .002) higher than that of HRE (7.2%), although the rates of neoplasias at the distal portion (angulus and antrum) were comparable for UTE and HRE. Small sample numbers in an enriched population. The diagnostic accuracy of UTE is significantly lower than that of HRE for superficial gastric neoplasia, and this difference is particularly striking for neoplasias in the proximal stomach. For UTE to be used as an alternative modality, improvements in optical quality and the incorporation of additional procedures, including close-range observations and chromoendoscopy, are required to enhance visualization.

  20. Quantitative attenuation analysis for identification of early Barrett's neoplasia in volumetric laser endomicroscopy

    Science.gov (United States)

    Swager, Anne-Fre; Faber, Dirk J.; de Bruin, Daniel M.; Weusten, Bas L.; Meijer, Sybren L.; Bergman, Jacques J.; Curvers, Wouter L.; van Leeuwen, Ton G.

    2017-08-01

    Early neoplasia in Barrett's esophagus (BE) is difficult to detect. Volumetric laser endomicroscopy (VLE) incorporates optical coherence tomography, providing a circumferential scan of the esophageal wall layers. The attenuation coefficient (μVLE) quantifies decay of detected backscattered light versus depth, and could potentially improve BE neoplasia detection. The aim is to investigate feasibility of μVLE for identification of early BE neoplasia. In vivo and ex vivo VLE scans with histological correlation from BE patients ± neoplasia were used. Quantification by μVLE was performed manually on areas of interest (AoIs) to differentiate neoplasia from nondysplastic (ND)BE. From ex vivo VLE scans from 16 patients (13 with neoplasia), 68 AoIs were analyzed. Median μVLE values (mm-1) were 3.7 [2.1 to 4.4 interquartile range (IQR)] for NDBE and 4.0 (2.5 to 4.9 IQR) for neoplasia, not statistically different (p=0.82). Fourteen in vivo scans were used: nine from neoplastic and five from NDBE patients. Median μVLE values were 1.8 (1.5 to 2.6 IQR) for NDBE and 2.1 (1.9 to 2.6 IQR) for neoplasia, with no statistically significant difference (p=0.37). In conclusion, there was no significant difference in μVLE values in VLE scans from early neoplasia versus NDBE. Future studies with a larger sample size should explore other quantitative methods for detection of neoplasia during BE surveillance.

  1. Elsevier Trophoblast Research Award Lecture: Unique properties of decidual T cells and their role in immune regulation during human pregnancy.

    Science.gov (United States)

    Tilburgs, T; Claas, F H J; Scherjon, S A

    2010-03-01

    Maternal lymphocytes at the fetal-maternal interface play a key role in the immune acceptance of the allogeneic fetus. Most studies focus on decidual NK cells and their interaction with fetal trophoblasts, whereas limited data are available on the mechanisms of fetus specific immune recognition and immune regulation by decidual T cells at the fetal-maternal interface. The aim of this review is to describe the phenotypic characteristics of decidual T cell subsets present at the fetal-maternal interface, their interaction with HLA-C expressed by fetal trophoblasts and their role in immune recognition and regulation at the fetal-maternal interface during human pregnancy. Copyright 2010 Elsevier Ltd. All rights reserved.

  2. Estimating Gestational Age From Ultrasound Fetal Biometrics.

    Science.gov (United States)

    Skupski, Daniel W; Owen, John; Kim, Sungduk; Fuchs, Karin M; Albert, Paul S; Grantz, Katherine L

    2017-08-01

    To compare the accuracy of a new formula with one developed in 1984 (and still in common use) and to develop and compare racial and ethnic-specific and racial and ethnic-neutral formulas. The Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD) Fetal Growth Studies-Singletons was a prospective cohort study that recruited women in four self-reported racial-ethnic groups-non-Hispanic black, Hispanic, non-Hispanic white, and Asian-with singleton gestations from 12 U.S. centers (2009-2013). Women with a certain last menstrual period confirmed by first-trimester ultrasonogram had longitudinal fetal measurements by credentialed study ultrasonographers blinded to the gestational age at their five follow-up visits. Regression analyses were performed with linear mixed models to develop gestational age estimating formulas. Repeated cross-validation was used for validation. The estimation error was defined as the mean squared difference between the estimated and observed gestational age and was used to compare the formulas' accuracy. The new formula estimated the gestational age (±2 SD) within ±7 days from 14 to 20 weeks of gestation, ±10 days from 21 to 27 weeks of gestation, and ±17 days from 28 to 40 weeks of gestation. The new formula performed significantly better than a formula developed in 1984 with an estimation error of 10.4 compared with 11.2 days from 21 to 27 weeks of gestation and 17.0 compared with 19.8 days at 28-40 weeks of gestation, respectively. Racial and ethnic-specific formulas did not outperform the racial and ethnic-neutral formula. The NICHD gestational age estimation formula is associated with smaller errors than a well-established historical formula. Racial and ethnic-specific formulas are not superior to a racial-ethnic-neutral one.

  3. Gestational diabetes mellitus screening and outcomes.

    Science.gov (United States)

    Aktün, Hale Lebriz; Uyan, Derya; Yorgunlar, Betül; Acet, Mustafa

    2015-01-01

    To verify the usefulness of the World Health Organization criteria for the diagnosis of gestational diabetes mellitus in pregnant women and its effectiveness in the prevention of maternal and neonatal adverse results in women younger than 35 years without apparent risk factors for gestational diabetes mellitus. This is a retrospective study based on population involving 1360 pregnant women who delivered and who were followed-up in a university hospital in Istanbul. All women underwent the 75-g oral glucose tolerance test screening, usually in between the 24(th)-28(th) weeks of pregnancy. In all cases, the identification of gestational diabetes mellitus was determined in accordance with the World Health Organization criteria. Approximately 28% of the pregnant women aged younger than 35 years with no risk factors for gestational diabetes mellitus were diagnosed with the oral glucose tolerance test in this study. In the gestational diabetes mellitus group, the primary cesarean section rate was importantly higher than that in the non-gestational diabetes mellitus group. Preterm delivery was also associated with gestational diabetes mellitus. The diagnosis of gestational diabetes mellitus was strongly associated with admittance to the neonatal intensive care unit. Neonatal respiratory problems didn't showed any significant deviation between the groups. There was a moderate association between gestational diabetes mellitus and metabolic complications. Pregnant women with no obvious risk factors were diagnosed with gestational diabetes mellitus using the World Health Organization criteria. The treatment of these women potentially reduced their risk of adverse maternal and neonatal hyperglycemia-related events, such as cesarean section, polyhydramnios, preterm delivery, admission to neonatal intensive care unit, large for gestational age, and higher neonatal weight.

  4. Imprinted NanoVelcro Microchips for Isolation and Characterization of Circulating Fetal Trophoblasts: Toward Noninvasive Prenatal Diagnostics

    OpenAIRE

    Hou, Shuang; Chen, Jie-Fu; Song, Min; Zhu, Yazhen; Jan, Yu Jen; Chen, Szu Hao; Weng, Tzu-Hua; Ling, Dean-An; Chen, Shang-Fu; Ro, Tracy; Liang, An-Jou; Lee, Tom; Jin, Helen; Li, Man; Liu, Lian

    2017-01-01

    Circulating fetal nucleated cells (CFNCs) in maternal blood offer an ideal source of fetal genomic DNA for noninvasive prenatal diagnostics (NIPD). We developed a class of nanoVelcro microchips to effectively enrich a subcategory of CFNCs, i.e., circulating trophoblasts (cTBs) from maternal blood, which can then be isolated with single-cell resolution by a laser capture microdissection (LCM) technique for downstream genetic testing. We first established a nanoimprinting fabrication process to...

  5. TCDD Induces the Hypoxia-Inducible Factor (HIF-1α Regulatory Pathway in Human Trophoblastic JAR Cells

    Directory of Open Access Journals (Sweden)

    Tien-Ling Liao

    2014-09-01

    Full Text Available The exposure to dioxin can compromise pregnancy outcomes and increase the risk of preterm births. 2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD has been demonstrated to induce placental hypoxia at the end of pregnancy in a rat model, and hypoxia has been suggested to be the cause of abnormal trophoblast differentiation and placental insufficiency syndromes. In this study, we demonstrate that the non-hypoxic stimulation of human trophoblastic cells by TCDD strongly increased hypoxia inducible factor-1 alpha (HIF-1α stabilization. TCDD exposure induced the generation of reactive oxygen species (ROS and nitric oxide. TCDD-induced HIF-1α stabilization and Akt phosphorylation was inhibited by pretreatment with wortmannin (a phosphatidylinositol 3-kinase (PI3K inhibitor or N-acetylcysteine (a ROS scavenger. The augmented HIF-1α stabilization by TCDD occurred via the ROS-dependent activation of the PI3K/Akt pathway. Additionally, a significant increase in invasion and metallomatrix protease-9 activity was found in TCDD-treated cells. The gene expression of vascular endothelial growth factor and placental growth factor was induced upon TCDD stimulation, whereas the protein levels of peroxisome proliferator-activated receptor γ (PPARγ, PPARγ coactivator-1α, mitochondrial transcription factor, and uncoupling protein 2 were decreased. Our results indicate that an activated HIF-1α pathway, elicited oxidative stress, and induced metabolic stress contribute to TCDD-induced trophoblastic toxicity. These findings may provide molecular insight into the TCDD-induced impairment of trophoblast function and placental development.

  6. Gadd45 α expression in preeclampsia placenta and the effect of Gadd45 α on trophoblast HTR8/Svneo

    Directory of Open Access Journals (Sweden)

    Li Wang

    2016-01-01

    Full Text Available Objective: To study the expression of Gadd45 α in preeclampsia placenta and the regulating effect of Gadd45 α knockdown on trophoblast HTR8/Svneo. Methods: Preeclampsia placenta tissue and normal placenta tissue were collected, and mRNA contents and protein contents of Gadd45 α were detected by fluorescent quantitative PCR and Western blotting respectively; trophoblast cells HTR8/Svneo were cultured and after transfection of Gadd45 α siRNA, cell invasion ability and expression of invasion-assiotiated molecules were detected. Results: mRNA content and protein content of Gadd45 α in preeclampsia placenta tissue were higher than those in normal placenta tissue; after transfection of Gadd45 α siRNA, mRNA content and protein content of Gadd45 α in HTR8/Svneo cells significantly decreased, and the number of invasive cells as well as expression of MMP1, MMP2, MMP3 and MMP9 significantly increased. Conclusion: The expression of Gadd45 α in preeclampsia placenta abnormally increases; inhibting the expression of Gadd45 α in trophoblasts HTR8/Svneo can promote invasion and increase the expression of MMPs molecules.

  7. Roles of the insulinlike growth factor family in nonpregnant human endometrium and at the decidual: trophoblast interface.

    Science.gov (United States)

    Giudice, L C; Irwin, J C

    1999-01-01

    The insulinlike growth factor (IGF) family is believed to be important in endometrial development during the menstrual cycle and in the process of implantation. The mitogenic, differentiative, and antiapoptotic properties of the IGFs and their binding proteins, as well as their spatial and temporal expression in cycling endometrium, suggest that they may participate in endometrial growth, differentiation, apoptosis, and perhaps angiogenesis. IGFBP proteases, which increase IGF bioavailability, have been localized to endometrial stromal cells and to the human cytotrophoblast and likely play important roles in endometrial, decidual, and trophoblast physiology. IGFBP-1 is a major protein product of nonpregnant endometrium during the mid-late secretory phase and occurs in abundance in decidua. Its roles as an IGF-binding protein and as a trophoblast integrin ligand suggest that it may have multiple roles in endometrial development and in interactions between the decidua and the invading trophoblast. Recent evidence suggests that it may have a role in the process of shallow implantation in the clinical disorder of preclampsia. In contrast to knowledge about the roles of IGF peptides, IGFBP proteases, and IGFBPs in normal endometrial development and early human pregnancy, little information is available regarding this family in abnormal endometrial development, in occult endometrial defects, and in uterine receptivity and nonreceptivity.

  8. Probiotics for preventing gestational diabetes.

    Science.gov (United States)

    Barrett, Helen L; Dekker Nitert, Marloes; Conwell, Louise S; Callaway, Leonie K

    2014-02-27

    Gestational diabetes mellitus (GDM) is associated with a range of adverse pregnancy outcomes for mother and infant. The prevention of GDM using lifestyle interventions has proven difficult. The gut microbiome (the composite of bacteria present in the intestines) influences host inflammatory pathways, glucose and lipid metabolism and, in other settings, alteration of the gut microbiome has been shown to impact on these host responses. Probiotics are one way of altering the gut microbiome but little is known about their use in influencing the metabolic environment of pregnancy. To assess the effects of probiotic supplementation when compared with other methods for the prevention of GDM. We searched the Cochrane Pregnancy and childbirth Group's Trials Register (31 August 2013) and reference lists of the articles of retrieved studies. Randomised and cluster-randomised trials comparing the use of probiotic supplementation with other methods for the prevention of the development of GDM. Cluster-randomised trials were eligible for inclusion but none were identified. Quasi-randomised and cross-over design studies are not eligible for inclusion in this review. Studies presented only as abstracts with no subsequent full report of study results would also have been excluded. Two review authors independently assessed study eligibility, extracted data and assessed risk of bias of included study. Data were checked for accuracy. Eleven reports (relating to five possible trials) were found. We included one study (six trial reports) involving 256 women. Four other studies are ongoing.The included trial consisted of three treatment arms: probiotic with dietary intervention, placebo and dietary intervention, and dietary intervention alone; it was at a low risk of bias. The study reported primary outcomes of a reduction in the rate of gestational diabetes mellitus (risk ratio (RR) 0.38, 95% confidence interval (CI) 0.20 to 0.70), with no statistical difference in the rates of

  9. Heritability of gestational weight gain

    DEFF Research Database (Denmark)

    Andersson, Elina Scheers; Silventoinen, Karri; Tynelius, Per

    2015-01-01

    Gestational weight gain (GWG) is a complex trait involving intrauterine environmental, maternal environmental, and genetic factors. However, the extent to which these factors contribute to the total variation in GWG is unclear. We therefore examined the genetic and environmental influences...... on the variation in GWG in the first and second pregnancy in monozygotic (MZ) and dizygotic (DZ) twin mother-pairs. Further, we explored if any co-variance existed between factors influencing the variation in GWG of the mothers’ first and second pregnancies. By using Swedish nationwide record-linkage data, we...... identified 694 twin mother-pairs with complete data on their first pregnancy and 465 twin mother-pairs with complete data on their second pregnancy during 1982–2010. For a subanalysis, 143 twin mother-pairs had complete data on two consecutive pregnancies during the study period. We used structural equation...

  10. Exercise: An Alternative Therapy for Gestational Diabetes.

    Science.gov (United States)

    Artal, Raul

    1996-01-01

    Exercise is encouraged in the management of pregnant women with gestational diabetes or women with Type II diabetes who become pregnant. Although non-weight-bearing exercises may be best for sedentary women, moderate workouts appear to be safe for most women with gestational diabetes. The role of exercise, risk factors, warning signs, and examples…

  11. Gestational food restriction decreases placental interleukin-10 expression and markers of autophagy and endoplasmic reticulum stress in murine intrauterine growth restriction.

    Science.gov (United States)

    Chu, Alison; Thamotharan, Shanthie; Ganguly, Amit; Wadehra, Madhuri; Pellegrini, Matteo; Devaskar, Sherin U

    2016-10-01

    Intrauterine growth restriction (IUGR) affects up to 10% of pregnancies and often results in short- and long-term sequelae for offspring. The mechanisms underlying IUGR are poorly understood, but it is known that healthy placentation is essential for nutrient provision to fuel fetal growth, and is regulated by immunologic inputs. We hypothesized that in pregnancy, maternal food restriction (FR) resulting in IUGR would decrease the overall immunotolerant milieu in the placenta, leading to increased cellular stress and death. Our specific objectives were to evaluate (1) key cytokines (eg, IL-10) that regulate maternal-fetal tolerance, (2) cellular processes (autophagy and endoplasmic reticulum [ER] stress) that are immunologically mediated and important for cellular survival and functioning, and (3) the resulting IUGR phenotype and placental histopathology in this animal model. After subjecting pregnant mice to mild and moderate FR from gestational day 10 to 19, we collected placentas and embryos at gestational day 19. We examined RNA sequencing data to identify immunologic pathways affected in IUGR-associated placentas and validated messenger RNA expression changes of genes important in cellular integrity. We also evaluated histopathologic changes in vascular and trophoblastic structures as well as protein expression changes in autophagy, ER stress, and apoptosis in the mouse placentas. Several differentially expressed genes were identified in FR compared with control mice, including a considerable subset that regulates immune tolerance, inflammation, and cellular integrity. In summary, maternal FR decreases the anti-inflammatory effect of IL-10 and suppresses placental autophagic and ER stress responses, despite evidence of dysregulated vascular and trophoblast structures leading to IUGR. Copyright © 2016 Elsevier Inc. All rights reserved.

  12. Disturbed Placental Imprinting in Preeclampsia Leads to Altered Expression of DLX5, a Human-Specific Early Trophoblast Marker.

    Science.gov (United States)

    Zadora, Julianna; Singh, Manvendra; Herse, Florian; Przybyl, Lukasz; Haase, Nadine; Golic, Michaela; Yung, Hong Wa; Huppertz, Berthold; Cartwright, Judith E; Whitley, Guy; Johnsen, Guro M; Levi, Giovanni; Isbruch, Annette; Schulz, Herbert; Luft, Friedrich C; Müller, Dominik N; Staff, Anne Cathrine; Hurst, Laurence D; Dechend, Ralf; Izsvák, Zsuzsanna

    2017-11-07

    Preeclampsia is a complex and common human-specific pregnancy syndrome associated with placental pathology. The human specificity provides both intellectual and methodological challenges, lacking a robust model system. Given the role of imprinted genes in human placentation and the vulnerability of imprinted genes to loss of imprinting changes, there has been extensive speculation, but no robust evidence, that imprinted genes are involved in preeclampsia. Our study aims to investigate whether disturbed imprinting contributes to preeclampsia. We first aimed to confirm that preeclampsia is a disease of the placenta by generating and analyzing genome-wide molecular data on well-characterized patient material. We performed high-throughput transcriptome analyses of multiple placenta samples from healthy controls and patients with preeclampsia. Next, we identified differentially expressed genes in preeclamptic placentas and intersected them with the list of human imprinted genes. We used bioinformatics/statistical analyses to confirm association between imprinting and preeclampsia and to predict biological processes affected in preeclampsia. Validation included epigenetic and cellular assays. In terms of human specificity, we established an in vitro invasion-differentiation trophoblast model. Our comparative phylogenetic analysis involved single-cell transcriptome data of human, macaque, and mouse preimplantation embryogenesis. We found disturbed placental imprinting in preeclampsia and revealed potential candidates, including GATA3 and DLX5 , with poorly explored imprinted status and no prior association with preeclampsia. As a result of loss of imprinting, DLX5 was upregulated in 69% of preeclamptic placentas. Levels of DLX5 correlated with classic preeclampsia markers. DLX5 is expressed in human but not in murine trophoblast. The DLX5 high phenotype resulted in reduced proliferation, increased metabolism, and endoplasmic reticulum stress-response activation in

  13. Differential appearance of placentomes and expression of prostaglandin H synthase type 2 in placentome subtypes after betamethasone treatment of sheep late in gestation.

    Science.gov (United States)

    Braun, T; Li, S; Moss, T J M; Connor, K L; Doherty, D A; Nitsos, I; Newnham, J P; Challis, J R G; Sloboda, D M

    2011-04-01

    Inappropriate fetal exposure to maternal glucocorticoid (GC) has been proposed as a mechanism for fetal programming where the effects of GC may be mediated by the placenta. However, the consequences of maternal GC on placental morphology and enzyme expression are unclear. We used betamethasone (BET) to determine effects on placentome subtype distribution and expression of prostaglandin H synthase type 2 (PGHS-2) enzyme. Pregnant sheep carrying male fetuses were randomized to receive injections of saline (n = 30) or one (104 days of gestation, (dG); n = 6), two (104, 111 dG; n = 6) or three (104, 111, 118 dG; n = 11) doses of BET (0.5 mg/kg). Placental tissue was collected prior to (75, 84, 101 dG), during (109, 116 dG) and after BET (122, 132, 146 dG). Total number of placentomes was not different between gestational ages. A- and B-subtypes were most affected by prenatal BET exposure; numbers of A-subtypes were increased and numbers of B-subtypes were decreased compared to controls at 116 dG. At term numbers of A-subtypes were lower after BET, but the weight range distribution was similar to controls. In controls, placental PGHS-2 protein levels increased with gestational age and PGHS-2 localized primarily to uninuclear trophoblast cells. After BET, PGHS-2 protein in C-subtypes at term was significantly increased compared to A-subtypes. Maternal BET treatment in late gestation affects the proportions of placentome subtypes and their differential expression of PGHS-2. Our data do not support previous hypotheses that A-subtypes develop into B-, C- and D-subtypes over the course of gestation. Copyright © 2011 Elsevier Ltd. All rights reserved.

  14. Radiographic findings in cats with intranasal neoplasia or chronic rhinitis: 29 cases (1982-1988)

    International Nuclear Information System (INIS)

    O'Brien, R.T.; Evans, S.M.; Wortman, J.A.; Hendrick, M.J.

    1996-01-01

    Objective: To compare radiographic findings and determine useful criteria to differentiate between intranasal neoplasia and chronic rhinitis in cats. Design: Retrospective study. Animals: Cats with chronic nasal disease caused by neoplasia (n = 18) or by chronic rhinitis (n = 11). Procedure: Radiographs were reviewed by 3 radiologists, followed by group review. Diagnosis was determined by intranasal biopsy or necropsy, and specimens were reviewed by a pathologist to confirm cause and histologic diagnosis. Results: Lymphosarcoma was the most common (n = 5) of the 6 histopathologic types in the neoplasia group. Cats in the neoplasia and chronic rhinitis groups had a high prevalence of aggressive radiographic lesions. Prevalence of a facial mass in cats with neoplasia (8/18) versus in those with chronic rhinitis (4/11) and of deviation (9/18 vs 6/11, respectively) or lysis (12/18 vs 7/11) of the nasal septum was similar. However, significantly (P = 0.02) more cats with neoplasia than with chronic rhinitis (13/16 vs 3/7, respectively) had unilateral turbinate destruction/lysis. Additionally, unilateral lateral bone erosion and loss of teeth associated with adjacent intranasal disease were more prevalent in cats with neoplasia (7/8 and 5/18, respectively) than in cats with chronic rhinitis (1/3 and 0/11, respectively). Clinical Implications: Features that may assist in radiographic diagnosis of neoplasia include the appearance of unilateral aggressive lesions, such as lysis of lateral bones, nasal turbinate destruction, and loss of teeth. Bilaterally symmetric lesions are more suggestive of chronic rhinitis than of neoplasia

  15. Psychological effects of diagnosis and treatment of cervical intraepithelial neoplasia

    DEFF Research Database (Denmark)

    Frederiksen, Maria Eiholm; Njor, Sisse; Lynge, Elsebeth

    2015-01-01

    BACKGROUND: Treatment of cervical intraepithelial neoplasia (CIN) is a common minor surgical procedure to prevent uterine cervical cancer. However, news of an abnormality detected at screening for cancer might cause the woman to worry. OBJECTIVES: To investigate the psychological consequences...... test results, but the impact decreased over time. In several but not all studies, CIN appeared to have similar psychological consequences to abnormal smears. No study showed a difference in psychological outcomes between CIN and cervical cancer diagnosis when these were measured some years after...... psychological outcomes in women with a histological diagnosis or treatment of CIN, and in women having an outcome other than CIN at cervical screening. DATA COLLECTION AND ANALYSIS: We abstracted the data using a pre-specified list of study characteristics and measured outcomes. For studies not reporting...

  16. Metastização pulmonar de neoplasia da mama

    Directory of Open Access Journals (Sweden)

    Jorge Dionísio

    2002-03-01

    Full Text Available RESUMO: Para caracterizar os doentes com metastização pulmonar de neoplasia da mama, procedemos a um estudo retrospectivo dos processos de 129 doentes referenciados à Unidade de Pneumologia entre Julho de 1990 e Janeiro de 2000.Foi considerada a existência de metastização pulmonar em 89 casos.Avaliámos as manifestações clínicas apresentadas, o intervalo de tempo até ao diagnóstico de metastização pulmonar, os aspectos radiológicos, endoscópicos, as terapêuticas efectuadas e a sobrevida.O intervalo médio entre o diagnóstico da neoplasia da mama e o diagnóstico de metastização pulmonar foi de 81,9±5,7 meses. Os sintomas respiratórios foram referidos em 83,1% dos doentes. O padrão radiológico mais comum foi a presença de massas ou nódulos pulmonares (66,3%. Foram observadas 49 com sinais directos de neoplasia na broncofibroscopia. Em 47 os aspectos anatomopatológicos encontrados foram compatíveis com metastização endobrônquica de tumor da mamaO tratamento mais frequentemente utilizado após o diagnóstico de metástase pulmonar foi a quimioterapia, em 60,2% dos casos.Após o diagnóstico de metastização, a sobrevida mediana foi de 20,1 meses, com 63,4% dos doentes vivos ao fim de 1 ano.Nos doentes com carcinoma da mama e suspeita de metastização verificámos um grande intervalo livre entre o diagnóstico do tumor da mama e o aparecimento de metastização. Os sintomas respiratórios tra-duziram a grande frequência de envolvimento endobrônquico. O diagnóstico anatomopatológico de metastização pulmonar foi obtido em 52,8% dos doentes. A terapêutica mais utilizada após diagnóstico de metastização foi a quimioterapia e a sobrevida ao ano foi de 63,4%.REV PORT PNEUMOL 2002; VIII (2: ABSTRACT: We performed a retrospective study of 129 patients observed in Pneumology unit between July 1990 and January 2000 to evaluate the clinical, radiological and endoscopic patterns as well as the clinical evolution of

  17. Neoplasia in Three Aye-Ayes (Daubentonia madagascariensis).

    Science.gov (United States)

    Rodriguez Barbon, A; Cowen, R; Knott, C; Hughes, K; Allinson, K; Williams, C V; Routh, A

    2018-02-01

    Tumours diagnosed in three aged captive aye-ayes (Daubentonia madagascariensis), held in two different institutions, are described. A cerebral glioblastoma was diagnosed based on histological and immunohistochemical findings in one of the animals following initial presentation with bilateral mydriasis, absent pupillary reflex, head tilt and ataxia. A second animal was humanely destroyed due to impaired locomotion associated with spondylosis and a post-mortem diagnosis of cholangiocarcinoma was made based on histology with further confirmation with immunohistochemical labelling for cytokeratin 7. A third aye-aye suffering from dental disease was diagnosed with an oral squamous cell carcinoma following an excisional biopsy from a non-healing wound in the lip. Due to progression of the neoplasia the animal was humanely destroyed and post-mortem examination revealed the presence on an additional unilateral phaeochromocytoma. Copyright © 2017 Elsevier Ltd. All rights reserved.

  18. Treatment of cervical intraepithelial neoplasia in Denmark 1991 to 2007

    DEFF Research Database (Denmark)

    Barken, Sidsel Svennekjær

    2010-01-01

    Abstract: Objectives: The number of invasive cervical cancers peaked in Denmark in 1966 with 963 cases. Cervical cancer is prevented by treatment of screen-detected cervical intraepithelial neoplasia (CIN). We assessed the trend in CIN treatments in Denmark. Material and Methods: From highly...... the data using the unique Danish identification numbers, and excluded all duplicate registrations. We excluded all destructive therapies and hysterectomies for which no CIN or cervical cancer diagnosis was found in the period from 3 months before to 1 month after the treatment date. We age......-standardized the number of cervical treatments using Danish women in 2007 as standard population. Results: The preliminary analysis shows that the number of treatments increased from about 6,000 in 1991 to about 8,200 in 2007, most noticeably due to an increase of about 2,600 in the number of conisations (Figure 1...

  19. Primary Hyperparathyroidism in Patients with Multiple Endocrine Neoplasia Type 1

    Directory of Open Access Journals (Sweden)

    Grzegorz Piecha

    2010-01-01

    Full Text Available Primary hyperparathyroidism may occur as a part of an inherited syndrome in a combination with pancreatic endocrine tumours and/or pituitary adenoma, which is classified as Multiple Endocrine Neoplasia type 1 (MEN-1. This syndrome is caused by a germline mutation in MEN-1 gene encoding a tumour-suppressor protein, menin. Primary hyperparathyroidism is the most frequent clinical presentation of MEN-1, which usually appears in the second decade of life as an asymptomatic hypercalcemia and progresses through the next decades. The most frequent clinical presentation of MEN-1-associated primary hyperparathyroidism is bone demineralisation and recurrent kidney stones rarely followed by chronic kidney disease. The aim of this paper is to present the pathomechanism, screening procedures, diagnosis, and management of primary hyperparathyroidism in the MEN-1 syndrome. It also summarises the recent advances in the pharmacological therapy with a new group of drugs—calcimimetics.

  20. Photodynamic therapy of Cervical Intraepithelial Neoplasia (CIN) high grade

    Science.gov (United States)

    Carbinatto, Fernanda M.; Inada, Natalia M.; Lombardi, Welington; da Silva, Eduardo V.; Belotto, Renata; Kurachi, Cristina; Bagnato, Vanderlei S.

    2016-02-01

    Cervical intraepithelial neoplasia (CIN) is the precursor of invasive cervical cancer and associated with human papillomavirus (HPV) infection. Photodynamic therapy (PDT) is a technique that has been used for the treatment of tumors. PDT is based on the accumulation of a photosensitizer in target cells that will generate cytotoxic reactive oxygen species upon illumination, inducing the death of abnormal tissue and PDT with less damaging to normal tissues than surgery, radiation, or chemotherapy and seems to be a promising alternative procedure for CIN treatment. The CIN high grades (II and III) presents potential indications for PDT due the success of PDT for CIN low grade treatment. The patients with CIN high grade that were treated with new clinic protocol shows lesion regression to CIN low grade 60 days after the treatment. The new clinical protocol using for treatment of CIN high grade shows great potential to become a public health technique.

  1. Effectiveness of cryotherapy treatment for cervical intraepithelial neoplasia.

    Science.gov (United States)

    Luciani, Silvana; Gonzales, Miguel; Munoz, Sergio; Jeronimo, Jose; Robles, Sylvia

    2008-05-01

    To assess the effectiveness of cryotherapy treatment delivered by general practitioners in primary care settings, as part of a screen-and-treat approach for cervical cancer prevention. Women aged between 25 and 49 years residing in San Martin, Peru, who were positive on visual inspection screening were treated, if eligible, with cryotherapy following biopsy. At 12 months post cryotherapy treatment the participants were evaluated for treatment effectiveness and examined by visual inspection and Papanicolaou test and, if positive, referred to a gynecologist for colposcopy and biopsy. Cryotherapy treatment was performed for 1398 women; of these, 531 (38%) had a histology result of cervical intraepithelial neoplasia (CIN). Cryotherapy effectively cured CIN in 418 (88%) women, including 49 (70%) women with a baseline diagnosis of CIN 3. Cryotherapy is an effective treatment for cervical precancerous lesions; it can easily be administered by general practitioners in primary care settings following visual inspection screening.

  2. Gastroenteropancreatic Neuroendocrine Tumors in Multiple Endocrine Neoplasia Type 1

    International Nuclear Information System (INIS)

    Tonelli, Francesco; Giudici, Francesco; Giusti, Francesca; Brandi, Maria Luisa

    2012-01-01

    We reviewed the literature about entero-pancreatic neuroendocrine tumors in Multiple Endocrine Neoplasia type 1 syndrome (MEN1) to clarify their demographic features, localization imaging, practice, and appropriate therapeutical strategies, analyzing the current approach to entero-pancreatic neuroendocrine tumors in MEN1. Despite the fact that hyperparathyroidism is usually the first manifestation of MEN1, the penetrance of these tumors is similar. They are characterized by multiplicity of lesions, variable expression of the tumors, and propensity for malignant degeneration. Both the histological type and the size of MEN1 neuroendocrine tumors correlate with malignancy. Monitoring of pancreatic peptides and use of imaging exams allow early diagnosis and prompt surgical treatment, resulting in prevention of metastatic disease and improvement of long-term survival. Surgery is often the treatment of choice for MEN1-neuroendocrine tumors. The rationale for surgical approach is to curtail malignant progression of the disease, and to cure the associated biochemical syndrome, should it be present

  3. Manejo de las adolescentes con neoplasia intraepitelial cervical

    OpenAIRE

    Martínez Chang, Ysis Margarita; Sarduy Nápoles, Miguel

    2006-01-01

    Se realizó un estudio descriptivo en pacientes adolescentes que acudieron a la consulta de patología de cuello del Hospital “Ramón González Coro” en el período comprendido de enero de 2003 a mayo de 2005. El número de pacientes atendidas ascendió a 144 y de ellas 32 presentaron neoplasia intraepitelial cervical. El grupo de edades más frecuente resultó el comprendido entre 17 y 18 años, con una frecuencia referida entre 2 y 3 parejas sexuales. La infección de transmisión sexual más común fue ...

  4. Thyroid neoplasia following radiation therapy for Hodgkin's lymphoma

    International Nuclear Information System (INIS)

    McHenry, C.; Jarosz, H.; Calandra, D.; McCall, A.; Lawrence, A.M.; Paloyan, E.

    1987-01-01

    The question of thyroid neoplasia following high-dose radiation treatment to the neck and mediastinum for malignant neoplasms such as Hodgkin's lymphoma in children and young adults has been raised recently. Five patients, 19 to 39 years old, were operated on for thyroid neoplasms that developed following cervical and mediastinal radiation therapy for Hodgkin's lymphoma. Three patients had papillary carcinomas and two had follicular adenomas. The latency period between radiation exposure and the diagnosis of thyroid neoplasm ranged from eight to 16 years. This limited series provided strong support for the recommendation that children and young adults who are to receive high-dose radiation therapy to the head, neck, and mediastinum should receive suppressive doses of thyroxine prior to radiation therapy in order to suppress thyrotropin (thyroid-stimulating hormone) and then be maintained on a regimen of suppression permanently

  5. Advanced colorectal neoplasia risk stratification by penalized logistic regression.

    Science.gov (United States)

    Lin, Yunzhi; Yu, Menggang; Wang, Sijian; Chappell, Richard; Imperiale, Thomas F

    2016-08-01

    Colorectal cancer is the second leading cause of death from cancer in the United States. To facilitate the efficiency of colorectal cancer screening, there is a need to stratify risk for colorectal cancer among the 90% of US residents who are considered "average risk." In this article, we investigate such risk stratification rules for advanced colorectal neoplasia (colorectal cancer and advanced, precancerous polyps). We use a recently completed large cohort study of subjects who underwent a first screening colonoscopy. Logistic regression models have been used in the literature to estimate the risk of advanced colorectal neoplasia based on quantifiable risk factors. However, logistic regression may be prone to overfitting and instability in variable selection. Since most of the risk factors in our study have several categories, it was tempting to collapse these categories into fewer risk groups. We propose a penalized logistic regression method that automatically and simultaneously selects variables, groups categories, and estimates their coefficients by penalizing the [Formula: see text]-norm of both the coefficients and their differences. Hence, it encourages sparsity in the categories, i.e. grouping of the categories, and sparsity in the variables, i.e. variable selection. We apply the penalized logistic regression method to our data. The important variables are selected, with close categories simultaneously grouped, by penalized regression models with and without the interactions terms. The models are validated with 10-fold cross-validation. The receiver operating characteristic curves of the penalized regression models dominate the receiver operating characteristic curve of naive logistic regressions, indicating a superior discriminative performance. © The Author(s) 2013.

  6. Endometrial Intraepithelial Neoplasia (EIN In An Endometrial Polyp

    Directory of Open Access Journals (Sweden)

    Devic Ana

    2015-12-01

    Full Text Available Endometrial intraepithelial neoplasia (EIN is a monoclonal neoplastic cell proliferation of the endometrium associated with a significantly increased risk of endometrioid endometrial adenocarcinoma. We herein present the case of a 58-year-old female patient who underwent a hysterectomy with bilateral salpingo-oophorectomy because of the existence of endometrial intraepithelial neoplasia in an endometrial polyp. The patient had irregular uterine bleeding, which lasted 10 days. An endometrial polyp was diagnosed by ultrasound examination. The polyp was located in the isthmus of the uterus, on the back wall, and measured 32 mm × 25 mm. The patient underwent fractional dilation and curettage, and the specimens were subjected to a histopathological examination. The histopathological findings were EIN, endometrioid type, a focus of which was found within the endometrial polyps, as well as the endometrial polyp and proliferative endometrium. The endocervical tissue was normal. Given the age of the patient and the histopathological findings, she underwent a total abdominal hysterectomy with bilateral salpingo-oophorectomy. The final histopathological findings were EIN, endometrioid type with a focus found within the endometrial polyp; endometrial polyp; simple hyperplasia; chronic inflammation of the uterine cervix; hyperkeratosis of the cervical squamous epithelium; and cervicitis chronica. There was also hydrosalpinx of the left fallopian tube, and cystic follicles in the left ovary. There was no significant morphological change in the right ovary or fallopian tube. The surgical and postoperative course were normal. The patient was sent home on the fifth postoperative day in good general condition. A check-up performed one month after surgery showed normal findings.

  7. Predictive cytogenetic biomarkers for colorectal neoplasia in medium risk patients.

    Science.gov (United States)

    Ionescu, E M; Nicolaie, T; Ionescu, M A; Becheanu, G; Andrei, F; Diculescu, M; Ciocirlan, M

    2015-01-01

    DNA damage and chromosomal alterations in peripheral lymphocytes parallels DNA mutations in tumor tissues. The aim of our study was to predict the presence of neoplastic colorectal lesions by specific biomarkers in "medium risk" individuals (age 50 to 75, with no personal or family of any colorectal neoplasia). We designed a prospective cohort observational study including patients undergoing diagnostic or opportunistic screening colonoscopy. Specific biomarkers were analyzed for each patient in peripheral lymphocytes - presence of micronuclei (MN), nucleoplasmic bridges (NPB) and the Nuclear Division Index (NDI) by the cytokinesis-blocked micronucleus assay (CBMN). Of 98 patients included, 57 were "medium risk" individuals. MN frequency and NPB presence were not significantly different in patients with neoplastic lesions compared to controls. In "medium risk" individuals, mean NDI was significantly lower for patients with any neoplastic lesions (adenomas and adenocarcinomas, AUROC 0.668, p 00.5), for patients with advanced neoplasia (advanced adenoma and adenocarcinoma, AUROC 0.636 p 0.029) as well as for patients with adenocarcinoma (AUROC 0.650, p 0.048), for each comparison with the rest of the population. For a cut-off of 1.8, in "medium risk" individuals, an NDI inferior to that value may predict any neoplastic lesion with a sensitivity of 97.7%, an advanced neoplastic lesion with a sensitivity of 97% and adenocarcinoma with a sensitivity of 94.4%. NDI score may have a role as a colorectal cancer-screening test in "medium risk" individuals. DNA = deoxyribonucleic acid; CRC = colorectal cancer; EU = European Union; WHO = World Health Organization; FOBT = fecal occult blood test; CBMN = cytokinesis-blocked micronucleus assay; MN = micronuclei; NPB = nucleoplasmic bridges; NDI = Nuclear Division Index; FAP = familial adenomatous polyposis; HNPCC = hereditary non-polypoid colorectal cancer; IBD = inflammatory bowel diseases; ROC = receiver operating

  8. Neoplasias de Cavidad nasal y senos paranasales en caninos

    Directory of Open Access Journals (Sweden)

    Giovanni Torres

    2008-10-01

    Full Text Available Las neoplasias de cavidad nasal y senos paranasales en caninos son de escasa presentación; llegan tan sóloal 1.5% de los quistes diagnosticados en esta especie.Con referencia al total de tumores del tracto respiratorio representan entre el 60 y el 80%. Son más comunes en caninos de nariz larga, no existe predilección por género; por el comportamiento, las neoplasias que se desarrollanen la cavidad nasal y senos paranasales son benignas y malignas, siendo estas últimas las más frecuentes. Teniendo en cuenta el tejido de origen pueden ser epiteliales, mesenquimales y de otro origen como los linfomas y el tumor venéreo transmisible. La apariciónde la sintomatología se asocia con la capacidad de obstruir las vías aéreas, la invasión y destrucción local de tejido. En general los signos clínicos asociados consistenen: dificultad respiratoria, estornudo, secreciónnasal, hemorragia nasal y la presencia de masas de características variadas en tamaño y forma. El diagnóstico se basa en signos clínicos, evaluación citológica e histológica de las lesiones. Esta última es 100% diagnóstica, para el tratamiento se utiliza la extracción quirúrgica combinada con terapia de radiación y quimioterapia.

  9. Long-term adherence to follow-up after treatment of cervical intraepithelial neoplasia

    DEFF Research Database (Denmark)

    Barken, Sidsel S; Lynge, Elsebeth; Andersen, Erik S.

    2013-01-01

    OBJECTIVE: To measure adherence to annual follow-up among women treated for cervical intraepithelial neoplasia. DESIGN: Prospective, population-based, register study. SETTING: Denmark, 1996-2007. POPULATION: All women treated for cervical intraepithelial neoplasia with conization. METHODS: Treated...... was poor in Denmark. Our findings suggest that because of this poor adherence, recommendations for long-term annual follow-up after treatment of cervical intraepithelial neoplasia may not be highly effective. Shorter follow-up schedules using highly sensitive tests appear attractive....

  10. Cell-to-Cell Contact Results in a Selective Translocation of Maternal Human Immunodeficiency Virus Type 1 Quasispecies across a Trophoblastic Barrier by both Transcytosis and Infection

    Science.gov (United States)

    Lagaye, S.; Derrien, M.; Menu, E.; Coïto, C.; Tresoldi, E.; Mauclère, P.; Scarlatti, G.; Chaouat, G.; Barré-Sinoussi, F.; Bomsel, M.

    2001-01-01

    Mother-to-child transmission can occur in utero, mainly intrapartum and postpartum in case of breastfeeding. In utero transmission is highly restricted and results in selection of viral variant from the mother to the child. We have developed an in vitro system that mimics the interaction between viruses, infected cells present in maternal blood, and the trophoblast, the first barrier protecting the fetus. Trophoblastic BeWo cells were grown as a tight polarized monolayer in a two-chamber system. Cell-free virions applied to the apical pole neither crossed the barrier nor productively infected BeWo cells. In contrast, apical contact with human immunodeficiency virus (HIV)-infected peripheral blood mononuclear cells (PBMCs) resulted in transcytosis of infectious virus across the trophoblastic monolayer and in productive infection correlating with the fusion of HIV-infected PBMCs with trophoblasts. We showed that viral variants are selected during these two steps and that in one case of in utero transmission, the predominant maternal viral variant characterized after transcytosis was phylogenetically indistinguishable from the predominant child's virus. Hence, the first steps of transmission of HIV-1 in utero appear to involve the interaction between HIV type 1-infected cells and the trophoblastic layer, resulting in the passage of infectious HIV by transcytosis and by fusion/infection, both leading to a selection of virus quasispecies. PMID:11312350

  11. Human trophoblast survival at low oxygen concentrations requires metalloproteinase-mediated shedding of heparin-binding EGF-like growth factor.

    Science.gov (United States)

    Armant, D Randall; Kilburn, Brian A; Petkova, Anelia; Edwin, Samuel S; Duniec-Dmuchowski, Zophia M; Edwards, Holly J; Romero, Roberto; Leach, Richard E

    2006-02-01

    Heparin-binding EGF-like growth factor (HBEGF), which is expressed in the placenta during normal pregnancy, is down regulated in pre-eclampsia, a human pregnancy disorder associated with poor trophoblast differentiation and survival. This growth factor protects against apoptosis during stress, suggesting a role in trophoblast survival in the relatively low O(2) ( approximately 2%) environment of the first trimester conceptus. Using a well-characterized human first trimester cytotrophoblast cell line, we found that a 4-hour exposure to 2% O(2) upregulates HBEGF synthesis and secretion independently of an increase in its mRNA. Five other expressed members of the EGF family are largely unaffected. At 2% O(2), signaling via HER1 or HER4, known HBEGF receptors, is required for both HBEGF upregulation and protection against apoptosis. This positive-feedback loop is dependent on metalloproteinase-mediated cleavage and shedding of the HBEGF ectodomain. The restoration of trophoblast survival by the addition of soluble HBEGF in cultures exposed to low O(2) and metalloproteinase inhibitor suggests that the effects of HBEGF are mediated by autocrine/paracrine, rather than juxtacrine, signaling. Our results provide evidence that a post-transcriptional mechanism induced in trophoblasts by low O(2) rapidly amplifies HBEGF signaling to inhibit apoptosis. These findings have a high clinical significance, as the downregulation of HBEGF in pre-eclampsia is likely to be a contributing factor leading to the demise of trophoblasts.

  12. Perceived psychosocial stress and gestational weight gain among women with gestational diabetes.

    Directory of Open Access Journals (Sweden)

    Ai Kubo

    Full Text Available Growing evidence links perceived stress-a potentially modifiable psychosocial risk factor-with health behaviors and obesity. Yet little is known about the relationship between stress during pregnancy and gestational weight gain, particularly among women with pregnancy complications. We conducted a cross-sectional analysis to examine associations between psychosocial stress during pregnancy and gestational weight gain among women with gestational diabetes. We used baseline data from the Gestational Diabetes's Effects on Moms (GEM study: 1,353 women with gestational diabetes who delivered a term singleton within Kaiser Permanente Northern California were included. Perceived stress near the time of gestational diabetes diagnosis was measured using the validated Perceived Stress Scale (PSS10. Gestational weight gain was categorized according to the 2009 Institute of Medicine recommendations. Binomial regression analyses adjusted for gestational age and maternal age at the time of gestational diabetes diagnosis, and race/ethnicity and estimated rate ratios (RR and their 95% confidence interval (CI. Among women with a normal pregravid Body Mass Index (BMI 18.5-24.9 kg/m2, there was a significant association between high (Q4 PSS score and risk of both exceeding and gaining below the Institute of Medicine recommendations compared to those with lower stress (Q1 [adjusted RR = 2.16 95% CI 1.45-3.21; RR = 1.39 95% CI 1.01-1.91, respectively.] Among women with pregravid overweight/obesity (BMI≥25 kg/m2, there was no association. Although the temporal relationship could not be established from this study, there may be a complex interplay between psychosocial stress and gestational weight gain among women with gestational diabetes. Further studies examining stress earlier in pregnancy, risk of developing gestational diabetes and excess/inadequate gestational weight gain are warranted to clarify these complex relationships.

  13. EEVD motif of heat shock cognate protein 70 contributes to bacterial uptake by trophoblast giant cells

    Directory of Open Access Journals (Sweden)

    Kim Suk

    2009-12-01

    Full Text Available Abstract Background The uptake of abortion-inducing pathogens by trophoblast giant (TG cells is a key event in infectious abortion. However, little is known about phagocytic functions of TG cells against the pathogens. Here we show that heat shock cognate protein 70 (Hsc70 contributes to bacterial uptake by TG cells and the EEVD motif of Hsc70 plays an important role in this. Methods Brucella abortus and Listeria monocytogenes were used as the bacterial antigen in this study. Recombinant proteins containing tetratricopeptide repeat (TPR domains were constructed and confirmation of the binding capacity to Hsc70 was assessed by ELISA. The recombinant TPR proteins were used for investigation of the effect of TPR proteins on bacterial uptake by TG cells and on pregnancy in mice. Results The monoclonal antibody that inhibits bacterial uptake by TG cells reacted with the EEVD motif of Hsc70. Bacterial TPR proteins bound to the C-terminal of Hsc70 through its EEVD motif and this binding inhibited bacterial uptake by TG cells. Infectious abortion was also prevented by blocking the EEVD motif of Hsc70. Conclusions Our results demonstrate that surface located Hsc70 on TG cells mediates the uptake of pathogenic bacteria and proteins containing the TPR domain inhibit the function of Hsc70 by binding to its EEVD motif. These molecules may be useful in the development of methods for preventing infectious abortion.

  14. Elsevier Trophoblast Research Award Lecture: origin, evolution and future of placenta miRNAs.

    Science.gov (United States)

    Morales-Prieto, D M; Ospina-Prieto, S; Schmidt, A; Chaiwangyen, W; Markert, U R

    2014-02-01

    MicroRNAs (miRNAs) regulate the expression of a large number of genes in plants and animals. Placental miRNAs appeared late in evolution and can be found only in mammals. Nevertheless, these miRNAs are constantly under evolutionary pressure. As a consequence, miRNA sequences and their mRNA targets may differ between species, and some miRNAs can only be found in humans. Their expression can be tissue- or cell-specific and can vary time-dependently. Human placenta tissue exhibits a specific miRNA expression pattern that dynamically changes during pregnancy and is reflected in the maternal plasma. Some placental miRNAs are involved in or associated with major pregnancy disorders, such as preeclampsia, intrauterine growth restriction or preterm delivery and, therefore, have a strong potential for usage as sensitive and specific biomarkers. In this review we summarize current knowledge on the origin of placental miRNAs, their expression in humans with special regard to trophoblast cells, interspecies differences, and their future as biomarkers. It can be concluded that animal models for human reproduction have a different panel of miRNAs and targets, and can only partly reflect or predict the situation in humans. Copyright © 2013. Published by Elsevier Ltd.

  15. [Gestational diabetes insipidus during a twin pregnancy].

    Science.gov (United States)

    De Mesmay, M; Rigouzzo, A; Bui, T; Louvet, N; Constant, I

    2013-02-01

    Gestational diabetes insipidus is an uncommon clinical disease whose prevalence is approximately two to three pregnancies per 100,000. It may be isolated or associated with preeclampsia. We report a case of gestational diabetes insipidus in a twin pregnancy, originally isolated during two months, and secondarily complicated by HELLP-syndrome. We recall the specific pathophysiology of polyuric-polydipsic syndrome during pregnancy and summarize its various causes. Finally, we discuss the indications, in case of isolated gestational diabetes insipidus, of treatment by dDAVP. Copyright © 2013. Published by Elsevier SAS.

  16. The Relationship Between Distal and Proximal Colonic Neoplasia : A Meta-Analysis

    NARCIS (Netherlands)

    Dodou, D.; De Winter, J.C.F.

    2011-01-01

    To investigate the association between proximal colonic neoplasia and distal lesions as a function of the lesion type. The extent to which health, demographic, and study characteristics moderate this association was also examined.

  17. The gestational age pattern of human mortality

    DEFF Research Database (Denmark)

    Schöley, Jonas; Vaupel, James W.; Jacobsen, Rune

    -infant lifetable by gestational age spanning week 23 until week 100 after the last menstrual period of the mother. This joint lifetable shows a remarkable regularity in the gestational age profile of fetal- and infant mortality: Mortality rates are declining over the whole observed age range with the exception......In order to check hypotheses about the cause for "ontogenescense" -- the phenomenon of a declining force of mortality prior to maturity -- I analyse data on human mortality by gestational age. Based on extensive microdata on births, fetal- and infant deaths in the US 2009 I calculate a joint fetal...... of a "birth hump" peaking week 38. The absolute rate of decline slows down over age. The observed gestational age pattern of the force of mortality is consistent with three hypotheses concerning the causes for ontogenescense: 1) Adaptation: as the organism growths it becomes more resilient towards death, 2...

  18. Fetal programming and gestational diabetes mellitus.

    Science.gov (United States)

    Monteiro, Lara J; Norman, Jane E; Rice, Gregory E; Illanes, Sebastián E

    2016-12-01

    Gestational diabetes mellitus is defined by new-onset glucose intolerance during pregnancy. About 2-5% of all pregnant women develop gestational diabetes during their pregnancies and the prevalence has increased considerably during the last decade. This metabolic condition is manifested when pancreatic β-cells lose their ability to compensate for increased insulin resistance during pregnancy, however, the pathogenesis of the disease remains largely unknown. Gestational diabetes is strongly associated with adverse pregnancy outcome as well as with long-term adverse effects on the offspring which likely occurs due to epigenetic modifications of the fetal genome. In the current review we address gestational diabetes and the short and long term complications for both mothers and offspring focusing on the importance of fetal programming in conferring risk of developing diseases in adulthood. Copyright © 2015 Elsevier Ltd. All rights reserved.

  19. Perceptions among women with gestational diabetes.

    Science.gov (United States)

    Parsons, Judith; Ismail, Khalida; Amiel, Stephanie; Forbes, Angus

    2014-04-01

    Women with gestational diabetes are at high risk of developing type 2 diabetes, which could be prevented or delayed by lifestyle modification. Lifestyle interventions need to take into account the specific situation of women with gestational diabetes. We aimed to gain a deeper understanding of women's experiences of gestational diabetes, their diabetes risk perceptions, and their views on type 2 diabetes prevention, to inform future lifestyle interventions. We conducted a metasynthesis that included 16 qualitative studies and identified 11 themes. Factors that require consideration when developing a type 2 diabetes prevention intervention in this population include addressing the emotional impact of gestational diabetes; providing women with clear and timely information about future diabetes risk; and offering an intervention that fits with women's multiple roles as caregivers, workers, and patients, and focuses on the health of the whole family.

  20. Neoplasia in Turner syndrome. The importance of clinical and screening practices during follow-up.

    Science.gov (United States)

    Larizza, Daniela; Albanesi, Michela; De Silvestri, Annalisa; Accordino, Giulia; Brazzelli, Valeria; Maffè, Gabriella Carnevale; Calcaterra, Valeria

    2016-05-01

    Turmer syndrome (TS) patients show increased morbidity due to metabolic, autoimmune and cardiovascular disorders. A risk of neoplasia is also reported. Here, we review the prevalence of neoplasia in a cohort of Turner patients. We retrospectively evaluated 87 TS women. Follow-up included periodic ultrasound of the neck, abdominal and pelvic organs, dermatologic evaluation and fecal occult blood test. Karyotype was 45,X in 46 patients. During follow-up, 63 girls were treated with growth hormone, 65 with estro-progestin replacement therapy and 20 with L-thyroxine. Autoimmune diseases were present in 29 TS. A total of 17 neoplasms in 14 out of 87 patients were found. Six skin neoplasia, 3 central nervous system tumors, 3 gonadal neoplasia, 2 breast tumors, 1 hepatocarcinoma, 1 carcinoma of the pancreas and 1 follicular thyroid cancer were detected. Age at tumor diagnosis was higher in 45,X pts than in those with other karyotypes (p = 0.003). Adenomioma gallbladdder (AG) was detected in 15.3% of the patients, with a lower age in girls at diagnosis with an associated neoplasia in comparison with TS without tumors (p = 0.017). No correlation between genetic make up, treatment, associated autoimmune diseases and neoplastia was found. In our TS population an increased neoplasia prevalence was reported. A high prevalence of AG was also noted and it might be indicative of a predisposition to neoplasia. Further studies are needed to define the overall risk for neoplasia, and to determine the role of the loss of the X-chromosome and hormonal therapies. Copyright © 2016 Elsevier Masson SAS. All rights reserved.

  1. A score to estimate the likelihood of detecting advanced colorectal neoplasia at colonoscopy.

    Science.gov (United States)

    Kaminski, Michal F; Polkowski, Marcin; Kraszewska, Ewa; Rupinski, Maciej; Butruk, Eugeniusz; Regula, Jaroslaw

    2014-07-01

    This study aimed to develop and validate a model to estimate the likelihood of detecting advanced colorectal neoplasia in Caucasian patients. We performed a cross-sectional analysis of database records for 40-year-old to 66-year-old patients who entered a national primary colonoscopy-based screening programme for colorectal cancer in 73 centres in Poland in the year 2007. We used multivariate logistic regression to investigate the associations between clinical variables and the presence of advanced neoplasia in a randomly selected test set, and confirmed the associations in a validation set. We used model coefficients to develop a risk score for detection of advanced colorectal neoplasia. Advanced colorectal neoplasia was detected in 2544 of the 35,918 included participants (7.1%). In the test set, a logistic-regression model showed that independent risk factors for advanced colorectal neoplasia were: age, sex, family history of colorectal cancer, cigarette smoking (padvanced neoplasia: 1.00 (95% CI 0.95 to 1.06)) and had moderate discriminatory power (c-statistic 0.62). We developed a score that estimated the likelihood of detecting advanced neoplasia in the validation set, from 1.32% for patients scoring 0, to 19.12% for patients scoring 7-8. Developed and internally validated score consisting of simple clinical factors successfully estimates the likelihood of detecting advanced colorectal neoplasia in asymptomatic Caucasian patients. Once externally validated, it may be useful for counselling or designing primary prevention studies. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.

  2. Role of the human papilloma virus in the development of cervical intraepithelial neoplasia and malignancy

    OpenAIRE

    Jastreboff, A; Cymet, T

    2002-01-01

    Human papilloma virus (HPV) is a public health problem as a sexually transmitted disease and as a critical factor in the pathogenesis of various cancers. The clinical manifestations, epidemiology, and virology that are critical to understanding the process of cervical dysplasia and neoplasia are reviewed. A discussion of the cervical transformation zone and the classification of cervical dysplasia and neoplasia leads into the importance of the Papanicolaou smear in prevention of potentially d...

  3. Gestational diabetes mellitus results in a higher prevalence of small for gestational age babies

    LENUS (Irish Health Repository)

    Avalos, G

    2011-09-01

    Background and aims: Gestational Diabetes Mellitus (GDM) is associated with increased foetal and maternal morbidity and mortality. Previous studies have shown that babies of diabetic mothers are more likely to be large for gestational age (LGA). This retrospective study aimed to assess whether the converse may also be true, that there may also a higher rate of small for gestational age (SGA) amongst babies of mothers with GDM.\\r\

  4. Increasing incidence of diabetes after gestational diabetes

    DEFF Research Database (Denmark)

    Lauenborg, Jeannet; Hansen, Torben; Jensen, Dorte Møller

    2004-01-01

    To study the incidence of diabetes among women with previous diet-treated gestational diabetes mellitus (GDM) in the light of the general increasing incidence of overweight and diabetes and to identify risk factors for the development of diabetes.......To study the incidence of diabetes among women with previous diet-treated gestational diabetes mellitus (GDM) in the light of the general increasing incidence of overweight and diabetes and to identify risk factors for the development of diabetes....

  5. Comparative studies of placentation and immunology in non-human primates suggest a scenario for the evolution of deep trophoblast invasion and an explanation for human pregnancy disorders

    DEFF Research Database (Denmark)

    Carter, Anthony Michael

    2011-01-01

    in the orangutan and became polymorphic in the lineage leading to gorilla, bonobo, chimpanzee, and human. Interaction between HLA-C1 and HLA-C2 on the surface of trophoblast and killer immunoglobulin-like receptors (KIRs) expressed by uterine natural killer cells are important regulators of trophoblast invasion....... Evolution of this system in great apes may have been one prerequisite for deep trophoblast invasion but seems to have come at a price. The evidence now suggests that certain combinations of maternal genotype for KIRs and fetal genotype for HLA-C imply an increased risk of preeclampsia, fetal growth...... restriction, and recurrent abortion. The fetal genotype is in part derived from the father providing an explanation for the paternal contribution to reproductive disorders....

  6. Sarcopenia is associated with an increased risk of advanced colorectal neoplasia.

    Science.gov (United States)

    Park, Youn Su; Kim, Ji Won; Kim, Byeong Gwan; Lee, Kook Lae; Lee, Jae Kyung; Kim, Joo Sung; Koh, Seong-Joon

    2017-04-01

    Although sarcopenia is associated with an increased risk for mortality after the curative resection of colorectal cancer, its influence on the development of advanced colonic neoplasia remains unclear. This study included 1270 subjects aged 40 years or older evaluated with first-time screening colonoscopy at Seoul National University Boramae Health Care Center from January 2010 to February 2015. Skeletal muscle mass was measured with a body composition analyzer (direct segmental multifrequency bioelectrical impedance analysis method). Multiple logistic regression analysis was performed to determine whether sarcopenia is associated with advanced colorectal neoplasia. Of 1270 subjects, 139 (10.9%) were categorized into the sarcopenia group and 1131 (89.1%) into the non-sarcopenia group. In the non-sarcopenia group, 55 subjects (4.9%) had advanced colorectal neoplasia. However, in the sarcopenia group, 19 subjects (13.7%) had advanced colorectal neoplasia, including 1 subject with invasive colorectal cancer (0.7%). In addition, subjects with sarcopenia had a higher prevalence of advanced adenoma (P sarcopenia. According to the multiple logistic regression analysis adjusted for variable confounders, age (odds ratio 1.062, 95% confidence interval 1.032-1.093; P sarcopenia (odds ratio 2.347, 95% confidence interval 1.311-4.202; P = 0.004) were associated with an advanced colorectal neoplasia. Sarcopenia is associated with an increased risk of advanced colorectal neoplasia.

  7. Human parvovirus B19 antibodies induce altered membrane protein expression and apoptosis of BeWo trophoblasts.

    Science.gov (United States)

    Tzang, Bor-Show; Chiang, Szu-Yi; Chan, Hsu-Chin; Liu, Chung-Hsien; Hsu, Tsai-Ching

    2016-11-01

    Human parvovirus B19 (B19) is harmful during pregnancy since it can be vertically transmitted to the developing fetus. In addition, the anti‑B19 antibodies induced by B19 infection are believed to have a cytopathic role in B19 transmission; however, knowledge regarding the effects of anti‑B19 antibodies during pregnancy is limited. To investigate the possible roles of anti‑B19 antibodies during pregnancy, the present study examined the effects of anti‑B19‑VP1 unique region (VP1u), anti‑B19‑VP2 and anti‑B19‑nonstructural protein 1 (NS1) immunoglobulin G (IgG) antibodies on BeWo trophoblasts. Briefly, BeWo trophoblasts were incubated with purified IgG against B19‑VP1u, B19‑VP2 and B19‑NS1. Subsequently, the expression of surface proteins and apoptotic molecules were assessed in BeWo trophoblasts using flow cytometry, ELISA and western blotting. The expression levels of human leukocyte antigen (HLA)‑G were significantly increased on BeWo trophoblasts treated with rabbit anti‑B19‑VP1u IgG, and were unchanged in those treated with rabbit anti‑B19‑NS1 and anti‑B19‑VP2 IgG, as compared with the control group. Furthermore, the expression levels of globoside (P blood group antigen) and cluster of differentiation (CD)29 (β1 integrin) were significantly increased in BeWo trophoblasts treated with rabbit anti‑B19‑NS1 and anti‑B19‑VP2 IgG, whereas only CD29 was also significantly increased in cells treated with anti‑B19‑VP1u IgG. In addition, the number of cells at sub‑G1 phase; caspase‑3 activity; and the expression of intrinsic and extrinsic apoptotic molecules, including Fas‑associated death domain protein, activated caspase‑8, activated caspase‑3, B‑cell lymphoma 2‑associated X protein, cytochrome c, apoptotic peptidase activating factor 1 and activated caspase‑9, were significantly increased in BeWo trophoblasts treated with anti‑B19‑VP1u and anti‑B19‑NS1 IgG. In conclusion, the present

  8. Edaravone inhibits hypoxia-induced trophoblast-soluble Fms-like tyrosine kinase 1 expression: a possible therapeutic approach to preeclampsia.

    Science.gov (United States)

    Zhao, Y; Zheng, Y F; Luo, Q Q; Yan, T; Liu, X X; Han, L; Zou, L

    2014-07-01

    To investigate the effects of edaravone, a potent free radical scavenger used clinically, on hypoxia-induced trophoblast-soluble Fms-like tyrosine kinase 1 (sFlt-1) expression. A trophoblast cell line (HRT-8/SVneo) impaired by cobalt chloride (CoCl2) was used as the cell model under hypoxic conditions. 3-[4, 5-dimethylthiazol-2-yl]-2, 5-diphenyl tetrazolium bromide (MTT) was used to measure the viability of cells exposed to CoCl2 and edaravone. The levels of intracellular reactive oxygen species (ROS) were analyzed by flow cytometry. mRNA expression of sFlt-1, vascular endothelial growth factor (VEGF), and placental growth factor (PlGF) in trophoblasts was measured by real-time polymerase chain reaction, and the secretion of sFlt-1, VEGF, and PlGF proteins was analyzed by enzyme-linked immunosorbent assays (ELISAs). A human umbilical vein endothelial cell (HUVEC) tube-formation assay was performed to identify the effects of CoCl2 and edaravone on vascular development. CoCl2 treatment caused the loss of trophoblast viability, the formation of ROS, and sFlt-1 mRNA and protein expression in a dose-dependent manner. Pretreatment with edaravone significantly inhibited hypoxia-induced oxidative stress formation and sFlt-1 expression in trophoblasts. Neither PlGF nor VEGF mRNA or protein expression was increased by CoCl2. In the in vitro tube formation assay, edaravone showed a protective role in vascular development under hypoxic conditions. This study demonstrated that hypoxia leading to increased sFlt-1 release in trophoblasts may contribute to the placental vascular formation abnormalities observed in preeclampsia and suggested that the free radical scavenger edaravone could be a candidate for the effective treatment of preeclampsia. Copyright © 2014 Elsevier Ltd. All rights reserved.

  9. Understanding Gestational Diabetes: A Practical Guide to a Healthy Pregnancy.

    Science.gov (United States)

    National Inst. of Child Health and Human Development (NIH), Bethesda, MD.

    This brochure addresses the problem of gestational diabetes and answers the most frequently asked questions about the disease. It begins by defining gestational diabetes and discussing its cause, then addresses such topics as: (1) how gestational diabetes differs from other types of diabetes; (2) who is at risk for developing gestational diabetes…

  10. Correlation between self-reported gestational age and ultrasound measurements

    DEFF Research Database (Denmark)

    Olesen, Annette Wind; Westergaard, Jes Grabow; Thomsen, Sten Grove

    2004-01-01

    BACKGROUND: We studied the agreement between different measurements of gestational age, i.e. self-reported gestational age in the Danish National Birth Cohort Study, ultrasound-estimated gestational age from the medical records in one Danish county and gestational age from the Danish National...

  11. Targeting and crossing of the human maternofetal barrier by Listeria monocytogenes: role of internalin interaction with trophoblast E-cadherin.

    Science.gov (United States)

    Lecuit, Marc; Nelson, D Michael; Smith, Steve D; Khun, Huot; Huerre, Michel; Vacher-Lavenu, Marie-Cécile; Gordon, Jeffrey I; Cossart, Pascale

    2004-04-20

    Listeria monocytogenes produces severe fetoplacental infections in humans. How it targets and crosses the maternofetal barrier is unknown. We used immunohistochemistry to examine the location of L. monocytogenes in placental and amniotic tissue samples obtained from women with fetoplacental listeriosis. The results raised the possibility that L. monocytogenes crosses the maternofetal barrier through the villous syncytiotrophoblast, with secondary infection occurring via the amniotic epithelium. Because epidemiological studies indicate that the bacterial surface protein, internalin (InlA), may play a role in human fetoplacental listeriosis, we investigated the cellular patterns of expression of its host receptor, E-cadherin, at the maternofetal interface. E-cadherin was found on the basal and apical plasma membranes of syncytiotrophoblasts and in villous cytotrophoblasts. Established trophoblastic cell lines, primary trophoblast cultures, and placental villous explants were each exposed to isogenic InlA+ or InlA- strains of L. monocytogenes, and to L. innocua expressing or not InlA. Quantitative assays of cellular invasion demonstrated that bacterial entry into syncytiotrophoblasts occurs via the apical membrane in an InlA-E-cadherin dependent manner. In human placental villous explants, bacterial invasion of the syncytiotrophoblast barrier and underlying villous tissue and subsequent replication produces histopathological lesions that mimic those seen in placentas of women with listeriosis. Thus, the InlA-E-cadherin interaction that plays a key role in the crossing of the intestinal barrier in humans is also exploited by L. monocytogenes to target and cross the placental barrier. Such a ligand-receptor interaction allowing a pathogen to specifically cross the placental villous trophoblast barrier has not been reported previously.

  12. Brucella suis vaccine strain 2 induces endoplasmic reticulum stress that affects intracellular replication in goat trophoblast cells in vitro

    Directory of Open Access Journals (Sweden)

    Xiangguo eWang

    2016-02-01

    Full Text Available Brucella has been reported to impair placental trophoblasts, a cellular target where Brucella efficiently replicates in association with the endoplasmic reticulum (ER, and ultimately trigger abortion in pregnant animals. However, the precise effects of Brucella on trophoblast cells remain unclear. Here, we describe the infection and replication of Brucella suis vaccine strain 2 (B.suis.S2 in goat trophoblast cells (GTCs and the cellular and molecular responses induced in vitro. Our studies demonstrated that B.suis.S2 was able to infect and proliferate to high titers, hamper the proliferation of GTCs and induce apoptosis due to ER stress. Tunicamycin (Tm, a pharmacological chaperone that strongly mounts ER stress-induced apoptosis, inhibited B.suis.S2 replication in GTCs. In addition, 4 phenyl butyric acid (4-PBA, a pharmacological chaperone that alleviates ER stress-induced apoptosis, significantly enhanced B.suis.S2 replication in GTCs. The Unfolded Protein Response (UPR chaperone molecule GRP78 also promoted B.suis.S2 proliferation in GTCs by inhibiting ER stress-induced apoptosis. We also discovered that the IRE1 pathway, but not the PERK or ATF6 pathway, was activated in the process. However, decreasing the expression of phosphoIRE1α and IRE1α proteins with Irestatin 9389 (IRE1 antagonist in GTCs did not affect the proliferation of B.suis.S2. Although GTC implantation was not affected upon B.suis.S2 infection, progesterone secretion was suppressed, and prolactin and estrogen secretion increased; these effects were accompanied by changes in the expression of genes encoding key steroidogenic enzymes. This study systematically explored the mechanisms of abortion in Brucella infection from the viewpoint of pathogen invasion, ER stress and reproductive endocrinology. Our findings may provide new insight for understanding the mechanisms involved in goat abortions caused by Brucella infection.

  13. Serum depletion induces changes in protein expression in the trophoblast-derived cell line HTR-8/SVneo.

    Science.gov (United States)

    Novoa-Herran, Susana; Umaña-Perez, Adriana; Canals, Francesc; Sanchez-Gomez, Myriam

    2016-01-01

    How nutrition and growth factor restriction due to serum depletion affect trophoblast function remains poorly understood. We performed a proteomic differential study of the effects of serum depletion on a first trimester human immortalized trophoblast cell line. The viability of HTR-8/SVneo trophoblast cells in culture with 0, 0.5 and 10 % fetal bovine serum (FBS) were assayed via MTT at 24, 48 and 64 h. A comparative proteomic analysis of the cells grown with those FBS levels for 24 h was performed using two-dimensional electrophoresis (2DE), followed by mass spectrometry for protein spot identification, and a database search and bioinformatics analysis of the expressed proteins. Differential spots were identified using the Kolmogorov-Smirnov test ( n  = 3, significance level 0.10, D > 0.642) and/or ANOVA ( n  = 3, p  depletion differentially affect cell growth and protein expression. Differential expression was seen in 25 % of the protein spots grown with 0.5 % FBS and in 84 % of those grown with 0 % FBS, using 10 % serum as the physiological control. In 0.5 % FBS, this difference was related with biological processes typically affected by the serum, such as cell cycle, regulation of apoptosis and proliferation. In addition to these changes, in the serum-depleted proteome we observed downregulation of keratin 8, and upregulation of vimentin, the glycolytic enzymes enolase and pyruvate kinase (PKM2) and tumor progression-related inosine-5'-monophosphate dehydrogenase 2 (IMPDH2) enzyme. The proteins regulated by total serum depletion, but not affected by growth in 0.5 % serum, are members of the glycolytic and nucleotide metabolic pathways and the epithelial-to-mesenchymal transition (EMT), suggesting an adaptive switch characteristic of malignant cells. This comparative proteomic analysis and the identified proteins are the first evidence of a protein expression response to serum depletion in a trophoblast cell model. Our results show that

  14. Effects of vitamin C, vitamin E, and molecular hydrogen on the placental function in trophoblast cells.

    Science.gov (United States)

    Guan, Zhong; Li, Huai-Fang; Guo, Li-Li; Yang, Xiang

    2015-08-01

    This study aimed to investigate the effects of three different antioxidants, namely vitamin C, vitamin E, and molecular hydrogen, on cytotrophoblasts in vitro. Two trophoblast cell lines, JAR and JEG-3, were exposed to different concentrations of vitamin C (0, 25, 50, 100, 500, 1,000, 5,000 μmol/L), vitamin E (0, 25, 50, 100, 500, 1,000, 5,000 μmol/L), and molecular hydrogen (0, 25, 50, 100, 500 μmol/L) for 48 h. The cell viability was detected using the MTS assay. The secretion of human chorionic gonadotropin (hCG) and the tumor necrosis factor-α (TNF-α) were assessed and the expression of TNF-α mRNA was observed by real-time RT-PCR. Cell viability was significantly suppressed by 500 μmol/L vitamins C and E (P 0.05). The expression of TNF-α was increased by 100 μmol/L vitamin C and 50 μmol/L vitamins E, separately or combined (P vitamin C and E, separately or combined. High levels of antioxidant vitamins C and E may have significant detrimental effects on placental function, as reflected by decreased cell viability and secretion of hCG; and placental immunity, as reflected by increased production of TNF-a. Meanwhile hydrogen showed no such effects on cell proliferation and TNF-α expression, but it could affect the level of hCG, indicating hydrogen as a potential candidate of antioxidant in the management of preeclampsia (PE) should be further studied.

  15. The ubiquitin ligase ASB4 promotes trophoblast differentiation through the degradation of ID2.

    Directory of Open Access Journals (Sweden)

    W H Davin Townley-Tilson

    Full Text Available Vascularization of the placenta is a critical developmental process that ensures fetal viability. Although the vascular health of the placenta affects both maternal and fetal well being, relatively little is known about the early stages of placental vascular development. The ubiquitin ligase Ankyrin repeat, SOCS box-containing 4 (ASB4 promotes embryonic stem cell differentiation to vascular lineages and is highly expressed early in placental development. The transcriptional regulator Inhibitor of DNA binding 2 (ID2 negatively regulates vascular differentiation during development and is a target of many ubiquitin ligases. Due to their overlapping spatiotemporal expression pattern in the placenta and contrasting effects on vascular differentiation, we investigated whether ASB4 regulates ID2 through its ligase activity in the placenta and whether this activity mediates vascular differentiation. In mouse placentas, ASB4 expression is restricted to a subset of cells that express both stem cell and endothelial markers. Placentas that lack Asb4 display immature vascular patterning and retain expression of placental progenitor markers, including ID2 expression. Using JAR placental cells, we determined that ASB4 ubiquitinates and represses ID2 expression in a proteasome-dependent fashion. Expression of ASB4 in JAR cells and primary isolated trophoblast stem cells promotes the expression of differentiation markers. In functional endothelial co-culture assays, JAR cells ectopically expressing ASB4 increased endothelial cell turnover and stabilized endothelial tube formation, both of which are hallmarks of vascular differentiation within the placenta. Co-transfection of a degradation-resistant Id2 mutant with Asb4 inhibits both differentiation and functional responses. Lastly, deletion of Asb4 in mice induces a pathology that phenocopies human pre-eclampsia, including hypertension and proteinuria in late-stage pregnant females. These results indicate that

  16. Estrogen regulates progesterone production by human placental trophoblast cells in culture

    International Nuclear Information System (INIS)

    Grimes, R.W.

    1990-01-01

    We have suggested that estrogen regulates placental low-density lipoprotein (LDL) uptake and thus progesterone (P 4 ) production during primate pregnancy based on results obtained in antiestrogen-treated baboons. The objectives of the present study, were to determine whether estrogen is also important to regulation of P 4 formation by the human placenta, and whether effects of estrogen were mediated by availability of cholesterol substrate via the LDL, de novo, or deesterification pathways. Term human placenta were dispersed in 0.125% trypsin, cytotrophoblasts were purified via a 70-5% Percoll gradient, incubated 72 h in DMEM with 10% FBS to stimulate formation of syncytia, then incubated an additional 48 h with estradiol (E2). In Experiment 1, 1 μg/ml E 2 and 500 μg/MI LDL-protein, stimulated P 4 (P 2 increased LDL uptake. Scatchard analysis indicated that trophoblast uptake of [ 125 I]LDL (ng/mg cell protein) was 50% greater (P 2 (mean ± SE, 638 +/- 23; n = 6) than DMEM in the presence of antiestrogen MER-25. Moreover, uptake and degradation of LDL, and cellular content of free and esterified cholesterol, increased in a dose-dependent manner with 0.1 to 1000 ng/ml E 2 . These results suggest that estrogen regulates placental cell uptake of LDL and thus availability of cholesterol for P 4 biosynthesis during human pregnancy. In Experiment 2, E 2 Stimulated P 4 formation (ng/mg cell protein/48 h) from a control level of 194 ± 25 to 357 ± 62, in the absence of LDL. Under these conditions, cholesterol for P 4 biosynthesis must have been derived from de novo synthesis and/or deesterification of cholesteryl ester stores

  17. Pharmacological Intervention through Dietary Nutraceuticals in Gastrointestinal Neoplasia.

    Science.gov (United States)

    Ullah, Mohammad F; Bhat, Showket H; Husain, Eram; Abu-Duhier, Faisel; Hadi, S M; Sarkar, Fazlul H; Ahmad, Aamir

    2016-07-03

    Neoplastic conditions associated with gastrointestinal (GI) tract are common worldwide with colorectal cancer alone accounting for the third leading rate of cancer incidence. Other GI malignancies such as esophageal carcinoma have shown an increasing trend in the last few years. The poor survival statistics of these fatal cancer diseases highlight the need for multiple alternative treatment options along with effective prophylactic strategies. Worldwide geographical variation in cancer incidence indicates a correlation between dietary habits and cancer risk. Epidemiological studies have suggested that populations with high intake of certain dietary agents in their regular meals have lower cancer rates. Thus, an impressive embodiment of evidence supports the concept that dietary factors are key modulators of cancer including those of GI origin. Preclinical studies on animal models of carcinogenesis have reflected the pharmacological significance of certain dietary agents called as nutraceuticals in the chemoprevention of GI neoplasia. These include stilbenes (from red grapes and red wine), isoflavones (from soy), carotenoids (from tomatoes), curcuminoids (from spice turmeric), catechins (from green tea), and various other small plant metabolites (from fruits, vegetables, and cereals). Pleiotropic action mechanisms have been reported for these diet-derived chemopreventive agents to retard, block, or reverse carcinogenesis. This review presents a prophylactic approach to primary prevention of GI cancers by highlighting the translational potential of plant-derived nutraceuticals from epidemiological, laboratory, and clinical studies, for the better management of these cancers through consumption of nutraceutical rich diets and their intervention in cancer therapeutics.

  18. Imiquimod in cervical, vaginal and vulvar intraepithelial neoplasia: a review.

    Science.gov (United States)

    de Witte, C J; van de Sande, A J M; van Beekhuizen, H J; Koeneman, M M; Kruse, A J; Gerestein, C G

    2015-11-01

    Human papillomavirus (HPV) infection is in the vast majority of patients accountable for the development of vulvar, cervical and vaginal intraepithelial neoplasia (VIN, CIN, VAIN); precursors of vulvar, cervical and vaginal cancers. The currently preferred treatment modality for high grade VIN, CIN and VAIN is surgical excision. Nevertheless surgical treatment is associated with adverse pregnancy outcomes and recurrence is not uncommon. The aim of this review is to present evidence on the efficacy, safety and tolerability of imiquimod (an immune response modifier) in HPV-related VIN, CIN and VAIN. A search for papers on the use of imiquimod in VIN, CIN and VAIN was performed in the MEDLINE, EMBASE and Cochrane library databases. Data was extracted and reviewed. Twenty-one articles met the inclusion criteria and were analyzed; 16 on VIN, 3 on CIN and 2 on VAIN. Complete response rates in VIN ranged from 5 to 88%. Although minor adverse effects were frequently reported, treatment with imiquimod was well tolerated in most patients. Studies on imiquimod treatment of CIN and VAIN are limited and lack uniformly defined endpoints. The available evidence however, shows encouraging effect. Complete response rates for CIN 2-3 and VAIN 1-3 ranged from 67 to 75% and 57 to 86% respectively. More randomized controlled trials on the use of imiquimod in CIN, VAIN and VIN with extended follow-up are necessary to determine the attributive therapeutic value in these patients. Copyright © 2015 Elsevier Inc. All rights reserved.

  19. Helicobacter pylori and colorectal neoplasia: Is there a causal link?

    Science.gov (United States)

    Papastergiou, Vasilios; Karatapanis, Stylianos; Georgopoulos, Sotirios D

    2016-01-01

    Ever since Helicobacter pylori (H. pylori) was recognized as an infectious cause of gastric cancer, there has been increasing interest in examining its potential role in colorectal carcinogenesis. Data from case-control and cross-sectional studies, mostly relying on hospital-based samples, and several meta-analyses have shown a positive statistical relationship between H. pylori infection and colorectal neoplasia. However, the possibility exists that the results have been influenced by bias, including the improper selection of patients and disparities with respect to potential confounders. While the evidence falls short of a definitive causal link, it appears that infection with H. pylori/H. pylori-related gastritis is associated with an increased, although modest, risk of colorectal adenoma and cancer. The pathogenic mechanisms responsible for this association remain uncertain. H. pylori has been detected in colorectal malignant tissues; however, the possibility that H. pylori is a direct activator of colonic carcinogenesis remains purely hypothetical. On the other hand, experimental data have indicated a series of potential oncogenic interactions between these bacteria and colorectal mucosa, including induction and perpetuation of inflammatory responses, alteration of gut microflora and release of toxins and/or hormonal mediators, such as gastrin, which may contribute to tumor formation. PMID:26811614

  20. Cervical Intraepithelial Neoplasia Is Associated With Genital Tract Mucosal Inflammation

    Science.gov (United States)

    Mhatre, Mohak; McAndrew, Thomas; Carpenter, Colleen; Burk, Robert D.; Einstein, Mark H.; Herold, Betsy C.

    2013-01-01

    Background Clinical studies demonstrate increased prevalence of human papillomavirus (HPV)-associated disease in HIV-infected individuals and an increased risk of HIV acquisition in HPV-infected individuals. The mechanisms underlying this synergy are not defined. We hypothesize that women with cervical intraepithelial neoplasia (CIN) will exhibit changes in soluble mucosal immunity that may promote HPV persistence and facilitate HIV infection. Methods The concentrations of immune mediators and endogenous anti-Escherichia coli activity in genital tract secretions collected by cervicovaginal lavage were compared in HIV-negative women with high-risk HPV-positive (HRHPV+) CIN-3 (n = 37), HRHPV+ CIN-1 (n = 12), or PAP-negative control subjects (n = 57). Results Compared with control subjects, women with CIN-3 or CIN-1 displayed significantly higher levels of proinflammatory cytokines including interleukin (IL)-1α, IL-1β, and IL-8 (P < 0.002) and significantly lower levels of anti-inflammatory mediators and antimicrobial peptides, including IL-1 receptor antagonist, secretory leukocyte protease inhibitor (P < 0.01), and human β defensins 2 and 3 (P < 0.02). There was no significant difference in endogenous anti-E. coli activity after controlling for age and sample storage time. Conclusion HRHPV+ CIN is characterized by changes in soluble mucosal immunity that could contribute to HPV persistence. The observed mucosal inflammation suggests a mechanism that may also contribute to the epidemiologic link between persistent HPV and HIV. PMID:22801340

  1. INFECTION WITH HUMAN PAPILLOMA VIRUS IN CERVICAL NEOPLASIA

    Directory of Open Access Journals (Sweden)

    Eduard Crauciuc

    2010-09-01

    Full Text Available The purpose of this study was to establish if the infection with human papilloma virus (HPV presents a potential irreversible evolution towards malignancy. Materials and methods. The study was made on a number of 1885 patients that were suspected to have cervical neoplasia, which were monitored between 2001-2010 in „Elena-Doamna” Clinical Hospital of Obstetrics and Gynecology in Ia�i, the Military Hospital Gala�i, the County Hospital Gala�i and the Emergency Hospital Buzau. Results and discussions. The study proved that the risk of contacting a genital infection with HPV and cervical cancer is influenced by the sexual activity, the risk of getting infected with HPV during a person’ s lifetime is at least 50% for those sexually active. Conclusions. The patients benefited from colposcopy and biopsy only if the repeated cytology suggested more severe changes. The conservative conduct is represented by a repeated cytology when the patients are admitted into the lot (the initial cytology is performed before this moment

  2. Immunologic assessment of patients with pulmonary metaplasia and neoplasia

    International Nuclear Information System (INIS)

    Gross, R.L.; Saccomanno, G.; Smith, D.M.; Saunders, R.; Thomas, R.G.

    1979-01-01

    Immune profiles have been obtained on 206 individuals including 57 controls, 50 lung cancer patients, and 99 uranium miners with well-defined sputum cytologies ranging from normal to carcinoma in situ. Little effect of smoking, uranium mining or a combination of mining plus smoking on immune function was observed if sputum cytology was normal. In heavy smokers there was a suggestion that total T cells are increased while T cell function is slightly depressed. Immunologic abnormalities were noted in the moderate atypia group where 40% had one or more abnormal immunologic parameters. Immunologic abnormalities were detected in 68 to 70 patients with marked atypia, carcinoma in situ, or invasive carcinoma. Further sequential study of the uranium miner population is necessary to define more precisely the predictive value of immunologic testing, and the role of early identification of high risk individuals in the early institution of definitive therapy, such as surgery or immunotherapy. Long-term prospective analysis of this population may also provide the answer to the question of whether alterations in immune function precede, or result from the appearance of cells committed to the development of neoplasia

  3. Thyroid neoplasia in Marshall Islanders exposed to nuclear fallout

    International Nuclear Information System (INIS)

    Hamilton, T.E.; van Belle, G.; LoGerfo, J.P.

    1987-01-01

    We studied the risk of thyroid neoplasia in Marshall Islanders exposed to radioiodines in nuclear fallout from the 1954 BRAVO thermonuclear test. We screened 7266 Marshall Islanders for thyroid nodules; the islanders were from 14 atolls, including several southern atolls, which were the source of the best available unexposed comparison group. Using a retrospective cohort design, we determined the prevalence of thyroid nodularity in a subgroup of 2273 persons who were alive in 1954 and who therefore were potentially exposed to fallout from the BRAVO test. For those 12 atolls previously thought to be unexposed to fallout, the prevalence of thyroid nodules ranged from 0.9% to 10.6%. Using the distance of each atoll from the test site as a proxy for the radiation dose to the thyroid gland, a weighted linear regression showed an inverse linear relationship between distance and the age-adjusted prevalence of thyroid nodules. Distance was the strongest single predictor in logistic regression analysis. A new absolute risk estimate was calculated to be 1100 excess cases/Gy/y/1 X 10(6) persons (11.0 excess cases/rad/y/1 million persons), 33% higher than previous estimates. We conclude that an excess of thyroid nodules was not limited only to the two northern atolls but extended throughout the northern atolls; this suggests a linear dose-response relationship

  4. Altered Peptidase Activities in Thyroid Neoplasia and Hyperplasia

    Directory of Open Access Journals (Sweden)

    Gorka Larrinaga

    2013-01-01

    Full Text Available Background. Papillary thyroid carcinoma (PTC, follicular thyroid adenoma (FTA, and thyroid nodular hyperplasia (TNH are the most frequent diseases of the thyroid gland. Previous studies described the involvement of dipeptidyl-peptidase IV (DPPIV/CD26 in the development of thyroid neoplasia and proposed it as an additional tool in the diagnosis/prognosis of these diseases. However, very little is known about the involvement of other peptidases in neoplastic and hyperplastic processes of this gland. Methods. The catalytic activity of 10 peptidases in a series of 30 PTC, 10 FTA, and 14 TNH was measured fluorimetrically in tumour and nontumour adjacent tissues. Results. The activity of DPPIV/CD26 was markedly higher in PTC than in FTA, TNH, and nontumour tissues. Aspartyl aminopeptidase (AspAP, alanyl aminopeptidase (AlaAP, prolyl endopeptidase, pyroglutamyl peptidase I, and aminopeptidase B activities were significantly increased in thyroid neoplasms when compared to nontumour tissues. AspAP and AlaAP activities were also significantly higher in PTC than in FTA and TNH. Conclusions. These data suggest the involvement of DPPIV/CD26 and some cytosolic peptidases in the neoplastic development of PTC and FTA. Further studies will help to define the possible clinical usefulness of AlaAP and AspAP in the diagnosis/prognosis of thyroid neoplasms.

  5. Altered peptidase activities in thyroid neoplasia and hyperplasia.

    Science.gov (United States)

    Larrinaga, Gorka; Blanco, Lorena; Errarte, Peio; Beitia, Maider; Sanz, Begoña; Perez, Itxaro; Irazusta, Amaia; Sánchez, Clara E; Santaolalla, Francisco; Andrés, Leire; López, José I

    2013-01-01

    Papillary thyroid carcinoma (PTC), follicular thyroid adenoma (FTA), and thyroid nodular hyperplasia (TNH) are the most frequent diseases of the thyroid gland. Previous studies described the involvement of dipeptidyl-peptidase IV (DPPIV/CD26) in the development of thyroid neoplasia and proposed it as an additional tool in the diagnosis/prognosis of these diseases. However, very little is known about the involvement of other peptidases in neoplastic and hyperplastic processes of this gland. The catalytic activity of 10 peptidases in a series of 30 PTC, 10 FTA, and 14 TNH was measured fluorimetrically in tumour and nontumour adjacent tissues. The activity of DPPIV/CD26 was markedly higher in PTC than in FTA, TNH, and nontumour tissues. Aspartyl aminopeptidase (AspAP), alanyl aminopeptidase (AlaAP), prolyl endopeptidase, pyroglutamyl peptidase I, and aminopeptidase B activities were significantly increased in thyroid neoplasms when compared to nontumour tissues. AspAP and AlaAP activities were also significantly higher in PTC than in FTA and TNH. These data suggest the involvement of DPPIV/CD26 and some cytosolic peptidases in the neoplastic development of PTC and FTA. Further studies will help to define the possible clinical usefulness of AlaAP and AspAP in the diagnosis/prognosis of thyroid neoplasms.

  6. Predictors of advanced colorectal neoplasia for colorectal cancer screening.

    Science.gov (United States)

    Wong, Martin C S; Lam, Thomas Y T; Tsoi, Kelvin K F; Chan, Victor C W; Hirai, Hoyee W; Ching, Jessica Y L; Sung, Joseph J Y

    2014-05-01

    The Asia-Pacific Colorectal Screening (APCS) score based on age, gender, family history, and smoking is useful to predict advanced colorectal neoplasia (ACN) in asymptomatic Asian subjects. To evaluate the factors in addition to those of APCS associated with ACN colonoscopic findings. Data from 5,220 asymptomatic subjects aged between 50 and 70 years who underwent screening colonoscopy in a community center between 2008 and 2012 were analyzed. One binary logistic regression analysis was conducted in 2013 with the presence of ACN or cancer as the outcome, controlling for APCS score, alcohol consumption, BMI, hypertension, and other chronic diseases as independent variables. The average participant age was 57.7 years (SD=4.9) and 47.5% were men. Advanced neoplasms or cancers were identified at colonoscopy in 5.6% of all screening participants. From multivariate regression analysis, APCS score≥4 (adjusted OR [AOR]=1.74, 95% CI=1.34, 2.25, pstatistic of APCS score alone was 0.560 (95% CI=0.524, 0.595, p=0.001) and that of APCS score plus BMI, hypertension, and alcohol consumption was 0.613 (95% CI=0.578, 0.648, p<0.001). Alcohol consumption, hypertension, and BMI are independent predictors of ACN, which could be incorporated into the APCS for prioritizing Asian asymptomatic subjects for colorectal cancer screening. Copyright © 2014. Published by Elsevier Inc.

  7. Problems in distinguishing spinal tuberculosis from neoplasia on MRI

    International Nuclear Information System (INIS)

    Gupta, R.K.; Agarwal, P.; Rastogi, H.; Kumar, S.; Phadke, R.V.; Krishnani, N.

    1996-01-01

    We reviewed MRI studies of 60 patients presenting with extradural compressive myeloradiculopathy secondary to vertebral disease to assess the imaging features which may help in differentiating tuberculous from neoplastic disease. Spin-echo T1-, proton density- and T2-weighted images were available for all patients and fast low-angle shot images with a low flip angle for 21 patients. Contrast-enhanced images were available for 28 patients. There were 41 patients with tuberculosis and 19 patients with neoplastic disease (metastases 11, lymphoma 6, plasmacytoma 1, and giant cell tumour 1). Discovertebral disease with or without involvement of the posterior arch was a feature not only of tuberculous spondylitis (30 patients) but also of metastases (6). The remaining 11 patients with tuberculosis had ''atypical'' involvement (vertebral body with or without posterior arch in 8 and posterior arch alone in 3) described as typical of neoplasms. This ''typical'' involvement was seen in metastases (5), lymphoma (6) and the 2 primary bone tumours. The presence of an abscess helped in differentiating tuberculosis from neoplasia in 22 of the 41 patients with tuberculosis and was absent in all with neoplasms. The presence of bone fragments in 16 patients (8 with and 8 without an abscess) was found to be specific for tuberculosis. In the absence of an abscess or bone fragments, image-guided biopsy is essential to establish the diagnosis. (orig.). With 9 figs., 2 tabs

  8. Neoplasias endocrinas múltiples. desde el laboratorio al paciente

    Directory of Open Access Journals (Sweden)

    Dr. G. Nelson Wohllk

    2013-09-01

    Full Text Available Las neoplasias endocrinas múltiples (NEM tipo 1 y 2 son enfermedades genéticas heredadas en forma autosómica dominante. Las principales manifestaciones clínicas en NEM1 incluyen tumores paratiroideos, hipofisiarios y gastroenteropancreáticos. El test genético se puede realizar en los pacientes y potenciales portadores de mutaciones en el gen menin, pero la correlación genotipo-fenotipo es menos directa en comparación a NEM2. En la NEM2 el cáncer medular de tíroides (CMT es común a los tres subtipos: NEM2A (feocromocitoma e hiperparatiroidismo, NEM2B (feocromocitoma y neuromas mucosos y CMT familiar. A aquellos pacientes con mutación RET se les debe recomendar la realización de tiroidectomía profiláctica en la niñez, de acuerdo a la categoría de riesgo ATA. Algunos casos de CMT aparentemente esporádicos son actualmente NEM2 después de la realización del estudio genético para proto-oncogen RET, por lo tanto se recomienda la aplicación rutinaria de este estudio a todos los pacientes con CMT aparentemente esporádico.

  9. Phenotypic relationships of prostatic intraepithelial neoplasia to invasive prostatic carcinoma.

    Science.gov (United States)

    Nagle, R. B.; Brawer, M. K.; Kittelson, J.; Clark, V.

    1991-01-01

    Thirty-one snap-frozen human prostate specimens containing examples of benign hyperplasia, prostatic intraepithelial neoplasia (PIN), and invasive carcinoma were analyzed using a panel of 24 antibodies and one lectin. Twenty-seven additional routinely processed radical prostatectomy specimens were studied using selected probes known to work on formalin-fixed paraffin-embedded material. Three probes, anticytokeratin KA4, anti-vimentin V9, and the lectin from Ulex europaeus (UEA-1), demonstrated phenotypic similarities between PIN and invasive carcinoma. Whereas the luminal cells of normal or hyperplastic prostatic epithelium are minimally reactive with KA4 (4%) or UEA-1 (0%) and strongly reactive with anti-vimentin (91%), both the PIN and invasive carcinoma are reactive with KA4 (89% and 93%, respectively) and UEA-1 (96% and 93%, respectively) and minimally reactive with anti-vimentin (15% and 0%, respectively). The increased KA4 staining was shown to be in part due to detection of cytokeratin 19, by using cytokeratin-19-specific antibodies, 4.62 and LP2K. The reasons for the increased expression of this cytokeratin and the decreased expression of vimentin are unclear but seem to indicate a phenotypic relationship between the PIN lesions and invasive carcinoma. Images Figure 4 Figure 1 Figure 2 Figure 3 PMID:1987760

  10. Histomorphometry and expression of Cdc47 and caspase-3 in hyperthyroid rat uteri and placentas during gestation and postpartum associated with fetal development.

    Science.gov (United States)

    Freitas, E S; Leite, E D; Souza, C A; Ocarino, N M; Ferreira, E; Cassali, G D; Gomes, M G; Serakides, R

    2007-01-01

    In two different experiments, the effects of hyperthyroidism on the histomorphometry and expression of Cdc47 and caspase-3 were evaluated in the uteri and placentas during gestation and postpartum. Fetal development was also evaluated during gestation. In the first experiment, 36 adult female Wistar rats were divided into two groups of 18 animals each: (1) hyperthyroid; and (2) euthyroid (control). Female rats were mated and killed at 7, 14 and 19 days of gestation. Uteri and placentas were weighed and subjected to histomorphometric and immunohistochemical evaluation to determine the expression of Cdc47 and caspase-3. Ovaries were also evaluated for weight and subjected to morphometric analysis. Fetuses were quantified and weighed individually. In the second experiment, 12 adult female Wistar rats were divided into two groups of six animals each: (1) hyperthyroid; and (2) euthyroid (control). Female rats were mated and killed 2 days postpartum. Uteri were evaluated in the same way as for the first experiment. Hyperthyroidism increased ovulation and conception rates without disturbing the size and viability of the fetuses. In the pregnant uteri, hyperthyroidism did not change the thickness of the layers or the expression of Cdc47 and caspase-3. However, in the placentas, hyperthyroidism increased the medium diameter of trophoblast cells, as well as the thickness and the expression of Cdc47 of spongiotrophoblast cells, at 14 days of gestation. During uterine involution, hyperthyroidism significantly increased the expression of Cdc47 and reduced the expression of caspase-3 in the uterine layers. In conclusion, hyperthyroidism increased the conception rate because of an ovulation gain, induced significant placental changes during pregnancy and, in the uterus, increased Cdc47 expression and decreased caspase-3 expression after parturition.

  11. Wheat shorts in diets of gestating swine.

    Science.gov (United States)

    Young, L G; King, G L

    1981-03-01

    Sixty-four gilts were assigned to be bred at first or third observed estrus and fed gestation diets of pelleted wheat shorts with a free choice mineral-vitamin supplement or fortified corn-soybean meal. Only the dietary effects are included in this report. The gilts were fed their respective diets starting at 25 days after insemination. The experiment continued through three gestation-lactation cycles. Females fed the wheat shorts received less digestible energy during gestation and weighed less at day 109 of gestation and days 1, 7 and 21 of lactation in each of the three gestation-lactation periods. Females fed wheat shorts had lighter pigs at birth, weaned more pigs per litter in each parity and returned to estrus more slowly after weaning than females fed a corn-soybean meal diet. Results of a metabolism trial conducted with 12 barrows revealed that wheat shorts contained approximately 2.93 kcal digestible energy/kg dry matter and had an apparent protein digestibility of 72%, compared with values of 4.0 kcal and 86%, respectively, for the corn-soybean meal diets.

  12. Lobular neoplasia - borderline type of lesion - risk of subsequent development of invasive lobular carcinoma of the breast, 13 years after excision of radial scar with multifocal lobular neoplasia

    International Nuclear Information System (INIS)

    Wardzynska, K.; Wesolowska, E.; Baranska, J.

    2010-01-01

    Background. Lobular neoplasia is a hyperplastic breast lesion - a borderline type of lesion with a high risk of subsequent development of invasive carcinoma. In case of radial scar diagnosis the risk of invasive carcinoma increases twice in comparison with healthy patients population while in the case of lobular neoplasia diagnosis within radial scar this risk increases 8 to 10 times. Basing on the presented case we analyse and review the literature regarding the clinical, radiological and pathological aspects of lobular neoplasia of the breast. Case report. A 67-yeas old patient was hospitalised in 1995 in order to consult the results of mammography, which revealed a radial scar lesion of the right breast. The patient was then referred to undergo wide local excision. Pathological examination showed dysplastic changes of the radial scar type with 1 cm multifocal lobular neoplasia. The patient was systematically followed clinically and radiologically during the decade 1996-2006 and all examination results were normal. In 2008, an ill-defined nodule appeared within the scar on mammography examination. This was categorized as BI-RADS 4C. The mammotomic biopsy performed under ultrasonography control revealed invasive lobular carcinoma. The tumor was totally locally excised and the sentinel node was histologically verified. The histopathological examination revealed a 1.6 cm focus of invasive lobular carcinoma and the sentinel node was negative. Conclusion. Patients with detected lobular neoplasia should be treated as a risk group of invasive breast cancer development (30-40% vs 10% in a healthy population during the entire life period). Systematic clinical and radiological follow-up should be mandatory. (authors)

  13. The lncRNA TUG1 modulates proliferation in trophoblast cells via epigenetic suppression of RND3.

    Science.gov (United States)

    Xu, Yetao; Ge, Zhiping; Zhang, Erbao; Zuo, Qing; Huang, Shiyun; Yang, Nana; Wu, Dan; Zhang, Yuanyuan; Chen, Yanzi; Xu, Haoqin; Huang, Huan; Jiang, Zhiyan; Sun, Lizhou

    2017-10-12

    Due to limited treatment options, pre-eclampsia (PE) is associated with fetal perinatal and maternal morbidity and mortality. During the causes of PE, failure of uterine spiral artery remodeling which might be related to functioning abnormally of trophoblast cells, result in the occurrence and progression of PE. Recently, abnormal expression of long non-coding RNAs (lncRNAs), as imperative regulators involved in human diseases progression (included PE), which has been indicated by increasing evidence. In this research, we found that TUG1, a lncRNA, was markedly reduced in placental samples from patients with PE. Loss-function assays indicated that knockdown TUG1 significantly affected cell proliferation, apoptosis, migration and network formation in vitro. RNA-seq revealed that TUG1 could affect abundant genes, and then explore the function and regulatory mechanism of TUG1 in trophoblast cells. Furthermore, RNA immunoprecipitation and chromatin immunoprecipitation assays validated that TUG1 can epigenetically inhibit the level of RND3 through binding to EZH2, thus promoting PE development. Therefore, via illuminating the TUG1 mechanisms underlying PE development and progression, our findings might furnish a prospective therapeutic strategy for PE intervention.

  14. Dysregulated DNA Methyltransferase 3A Upregulates IGFBP5 to Suppress Trophoblast Cell Migration and Invasion in Preeclampsia.

    Science.gov (United States)

    Jia, Yuanhui; Li, Ting; Huang, Xiaojie; Xu, Xianghong; Zhou, Xinyao; Jia, Linyan; Zhu, Jingping; Xie, Dandan; Wang, Kai; Zhou, Qian; Jin, Liping; Zhang, Jiqin; Duan, Tao

    2017-02-01

    Preeclampsia is a unique multiple system disorder during human pregnancy, which affects ≈5% to 8% of pregnancies. Its risks and complications have become the major causes of maternal and fetal morbidity and mortality. Although abnormal placentation to which DNA methylation dysregulation is always linked is speculated to be one of the reasons causing preeclampsia, the underlying mechanisms still remain elusive to date. Here we revealed that aberrant DNA methyltransferase 3A (DNMT3A) plays a critical role in preeclampsia. Our results show that the expression and localization of DNMT3A are dysregulated in preeclamptic placenta. Moreover, knockdown of DNMT3A obviously inhibits trophoblast cell migration and invasion. Mechanistically, IGFBP5 (insulin-like growth factor-binding protein 5), known as a suppressor, is upregulated by decreased DNMT3A because of promoter hypomethylation. Importantly, IGFBP5 downregulation can rescue the defects caused by DNMT3A knockdown, thereby, consolidating the significance of IGFBP5 in the downstream of DNMT3A in trophoblast. Furthermore, we detected low promoter methylation and high protein expression of IGFBP5 in the clinical samples of preeclamptic placenta. Collectively, our study suggests that dysregulation of DNMT3A and IGFBP5 is relevant to preeclampsia. Thus, we propose that DNMT3A and IGFBP5 can serve as potential markers and targets for the clinical diagnosis and therapy of preeclampsia. © 2017 American Heart Association, Inc.

  15. Determination of gestational age by ultrasound.

    Science.gov (United States)

    Butt, Kimberly; Lim, Ken

    2014-02-01

    To assist clinicians in assigning gestational age based on ultrasound biometry. To determine whether ultrasound dating provides more accurate gestational age assessment than menstrual dating with or without the use of ultrasound. To provide maternity health care providers and researchers with evidence-based guidelines for the assignment of gestational age. To determine which ultrasound biometric parameters are superior when gestational age is uncertain. To determine whether ultrasound gestational age assessment is cost effective. Published literature was retrieved through searches of PubMed or MEDLINE and The Cochrane Library in 2013 using appropriate controlled vocabulary and key words (gestational age, ultrasound biometry, ultrasound dating). Results were restricted to systematic reviews, randomized control trials/controlled clinical trials, and observational studies written in English. There were no date restrictions. Searches were updated on a regular basis and incorporated in the guideline to July 31, 2013. Grey (unpublished) literature was identified through searching the websites of health technology assessment and health technology-related agencies, clinical practice guideline collections, clinical trial registries, and national and international medical specialty societies. The quality of evidence in this document was rated using the criteria described in the Report of the Canadian Task Force on Preventive Health Care (Table 1). Accurate assignment of gestational age may reduce post-dates labour induction and may improve obstetric care through allowing the optimal timing of necessary interventions and the avoidance of unnecessary ones. More accurate dating allows for optimal performance of prenatal screening tests for aneuploidy. A national algorithm for the assignment of gestational age may reduce practice variations across Canada for clinicians and researchers. Potential harms include the possible reassignment of dates when significant fetal pathology

  16. Factors affecting gestation duration in the bitch.

    Science.gov (United States)

    Eilts, Bruce E; Davidson, Autumn P; Hosgood, Giselle; Paccamonti, Dale L; Baker, David G

    2005-07-15

    A retrospective analysis was performed to determine the effects of age, breed, parity, and litter size on the duration of gestation in the bitch. Bitches at two locations were monitored from breeding to whelping. A total of 764 litters whelped from 308 bitches (36 large hounds, 34 Golden Retrievers, 23 German Shepherd Dogs (GSD), and 215 Labrador Retrievers). By breed, the number of whelpings was 152, 72, 58, and 482 for the hounds, Golden Retrievers, German Shepherd Dogs, and Labrador Retrievers, respectively. Whelping was predicted to be 57 d from the first day of cytologic diestrus in the hounds or 65 d from the initial progesterone rise in the other breeds. The average gestation duration (calculated as 8 d prior to Day 1 of cytologic diestrus in hounds or measured from the initial progesterone rise in other breeds) by breed (days +/- S.D.) was 66.0 +/- 2.8, 64.7 +/- 1.5, 63.6 +/- 2.1, and 62.9 +/- 1.3 for the hounds, Golden Retrievers, German Shepherd Dogs, and Labrador Retrievers, respectively. The relationship of age, breed, parity, and litter size with the difference in gestation duration was evaluated using log linear modeling. Age or parity had no effect on gestation duration. Compared to Labrador Retrievers, the German Shepherd Dogs, Golden Retrievers and hounds were more likely to have a longer gestation duration; three, four and nearly eight times as likely, respectively. Bitches whelping four or fewer pups were significantly more likely to have a longer gestation duration than those whelping five or more pups; the prolongation averaging 1 d.

  17. Human Papillomaviruses; Epithelial Tropisms, and the Development of Neoplasia

    Directory of Open Access Journals (Sweden)

    Nagayasu Egawa

    2015-07-01

    Full Text Available Papillomaviruses have evolved over many millions of years to propagate themselves at specific epithelial niches in a range of different host species. This has led to the great diversity of papillomaviruses that now exist, and to the appearance of distinct strategies for epithelial persistence. Many papillomaviruses minimise the risk of immune clearance by causing chronic asymptomatic infections, accompanied by long-term virion-production with only limited viral gene expression. Such lesions are typical of those caused by Beta HPV types in the general population, with viral activity being suppressed by host immunity. A second strategy requires the evolution of sophisticated immune evasion mechanisms, and allows some HPV types to cause prominent and persistent papillomas, even in immune competent individuals. Some Alphapapillomavirus types have evolved this strategy, including those that cause genital warts in young adults or common warts in children. These strategies reflect broad differences in virus protein function as well as differences in patterns of viral gene expression, with genotype-specific associations underlying the recent introduction of DNA testing, and also the introduction of vaccines to protect against cervical cancer. Interestingly, it appears that cellular environment and the site of infection affect viral pathogenicity by modulating viral gene expression. With the high-risk HPV gene products, changes in E6 and E7 expression are thought to account for the development of neoplasias at the endocervix, the anal and cervical transformation zones, and the tonsilar crypts and other oropharyngeal sites. A detailed analysis of site-specific patterns of gene expression and gene function is now prompted.

  18. Multiple endocrine neoplasia detection on I-123 MIBG imaging

    International Nuclear Information System (INIS)

    Reinhardt, C.A.; McEwan, L.M.; Wong, J.C.H.

    2000-01-01

    Full text: An 123 I meta-iodobenzylguanidine (MIBG) scan was performed on a 54-year-old lady with familial phaeochromocytoma, to evaluate for bilateral or extra-adrenal disease. She has hypertension with raised catecholamines and CT evidence of a right adrenal phaeochromocytoma, and a female sibling with bilateral phaeochromocytoma. Thyroid blockade using Lugol's Iodine was given orally prior to intravenous administration of 370 MBq 123 I MIBG. Planar and SPECT imaging were acquired at 24 hours. There was intense uptake in the known right phaeochromocytoma. An unexpected finding was focal intense uptake in the region of the right thyroid lobe, which may be either a functioning paraganglioma arising from the cervical sympathetic ganglia or a medullary thyroid carcinoma (MTC). At 48 hours, a further image of the neck showed no changes. This was followed by a standard injection of 150 MBq 99 Tc m pertechnetate for thyroid scanning. Imaging obtained on 99 Tc m energy window setting showed a large hypofunctioning region in the right thyroid lobe, corresponding in location to the focal 123 I MIBG uptake. This is in keeping with a MTC, a neuroendocrine tumour, as other thyroid carcinomas are non-MIBG avid. A subsequent serum calcitonin assay showed elevated levels. The patient underwent surgical removal of the right phaeochromocytoma followed several weeks later by a right hemithyroidectomy. Histological reports confirmed the tumour diagnoses. The patient's familial phaeochromocytoma is therefore part of the multiple endocrine neoplasia syndrome Type 2A (MEN 2A). To date, biochemistry has not shown any evidence of hyperparathyroidism which occurs in 15-20 per cent of patients with MEN 2A. Copyright (2000) The Australian and New Zealand Society of Nuclear Medicine Inc

  19. Human Papillomaviruses; Epithelial Tropisms, and the Development of Neoplasia

    Science.gov (United States)

    Egawa, Nagayasu; Egawa, Kiyofumi; Griffin, Heather; Doorbar, John

    2015-01-01

    Papillomaviruses have evolved over many millions of years to propagate themselves at specific epithelial niches in a range of different host species. This has led to the great diversity of papillomaviruses that now exist, and to the appearance of distinct strategies for epithelial persistence. Many papillomaviruses minimise the risk of immune clearance by causing chronic asymptomatic infections, accompanied by long-term virion-production with only limited viral gene expression. Such lesions are typical of those caused by Beta HPV types in the general population, with viral activity being suppressed by host immunity. A second strategy requires the evolution of sophisticated immune evasion mechanisms, and allows some HPV types to cause prominent and persistent papillomas, even in immune competent individuals. Some Alphapapillomavirus types have evolved this strategy, including those that cause genital warts in young adults or common warts in children. These strategies reflect broad differences in virus protein function as well as differences in patterns of viral gene expression, with genotype-specific associations underlying the recent introduction of DNA testing, and also the introduction of vaccines to protect against cervical cancer. Interestingly, it appears that cellular environment and the site of infection affect viral pathogenicity by modulating viral gene expression. With the high-risk HPV gene products, changes in E6 and E7 expression are thought to account for the development of neoplasias at the endocervix, the anal and cervical transformation zones, and the tonsilar crypts and other oropharyngeal sites. A detailed analysis of site-specific patterns of gene expression and gene function is now prompted. PMID:26193301

  20. Gigantism in sibling unrelated to multiple endocrine neoplasia: case report.

    Science.gov (United States)

    Matsuno, A; Teramoto, A; Yamada, S; Kitanaka, S; Tanaka, T; Sanno, N; Osamura, R Y; Kirino, T

    1994-11-01

    The cases of gigantism sisters with somatotroph adenomas unrelated to multiple endocrine neoplasia (MEN) Type 1 are reported. The sisters grew rapidly since they were 5 or 6 years old and were diagnosed to have gigantism with pituitary adenoma by computed tomographic scan and magnetic resonance imaging. A serum endocrinological examination showed the elevated growth hormone values. After thyroxine-releasing hormone stimulation, growth hormone values exhibited a paradoxical rise. They were supposed to be unrelated to MEN Type 1, because analysis of the 11th chromosomes and the other endocrine functions were normal. They were operated on by the transphenoidal method. Immunohistochemical staining of both tumor specimens confirmed somatotroph adenomas. Pituitary adenoma associated with MEN Type 1 is a well-recognized entity. However, the sporadic occurrence of pituitary adenoma unrelated to MEN Type 1, especially in siblings, is extremely rare. Fifteen cases of pituitary adenomas in siblings were described in the literature. As for gigantism, only two brothers were reported. Our case of gigantism sisters is the second sporadic case. In our review of the isolated cases of pituitary adenoma in siblings described in the literature, 12 (70%) of 17 cases including ours are acromegaly or gigantism. This incidence is much higher than that of MEN Type 1 patients with pituitary adenomas. The cause of the familial occurrence of pituitary adenomas is still unclear, although autosomal recessive inheritance has been suggested. It has been stated that point mutations in codon 201 or 227 of the Gs alpha gene located in chromosome 20 were found in about 35 to 40% of somatotroph adenomas.(ABSTRACT TRUNCATED AT 250 WORDS)

  1. DNA-Cytometry of Progressive and Regressive Cervical Intraepithelial Neoplasia

    Directory of Open Access Journals (Sweden)

    Antonius G. J. M. Hanselaar

    1998-01-01

    Full Text Available A retrospective analysis was performed on archival cervical smears from a group of 56 women with cervical intraepithelial neoplasia (CIN, who had received follow‐up by cytology only. Automated image cytometry of Feulgen‐stained DNA was used to determine the differences between progressive and regressive lesions. The first group of 30 smears was from women who had developed cancer after initial smears with dysplastic changes (progressive group. The second group of 26 smears with dysplastic changes had shown regression to normal (regressive group. The goal of the study was to determine if differences in cytometric features existed between the progressive and regressive groups. CIN categories I, II and III were represented in both groups, and measurements were pooled across diagnostic categories. Images of up to 700 intermediate cells were obtained from each slide, and cells were scanned exhaustively for the detection of diagnostic cells. Discriminant function analysis was performed for both intermediate and diagnostic cells. The most significant differences between the groups were found for diagnostic cells, with a cell classification accuracy of 82%. Intermediate cells could be classified with 60% accuracy. Cytometric features which afforded the best discrimination were characteristic of the chromatin organization in diagnostic cells (nuclear texture. Slide classification was performed by thresholding the number of cells which exhibited progression associated changes (PAC in chromatin configuration, with an accuracy of 93 and 73% for diagnostic and intermediate cells, respectively. These results indicate that regardless of the extent of nuclear atypia as reflected in the CIN category, features of chromatin organization can potentially be used to predict the malignant or progressive potential of CIN lesions.

  2. Mutational spectrum of intraepithelial neoplasia in pancreatic heterotopia.

    Science.gov (United States)

    Ma, Changqing; Gocke, Christopher D; Hruban, Ralph H; Belchis, Deborah A

    2016-02-01

    Heterotopic pancreatic parenchyma recapitulates the normal pancreas in extrapancreatic locations and, on rare occasions, can even give rise to pancreatic adenocarcinoma. The genetic signatures of pancreatic adenocarcinoma and its precursor lesions are well characterized. We explored the genetic alterations in precursor lesions (intraductal papillary mucinous neoplasms [IPMN], pancreatic intraepithelial neoplasia [PanIN]) in patients with pancreatic heterotopias but without concomitant pancreatic ductal adenocarcinomas. This allowed us to determine whether the stereotypical dysplasia--infiltrating carcinoma sequence also occurs in these extrapancreatic foci. Seven cases of heterotopic pancreas with ductal precursor lesions were identified. These included 2 IPMNs with focal high-grade dysplasia and 5 PanINs with low- to moderate-grade dysplasia (PanIN grades 1-2). Neoplastic epithelium was microdissected and genomic DNA was extracted. Sequencing of commonly mutated hotspots (KRAS, TP53, CDKN2A, SMAD4, BRAF, and GNAS) in pancreatic ductal adenocarcinoma and its precursor lesions was performed. Both IPMNs were found to have KRAS codon 12 mutations. The identification of KRAS mutations suggests a genetic pathway shared with IPMN of the pancreas. No mutations were identified in our heterotopic PanINs. One of the possible mechanisms for the development of dysplasia in these lesions is field effect. At the time of these resections, there was no clinical or pathologic evidence of a prior or concomitant pancreatic lesion. However, a clinically undetectable lesion is theoretically possible. Therefore, although a field effect cannot be excluded, there was no evidence for it in this study. Copyright © 2015 Elsevier Inc. All rights reserved.

  3. Pathologic audit of 164 consecutive cases of vulvar intraepithelial neoplasia.

    Science.gov (United States)

    Scurry, James; Campion, Michael; Scurry, Bonnie; Kim, Soo Nyung; Hacker, Neville

    2006-04-01

    There are 2 types of vulvar intraepithelial neoplasia (VIN): warty-basaloid and differentiated. Differentiated VIN is uncommon and seldom diagnosed prior to carcinoma and, traditionally, is not graded. There are currently 3 grading systems for warty-basaloid VIN: the World Health Organization (WHO) 3 grade system of VIN 1-3, a 2 grade system of low and high grade vulvar intraepithelial lesions, and the revised International Society for the Study of Vulvovaginal Disease (ISSVD) classification which has no grading of VIN. According to the ISSVD, VIN 1 should be abolished and VIN 2 and 3 combined into a single category, simply termed warty-basaloid VIN. To determine the best system for grading warty-basaloid VIN and learn more about differentiated VIN, we reviewed the pathology of 164 consecutive women with VIN. Of these, 134 (82.3%) had warty-basaloid VIN, 29 (18.2%) had differentiated VIN, and 1 had both. Of warty-basaloid VIN cases, 4 had VIN 1, 13 VIN 2, and 118 VIN 3 when graded according to the WHO. All VIN 1 occurred in condylomata acuminata. VIN 2 and 3 were distinguished only by degree of abnormality. Differentiated VIN was diagnosed before SCC in only 7 cases (26.7%). Because the only VIN 1 cases seen were in condylomata acuminata and because VIN 2 and 3 were difficult to distinguish and there appears little clinical reason to do so, our study supports the ISSVD proposal that VIN 1 be abolished and VIN 2 and 3 be combined. There needs to be more clinical awareness of vulvar conditions, so that differentiated VIN is biopsied before cancer has supervened.

  4. [Serrated polyps and their association with synchronous advanced colorectal neoplasia].

    Science.gov (United States)

    Urman, Jesús; Gomez, Marta; Basterra, Marta; Mercado, María Del Rosario; Montes, Marta; Gómez Dorronsoro, Marisa; Garaigorta, Maitane; Fraile, María; Rubio, Eva; Aisa, Gregorio; Galbete, Arkaitz

    2016-11-01

    Large serrated polyps (SP), proximal SP, SP with dysplasia and the presence of multiple sessile serrated adenomas/polyps (SSA/P), which we refer to as SP with increased risk of metachronous lesions (SPIRML), have been associated with an increased risk of advanced colon lesions on follow-up. It is unclear, however, whether SPIRML are also associated with an increased risk of synchronous advanced colorectal neoplasia (ACN). The aim of this study was to estimate the prevalence of SPIRML and to evaluate the association between SPIRML and synchronous ACN. A cross-sectional population-based study in all patients (1,538) with histological diagnosis of SP obtained from colonoscopies, sigmoidoscopies and colonic surgery performed in Navarra Health Service hospitals (Spain) in 2011. Demographic parameters and synchronous colonic lesions (adenomas, advanced adenomas [AA] and ACN) were analyzed. One fourth of the sample (384 patients) presented SPIRML. These were older patients, with a slight predominance of women, and with no differences in body mass index (BMI) compared to patients without SPIRML. In the univariate analysis, patients with SPIRML showed an increased risk of adenoma, AA and ACN. In the multivariate analysis, the SPIRML group had a higher risk of synchronous AA and ACN (odds ratio [OR]: 2.38 [1.77-3.21] and OR: 2.29 [1.72-3.05], respectively); in the case of ACN, this risk was statistically significant in both locations (proximal or distal), with OR slightly higher for the proximal location. Different subtypes of SPIRML had a higher risk of AA and synchronous NA. SPIRML were common in patients with SP, and their presence was associated with an increased risk of synchronous ACN. Copyright © 2016 Elsevier España, S.L.U. y AEEH y AEG. All rights reserved.

  5. Antiphospholipid antibody-induced miR-146a-3p drives trophoblast interleukin-8 secretion through activation of Toll-like receptor 8.

    Science.gov (United States)

    Gysler, Stefan M; Mulla, Melissa J; Guerra, Marta; Brosens, Jan J; Salmon, Jane E; Chamley, Lawrence W; Abrahams, Vikki M

    2016-07-01

    What is the role of microRNAs (miRs) in antiphospholipid antibody (aPL)-induced trophoblast inflammation? aPL-induced up-regulation of trophoblast miR-146a-3p is mediated by Toll-like receptor 4 (TLR4), and miR-146a-3p in turn drives the cells to secrete interleukin (IL)-8 by activating the RNA sensor, TLR8. Obstetric antiphospholipid syndrome (APS) is an autoimmune disorder characterized by circulating aPL and an increased risk of pregnancy complications. We previously showed that aPL recognizing beta2 glycoprotein I (β2GPI) elicit human first trimester trophoblast secretion of IL-8 by activating TLR4. Since some miRs control TLR responses, their regulation in trophoblast cells by aPL and functional role in the aPL-mediated inflammatory response was investigated. miRs can be released from cells via exosomes, and therefore, miR exosome expression was also examined. A panel of miRs was selected based on their involvement with TLR signaling: miR-9; miR-146a-5p and its isomiR, miR-146a-3p; miR-155, miR-210; and Let-7c. Since certain miRs can activate the RNA sensor, TLR8, this was also investigated. For in vitro studies, the human first trimester extravillous trophoblast cell line, HTR8 was studied. HTR8 cells transfected to express a TLR8 dominant negative (DN) were also used. Plasma was evaluated from pregnant women who have aPL, either with or without systemic lupus erythematous (SLE) (n = 39); SLE patients without aPL (n = 30); and healthy pregnant controls (n = 20). Trophoblast HTR8 wildtype and TLR8-DN cells were incubated with or without aPL (mouse anti-human β2GPI mAb) for 48-72 h. HTR8 cells were also treated with or without aPL in the presence and the absence of a TLR4 antagonist (lipopolysaccharide from Rhodobacter sphaeroides; LPS-RS), specific miR inhibitors or specific miR mimics. miR expression levels in trophoblast cells, trophoblast-derived exosomes and exosomes isolated from patient plasma were measured by qPCR. Trophoblast IL-8 secretion was

  6. Temporal and spatial expression of matrix metalloproteinase-2 and matrix metalloproteinase-9 in trophoblast and endometrial epithelium during pregnancy of pig

    Czech Academy of Sciences Publication Activity Database

    Georgieva, R.; Rashev, P.; Pěknicová, Jana; Michailova, A.

    2004-01-01

    Roč. 52, Suppl.1 (2004), s. 42-43 ISSN 1046-7408. [International Congress of Reproductive Immunology /9./. Hakone, 11.10.2004-15.10.2004] Institutional research plan: CEZ:AV0Z5052915 Keywords : matrix metalloproteinase * trophoblast * endometrium Subject RIV: EC - Immunology Impact factor: 1.808, year: 2004

  7. A Primary Human Trophoblast Model to Study the Effect of Inflammation Associated with Maternal Obesity on Regulation of Autophagy in the Placenta.

    Science.gov (United States)

    Simon, Bailey; Bucher, Matthew; Maloyan, Alina

    2017-09-27

    Maternal obesity is associated with an increased risk of adverse perinatal outcomes that are likely mediated by compromised placental function that can be attributed to, in part, the dysregulation of autophagy. Aberrant changes in the expression of autophagy regulators in the placentas from obese pregnancies may be regulated by inflammatory processes associated with both obesity and pregnancy. Described here is a protocol for sampling of villous tissue and isolation of villous cytotrophoblasts from the term human placenta for primary cell culture. This is followed by a method for simulating the inflammatory milieu in the obese intrauterine environment by treating primary trophoblasts from lean pregnancies with tumor necrosis factor alpha (TNFα), a proinflammatory cytokine that is elevated in obesity and in pregnancy. Through the implementation of the protocol described here, it is found that exposure to exogenous TNFα regulates the expression of Rubicon, a negative regulator of autophagy, in trophoblasts from lean pregnancies with female fetuses. While a variety of biological factors in the obese intrauterine environment maintain the potential to modulate critical pathways in trophoblasts, this ex vivo system is especially useful for determining if expression patterns observed in vivo in human placentas with maternal obesity are a direct result of TNFα signaling. Ultimately, this approach affords the opportunity to parse out the regulatory and molecular implications of inflammation associated with maternal obesity on autophagy and other critical cellular pathways in trophoblasts that have the potential to impact placental function.

  8. Mutations within the LINC-HELLP non-coding RNA differentially bind ribosomal and RNA splicing complexes and negatively affect trophoblast differentiation

    NARCIS (Netherlands)

    van Dijk, M.; Visser, A.; Buabeng, K.M.L.; Poutsma, A.; van der Schors, R.C.; Oudejans, C.B.M.

    2015-01-01

    LINC-HELLP, showing chromosomal linkage with the pregnancy-specific HELLP syndrome in Dutch families, reduces differentiation from a proliferative to an invasive phenotype of first-trimester extravillous trophoblasts. Here we show that mutations in LINC-HELLP identified in HELLP families negatively

  9. Role of prostate apoptosis response 4 in translocation of GRP78 from the endoplasmic reticulum to the cell surface of trophoblastic cells.

    Directory of Open Access Journals (Sweden)

    Marie Cohen

    Full Text Available Glucose-regulated protein 78 (GRP78 is an endoplasmic reticulum (ER molecular chaperone that belongs to the heat shock protein 70 family. GRP78 is also present on the cell surface membrane of trophoblastic cells, where it is associated with invasive or fusion properties of these cells. Impaired mechanism of GRP78 relocation from ER to the cell surface was observed in preeclamptic cytotrophoblastic cells (CTB and could take part in the pathogenesis of preeclampsia. In this study, we have investigated whether prostate apoptosis response 4 (Par-4, a protein identified as a partner of GRP78 relocation to the cell surface in prostate cancer cells, is present in trophoblastic cells and is involved in the translocation of GRP78 to the cell surface of CTB. Par-4 is indeed present in trophoblastic cells and its expression correlates with expression of membrane GRP78. Moreover, overexpression of Par-4 led to an increase of cell surface expression of GRP78 and decreased Par-4 gene expression reduced cell surface localization of GRP78 confirming a role of Par-4 in relocation of GRP78 from ER to the cell surface. Accordingly, invasive property was modified in these cells. In conclusion, we show that Par-4 is expressed in trophoblastic cells and is involved in transport of GRP78 to the cell surface and thus regulates invasive property of extravillous CTB.

  10. The STOX1 genotype associated with pre-eclampsia leads to a reduction of trophoblast invasion by alpha-T-catenin upregulation

    NARCIS (Netherlands)

    van Dijk, Marie; van Bezu, Jan; van Abel, Daan; Dunk, Caroline; Blankenstein, Marinus A.; Oudejans, Cees B. M.; Lye, Stephen J.

    2010-01-01

    By using complementary in vitro and ex vivo approaches, we show that the risk allele (Y153H) of the pre-eclampsia susceptibility gene STOX1 negatively regulates trophoblast invasion by upregulation of the cell-cell adhesion protein alpha-T-catenin (CTNNA3). This is effectuated at the crucial

  11. Identification of differences in gene expression in primary cell cultures of human endometrial epithelial cells and trophoblast cells following their interaction

    DEFF Research Database (Denmark)

    Høgh, Mette; Islin, Henrik; Møller, Charlotte

    2006-01-01

    The interaction between the cell types was simulated in vitro by growing primary cell cultures of human endometrial epithelial cells and trophoblast cells together (co-culture) and separately (control cultures). Gene expression in the cell cultures was compared using the Differential Display method and confirmed...

  12. Identification of patients with persistent trophoblastic disease after complete hydatidiform mole by using a normal 24-hour urine hCG regression curve

    NARCIS (Netherlands)

    Cromvoirt, S.M. van; Thomas, C.M.G.; Quinn, M.A.; McNally, O.M.; Bekkers, R.L.M.

    2014-01-01

    OBJECTIVE: The aim of this study was to establish a reference 24-hour urine human chorionic gonadotropin (hCG) regression curve in patients with complete hydatidiform mole (CHM) as diagnostic tool in the prediction of persistent trophoblastic disease (PTD). METHODS: From 2004 to 2011, 312 cases

  13. Concurrent endocrine neoplasias in dogs and cats: a retrospective study (2004-2014).

    Science.gov (United States)

    Beatrice, Laura; Boretti, Felicitas Schär; Sieber-Ruckstuhl, Nadja S; Mueller, Claudia; Kümmerle-Fraune, Claudia; Hilbe, Monika; Grest, Paula; Reusch, Claudia E

    2018-03-17

    Multiple endocrine neoplasia (MEN) is a well-known syndrome in human medicine, whereas only a few cases of concurrent endocrine neoplasias have been reported in dogs and cats. The aim of this study was to evaluate the prevalence of concurrent endocrine neoplasias in dogs and cats at our clinic, identify possible breed and sex predispositions and investigate similarities with MEN syndromes in humans. Postmortem reports of 951 dogs and 1155 cats that died or were euthanased at the Clinic for Small Animal Internal Medicine, University of Zurich, between 2004 and 2014 were reviewed, and animals with at least two concurrent endocrine neoplasias and/or hyperplasias were included. Twenty dogs and 15 cats met the inclusion criteria. In dogs, the adrenal glands were most commonly affected. Multiple tumours affecting the adrenal glands and the association of these tumours with pituitary adenomas were the most common tumour combinations. Only one dog had a combination resembling human MEN type 1 syndrome (pituitary adenoma and insulinoma). In cats, the thyroid glands were most commonly affected and there were no similarities to human MEN syndromes. The prevalence of concurrent endocrine neoplasia was 2.1 per cent in dogs and 1.3 per cent in cats and MEN-like syndromes are very rare in these species. © British Veterinary Association (unless otherwise stated in the text of the article) 2018. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

  14. Defining the genetic susceptibility to cervical neoplasia-A genome-wide association study.

    Directory of Open Access Journals (Sweden)

    Paul J Leo

    2017-08-01

    Full Text Available A small percentage of women with cervical HPV infection progress to cervical neoplasia, and the risk factors determining progression are incompletely understood. We sought to define the genetic loci involved in cervical neoplasia and to assess its heritability using unbiased unrelated case/control statistical approaches. We demonstrated strong association of cervical neoplasia with risk and protective HLA haplotypes that are determined by the amino-acids carried at positions 13 and 71 in pocket 4 of HLA-DRB1 and position 156 in HLA-B. Furthermore, 36% (standard error 2.4% of liability of HPV-associated cervical pre-cancer and cancer is determined by common genetic variants. Women in the highest 10% of genetic risk scores have approximately >7.1% risk, and those in the highest 5% have approximately >21.6% risk, of developing cervical neoplasia. Future studies should examine genetic risk prediction in assessing the risk of cervical neoplasia further, in combination with other screening methods.

  15. Birth Weight, Gestational Age, and Infantile Colic

    DEFF Research Database (Denmark)

    Milidou, Ioanna; Søndregaard, Charlotte; Jensen, Morten Søndergaard

    Background Infantile colic is a condition of unknown origin characterized by paroxysms of crying during the first months of life. A few studies have identified low birth weight (BW) as a risk factor among infants born at term, while the association between gestational age (GA) and infantile colic...... interviews of the mother during pregnancy and post partum. Adjusted odds ratios (OR) with 95% confidence intervals (in brackets) are presented. Infantile colic was defined as crying for more than three hours per day and for more than three days per week (modified Wessel’s criteria). Results A total of 4...... with GA gestational weeks 32-40. Finally, after adjusting for GA...

  16. In Vivo Chromatin Targets of the Transcription Factor Yin Yang 2 in Trophoblast Stem Cells

    Science.gov (United States)

    Pérez-Palacios, Raquel; Macías-Redondo, Sofía; Climent, María; Contreras-Moreira, Bruno; Muniesa, Pedro; Schoorlemmer, Jon

    2016-01-01

    Background Yin Yang 2 (YY2) is a zinc finger protein closely related to the well-characterized Yin Yang 1 (YY1). YY1 is a DNA-binding transcription factor, with defined functions in multiple developmental processes, such as implantation, cell differentiation, X inactivation, imprinting and organogenesis. Yy2 has been treated as a largely immaterial duplication of Yy1, as they share high homology in the Zinc Finger-region and similar if not identical in vitro binding sites. In contrast to these similarities, gene expression alterations in HeLa cells with attenuated levels of either Yy1 or Yy2 were to some extent gene-specific. Moreover, the chromatin binding sites for YY2, except for its association with transposable retroviral elements (RE) and Endogenous Retroviral Elements (ERVs), remain to be identified. As a first step towards defining potential Yy2 functions matching or complementary to Yy1, we considered in vivo DNA binding sites of YY2 in trophoblast stem (TS) cells. Results We report the presence of YY2 protein in mouse-derived embryonic stem (ES) and TS cell lines. Following up on our previous report on ERV binding by YY2 in TS cells, we investigated the tissue-specificity of REX1 and YY2 binding and confirm binding to RE/ERV targets in both ES cells and TS cells. Because of the higher levels of expression, we chose TS cells to understand the role of Yy2 in gene and chromatin regulation. We used in vivo YY2 association as a measure to identify potential target genes. Sequencing of chromatin obtained in chromatin-immunoprecipitation (ChIP) assays carried out with αYY2 serum allowed us to identify a limited number of chromatin targets for YY2. Some putative binding sites were validated in regular ChIP assays and gene expression of genes nearby was altered in the absence of Yy2. Conclusions YY2 binding to ERVs is not confined to TS cells. In vivo binding sites share the presence of a consensus binding motif. Selected sites were uniquely bound by YY2 as

  17. Overexpression of Endogenous Anti-Oxidants with Selenium Supplementation Protects Trophoblast Cells from Reactive Oxygen Species-Induced Apoptosis in a Bcl-2-Dependent Manner.

    Science.gov (United States)

    Khera, Alisha; Vanderlelie, Jessica J; Holland, Olivia; Perkins, Anthony V

    2017-06-01

    The human placenta provides life support for the developing foetus, and a healthy placenta is a prerequisite to a healthy start to life. Placental tissue is subject to oxidative stress which can lead to pathological conditions of pregnancy such as preeclampsia, preterm labour and intrauterine growth restriction. Up-regulation of endogenous anti-oxidants may alleviate placental oxidative stress and provide a therapy for these complications of pregnancy. In this study, selenium supplementation, as inorganic sodium selenite (NaSel) or organic selenomethionine (SeMet), was used to increase the protein production and cellular activity of the important redox active proteins glutathione peroxidase (GPx) and thioredoxin reductase (Thx-Red). Placental trophoblast cell lines, BeWo, JEG-3 and Swan-71, were cultured in various concentrations of NaSel or SeMet for 24 h and cell extracts prepared for western blots and enzyme assays. Rotenone and antimycin were used to stimulate mitochondrial reactive oxygen species (ROS) production and induce apoptosis. Trophoblast cells supplemented with 100 nM NaSel and 500 nM SeMet exhibited significantly enhanced expression and activity of both GPx and Thx-Red. Antimycin and rotenone were found to generate ROS when measured by 2',7'-dichlorofluorescein diacetate (DCFDA) assay, and selenium supplementation was shown to reduce ROS production in a dose-dependent manner. Rotenone, 100 μM treatment for 4 h, caused trophoblast cell apoptosis as evidenced by increased Annexin V binding and decreased expression of Bcl-2. In both assays of apoptosis, selenium supplementation was able to prevent apoptosis, preserve Bcl-2 expression and protect trophoblast cells from mitochondrial oxidative stress. This data suggests that selenoproteins such as GPx and Thx-Red have an important role in protecting trophoblast cells from mitochondrial oxidative stress and that selenium supplementation may be important in treating some placental pathologies.

  18. Comparative studies of placentation and immunology in non-human primates suggest a scenario for the evolution of deep trophoblast invasion and an explanation for human pregnancy disorders.

    Science.gov (United States)

    Carter, Anthony M

    2011-04-01

    Deep trophoblast invasion in the placental bed has been considered the hallmark of human pregnancy. It occurs by two routes, interstitial and endovascular, and results in transformation of the walls of the spiral arteries as they traverse the decidua and the inner third of the myometrium. Disturbances in this process are associated with reproductive disorders such preeclampsia. In contrast, trophoblast invasion in Old World monkeys occurs only by the endovascular route and seldom reaches the myometrium. Recently, it was shown that this pattern is maintained in gibbons, but that the human arrangement also occurs in chimpanzee and gorilla. There is an interesting parallel with results from placental immunology regarding the evolution of the major histocompatability complex class I antigen HLA-C and its cognate receptors. HLA-C is not present in Old World monkeys or gibbons. It emerged in the orangutan and became polymorphic in the lineage leading to gorilla, bonobo, chimpanzee, and human. Interaction between HLA-C1 and HLA-C2 on the surface of trophoblast and killer immunoglobulin-like receptors (KIRs) expressed by uterine natural killer cells are important regulators of trophoblast invasion. Evolution of this system in great apes may have been one prerequisite for deep trophoblast invasion but seems to have come at a price. The evidence now suggests that certain combinations of maternal genotype for KIRs and fetal genotype for HLA-C imply an increased risk of preeclampsia, fetal growth restriction, and recurrent abortion. The fetal genotype is in part derived from the father providing an explanation for the paternal contribution to reproductive disorders.

  19. miR-346 and miR-582-3p-regulated EG-VEGF expression and trophoblast invasion via matrix metalloproteinases 2 and 9.

    Science.gov (United States)

    Su, Mei-Tsz; Tsai, Pei-Yin; Tsai, Hui-Ling; Chen, Yi-Chi; Kuo, Pao-Lin

    2017-03-01

    Endocrine gland-derived vascular endothelial growth factor (EG-VEGF) is an important regulator for embryo implantation and placental development, and is clinically associated with several obstetric disorders related to insufficient or inappropriate trophoblast invasion, such as recurrent abortion, preeclampsia, and intrauterine fetal growth restriction. This study was performed to identify the microRNAs targeting EG-VEGF, and evaluate the regulatory effect on trophoblast biology. miR-346 and miR-582-3p were initially identified via bioinformatic tools, and their specific binding sites on the EG-VEGF 3'UTR were further confirmed using dual luciferase and a co-transfection assays. miR-346 and miR-582-3p were demonstrated not only to suppress EG-VEGF expression, but also inhibit trophoblast invasion and migration in the JAR and HTR-8/SVneo cell lines. We further evaluated the effect of microRNAs in HTR-8/SVneo cells coexpressing EG-VEGF and miR-346 or miR-582-3p on matrix metalloproteinase (MMP 2 and MMP 9) and the tissue inhibitors of metalloproteinase (TIMP 1 and TIMP 2) using RT-PCR, western blotting and gelatin zymography. TIMP 1 and TIMP 2 were not affected by the two microRNAs, whereas the expressions and activities of MMP 2 and MMP 9 were significantly downregulated, which in turn inhibited the invasion ability of trophoblasts. In conclusion, miR-346 and miR-582-3p regulate EG-VEGF-induced trophoblast invasion through repressing MMP 2 and MMP 9, and may become novel diagnostic biomarkers or therapeutic targets for EG-VEGF-related obstetric disorders. © 2016 BioFactors, 43(2):210-219, 2017. © 2016 International Union of Biochemistry and Molecular Biology.

  20. High-Fibre feeding in gestation

    NARCIS (Netherlands)

    Meunier-Salaün, M.C.; Bolhuis, J.E.

    2015-01-01

    Gestating sows are usually fed low levels of feed, which may not provide sufficient satiety, and does not allow sows to fully fulfil their motivation to express foraging and feeding behaviours. Feed restriction may therefore lead to high occurrences of non-feeding oral activities, including

  1. Mothers after Gestational Diabetes in Australia (MAGDA)

    DEFF Research Database (Denmark)

    O’Reilly, Sharleen L.; Dunbar, James A.; Versace, Vincent

    2016-01-01

    Background: Gestational diabetes mellitus (GDM) is an increasingly prevalent risk factor for type 2 diabetes. We evaluated the effectiveness of a group-based lifestyle modification program in mothers with prior GDM within their first postnatal year. Methods and Findings: In this study, 573 women...

  2. Serum chromium levels in gestational diabetes mellitus

    Directory of Open Access Journals (Sweden)

    P G Sundararaman

    2012-01-01

    Full Text Available Objective: To measure serum chromium level in women with gestational diabetes mellitus (GDM from Chennai, South India. Materials and Methods: Thirty women with gestational diabetes, 60 age matched controls. Inclusion criteria: Gestational age 22-28 weeks, age group 20-35 years. Exclusion Criteria: Gestational age beyond 28 weeks, malnutrition or presence of infection. Serum chromium was measured using inductive couple plasma emission spectrometer. Results: Serum chromium levels of women with GDM, 1.59+/-0.02 ng/ml (range: 0.16-4.0 ng/ml were lower than in controls (4.58+/-0.62 ng/ml; range 0.82-5.33 ng/ml (P < 0.001. However, there were no significant differences among cases and controls when subdivided by parity. Conclusions: Women with GDM from a South Indian city had lower levels of serum chromium compared to pregnant women without GDM. Studies may be done whether chromium supplementation is useful in this group of women.

  3. Gestation period and twinning in chimpanzees.

    Science.gov (United States)

    PEACOCK, L J; ROGERS, C M

    1959-04-10

    The length of the gestation period in 118 births in a colony of chimpanzees was found to be 226.8 days, with a standard deviation of 13.3 and a range of 196 to 260 days. Six pairs of twins were born in 120 parturitions; thus the apparent twinning rate is higher than that in man.

  4. Iron, Oxidative Stress and Gestational Diabetes

    Directory of Open Access Journals (Sweden)

    Taifeng Zhuang

    2014-09-01

    Full Text Available Both iron deficiency and hyperglycemia are highly prevalent globally for pregnant women. Iron supplementation is recommended during pregnancy to control iron deficiency. The purposes of the review are to assess the oxidative effects of iron supplementation and the potential relationship between iron nutrition and gestational diabetes. High doses of iron (~relative to 60 mg or more daily for adult humans can induce lipid peroxidation in vitro and in animal studies. Pharmaceutical doses of iron supplements (e.g., 10× RDA or more for oral supplements or direct iron supplementation via injection or addition to the cell culture medium for a short or long duration will induce DNA damage. Higher heme-iron intake or iron status measured by various biomarkers, especially serum ferritin, might contribute to greater risk of gestational diabetes, which may be mediated by iron oxidative stress though lipid oxidation and/or DNA damage. However, information is lacking about the effect of low dose iron supplementation (≤60 mg daily on lipid peroxidation, DNA damage and gestational diabetes. Randomized trials of low-dose iron supplementation (≤60 mg daily for pregnant women are warranted to test the relationship between iron oxidative stress and insulin resistance/gestational diabetes, especially for iron-replete women.

  5. Gestational surrogacy: Viewpoint of Iranian infertile women.

    Science.gov (United States)

    Rahmani, Azad; Sattarzadeh, Nilofar; Gholizadeh, Leila; Sheikhalipour, Zahra; Allahbakhshian, Atefeh; Hassankhani, Hadi

    2011-09-01

    Surrogacy is a popular form of assisted reproductive technology of which only gestational form is approved by most of the religious scholars in Iran. Little evidence exists about the Iranian infertile women's viewpoint regarding gestational surrogacy. To assess the viewpoint of Iranian infertile women toward gestational surrogacy. This descriptive study was conducted at the infertility clinic of Tabriz University of Medical Sciences, Iran. The study sample consisted of 238 infertile women who were selected using the eligible sampling method. Data were collected by using a researcher developed questionnaire that included 25 items based on a five-point Likert scale. Data analysis was conducted by SPSS statistical software using descriptive statistics. Viewpoint of 214 women (89.9%) was positive. 36 (15.1%) women considered gestational surrogacy against their religious beliefs; 170 women (71.4%) did not assume the commissioning couple as owners of the baby; 160 women (67.2%) said that children who were born through surrogacy would better not know about it; and 174 women (73.1%) believed that children born through surrogacy will face mental problems. Iranian infertile women have positive viewpoint regarding the surrogacy. However, to increase the acceptability of surrogacy among infertile women, further efforts are needed.

  6. Gestational surrogacy: Viewpoint of Iranian infertile women

    Directory of Open Access Journals (Sweden)

    Azad Rahmani

    2011-01-01

    Full Text Available Background: Surrogacy is a popular form of assisted reproductive technology of which only gestational form is approved by most of the religious scholars in Iran. Little evidence exists about the Iranian infertile women′s viewpoint regarding gestational surrogacy. Aim: To assess the viewpoint of Iranian infertile women toward gestational surrogacy. Setting and Design: This descriptive study was conducted at the infertility clinic of Tabriz University of Medical Sciences, Iran. Materials and Methods: The study sample consisted of 238 infertile women who were selected using the eligible sampling method. Data were collected by using a researcher developed questionnaire that included 25 items based on a five-point Likert scale. 0 Statistical Analysis: Data analysis was conducted by SPSS statistical software using descriptive statistics. 0 Results: Viewpoint of 214 women (89.9% was positive. 36 (15.1% women considered gestational surrogacy against their religious beliefs; 170 women (71.4% did not assume the commissioning couple as owners of the baby; 160 women (67.2% said that children who were born through surrogacy would better not know about it; and 174 women (73.1% believed that children born through surrogacy will face mental problems. Conclusion: Iranian infertile women have positive viewpoint regarding the surrogacy. However, to increase the acceptability of surrogacy among infertile women, further efforts are needed.

  7. Screening for gestational diabetes in Europe

    DEFF Research Database (Denmark)

    Benhalima, Katrien; Damm, Peter; van Assche, Andre

    2016-01-01

    The incidence of gestational diabetes (GDM) is rising globally and it represents an important modifiable risk factor for adverse pregnancy outcomes. GDM is also associated with negative long-term health outcomes for both mothers and offspring. Acceptance and implementation of the 2013 World Health...

  8. Gestational Age and Autism Spectrum Disorder

    DEFF Research Database (Denmark)

    Atladóttir, H Ó; Schendel, D.E.; Henriksen, T B

    2016-01-01

    Autism Spectrum Disorder (ASD) is a serious neurodevelopmental disorder. Several previous studies have identified pre-term birth as a risk factor for ASD but none has studied whether the association between gestational age and ASD has changed over time. This is a Danish population-based follow...

  9. an alternative therapy for gestational diabetes mellitus

    African Journals Online (AJOL)

    Toxic effects of glibenclamide in fetuses of normoglycemic rats: an alternative therapy for gestational diabetes mellitus. ... However, GLIB animals presented a light brownish precipitate into the center-lobular veins and in the liver parenchyma among the hepatocytes. These results indicated a possible passage of the drug ...

  10. Genetics Home Reference: X-linked immunodeficiency with magnesium defect, Epstein-Barr virus infection, and neoplasia

    Science.gov (United States)

    ... Conditions XMEN X-linked immunodeficiency with magnesium defect, Epstein-Barr virus infection, and neoplasia Printable PDF Open All Close ... boxes. Description X-linked immunodeficiency with magnesium defect, Epstein-Barr virus infection, and neoplasia (typically known by the acronym ...

  11. Immunohistochemical localization of human papilloma virus in conjunctival neoplasias: A retrospective study

    Science.gov (United States)

    Sharma, Anjana; Panda, Anita

    2007-01-01

    Background: The extent of association of human papilloma virus (HPV) in human conjunctival neoplasias has been debated in studies originating from different parts of the world, but no substantial evidence has been generated on Indian subjects. This prompted us to carry out a retrospective study on conjunctival neoplasias diagnosed over the past 12 years. Materials and Methods: Histopathological and immunohistochemical analysis of 65 specimens of ocular neoplasias and 30 normal controls diagnosed between 1991 and 2002 at a tertiary eye care hospital, was undertaken. Formalin-fixed, paraffin-embedded tissues were reviewed for confirming histopathological diagnosis, presence of koilocytosis and changes related to actinic keratosis. Immunohistochemical analysis was done using HPV-specific monoclonal antibodies. Clinicopathological correlation and the association of HPV antigen with the histopathological features were performed. Results: Out of the 65 cases analyzed, 35 were papillomas and 30 were ocular surface squamous neoplasias (OSSN). The mean age was 48 years with a male preponderance. Histologically, koilocytosis was observed in 17.1% of papillomas and 36.6% of OSSN. Actinic keratosis was present in 33% of OSSN. Immunohistochemically 17.1% conjunctival papillomas stained positive for HPV antigen, all cases of OSSN were negative for HPV. There was no correlation between koilocytosis or actinic keratosis and the detection of HPV antigen. Conclusions: The association between HPV and conjunctival neoplasias is variable in different geographical areas and also depends on the methods of detection used. This study warrants the need for applying more advanced techniques at a molecular level to determine the possible etiology of HPV in conjunctival neoplasias among Asian-Indians. PMID:17699945

  12. Clinical significance of serum anti-human papillomavirus 16 and 18 antibodies in cervical neoplasia.

    Science.gov (United States)

    Chay, Doo Byung; Cho, Hanbyoul; Kim, Bo Wook; Kang, Eun Suk; Song, Eunseop; Kim, Jae-Hoon

    2013-02-01

    To estimate the clinical significance of serum anti-human papillomavirus (HPV) antibodies and high-risk cervical HPV DNA in cervical neoplasia. The study population comprised patients who were histopathologically diagnosed with cervical intraepithelial neoplasia (CIN) 1 (n=64), CIN 2 and 3 (n=241), cervical cancer (n=170), and normal control participants (n=975). Cervical HPV DNA tests were performed through nucleic acid hybridization assay tests, and serum anti-HPV 16 and 18 antibodies were measured by competitive immunoassay. The associations of HPV DNA and anti-HPV antibodies were evaluated with demographic characteristics and compared according to the levels of disease severity. Anti-HPV antibodies were also investigated with clinicopathologic parameters, including survival data. Among various demographic characteristics, factors involving sexual behavior had a higher tendency of HPV DNA positivity and HPV seropositivity. Human papillomavirus DNA mean titer and positivity were both increased in patients with cervical neoplasia compared with those with normal control participants, but there was no statistical difference among types of cervical neoplasia. Serum anti-HPV 16 antibodies were also able to differentiate cervical neoplasia from a normal control participant and furthermore distinguished CIN 1 from CIN 2 and 3 (odd ratio 2.87 [1.43-5.78], P=.002). In cervical cancer, HPV 16 seropositivity was associated with prolonged disease-free survival according to the univariable analysis (hazard ratio=0.12 [0.01-0.94], P=.044). Serum anti-HPV 16 antibodies can distinguish cervical neoplasia from a normal control and has the advantage of identifying high-grade CIN. Moreover, in cervical cancer, HPV 16 seropositivity may be associated with a more favorable prognosis. II.

  13. Parathyroid mitogenic activity in plasma from patients with familial multiple endocrine neoplasia type 1

    International Nuclear Information System (INIS)

    Brandi, M.L.; Aurbach, G.D.; Fitzpatrick, L.A.; Quarto, R.; Spiegel, A.M.; Bliziotes, M.M.; Norton, J.A.; Doppman, J.L.; Marx, S.J.

    1986-01-01

    Hyperplasia of the parathyroid glands is a central feature of familial multiple endocrine neoplasia type 1. We used cultured bovine parathyroid cells to test for mitogenic activity in plasma from patients with this disorder. Normal plasma stimulated [ 3 H]thymidine incorporation, on the average, to the same extent as it was stimulated in a plasma-free control culture. This contrasted with the results of the tests with plasma from patients with familial multiple endocrine neoplasia type 1, in which parathyroid mitogenic activity increased 2400 percent over the control value (P less than 0.001). Plasma from these patients also stimulated the proliferation of bovine parathyroid cells in culture, whereas plasma from normal subjects inhibited it. Parathyroid mitogenic activity in plasma from the patients with familial multiple endocrine neoplasia type 1 was greater than that in plasma from patients with various other disorders, including sporadic primary hyperparathyroidism (with adenoma, hyperplasia, or cancer of the parathyroid), sporadic primary hypergastrinemia, sporadic pituitary tumor, familial hypocalciuric hypercalcemia, and multiple endocrine neoplasia type 2 (P less than 0.05). Parathyroid mitogenic activity in the plasma of patients with familial multiple endocrine neoplasia type 1 persisted for up to four years after total parathyroidectomy. The plasma also had far more mitogenic activity in cultures of parathyroid cells than did optimal concentrations of known growth factors or of any parathyroid secretagogue. This mitogenic activity had an apparent molecular weight of 50,000 to 55,000. We conclude that primary hyperparathyroidism in familial multiple endocrine neoplasia type 1 may have a humoral cause

  14. Involvement of reactive oxygen species in brominated diphenyl ether-47-induced inflammatory cytokine release from human extravillous trophoblasts in vitro

    International Nuclear Information System (INIS)

    Park, Hae-Ryung; Kamau, Patricia W.; Loch-Caruso, Rita

    2014-01-01

    Polybrominated diphenyl ethers (PBDEs) are widely used flame retardant compounds. Brominated diphenyl ether (BDE)-47 is one of the most prevalent PBDE congeners found in human breast milk, serum and placenta. Despite the presence of PBDEs in human placenta, effects of PBDEs on placental cell function are poorly understood. The present study investigated BDE-47-induced reactive oxygen species (ROS) formation and its role in BDE-47-stimulated proinflammatory cytokine release in a first trimester human extravillous trophoblast cell line, HTR-8/SVneo. Exposure of HTR-8/SVneo cells for 4 h to 20 μM BDE-47 increased ROS generation 1.7 fold as measured by the dichlorofluorescein (DCF) assay. Likewise, superoxide anion production increased approximately 5 fold at 10 and 15 μM and 9 fold at 20 μM BDE-47 with a 1-h exposure, as measured by cytochrome c reduction. BDE-47 (10, 15 and 20 μM) decreased the mitochondrial membrane potential by 47–64.5% at 4, 8 and 24 h as assessed with the fluorescent probe Rh123. Treatment with 15 and 20 μM BDE-47 stimulated cellular release and mRNA expression of IL-6 and IL-8 after 12 and 24-h exposures: the greatest increases were a 35-fold increased mRNA expression at 12 h and a 12-fold increased protein concentration at 24 h for IL-6. Antioxidant treatments (deferoxamine mesylate, (±)α-tocopherol, or tempol) suppressed BDE-47-stimulated IL-6 release by 54.1%, 56.3% and 37.7%, respectively, implicating a role for ROS in the regulation of inflammatory pathways in HTR-8/SVneo cells. Solvent (DMSO) controls exhibited statistically significantly decreased responses compared with non-treated controls for IL-6 release and IL-8 mRNA expression, but these responses were not consistent across experiments and times. Nonetheless, it is possible that DMSO (used to dissolve BDE-47) may have attenuated the stimulatory actions of BDE-47 on cytokine responses. Because abnormal activation of proinflammatory responses can disrupt trophoblast functions

  15. Involvement of reactive oxygen species in brominated diphenyl ether-47-induced inflammatory cytokine release from human extravillous trophoblasts in vitro

    Energy Technology Data Exchange (ETDEWEB)

    Park, Hae-Ryung, E-mail: heaven@umich.edu; Kamau, Patricia W.; Loch-Caruso, Rita

    2014-01-15

    Polybrominated diphenyl ethers (PBDEs) are widely used flame retardant compounds. Brominated diphenyl ether (BDE)-47 is one of the most prevalent PBDE congeners found in human breast milk, serum and placenta. Despite the presence of PBDEs in human placenta, effects of PBDEs on placental cell function are poorly understood. The present study investigated BDE-47-induced reactive oxygen species (ROS) formation and its role in BDE-47-stimulated proinflammatory cytokine release in a first trimester human extravillous trophoblast cell line, HTR-8/SVneo. Exposure of HTR-8/SVneo cells for 4 h to 20 μM BDE-47 increased ROS generation 1.7 fold as measured by the dichlorofluorescein (DCF) assay. Likewise, superoxide anion production increased approximately 5 fold at 10 and 15 μM and 9 fold at 20 μM BDE-47 with a 1-h exposure, as measured by cytochrome c reduction. BDE-47 (10, 15 and 20 μM) decreased the mitochondrial membrane potential by 47–64.5% at 4, 8 and 24 h as assessed with the fluorescent probe Rh123. Treatment with 15 and 20 μM BDE-47 stimulated cellular release and mRNA expression of IL-6 and IL-8 after 12 and 24-h exposures: the greatest increases were a 35-fold increased mRNA expression at 12 h and a 12-fold increased protein concentration at 24 h for IL-6. Antioxidant treatments (deferoxamine mesylate, (±)α-tocopherol, or tempol) suppressed BDE-47-stimulated IL-6 release by 54.1%, 56.3% and 37.7%, respectively, implicating a role for ROS in the regulation of inflammatory pathways in HTR-8/SVneo cells. Solvent (DMSO) controls exhibited statistically significantly decreased responses compared with non-treated controls for IL-6 release and IL-8 mRNA expression, but these responses were not consistent across experiments and times. Nonetheless, it is possible that DMSO (used to dissolve BDE-47) may have attenuated the stimulatory actions of BDE-47 on cytokine responses. Because abnormal activation of proinflammatory responses can disrupt trophoblast functions

  16. Allelic imbalance modulates surface expression of the tolerance-inducing HLA-G molecule on primary trophoblast cells.

    Science.gov (United States)

    Djurisic, S; Teiblum, S; Tolstrup, C K; Christiansen, O B; Hviid, T V F

    2015-03-01

    The HLA-G molecule is expressed on trophoblast cells at the feto-maternal interface, where it interacts with local immune cells, and upholds tolerance against the semi-allogeneic fetus. Aberrant HLA-G expression in the placenta and reduced soluble HLA-G levels are observed in pregnancy complications, partly explained by HLA-G polymorphisms which are associated with differences in the alternative splicing pattern and of the stability of HLA-G mRNA. Of special importance is a 14 bp insertion/deletion polymorphism located in the 3'-untranslated region of the HLA-G gene. In the current study, we present novel evidence for allelic imbalance of the 14 bp insertion/deletion polymorphism, using a very accurate and sensitive Digital droplet PCR technique. Allelic imbalance in heterozygous samples was observed as differential expression levels of 14 bp insertion/deletion allele-specific mRNA transcripts, which was further associated with low levels of HLA-G surface expression on primary trophoblast cells. Full gene sequencing of HLA-G allowed us to study correlations between HLA-G extended haplotypes and single-nucleotide polymorphisms and HLA-G surface expression. We found that a 1:1 expression (allelic balance) of the 14 bp insertion/deletion mRNA alleles was associated with high surface expression of HLA-G and with a specific HLA-G extended haplotype. The 14 bp del/del genotype was associated with a significantly lower abundance of the G1 mRNA isoform, and a higher abundance of the G3 mRNA isoform. Overall, the present study provides original evidence for allelic imbalance of the 14 bp insertion/deletion polymorphism, which influences HLA-G surface expression on primary trophoblast cells, considered to be important in the pathogenesis of pre-eclampsia and other pregnancy complications. © The Author 2014. Published by Oxford University Press on behalf of the European Society of Human Reproduction and Embryology. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

  17. Fluoxetine effect on gestation and fetal development

    Directory of Open Access Journals (Sweden)

    Ösz Bianca Eugenia

    2014-08-01

    Full Text Available The prenatal exposure to selective serotonin reuptake inhibitors (SSRIs is very controversial. There is no conclusive evidence for increased risk of malformations after SSRI use in pregnancy. The aim of the study was to determine how fluoxetine is affecting gestation and fetal development in rats. Twenty sexually mature female Wistar rats weighting between 250-260 g received 20 mg/kg body weight fluoxetine from the first day of gestation and during the entire gestation period.The drug was administered by oral route. Healthy, primipareus animals were selected along with 20 female Wistar rats, as control group. Mature males were caged with virgin females for an entire week. Rat’s behaviour during gestation, after birth and rats body weight was examined. The number of healthy pups was also noted. The females not giving birth after 21 days to any pup were anesthetized (halothane through gas scavenging apparatus untilled death and the gravid uterus were dissected out and examined. Compared to the controlled group, in which weight gain was more significant, the animals from the experimental group had a slight increase in body weight. The weight gain normally induced by gestation, is less significant in fluoxetine treated rats due to the increase serotonin levels in the brain. The uteri examination of pregnant rats showed an increase in the number of dead and resorbed rat embryos. Preclinical studies suggest that the inclusion of fluoxetine in pregnancy category C is justified and the appropriateness of its administration in pregnancy is still an unresolved issue.

  18. The prognostic significance of virus-associated changes in grade 1 cervical intra-epithelial neoplasia

    DEFF Research Database (Denmark)

    Bagi, P; Worning, A M; Nordsten, M

    1987-01-01

    Virus-associated changes of the cervix uteri were assessed in patients treated for grade 1 cervical intra-epithelial neoplasia (CIN). Of 106 patients evaluated, 67 (63%) had virus-associated changes. The patients were treated without regard to the presence/absence of virus-associated changes. In 26...... patients the treatment was unsuccessful (persistence, recurrence, or progression of the neoplasia). The frequency of treatment failure was 33% in patients with, and 10% in patients without virus-associated changes (p less than 0.025). It is recommended that patients with CIN 1 and virus-associated changes...

  19. Comparison of computed tomography and radiography for detecting changes induced by malignant nasal neoplasia in dogs

    International Nuclear Information System (INIS)

    Park, R.D.; Beck, E.R.; LeCouteur, R.A.

    1992-01-01

    The ability of computed tomography and radiography to detect changes associated with nasal neoplasia was compared in dogs. Eighteen areas or anatomic structures were evaluated in 21 dogs for changes indicative of neoplasia. Computed tomography was superior (P < or = 0.05) to radiography for detecting changes in 14 of 18 areas. Radiography was not superior for detecting changes in any structure or area. Computed tomography reveals vital information not always detected radiographically to assist in providing a prognosis and in planning treatment for nasal neoplasms in dogs

  20. Role of the human papilloma virus in the development of cervical intraepithelial neoplasia and malignancy.

    Science.gov (United States)

    Jastreboff, A M; Cymet, T

    2002-04-01

    Human papilloma virus (HPV) is a public health problem as a sexually transmitted disease and as a critical factor in the pathogenesis of various cancers. The clinical manifestations, epidemiology, and virology that are critical to understanding the process of cervical dysplasia and neoplasia are reviewed. A discussion of the cervical transformation zone and the classification of cervical dysplasia and neoplasia leads into the importance of the Papanicolaou smear in prevention of potentially devastating sequelae of this virus. The role of the immune system in the progression of the disease and how it relates to vaccines, as well as treatment and prevention of HPV, are reviewed.

  1. Diagnostic criteria for gestational diabetes mellitus (WS 331-2011)

    Institute of Scientific and Technical Information of China (English)

    Medical Service Specialty Standard Committee of Mi

    2012-01-01

    The criteria provide the screening and diagnosis for gestational diabetes mellitus and it should be applied to all medical institutions and health care practitioners for gestational diabetes mellitus (DM) diagnosis in China.

  2. Clinical and pathological heterogeneity of cervical intraepithelial neoplasia grade 3.

    Directory of Open Access Journals (Sweden)

    Hannah P Yang

    Full Text Available Cervical intraepithelial neoplasia grade 3 (CIN3, the immediate cervical cancer precursor, is a target of cervical cancer prevention. However, less than half of CIN3s will progress to cancer. Routine treatment of all CIN3s and the majority of CIN2s may lead to overtreatment of many lesions that would not progress. To improve our understanding of CIN3 natural history, we performed a detailed characterization of CIN3 heterogeneity in a large referral population in the US.We examined 309 CIN3 cases in the SUCCEED, a large population-based study of women with abnormal cervical cancer screening results. Histology information for 12 individual loop electrosurgical excision procedure (LEEP segments was evaluated for each woman. We performed case-case comparisons of CIN3s to analyze determinants of heterogeneity and screening test performance.CIN3 cases varied substantially by size (1-10 LEEP segments and by presentation with concomitant CIN2 and CIN1. All grades of CINs were equally distributed over the cervical surface. In half of the women, CIN3 lesions were found as multiple distinct lesions on the cervix. Women with large and solitary CIN3 lesions were more likely to be older, have longer sexual activity span, and have fewer multiple high risk HPV infections. Screening frequency, but not HPV16 positivity, was an important predictor of CIN3 size. Large CIN3 lesions were also characterized by high-grade clinical test results.We demonstrate substantial heterogeneity in clinical and pathological presentation of CIN3 in a US population. Time since sexual debut and participation in screening were predictors of CIN3 size. We did not observe a preferential site of CIN3 on the cervical surface that could serve as a target for cervical biopsy. Cervical cancer screening procedures were more likely to detect larger CIN3s, suggesting that CIN3s detected by multiple independent diagnostic tests may represent cases with increased risk of invasion.

  3. Heat shock protein90 in lobular neoplasia of the breast

    International Nuclear Information System (INIS)

    Zagouri, Flora; Nonni, Afrodite; Sergentanis, Theodoros N; Papadimitriou, Christos A; Michalopoulos, Nikolaos V; Lazaris, Andreas C; Patsouris, Efstratios; Zografos, George C

    2008-01-01

    Heat shock protein 90 (Hsp90) overexpression has been implicated in breast carcinogenesis, with putative prognostic and therapeutic implications. The purpose of this study is to evaluate the immunohistochemical expression of Hsp90 and to examine whether Hsp90 expression is associated with estrogen receptor alpha (ER-alpha) and beta (ER-beta) immunostaining in lobular neoplasia (LN) of the breast. Tissue specimens were taken from 44 patients with LN. Immunohistochemical assessment of Hsp90, ER-alpha and ER-beta was performed both in the lesion and the adjacent normal breast ducts and lobules; the latter serving as control. As far as Hsp90 evaluation is concerned: i) the percentage of positive cells, and ii) the intensity was separately analyzed. Additionally, the Allred score was adopted and calculated. Accordingly, Allred score was separately evaluated for ER-alpha and ER-beta. The intensity was treated as an ordinal variable-score (0: negative, low: 1, moderate: 2, high: 3). Statistical analysis followed. Hsp90 immunoreactivity was mainly cytoplasmic in both the epithelial cells of normal breast (ducts and lobules) and LN. Some epithelial cells of LN also showed nuclear staining, but all the LN foci mainly disclosed a positive cytoplasmic immunoreaction for Hsp90. In addition, rare intralobular inflammatory cells showed a slight immunoreaction. The percentage of Hsp90 positive cells in the LN areas was equal to 67.1 ± 12.2%, whereas the respective percentage in the normal adjacent breast tissue was 69.1 ± 11.6%; the difference was not statistically significant. The intensity score of Hsp90 staining was 1.82 ± 0.72 in LN foci, while in the normal adjacent tissue the intensity score was 2.14 ± 0.64. This difference was statistically significant (p = 0.029, Wilcoxon matched-pairs signed-ranks test). The Hsp90 Allred score was 6.46 ± 1.14 in the LN foci, significantly lower than in the normal adjacent tissue (6.91 ± 0.92, p = 0.049, Wilcoxon matched-pairs signed

  4. Heat shock protein90 in lobular neoplasia of the breast

    Directory of Open Access Journals (Sweden)

    Patsouris Efstratios

    2008-10-01

    Full Text Available Abstract Background Heat shock protein 90 (Hsp90 overexpression has been implicated in breast carcinogenesis, with putative prognostic and therapeutic implications. The purpose of this study is to evaluate the immunohistochemical expression of Hsp90 and to examine whether Hsp90 expression is associated with estrogen receptor alpha (ER-alpha and beta (ER-beta immunostaining in lobular neoplasia (LN of the breast. Methods Tissue specimens were taken from 44 patients with LN. Immunohistochemical assessment of Hsp90, ER-alpha and ER-beta was performed both in the lesion and the adjacent normal breast ducts and lobules; the latter serving as control. As far as Hsp90 evaluation is concerned: i the percentage of positive cells, and ii the intensity was separately analyzed. Additionally, the Allred score was adopted and calculated. Accordingly, Allred score was separately evaluated for ER-alpha and ER-beta. The intensity was treated as an ordinal variable-score (0: negative, low: 1, moderate: 2, high: 3. Statistical analysis followed. Results Hsp90 immunoreactivity was mainly cytoplasmic in both the epithelial cells of normal breast (ducts and lobules and LN. Some epithelial cells of LN also showed nuclear staining, but all the LN foci mainly disclosed a positive cytoplasmic immunoreaction for Hsp90. In addition, rare intralobular inflammatory cells showed a slight immunoreaction. The percentage of Hsp90 positive cells in the LN areas was equal to 67.1 ± 12.2%, whereas the respective percentage in the normal adjacent breast tissue was 69.1 ± 11.6%; the difference was not statistically significant. The intensity score of Hsp90 staining was 1.82 ± 0.72 in LN foci, while in the normal adjacent tissue the intensity score was 2.14 ± 0.64. This difference was statistically significant (p = 0.029, Wilcoxon matched-pairs signed-ranks test. The Hsp90 Allred score was 6.46 ± 1.14 in the LN foci, significantly lower than in the normal adjacent tissue (6.91

  5. Expression patterns of ERVWE1/Syncytin-1 and other placentally expressed human endogenous retroviruses along the malignant transformation process of hydatidiform moles.

    Science.gov (United States)

    Bolze, Pierre-Adrien; Patrier, Sophie; Cheynet, Valérie; Oriol, Guy; Massardier, Jérôme; Hajri, Touria; Guillotte, Michèle; Bossus, Marc; Sanlaville, Damien; Golfier, François; Mallet, François

    2016-03-01

    Up to 20% of hydatidiform moles are followed by malignant transformation in gestational trophoblastic neoplasia and require chemotherapy. Syncytin-1 is involved in human placental morphogenesis and is also expressed in various cancers. We assessed the predictive value of the expression of Syncytin-1 and its interactants in the malignant transformation process of hydatidiform moles. Syncytin-1 glycoprotein was localized by immunohistochemistry in hydatidiform moles, gestational trophoblastic neoplasia and control placentas. The transcription levels of its locus ERVWE1, its interaction partners (hASCT1, hASCT2, TLR4 and DC-SIGN) and two loci (ERVFRDE1 and ERV3) involved the expression of other placental envelopes were assessed by real-time PCR. Syncytin-1 glycoprotein was expressed in syncytiotrophoblast of hydatidiform moles with an apical enhancement when compared with normal placentas. Moles with further malignant transformation had a higher staining intensity of Syncytin-1 surface unit C-terminus but the transcription level of its locus ERVWE1 was not different from that of moles with further remission and normal placentas. hASCT1 and TLR4, showed lower transcription levels in complete moles when compared to normal placentas. ERVWE1, ERVFRDE1 and ERV3 transcription was down-regulated in hydatidiform moles and gestational trophoblastic neoplasia. Variations of Syncytin-1 protein localization and down-regulation of hASCT1 and TLR4 transcription are likely to reflect altered functions of Syncytin-1 in the premalignant context of complete moles. The reduced transcription in gestational trophoblastic diseases of ERVWE1, ERVFRDE1 and ERV3, which expression during normal pregnancy is differentially regulated by promoter region methylation, suggest a joint dysregulation mechanism in malignant context. Copyright © 2016 Elsevier Ltd. All rights reserved.

  6. Recent Declines in Induction of Labor by Gestational Age

    Science.gov (United States)

    ... for singleton births per 100 singleton births. Gestational age categories : Early preterm: Births prior to 34 completed weeks of ... delivery is managed for multiple gestation pregnancies. The primary measure used to determine gestational age is the interval between the first day of ...

  7. Risk factors for gestational diabetes mellitus in Sudanese pregnant ...

    African Journals Online (AJOL)

    McRoy

    Key words: Diabetes mellitus, gestation, risk factors, Sudan. INTRODUCTION. Gestational diabetes mellitus (GDM) is a universal risk factor for maternal and neonatal morbidity and mortality.[1] Low gestational age, neonatal macrosomia, hypoglycemia, respiratory distress syndrome are frequent complications of GDM and ...

  8. Mitochondrial function and glucose metabolism in the placenta with gestational diabetes mellitus: role of miR-143.

    Science.gov (United States)

    Muralimanoharan, Sribalasubashini; Maloyan, Alina; Myatt, Leslie

    2016-06-01

    A predisposing factor for development of the hyperglycaemic state of gestational diabetes mellitus (GDM) is obesity. We previously showed that increasing maternal obesity is associated with significant reductions in placental mitochondrial respiration. MicroRNA (miR)-143 has been previously shown to regulate the metabolic switch from oxidative phosphorylation to aerobic glycolysis in cancer tissues. We hypothesized that mitochondrial respiration is reduced and aerobic glycolysis is up-regulated via changes in miR-143 expression in the placenta of women with GDM. Placental tissue was collected at term from women with A1GDM (controlled by diet), A2GDM (controlled by medication) and body mass index (BMI)-matched controls (CTRL). miR-143 expression was measured by RT-PCR. Expression of mitochondrial complexes, transcription factors peroxisome proliferator-activated receptor-γ co-activator 1α (PGC1α) and peroxisome proliferator-activated receptor γ (PPARγ), components of mammalian target of rapamycin (mTOR) signalling, glucose transporter GLUT1 and glycolytic enzymes [hexokinase-2 (HK-2), phosphofructokinase (PFK) and lactate dehydrogenase (LDH)] were measured by Western blot. Trophoblast respiration was measured by XF24 Analyser. Expression of miR-143, mitochondrial complexes, and PPARγ and PGC1α, which act downstream of miR-143, were significantly decreased in A2GDM placentae compared with A1GDM and CTRL (P<0.01). Placental hPL (human placental lactogen) levels, expression of glycolytic enzymes, GLUT1 and mTOR signalling were also significantly increased by more than 2-fold in A2GDM compared with A1GDM and CTRL (P<0.05). There was a 50% reduction in mitochondrial respiration in trophoblast cells isolated from A2GDM placentae. Overexpression of miR-143 was able to increase mitochondrial respiration, increase protein expression of mitochondrial complexes and decrease expression of glycolytic enzymes by 40% compared with A2GDM. Down-regulation of miR-143 mediates

  9. Interleukin-1β inhibits insulin signaling and prevents insulin-stimulated system A amino acid transport in primary human trophoblasts.

    Science.gov (United States)

    Aye, Irving L M H; Jansson, Thomas; Powell, Theresa L

    2013-12-05

    Interleukin-1β (IL-1β) promotes insulin resistance in tissues such as liver and skeletal muscle; however the influence of IL-1β on placental insulin signaling is unknown. We recently reported increased IL-1β protein expression in placentas of obese mothers, which could contribute to insulin resistance. In this study, we tested the hypothesis that IL-1β inhibits insulin signaling and prevents insulin-stimulated amino acid transport in cultured primary human trophoblast (PHT) cells. Cultured trophoblasts isolated from term placentas were treated with physiological concentrations of IL-1β (10pg/ml) for 24h. IL-1β increased the phosphorylation of insulin receptor substrate-1 (IRS-1) at Ser307 (inhibitory) and decreased total IRS-1 protein abundance but did not affect insulin receptor β expression. Furthermore, IL-1β inhibited insulin-stimulated phosphorylation of IRS-1 (Tyr612, activation site) and Akt (Thr308) and prevented insulin-stimulated increase in PI3K/p85 and Grb2 protein expression. IL-1β alone stimulated cRaf (Ser338), MEK (Ser221) and Erk1/2 (Thr202/Tyr204) phosphorylation. The inflammatory pathways nuclear factor kappa B and c-Jun N-terminal kinase, which are involved in insulin resistance, were also activated by IL-1β treatment. Moreover, IL-1β inhibited insulin-stimulated System A, but not System L amino acid uptake, indicating functional impairment of insulin signaling. In conclusion, IL-1β inhibited the insulin signaling pathway by inhibiting IRS-1 signaling and prevented insulin-stimulated System A transport, thereby promoting insulin resistance in cultured PHT cells. These findings indicate that conditions which lead to increased systemic maternal or placental IL-1β levels may attenuate the effects of maternal insulin on placental function and consequently fetal growth. Published by Elsevier Ireland Ltd.

  10. Variable DAXX gene methylation is a common feature of placental trophoblast differentiation, preeclampsia, and response to hypoxia.

    Science.gov (United States)

    Novakovic, Boris; Evain-Brion, Danièle; Murthi, Padma; Fournier, Thiery; Saffery, Richard

    2017-06-01

    Placental functioning relies on the appropriate differentiation of progenitor villous cytotrophoblasts (CTBs) into extravillous cytotrophoblasts (EVCTs), including invasive EVCTs, and the multinucleated syncytiotrophoblast (ST) layer. This is accompanied by a general move away from a proliferative, immature phenotype. Genome-scale expression studies have provided valuable insight into genes that are associated with the shift to both an invasive EVCT and ST phenotype, whereas genome-scale DNA methylation analysis has shown that differentiation to ST involves widespread methylation shifts, which are counteracted by low oxygen. In the current study, we sought to identify DNA methylation variation that is associated with transition from CTB to ST in vitro and from a noninvasive to invasive EVCT phenotype after culture on Matrigel. Of the several hundred differentially methylated regions that were identified in each comparison, the majority showed a loss of methylation with differentiation. This included a large differentially methylated region (DMR) in the gene body of death domain-associated protein 6 ( DAXX ), which lost methylation during both CTB syncytialization to ST and EVCT differentiation to invasive EVCT. Comparison to publicly available methylation array data identified the same DMR as among the most consistently differentially methylated genes in placental samples from preeclampsia pregnancies. Of interest, in vitro culture of CTB or ST in low oxygen increases methylation in the same region, which correlates with delayed differentiation. Analysis of combined epigenomics signatures confirmed DAXX DMR as a likely regulatory element, and direct gene expression analysis identified a positive association between methylation at this site and DAXX expression levels. The widespread dynamic nature of DAXX methylation in association with trophoblast differentiation and placenta-associated pathologies is consistent with an important role for this gene in proper

  11. Relevance of the NR4A sub-family of nuclear orphan receptors in trophoblastic BeWo cell differentiation.

    Science.gov (United States)

    Malhotra, Sudha Saryu; Gupta, Satish Kumar

    2017-01-01

    Nur-77, a member of the NR4A sub-family of nuclear orphan receptors, is downregulated in the placentae of pre-eclamptic women. Here, we investigate the relevance of Nor-1, Nurr-1 and Nur-77 in trophoblastic cell differentiation. Their transcript levels were found to be significantly upregulated in BeWo cells treated with forskolin. The maximum increase was observed after 2 h, with a second peak in the expression levels after 48 h. The expression of NR4A sub-family members was also found to be upregulated in BeWo cells after treatment with hCG and GnRH. A similar significant increase was observed at the respective protein levels after 2 and 48 h of treatment with forskolin, hCG or GnRH. Silencing Nor-1, Nurr-1 or Nur-77 individually did not show any effect on forskolin-, hCG- and/or GnRH-mediated BeWo cell fusion and/or hCG secretion. After silencing any one member of the NR4A sub-family, an increase in the transcript levels of the other sub-family members was observed, indicating a compensatory effect due to their functional redundancy. Simultaneously silencing all three NR4A sub-family members significantly downregulated forskolin- and hCG-mediated BeWo cell fusion and/or hCG secretion. However, a considerable amount of cell death occurred after forskolin or hCG treatment as compared to the control siRNA-transfected cells. These results suggest that the NR4A sub-family of nuclear orphan receptors has a role in trophoblastic cell differentiation.

  12. Immunoglobulins from sera of APS patients bind HTR-8/SVneo trophoblast cell line and reduce additional mediators of cell invasion.

    Science.gov (United States)

    Jovanović Krivokuća, Milica; Abu Rabi, Tamara; Stefanoska, Ivana; Vrzić-Petronijević, Svetlana; Petronijević, Miloš; Vićovac, Ljiljana

    2017-12-01

    Immunoglobulins from sera of patients with antiphospholipid syndrome (APS) decrease trophoblast cell invasion in vitro. This study aimed to extend understanding of cellular effects of immunoglobulins from APS (aPL+) in HTR-8/SVneo cells. aPL+ IgG induced change in effector molecules important for cell invasion was investigated further. After 1h of culture 21% cells bound aPL+ IgG, as opposed to 6% in control (aPL-). This was accompanied by increase in phospho-p38 at 30min. After 24h treatment aPL+IgG decreased protein levels of integrin subunits α1 (78% of control; p<0.01), α4 (65% of control, p<0.01), α5 (76% of control; p<0.01) and β1 (80% of control; p<0.01), and secreted gal-1 (68% of control; p<0.05). ProMMP-9 was reduced to 70% of control (p<0.001). Treatment with inhibitor of p38 MAPK signaling SB202190 reversed inhibition in integrin β1 and secreted gal-1. Involvement of p38 MAPK signaling and decrease in integrin subunit α4 , proMMP-9, and secreted gal-1 in HTR-8/SVneo cells are novel and extend the list of mediators of trophoblast invasion affected by aPL. Copyright © 2017 Society for Biology of Reproduction & the Institute of Animal Reproduction and Food Research of Polish Academy of Sciences in Olsztyn. Published by Elsevier Urban & Partner Sp. z o.o. All rights reserved.

  13. No Association of Blood Type O With Neuroendocrine Tumors in Multiple Endocrine Neoplasia Type 1

    NARCIS (Netherlands)

    Nell, Sjoerd; van Leeuwaarde, Rachel S.; Pieterman, Carolina R. C.; de Laat, Joanne M.; Hermus, Ad R.; Dekkers, Olaf M.; de Herder, Wouter W.; van der Horst-Schrivers, Anouk N.; Drent, Madeleine L.; Bisschop, Peter H.; Havekes, Bas; Borel Rinkes, Inne H. M.; Vriens, Menno R.; Valk, Gerlof D.

    2015-01-01

    An association between ABO blood type and the development of cancer, in particular, pancreatic cancer, has been reported in the literature. An association between blood type O and neuroendocrine tumors in multiple endocrine neoplasia type 1 (MEN1) patients was recently suggested. Therefore, blood

  14. No Association of Blood Type O With Neuroendocrine Tumors in Multiple Endocrine Neoplasia Type 1

    NARCIS (Netherlands)

    Nell, S.; Leeuwaarde, R.S. van; Pieterman, C.R.; Laat, J.M. de; Hermus, A.R.M.M.; Dekkers, O.M.; Herder, W.W. de; Horst-Schrivers, A.N. van der; Drent, M.L.; Bisschop, P.H.; Havekes, B.; Rinkes, I.H.; Vriens, M.R.; Valk, G.D.

    2015-01-01

    CONTEXT: An association between ABO blood type and the development of cancer, in particular, pancreatic cancer, has been reported in the literature. An association between blood type O and neuroendocrine tumors in multiple endocrine neoplasia type 1 (MEN1) patients was recently suggested. Therefore,

  15. No Association of Blood Type O With Neuroendocrine Tumors in Multiple Endocrine Neoplasia Type 1

    NARCIS (Netherlands)

    Nell, Sjoerd; Van Leeuwaarde, Rachel S.; Pieterman, Carolina R. C.; de Laat, Joanne M.; Hermus, Ad R.; Dekkers, Olaf M.; de Herder, Wouter W.; van der Horst-Schrivers, Anouk N.; Drent, Madeleine L.; Bisschop, Peter H.; Havekes, Bas; Rinkes, Inne H. M. Borel; Vriens, Menno R.; Valk, Gerlof D.

    2015-01-01

    Context: An association between ABO blood type and the development of cancer, in particular, pancreatic cancer, has been reported in the literature. An association between blood type O and neuroendocrine tumors in multiple endocrine neoplasia type 1 (MEN1) patients was recently suggested. Therefore,

  16. Topical 5-fluorouracil treatment of anal intraepithelial neoplasia in human immunodeficiency virus-positive men

    NARCIS (Netherlands)

    Richel, O.; Wieland, U.; de Vries, H. J. C.; Brockmeyer, N. H.; van Noesel, C.; Potthoff, A.; Prins, J. M.; Kreuter, A.

    2010-01-01

    Background Anal intraepithelial neoplasia (AIN), a human papillomavirus (HPV) induced potential precursor lesion of anal cancer, is frequent among human immunodeficiency virus (HIV)-positive men who have sex with men (MSM). So far, only a few prospective studies have been performed on the topical

  17. Prevalence of small-bowel neoplasia in Lynch syndrome assessed by video capsule endoscopy

    NARCIS (Netherlands)

    Haanstra, Jasmijn F.; Al-Toma, Abdul; Dekker, Evelien; Vanhoutvin, Steven A. L. W.; Nagengast, Fokko M.; Mathus-Vliegen, Elisabeth M.; van Leerdam, Monique E.; de Vos tot Nederveen Cappel, Wouter H.; Sanduleanu, Silvia; Veenendaal, Roeland A.; Cats, Annemieke; Vasen, Hans F. A.; Kleibeuker, Jan H.; Koornstra, Jan J.

    2015-01-01

    The aim was to determine the prevalence of small-bowel neoplasia in asymptomatic patients with Lynch syndrome (LS) by video capsule endoscopy (VCE). After obtaining informed consent, asymptomatic proven gene mutation carriers aged 35-70 years were included in this prospective multicentre study in

  18. Prevalence of small-bowel neoplasia in Lynch syndrome assessed by video capsule endoscopy

    NARCIS (Netherlands)

    Haanstra, Jasmijn F.; Al-Toma, Abdul; Dekker, Evelien; Vanhoutvin, Steven A. L. W.; Nagengast, Fokko M.; Mathus-Vliegen, Elisabeth M.; van Leerdam, Monique E.; Cappel, Wouter H. de Vos tot Nederveen; Sanduleanu, Silvia; Veenendaal, Roeland A.; Cats, Annemieke; Vasen, Hans F. A.; Kleibeuker, Jan H.; Koornstra, Jan J.

    2015-01-01

    Objective The aim was to determine the prevalence of small-bowel neoplasia in asymptomatic patients with Lynch syndrome (LS) by video capsule endoscopy (VCE). Design After obtaining informed consent, asymptomatic proven gene mutation carriers aged 3570 years were included in this prospective

  19. Disseminated medullary thyroid carcinoma despite early thyroid surgery in the multiple endocrine neoplasia-2A syndrome

    NARCIS (Netherlands)

    van Santen, H. M.; Aronson, D. C.; van Trotsenburg, A. S. P.; ten Kate, F. J. W.; van de Wetering, M. D.; Wiersinga, W. M.; de Vijlder, J. J. M.; Vulsma, T.

    2005-01-01

    A 5 1/2-year-old boy, with a family history of multiple endocrine neoplasia (MEN)-2A syndrome, was evaluated for presence of MEN-2A and medullary thyroid carcinoma (MTC). DNA diagnostics confirmed MEN-2A. Basal (360 ng/L) and pentagastrin stimulated (430 ng/L) calcitonin (CT) levels were slightly

  20. High-Resolution Anoscopy: Clinical Features of Anal Intraepithelial Neoplasia in HIV-positive Men

    NARCIS (Netherlands)

    Richel, Olivier; Hallensleben, Nora D. L.; Kreuter, Alexander; van Noesel, Carel J. M.; Prins, Jan M.; de Vries, Henry J. C.

    2013-01-01

    BACKGROUND: High-resolution anoscopy is increasingly advocated to screen HIV+ men who have sex with men for anal cancer and its precursor lesions, anal intraepithelial neoplasia. A systematic comparison between clinical features and the histopathology of suspect lesions is lacking. OBJECTIVE: This

  1. Adult Immunohistochemical Markers Fail to Detect Intratubular Germ Cell Neoplasia in Prepubertal Boys with Cryptorchidism

    DEFF Research Database (Denmark)

    Kvist, Kolja; Clasen-Linde, Erik; Cortes, Dina

    2013-01-01

    Intratubular germ cell neoplasia (ITGCN) is a precursor to testicular germ cell cancer. It is characterized by large germ cells with large nuclei with a hyperchromatic, coarse chromatin pattern, large prominent nucleoli and abundant pale cytoplasm. In prepubertal boys these cells are located both...

  2. Stepwise radical endoscopic resection for Barrett's esophagus with early neoplasia: report on a Brussels' cohort

    NARCIS (Netherlands)

    Pouw, R. E.; Peters, F. P.; Sempoux, C.; Piessevaux, H.; Deprez, P. H.

    2008-01-01

    Background and study aims: The aim of this retrospective study was to assess safety and efficacy of stepwise radical endoscopic resection (SRER) in patients with Barrett's esophagus with high-grade intraepithelial neoplasia (HGIN) or early cancer. Patients and methods: Patients undergoing SRER

  3. 3-GROUP METAPHASE AS A MORPHOLOGIC CRITERION OF PROGRESSIVE CERVICAL INTRAEPITHELIAL NEOPLASIA

    NARCIS (Netherlands)

    MOURITS, MJE; PIETERS, WJLM; HOLLEMA, H; BURGER, MPM

    OBJECTIVE: The purpose of our study was to investigate the presence of three-group metaphase in progressive cervical intraepithelial neoplasia. STUDY DESIGN: This was a retrospective histologic study on the conization specimens of 41 women with microinvasive cervical carcinoma, 28 of whom were

  4. Risk of cervical cancer after completed post-treatment follow-up of cervical intraepithelial neoplasia

    DEFF Research Database (Denmark)

    Rebolj, Matejka; Helmerhorst, Theo; Habbema, Dik

    2012-01-01

    To compare the risk of cervical cancer in women with histologically confirmed cervical intraepithelial neoplasia who returned to routine screening after having completed post-treatment follow-up with consecutive normal smear test results with women with a normal primary smear test result....

  5. ATYPICAL MITOTIC FIGURES AND THE MITOTIC INDEX IN CERVICAL INTRAEPITHELIAL NEOPLASIA

    NARCIS (Netherlands)

    VANLEEUWEN, AM; PIETERS, WJLM; HOLLEMA, H; BURGER, MPM

    1995-01-01

    We surveyed cervical intraepithelial neoplasia (CIN) to quantify the proliferation rate and the presence of normal and atypical mitotic figures. In the cervical tissue specimens of 127 women with CIN, the area with the highest cell proliferation was identified and, at that site, the proliferation

  6. Three-group metaphase as a morphologic criterion of progressive cervical intraepithelial neoplasia

    NARCIS (Netherlands)

    Mourits, M. J.; Pieters, W. J.; Hollema, H.; Burger, M. P.

    1992-01-01

    OBJECTIVE: The purpose of our study was to investigate the presence of three-group metaphase in progressive cervical intraepithelial neoplasia. STUDY DESIGN: This was a retrospective histologic study on the conization specimens of 41 women with microinvasive cervical carcinoma, 28 of whom were

  7. Risk of head-and-neck cancer following a diagnosis of severe cervical intraepithelial neoplasia

    DEFF Research Database (Denmark)

    Svahn, Malene F; Munk, C; Jensen, S M

    2016-01-01

    OBJECTIVE: Women with a history of cervical intraepithelial neoplasia grade 3 including adenocarcinoma in situ (CIN3/AIS) may be more prone to develop cancers of the ano-genital region and head-and-neck cancers. The current literature is, however, limited. METHODS: We established a nationwide...

  8. The negative association between a history of recurrent herpes labialis and cervical neoplasia

    NARCIS (Netherlands)

    Burger, M. P.; Wilterdink, J. B.

    1988-01-01

    We considered the possibility that herpetic recurrences and herpes virus associated neoplasia are mutually exclusive disorders because they are expressions of different herpes virus-host relationships. We assumed that the human body copes with orofacial and genital herpes infections in the same

  9. Germline CDKN1B/p27Kip1 mutation in multiple endocrine neoplasia

    NARCIS (Netherlands)

    Georgitsi, Marianthi; Raitila, Anniina; Karhu, Auli; van der Luijt, Rob B.; Aalfs, Cora M.; Sane, Timo; Vierimaa, Outi; Mäkinen, Markus J.; Tuppurainen, Karoliina; Paschke, Ralph; Gimm, Oliver; Koch, Christian A.; Gündogdu, Sadi; Lucassen, Anneke; Tischkowitz, Marc; Izatt, Louise; Aylwin, Simon; Bano, Gul; Hodgson, Shirley; de Menis, Ernesto; Launonen, Virpi; Vahteristo, Pia; Aaltonen, Lauri A.

    2007-01-01

    Germline mutations in the MEN1 gene predispose to multiple endocrine neoplasia type 1 (MEN1) syndrome, but in up to 20-25% of clinical MEN1 cases, no MEN1 mutations can be found. Recently, a germline mutation in the CDKN1B gene, encoding p27(Kip1), was reported in one suspected MEN1 family with two

  10. A rare presentation of multiple endocrine neoplasia (MEN type 2A syndrome

    Directory of Open Access Journals (Sweden)

    Elroy Patrick Weledji

    2016-02-01

    Full Text Available Peptic ulcer disease may be a manifestation of symptomatic primary hyperparathyroidism. A case of an intractable complicated peptic ulcer disease secondary to hypercalcaemia from multiple endocrine neoplasia type 2A is presented. Hypercalcaemia should always be excluded as a cause of recurrent, or complicated peptic ulcer disease.

  11. Surgical approach in patients with hyperparathyroidism in multiple endocrine neoplasia type 1: total versus partial parathyroidectomy

    Directory of Open Access Journals (Sweden)

    Francesco Tonelli

    2012-01-01

    Full Text Available Usually, primary hyperparathyroidism is the first endocrinopathy to be diagnosed in patients with multiple endocrine neoplasia type 1, and is also the most common one. The timing of the surgery and strategy in multiple endocrine neoplasia type 1/hyperparathyroidism are still under debate. The aims of surgery are to: 1 correct hypercalcemia, thus preventing persistent or recurrent hyperparathyroidism; 2 avoid persistent hypoparathyroidism; and 3 facilitate the surgical treatment of possible recurrences. Currently, two types of surgical approach are indicated: 1 subtotal parathyroidectomy with removal of at least 3-3 K glands; and 2 total parathyroidectomy with grafting of autologous parathyroid tissue. Transcervical thymectomy must be performed with both of these procedures. Unsuccessful surgical treatment of hyperparathyroidism is more frequently observed in multiple endocrine neoplasia type 1 than in sporadic hyperparathyroidism. The recurrence rate is strongly influenced by: 1 the lack of a pre-operative multiple endocrine neoplasia type 1 diagnosis; 2 the surgeon's experience; 3 the timing of surgery; 4 the possibility of performing intra-operative confirmation (histologic examination, rapid parathyroid hormone assay of the curative potential of the surgical procedure; and, 5 the surgical strategy. Persistent hyperparathyroidism seems to be more frequent after subtotal parathyroidectomy than after total parathyroidectomy with autologous graft of parathyroid tissue. Conversely, recurrent hyperparathyroidism has a similar frequency in the two surgical strategies. To plan further operations, it is very helpful to know all the available data about previous surgery and to undertake accurate identification of the site of recurrence.

  12. [Multiple gestation epidemiology--15 years survey].

    Science.gov (United States)

    Rodrigues, Carla T; Branco, Miguel R; Ferreira, Isabel D; Nordeste, Ana; Fonseca, Margarida; Taborda, Adelaide; Silva, Isabel S; Almeida, Maria do Céu

    2005-01-01

    Between January of 1987 and December of 2001 were born 1243 twins related to 609 multiple pregnancies, in Maternidade Bissaya-Barreto. Data were grouped in periods of three years and several parameters were studied. The rate of multiple gestation has increased probably due to the contribution of the assisted conception techniques, and to the increase of the number of multiple fetal pregnancies (two or more) and to the increase of the mother age. These more frequent obstetric problems were preterm birth, gestational hypertension and abnormal sonographic data of fetal growth. The average age of delivery was 34 weeks and the birth weight has decreased. The most important factors for neonatal morbidity were hyaline membranous disease, intraventricular haemorrhage and the twin-twin transfusion syndrome. The neonatal mortality decreased in the last studied period.

  13. Ethical and Legal Issues in Gestational Surrogacy.

    Science.gov (United States)

    Casella, Claudia; Capasso, Emanuele; Terracciano, Lucia; Delbon, Paola; Fedeli, Piergiorgio; Salzano, Francesco Antonio; Policino, Fabio; Niola, Massimo

    2018-01-01

    This study originated from events that occurred in 2014 in an Italian hospital, where the embryos of a couple, obtained by means of homologous insemination, were mistakenly implanted into the uterus of another woman who, along with her husband, underwent the same treatment. Faced with this serious adverse circumstance, that gives rise to ethical and legal issues, the authors conducted a comparative examination of how to consider the division of maternity (between biological mother and uterine mother) and the related division of paternity (between genetic father and legal father, husband or partner of the gestational mother). Some preliminary observations are made concerning parenthood and filiation within the context of currently applicable Italian law. The following is a detailed analysis of the arguments in favour of the parental figures involved (gestational mother/genetic mother).

  14. Galectins in angiogenesis: consequences for gestation.

    Science.gov (United States)

    Blois, Sandra M; Conrad, Melanie L; Freitag, Nancy; Barrientos, Gabriela

    2015-04-01

    Members of the galectin family have been shown to exert several roles in the context of reproduction. They contribute to placentation, maternal immune regulation and facilitate angiogenesis encompassing decidualisation and placenta formation during pregnancy. In the context of neo-vascularisation, galectins have been shown to augment signalling pathways that lead to endothelial cell activation, cell proliferation, migration and tube formation in vitro in addition to angiogenesis in vivo. Angiogenesis during gestation ensures not only proper foetal growth and development, but also maternal health. Consequently, restriction of placental blood flow has major consequences for both foetus and mother, leading to pregnancy diseases. In this review we summarise both the established and the emerging roles of galectin in angiogenesis and discuss the possible implications during healthy and pathological gestation. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

  15. Hormone patterns in early human gestation

    International Nuclear Information System (INIS)

    Mishell, D.R. Jr.; Thorneycroft, I.H.; Nagata, Y.; Murata, T.; Nakamura, R.M.

    1974-01-01

    Accurate measurement of the low concentration of gonadotropins and steroid hormones present in human serum has been made possible by the development of sensitive radioimmunoassay (RIA) techniques. With the use of RIA FSH and LH, progesterone and 17OH-progesterone have been previously measured in early normal pregnancy. In order to determine the daily pattern of hormone levels in early normal pregnancy, gonadotropins as well as steroid hormone levels were measured in serum samples obtained daily from three women from the time of the last menstrual period prior to conception throughout the first few months of gestation