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1

The Role of Maternal VegT in Establishing the Primary Germ Layers in Xenopus Embryos  

Microsoft Academic Search

VegT is a T-box transcription factor whose mRNA is synthesized during oogenesis and localized in the vegetal hemisphere of the egg and early embryo. We show that maternally expressed VegT controls the pattern of primary germ layer specification in Xenopus embryos. Reduction of the maternal store completely alters the fates of different regions of the blastula so that animal cell

Jian Zhang; Douglas W Houston; Mary Lou King; Christopher Payne; Christopher Wylie; Janet Heasman

1998-01-01

2

Chemotherapy trials in recurrent primary intracranial germ cell tumors.  

PubMed

Gonadal germ cell tumors respond favorably to chemotherapy either at diagnosis or when they recur. Histologically similar tumors may arise in the CNS usually in the pineal or suprasellar regions. Although radiation therapy may produce a 5 year disease-free survival in excess of 60% in localized pure germinoma, germ cell tumors of other histology tend to recur. We have conducted 14 chemotherapy trials in 8 patients with recurrent CNS germ cell tumors using 3 different single agent and 2 multi-agent chemotherapy regimens. The histologic diagnoses of the patients were germinoma (4), endodermal sinus tumor (2), embryonal carcinoma (1), and mixed tumor - germinoma plus choriocarcinoma (1). There were 7 males and 1 female with a median age of 13 years. The primary tumor arose in the pineal region in 6 and was multicentric in 2. Seven patients had local recurrences and one developed an initial recurrence in the spinal canal. Three patients had CNS metastases at relapse and 2 had systemic metastases. Objective responses were documented in 7 of 14 trials (50%). Responses were observed with cyclophosphamide (80 mg/kg) in 3 of 4 patients for 2+, 3, and 5 mos, cisplatin (120 mg/m2) in 1 of 2 patients for 2+ mos, and the VAB 6 protocol (vinblastine, bleomycin, cyclophosphamide, actinomycin-d, cisplatin) in 3 of 5 patients for 5, 8, and 18 mos. The median duration of response was 5 mos. (2+-18). High doses of single chemotherapy agents such as cyclophosphamide and cisplatin as well as VAB 6 regimen have definite activity in recurrent CNS germ cell tumors, especially germinoma. Good palliation may be achieved with chemotherapy alone with acceptable morbidity.(ABSTRACT TRUNCATED AT 250 WORDS) PMID:3897472

Allen, J C; Bosl, G; Walker, R

1985-01-01

3

Generation of organized germ layers from a single mouse embryonic stem cell  

PubMed Central

Mammalian inner cell mass cells undergo lineage-specific differentiation into germ layers of endoderm, mesoderm and ectoderm during gastrulation. It has been a long-standing challenge in developmental biology to replicate these organized germ layer patterns in culture. Here we present a method of generating organized germ layers from a single mouse embryonic stem cell cultured in a soft fibrin matrix. Spatial organization of germ layers is regulated by cortical tension of the colony, matrix dimensionality and softness, and cell–cell adhesion. Remarkably, anchorage of the embryoid colony from the 3D matrix to collagen-1-coated 2D substrates of ~1?kPa results in self-organization of all three germ layers: ectoderm on the outside layer, mesoderm in the middle and endoderm at the centre of the colony, reminiscent of generalized gastrulating chordate embryos. These results suggest that mechanical forces via cell–matrix and cell–cell interactions are crucial in spatial organization of germ layers during mammalian gastrulation. This new in vitro method could be used to gain insights on the mechanisms responsible for the regulation of germ layer formation. PMID:24873804

Poh, Yeh-Chuin; Chen, Junwei; Hong, Ying; Yi, Haiying; Zhang, Shuang; Chen, Junjian; Wu, Douglas C.; Wang, Lili; Jia, Qiong; Singh, Rishi; Yao, Wenting; Tan, Youhua; Tajik, Arash; Tanaka, Tetsuya S.; Wang, Ning

2014-01-01

4

Primary germ cell tumors of the mediastinum: 10 years of experience in a tertiary teaching hospital.  

PubMed

Germ cell tumors occur mostly in the gonad. Extragonadal germ cell tumors are rare, and most occur in the retroperitoneum and mediastinum. Primary mediastinal germ cell tumors are often found in the anterior portion of the mediastinum and include teratomas and non-teratomatous tumors. Non-teratomatous tumors include seminomas and malignant non-seminomatous germ cell tumors (MNSGCTs). MNSGCTs include yolk sac tumors, choriocarcinomas, embryonal carcinomas, and mixed type germ cell tumors. Teratomas are the most common germ cell tumors of the mediastinum, and seminomas are the most common non-teratomatous germ cell tumors of the mediastinum. Cases of primary mediastinal MNSGCT reported in the literature are rare. In this report, we review all primary mediastinal germ cell tumors from a 10-year period at the Chung-Ho Memorial Hospital of Kaohsiung Medical University. A total of 14 cases were reviewed, including 11 patients with mature teratomas, two with yolk sac tumors, and one with seminoma. We discuss the differences in clinical presentation, histopathologic characteristics, treatment, and prognosis. PMID:16248122

Yang, Chih-Jen; Cheng, Meng-Shuan; Chou, Shah-Hwa; Tsai, Kun-Bow; Huang, Ming-Shyan

2005-09-01

5

RPLND or Primary Chemotherapy in Clinical Stage IIA/B Nonseminomatous Germ Cell Tumors?  

Microsoft Academic Search

Background: In order to reduce therapy–related morbidity in patients with nonseminomatous testicular germ cell tumors in clinical stage IIA/B, we performed a prospective multicenter trial comparing the standard retroperitoneal lymph node dissection (RPLND) +2 cycles of chemotherapy (arm A) with 3–4 cycles of primary chemotherapy (arm B).Methods: From February 1991 to July 1995, 57 participating centers from Germany and Austria

Lothar Weissbach; Henning Flechtner; Uwe Pichlmeier; Michael Hartmann; Lutz Keller

2000-01-01

6

Primary malignant germ cell tumours of the mediastinum--results of multimodality treatment.  

PubMed

Primary malignant mediastinal germ cell tumours are rare and considered to have poorer prognosis compared with those arising from gonads. Eighteen patients with primary mediastinal germ cell tumour were treated over an 1-year period; 9 had seminoma and 9 non-seminoma. Eight patients, 4 each with seminoma and non-seminoma underwent initial tumour excision and the rest had biopsy only. All patients received cisplatin-based chemotherapy. All patients with seminoma received consolidation radiotherapy to mediastinum. Three patients with non-seminoma received radiotherapy following partial response. All 9 patients with seminoma achieved complete response at the end of chemotherapy. Two patients with NSGCT had complete response to chemotherapy, 5 partial response and 2 no response. Two patients who underwent resection of the residual tumour mass are surviving free of disease. Addition of radiotherapy or second-line chemotherapy did not bring about any added response in partial and non-responders. Nine out of 9 patients with seminoma and 4/9 with non-seminoma are surviving disease-free at a median follow-up of 48 months (range 16 153 months). Mediastinal seminoma has excellent prognosis with cisplatin combination chemotherapy, whereas non-seminoma carries poor prognosis, and aggressive chemotherapy with resection of residual masses may improve the outcome. The role of additional radiotherapy and initial tumour debulking needs further evaluation. PMID:9208904

Jyothirmayi, R; Ramadas, K; Jacob, R; Gangadharan, V P; Nair, M K

1997-01-01

7

Management of the primary malignant mediastinal germ cell tumors: experience with 54 patients  

PubMed Central

Background Primary malignant mediastinal germ cell tumor (PMMGCT) is rare and sometimes the prognosis of the patients with PMMGCT is not very satisfactory. Methods A total of 54 patients with PMMGCT in a follow-up from 1990 to 2009. We evaluated the role of the surgical treatment and the effect of multimodality treatment strategy for patients with PMMGCT. Results Fifty-two patients underwent surgical resections, while the other two patients just received chemoradiotherapy. Among the 52 patients, 28 cases received preoperative adjuvant therapy and 24 cases underwent surgery as initial treatment; 30 cases with complete resections, 18 cases with partial resections and 4 cases with only biopsies. There was no perioperative mortality. Histopathologic results revealed 18 cases of seminomas and 36 cases of nonseminomatous germ cell tumors (NSGCT). The last follow-up showed that 17 patients were alive, including 11 patients with seminoma and 6 patients with NSGCT. The 5-year overall survival rate of patients with seminomas was 87.7%. The 3-year and 5-year overall survival rates of patients with NSGCT were 47.4% and 23.0%, respectively. Conclusions It could be concluded that a complete surgical resection of PMMGCT after chemoradiotherapy showed favorable long-term survival. Patients with pure seminomas have a better prognosis compared with that with NSGCT. Virtual slides The virtual slides for this article can be found here: http://www.diagnosticpathology.diagnomx.eu/vs/1676987232116837. PMID:24552239

2014-01-01

8

Clinicopathological and immunohistochemical features of primary central nervous system germ cell tumors: a 24-years experience  

PubMed Central

Primary central nervous system (CNS) germ cell tumors (GCTs) are a rare heterogeneous group of lesions, which the clinicopathological features have a marked degree of heterogeneity comparing with that of gonadal GCTs. Accurately diagnosing CNS GCTs might be extremely difficult and requires immunohistochemical verification. This study was to investigate the biological feature of CNS GCTs and diagnostic value of immunohistochemical markers OCT3/4, C-kit, PLAP, and CD30 in CNS GCTs. A retrospective study was performed on 34 patients with CNS germ cell tumors between 1990 and 2014. 34 CNS GCTs account for 9.2% of all primary CNS neoplasms. The sellar region (35.3%) and pineal gland (17.6%) were the most common sites of intracranial GCTs. Hydrocephalus (82.4%) and diplopia (46.9%) were the two most common clinical presentations. The most common histological subtypes were germinoma (67.6%). PLAP, c-kit, OCT3/4 were highly expressed in gernimomas. CD30 and CK AE1/3 stainings were positive in embryonal carcinoma. Yolk sac tumor component showed positive staining for AFP and CK AE1/3. ?-HCG staining was positive in choriocarcinoma and STGC. Patients with mature teratomas and germinomas had a better prognosis (a 5-year survival rate) than those with embryonal carcinoma and choriocarcinoma (a 5-year survival rates were 0). Our finding suggest that the incidences of primary CNS GCTs are higher in South China than in the West, but mixed GCTs are uncommon in our study. The judicious use of a panel of selected markers is helpful in diagnosing and predicting the prognosis for CNS GCTs. PMID:25400782

Gao, Yuping; Jiang, Jiyao; Liu, Qiang

2014-01-01

9

Clinicopathological and immunohistochemical features of primary central nervous system germ cell tumors: a 24-years experience.  

PubMed

Primary central nervous system (CNS) germ cell tumors (GCTs) are a rare heterogeneous group of lesions, which the clinicopathological features have a marked degree of heterogeneity comparing with that of gonadal GCTs. Accurately diagnosing CNS GCTs might be extremely difficult and requires immunohistochemical verification. This study was to investigate the biological feature of CNS GCTs and diagnostic value of immunohistochemical markers OCT3/4, C-kit, PLAP, and CD30 in CNS GCTs. A retrospective study was performed on 34 patients with CNS germ cell tumors between 1990 and 2014. 34 CNS GCTs account for 9.2% of all primary CNS neoplasms. The sellar region (35.3%) and pineal gland (17.6%) were the most common sites of intracranial GCTs. Hydrocephalus (82.4%) and diplopia (46.9%) were the two most common clinical presentations. The most common histological subtypes were germinoma (67.6%). PLAP, c-kit, OCT3/4 were highly expressed in gernimomas. CD30 and CK AE1/3 stainings were positive in embryonal carcinoma. Yolk sac tumor component showed positive staining for AFP and CK AE1/3. ?-HCG staining was positive in choriocarcinoma and STGC. Patients with mature teratomas and germinomas had a better prognosis (a 5-year survival rate) than those with embryonal carcinoma and choriocarcinoma (a 5-year survival rates were 0). Our finding suggest that the incidences of primary CNS GCTs are higher in South China than in the West, but mixed GCTs are uncommon in our study. The judicious use of a panel of selected markers is helpful in diagnosing and predicting the prognosis for CNS GCTs. PMID:25400782

Gao, Yuping; Jiang, Jiyao; Liu, Qiang

2014-01-01

10

Expression of OCT4 in the primary germ cell tumors and thymoma in the mediastinum.  

PubMed

Primary germ cell tumors (GCTs) and thymoma are both located in the anterior mediastinum. A previous study has postulated that octamer binding transcription factor (OCT4) is a nuclear transcription factor that is expressed in pluripotent embryonic germ cells. This study examined OCT4 expression in GCTs and thymoma originating from the mediastinum. A retrospective study included 46 consecutive patients with GCTs conducted between 1983 and 2005, and 22 consecutive thymoma in the mediastinum whose tumors had been surgically excised. The 46 primary GCTs in mediastinum included teratoma (n=27; 58.7%), seminoma (n=10; 21.7%), yolk sac tumor (n=6; 13%), embryonal carcinoma (n=1; 2.1%), and mixed GCTs (n=2; 4%; one consisted of teratoma and yolk sac tumor, and the other teratoma, yolk sac tumor, and seminoma); and 22 thymoma including World Health Organization type A (n=3, 13.6%), type AB (n=4, 18.2%), type B1 (n=6, 27.3%), type B2 (n=4, 13.6%), and type B3 (n=5, 22.7%). Each tumor was examined with hematoxylin and eosin staining, and with antibodies to OCT4. All 10 seminoma cases, 1 embryonal carcinoma case, and 1 mixed GCT case containing seminoma were immunopositive for OCT4. On the other hand, the 22 thymoma, 6 yolk sac tumor, 27 teratomas, and 1 case with mixed GCT without component of seminoma were immunonegative for OCT4. We conclude that immunostaining with antibodies to OCT4 is a useful diagnostic tool in the identification of seminomas and primary embryonal carcinomas in GCTs originating from the mediastinum. PMID:16932017

Jung, Shih-Ming; Chu, Pao-Hsien; Shiu, Tzu-Fang; Wu, Hsueh-Hua; Kuo, Tseng-Tong; Chu, Jaw-Ji; Lin, Pyng-Jing

2006-09-01

11

[Diagnosis and treatment of primary germ cell tumors of the mediastinum. Report of six cases].  

PubMed

Primary germ cell tumours of the mediastinum are rare. We report a retrospective study of six cases. Sex ratio was 2/1. The tumor site was the posterior mediastinum in two patients and anterior in the remaining cases. High level serum markers was noted in two patients. At histologic exam we found two cases of seminoma, one embryonal carcinoma, one case of yolk sac tumor and two cases of composite tumor. All patients had non metastatic but locally advanced disease at diagnosis. Three patients were treated with cisplatin based chemotherapy followed by radiotherapy or surgical resection of residual masses. Only one patient is still alive. As it is often reported in the literature, the prognosis of this disease is poor especially for non seminomatous tumours. PMID:14534949

Landolsi, Amel; Tarmiz, Hasna; Ben Fatma, Leila; Kallel, Lamia; Gharbi, Olfa; Kraïem, Chakib; Korbi, Sadok; Ben Ahmed, Slim

2003-06-01

12

Effects of Wheat Germ Extract on the Severity and Systemic Symptoms of Primary Dysmenorrhea: A Randomized Controlled Clinical Trial  

PubMed Central

Background: Primary dysmenorrhea is one of the most common disorders in women and the main cause of absenteeism from work and school. Objectives: Considering the anti-inflammatory properties of wheat germ, the present study examined the effects of wheat germ extract on the severity and systemic symptoms of primary dysmenorrhea. Patients and Methods: This triple-blinded clinical trial was performed on 80 employed women in hospitals affiliated with Hamadan University of Medical Sciences (Hamadan, IR Iran). Subjects were allocated to two groups of 45 patients. Three 400-mg capsules of wheat germ extract or placebo were used daily? between the 16th day of the menstrual cycle to the fifth day of the next menstrual cycle for two consecutive months. Pain intensity was measured by a visual analogue scale thrice a day and a four-point verbal rating scale was employed to assess systemic symptoms. Results: Pain severity decreased only in the wheat germ extract group (P < 0.001) and there was no statistically significant change in the placebo group. In the wheat germ extract group, the pain severity decreased from 4.701 at baseline to 1.120 at the second cycle. The reduction in total scores of systemic symptoms of dysmenorrhea was statistically significant only in the wheat germ extract group (P < 0.001) and there was not a statistically significant change in the placebo group. It revealed statistically significant differences in systemic symptoms associated with dysmenorrhea including fatigue, headache, and mood swings in experimental group. Conclusions: Wheat germ extract seems to be an effective treatment for dysmenorrhea and its systemic symptoms, probably because of its anti-inflammatory effects. PMID:25389490

Atallahi, Maryam; Amir Ali Akbari, Sedigheh; Mojab, Faraz; Alavi Majd, Hamid

2014-01-01

13

An ancient role for nuclear beta-catenin in the evolution of axial polarity and germ layer segregation  

NASA Technical Reports Server (NTRS)

The human oncogene beta-catenin is a bifunctional protein with critical roles in both cell adhesion and transcriptional regulation in the Wnt pathway. Wnt/beta-catenin signalling has been implicated in developmental processes as diverse as elaboration of embryonic polarity, formation of germ layers, neural patterning, spindle orientation and gap junction communication, but the ancestral function of beta-catenin remains unclear. In many animal embryos, activation of beta-catenin signalling occurs in blastomeres that mark the site of gastrulation and endomesoderm formation, raising the possibility that asymmetric activation of beta-catenin signalling specified embryonic polarity and segregated germ layers in the common ancestor of bilaterally symmetrical animals. To test whether nuclear translocation of beta-catenin is involved in axial identity and/or germ layer formation in 'pre-bilaterians', we examined the in vivo distribution, stability and function of beta-catenin protein in embryos of the sea anemone Nematostella vectensis (Cnidaria, Anthozoa). Here we show that N. vectensis beta-catenin is differentially stabilized along the oral-aboral axis, translocated into nuclei in cells at the site of gastrulation and used to specify entoderm, indicating an evolutionarily ancient role for this protein in early pattern formation.

Wikramanayake, Athula H.; Hong, Melanie; Lee, Patricia N.; Pang, Kevin; Byrum, Christine A.; Bince, Joanna M.; Xu, Ronghui; Martindale, Mark Q.

2003-01-01

14

Null association between histology of first and second primary malignancies in men with bilateral testicular germ cell tumors.  

PubMed

Testicular germ cell tumors (TGCTs), the most common neoplasms of young men, are categorized histologically as either seminomas or nonseminomas/mixed germ cell tumors. These subtypes differ by age at diagnosis and clinical course, but little is known about etiological distinctions. To test the hypothesis that histological subtypes have distinct sets of unrecognized etiological factors, we used a recently described approach, estimating the association between histological types of first and second tumors of men with 2 primary TGCTs. The study population of 488 men each with 2 primary TGCTs was ascertained through population-based cancer registries in the United States between 1972 and 2006. Univariate logistic regression analysis revealed that the histology of second primary TGCTs was associated with the histology of first TGCTs (odds ratio = 1.70, 95% confidence interval: 1.14, 2.52); however, the association did not persist in analyses adjusted for age at diagnosis of first TGCT (odds ratio = 1.09, 95% confidence interval: 0.71, 1.70). These results would be expected if the subtypes share etiology but experience different rates of progression to diagnosis or if the histological fate of TGCTs is influenced by age-related processes. Men with 2 primary TGCTs provide novel opportunities to learn whether histological subtypes are likely to share etiology, so results may inform research designed to identify causes. PMID:23928263

Thomas, Jennifer Phay Johnson; Davis-Dao, Carol; Lewinger, Juan Pablo; Siegmund, Kimberly D; Hamilton, Ann S; Daneshmand, Siamak; Skinner, Eila C; Thomas, Duncan C; Cortessis, Victoria K

2013-10-15

15

Primary Germ Cell Tumor of the Mediastinum - Presenting as a Huge Mass  

PubMed Central

Germ cell tumors compromise 15-20% of all anterior mediastinal masses; 50-60% of these are benign mediastinal teratoma. There may be mature, immature, and rarely with malignant component within the tumor mass. There are more chances of malignancy with immature type. We are reporting a case in 20-year young male diagnosed as giant benign cystic teratoma which was adherent to superior vena cava. The patient underwent surgical excision. In follow up of 2 years, the patient is not having any complaints. PMID:24627752

Dalal, Usha; Jora, Manjit Singh; Dalal, Ashwani K.; Attri, Ashok K.; Singal, Rikki; Gupta, Samita

2014-01-01

16

nAture methods | VOL.11 NO.8 | AUGUST2014 | 847 embryos allocate cells to the three germ layers in a spatially  

E-print Network

layers in culture; however, differentiation is typically heterogeneous and spatially disordered. We show of these three germ layers2�5, it is unclear to what degree this spatial order can be recapitulated in vitro that establishes polarity6,7. The same three pathways can be manipulated to differ- entiate hESCs to any

Cai, Long

17

Development of Acute Megakaryoblastic Leukemia with Isochromosome (12p) after a Primary Mediastinal Germ Cell Tumor in Korea  

PubMed Central

The association of hematological malignancies with a mediastinal germ cell tumor (GCT) is very rare. We report one case of a young adult male with primary mediastinal GCT who subsequently developed acute megakaryoblastic leukemia involving isochromosome (12p). A 25-yr-old man had been diagnosed with a mediastinal GCT and underwent surgical resection and adjuvant chemotherapy. At 1 week after the last cycle of chemotherapy, his peripheral blood showed leukocytosis with blasts. A bone marrow study confirmed the acute megakaryoblastic leukemia. A cytogenetic study revealed a complex karyotype with i(12p). Although additional chemotherapy was administered, the patient could not attain remission and died of septic shock. This case was definitely distinct from therapy-related secondary leukemia in terms of clinical, morphologic, and cytogenetic features. To our knowledge, this is the first case report of a patient with mediastinal GCT subsequently developing acute megakaryoblastic leukemia involving i(12p) in Korea. PMID:21860563

Yu, Nae; Cha, Young-Joo; Park, Eun Kyung; Kim, Jeong Wook

2011-01-01

18

The clinical characteristics and treatment outcome of 57 children and adolescents with primary central nervous system germ cell tumors.  

PubMed

Primary central nervous system germ cell tumors (CNS-GCTs) in children and adolescents have unique clinical features and methods of treatment compared with those in adults. There is little information about Chinese children and adolescents with CNS-GCTs. Therefore, in this study we retrospectively analyzed the clinical features and treatment outcome of Chinese children and adolescents with primary CNS-GCTs. Between January 2002 and December 2012, 57 untreated patients from a single institution were enrolled. They were diagnosed with CNS-GCTs after pathologic or clinical assessment. Of the 57 patients, 41 were males and 16 were females, with a median age of 12.8 years (range, 2.7 to 18.0 years) at diagnosis; 43 (75.4%) had non-germinomatous germ cell tumors (NGGCTs) and 14 (24.6%) had germinomas; 44 (77.2%) had localized disease and 13 (22.8%) had extensive lesions. Fifty-three patients completed the prescribed treatment, of which 18 underwent monotherapy of surgery, radiotherapy, or chemotherapy, and 35 underwent multimodality therapies that included radiotherapy combined with chemotherapy or surgery combined with chemotherapy and/or radiotherapy. PEB (cisplatin, etoposide, and bleomycin) protocol was the major chemotherapy regimen. The median follow-up time was 32.3 months (range, 1.2 to 139 months). Fourteen patients died of relapse or disease progression. The 3-year event-free survival (EFS) and overall survival rates for all patients were 72.2% and 73.8%, respectively. The 3-year EFS was 92.9% for germinomas and 64.8% for NGGCTs (P = 0.064). The 3-year EFS rates for patients with NGGCTs who underwent monotherapy and multimodality therapies were 50.6% and 73.5%, respectively (P = 0.042). Our results indicate that multimodality therapies including chemotherapy plus radiotherapy were better treatment option for children and adolescents with CNS-GCTs. PMID:25011460

Sun, Xiao-Fei; Zhang, Fei; Zhen, Zi-Jun; Yang, Qun-Ying; Xia, Yun-Fei; Wu, Shao-Xiong; Zhu, Jia; Lu, Su-Ying; Wang, Juan; Sun, Fei-Fei; Cai, Rui-Qing; Chen, Yan; Li, Peng-Fei

2014-08-01

19

Platinum-based chemotherapy of primary extragonadal germ cell tumours: the Hellenic Cooperative Oncology Group experience.  

PubMed

Extragonadal germ cell tumours (EGCT) are uncommon, most frequently arise in the mediastinum and retroperitoneum and have variable responses to platinum-based chemotherapy. A retrospective analysis was performed on 38 patients with EGCT treated with cisplatin-based (CDDP) or carboplatin-based (CBDCA) chemotherapy between 1984 and 1998. Twenty-four patients had nonseminomatous germ cell tumours (NSGCT) and 14 seminoma. Twenty-two tumours arose in the mediastinum (13 nonseminomas, 9 seminomas) and 16 in the retroperitoneum (11 NSGCT, 5 seminomas). Initial surgery included complete resection in 1 patient, biopsy in 27 patients and debulking surgery in 10 patients. Complete response rates with chemotherapy +/- surgery were as follows: mediastinum 14 of 21 (66.66%) patients (8 of 12-75% NSGCT, 6 of 9-66.66% seminomas) and retroperitoneum 14 of 16 (87.5%) patients (9 of 11-81.81% NSGCT, 5 of 5-100% seminomas). One patient who underwent complete resection of a mediastinal malignant teratoma combined, received PVB chemotherapy on an adjuvant basis and remains alive and disease-free. Three additional seminoma patients who achieved partial response after chemotherapy remain alive and disease-free following mediastinal radiotherapy. All 14 patients with extragonadal seminomas remain alive with no evidence of disease at a median follow-up of 49 months (range 7-164), giving an overall survival of 100%. Nine of 13 (69.23%) patients with mediastinal NSGCT are long-term disease-free at a median follow-up of 43.5 months (range 7-152). Nine of 11 (81.81%) patients with retroperitoneal NSGCT remain alive and disease-free at a median follow-up of 56 months (range 14-110). Complete surgical resection of residual mass was undertaken in 10 patients (3 seminomas, 7 nonseminomas). The histology revealed necrosis/fibrosis in 6 patients (3 seminomas, 3 NSGCT) and viable cancer in 4 patients. Patients who had viable malignant cells in the resected specimens received two more courses of VelP chemotherapy. None of our patients had relapsed at the time of this analysis. None of our 6 patients who underwent testicular biopsy (1 patient) or orchiectomy (5 patients) due to suspicious ultrasound of the testis were found to have testicular tumour or fibrotic scar. In conclusion, this retrospective analysis showed significant responses in patients with either mediastinal or retroperitoneal NSGCT treated with CDDP- or CBDCA-based chemotherapy +/- surgery. All patients with extragonadal seminomas remain alive with no evidence of disease, regardless of the site at presentation. PMID:10394118

Pectasides, D; Aravantinos, G; Visvikis, A; Bakoyiannis, C; Halikia, A; Kalofonos, C; Kosmidis, P; Skarlos, D; Fountzilas, G

1999-07-01

20

Clinical stage B non-seminomatous germ cell testis cancer: The Indiana University experience (1965–1989) using routine primary retroperitoneal lymph node dissection  

Microsoft Academic Search

Between 1965 and 1989, 1180 patients at Indiana University, U.S.A., underwent retroperitoneal lymph node dissection (RPLND) for non-seminomatous germ cell (NSGC) testis cancer of whom 638 cases had primary RPLND. A subset of 174 cases were considered clinical stage B (or II) before surgery (retroperitoneal nodal metastases by clinical staging). Surgery revealed that 23% (n = 41) had pathological stage

J. P. Donohue; J. A. Thornhill; R. S. Foster; R. G. Rowland; R. Bihrle

1995-01-01

21

Human Embryonic Stem Cells and Germ Cell Development  

Microsoft Academic Search

\\u000a Embryonic stem cells (ESCs) are derived from the inner cell mass (ICM) of blastocysts and are characterized by the ability\\u000a to differentiate into the three primary germ layers. Evidence shows, however, that the cells of the ICM and derived ESCs are\\u000a not identical. Expression of early germ cell–specific markers in undifferentiated ESCs and the ability of ESCs to differentiate\\u000a into

Nina J. Kossack; Joerg Gromoll; Renee A. Reijo Pera

22

Automatic identification and delineation of germ layer components in H&E stained images of teratomas derived from human and nonhuman primate embryonic stem cells  

Microsoft Academic Search

We present a methodology for the automatic identification and delineation of germ-layer components in H&E stained images of teratomas derived from human and nonhuman primate embryonic stem cells. A knowledge and understanding of the biology of these cells may lead to advances in tissue regeneration and repair, the treatment of genetic and developmental syndromes, and drug testing and discovery. As

Ramamurthy Bhagavatula; Matthew C. Fickus; W. Kelly; Chenlei Guo; John A. Ozolek; Carlos A. Castro; Jelena Kovacevic

2010-01-01

23

Transcriptional profiling of endogenous germ layer precursor cells identifies dusp4 as an essential gene in zebrafish endoderm specification  

PubMed Central

A major goal for developmental biologists is to define the behaviors and molecular contents of differentiating cells. We have devised a strategy for isolating cells from diverse embryonic regions and stages in the zebrafish, using computer-guided laser photoconversion of injected Kaede protein and flow cytometry. This strategy enabled us to perform a genome-wide transcriptome comparison of germ layer precursor cells. Mesendoderm and ectoderm precursors cells isolated by this method differentiated appropriately in transplantation assays. Microarray analysis of these cells reidentified known genes at least as efficiently as previously reported strategies that relied on artificial mesendoderm activation or inhibition. We also identified a large set of uncharacterized mesendoderm-enriched genes as well as ectoderm-enriched genes. Loss-of-function studies revealed that one of these genes, the MAP kinase inhibitor dusp4, is essential for early development. Embryos injected with antisense morpholino oligonucleotides that targeted Dusp4 displayed necrosis of head tissues. Marker analysis during late gastrulation revealed a specific loss of sox17, but not of other endoderm markers, and analysis at later stages revealed a loss of foregut and pancreatic endoderm. This specific loss of sox17 establishes a new class of endoderm specification defect. PMID:18719100

Brown, Jamie L.; Snir, Mirit; Noushmehr, Houtan; Kirby, Martha; Hong, Sung-Kook; Elkahloun, Abdel G.; Feldman, Benjamin

2008-01-01

24

Trainee Primary Teachers’ Ideas about the Ozone Layer  

Microsoft Academic Search

The ideas of trainee primary teachers about the ozone layer have been examined. Students were well informed about the nature and location of the ozone layer and appreciated that it screens the Earth from ultraviolet (UV) rays, although some thought that it protects the Earth from acid rain. Most identified real causes of ozone layer depletion, but many thought that

Edward Boyes; William Chambers; Martin Stanisstreet

1995-01-01

25

Germ Tag  

NSDL National Science Digital Library

In this version of tag, a large group of learners model how the body fights infection. Learners act as germs, as lymphocytes, and as the body's cells threatened by germs. After playing one round, subsequent rounds can use different numbers of germs and/or lymphocytes to see how the infection rate is changed. When learners set up a free account at Kinetic City, they can answer bonus questions at the end of the activity as a quick assessment. They can also keep track of their progress in all of the Kinetic City activities, and compare their progress to other participants worldwide.

Science, American A.

2009-01-01

26

Influence of commercially derived lipids and a surfactant on the mode of germination and process of germ-tube formation in primary conidia of two species of Erynia subgenus Neopandora (Zygomycotina: Entomophthorales  

Microsoft Academic Search

Primary conidia of the entomopathogens Erynia (subgenus Neopandora) delphacis (1 isolate) and Erynia ( Neopandora) neoaphidis\\u000a (3 isolates) were stimulated to form germ-tubes with Tween 20 and with free, long-chain fatty acids, each incorporated into\\u000a Entomophthora complete medium (ECM). When combined with other basal media (three tested), these compounds did not stimulate\\u000a germ-tube formation. Triacylglycerols and vegetable oils, added to

Aviva Uziel; Robert G. Kenneth

1998-01-01

27

Non-primary layering in some Adirondack orthogneisses  

SciTech Connect

Metamorphic, as opposed to primary, layering has been shown to be important in many tectonites. Within orthogneisses additional types of non-primary layering are common and have important genetic implications. Here the authors cite three Adirondack examples. (1) Hyde School Gneiss of the Adirondack Lowlands contains semi-continuous layers of foliated amphibolite arranged parallel to contacts and early foliation and disrupted by pegmatitic, alaskitic, and tonalitic host rock. Layering appears to be the result of penetration of amphibolite by granitoid magma first along extensional fractures and then parallel to foliation. Intrusion is envisaged to take place in active shear zones initially occupied by foliated amphibolite that is subsequently penetrated parallel to foliation by granitoids. (2) South of Elizabethtown foliated, isoclinally folded gabbroic anorthosite is well layered with garnetiferous amphibolite, quartz-feldspar gneiss, and calcsilicate. Because of rock composition, the layering cannot be due to metavolcanic sequences nor can disruption be attributed to partial melting. A satisfactory interpretation is that gabbroic anorthosite intruded mafic and carbonate-rich rocks in lit-par-lit fashion. (3) North of Speculator a garnetiferous amphibolite/gabbro has been intruded by granite now containing xenoliths, some with ophitic opx. Much of the layering in the granite consists of clots of plagioclase, garnet, pyroxene (chloritized) arranged in parallel. These are interpreted as small xenoliths of garnetiferous amphibolite/gabbro entrained into the granitic magma and strung out in the direction of flow. These examples provide further evidence that layering can develop during magmatic emplacement and need not represent primary stratification. Assignment of a primary origin to such layering necessarily results in misinterpretation of geologic history.

Levy, R.; McLelland, J.; Ritter, A. (Colgate Univ., Hamilton, NY (United States). Geology Dept.)

1993-03-01

28

Trainee Primary Teachers' Ideas about the Ozone Layer.  

ERIC Educational Resources Information Center

Survey results reveal trainee primary teachers are well informed about the nature and location of the ozone layer and appreciated that it screens the earth from ultraviolet (UV) rays, although some thought that it protects the earth from acid rain. Identifies themes in students' thinking and groups of students with different concepts. (LZ)

Boyes, Edward; And Others

1995-01-01

29

Pediatric primary central nervous system germ cell tumors of different prognosis groups show characteristic miRNome traits and chromosome copy number variations  

Microsoft Academic Search

BACKGROUND: Intracranial pediatric germ cell tumors (GCTs) are rare and heterogeneous neoplasms and vary in histological differentiation, prognosis and clinical behavior. Germinoma and mature teratoma are GCTs that have a good prognosis, while other types of GCTs, termed nongerminomatous malignant germ cell tumors (NGMGCTs), are tumors with an intermediate or poor prognosis. The second group of tumors requires more extensive

Hsei-Wei Wang; Yu-Hsuan Wu; Jui-Yu Hsieh; Muh-Lii Liang; Meng-En Chao; Da-Jung Liu; Ming-Ta Hsu; Tai-Tong Wong

2010-01-01

30

Human Mesenchymal Stem Cells Derived From Limb Bud Can Differentiate into All Three Embryonic Germ Layers Lineages  

PubMed Central

Abstract Mesenchymal stem cells (MSCs) have been isolated from many sources, including adults and fetuses. Previous studies have demonstrated that, compared with their adult counterpart, fetal MSCs with several remarkable advantages may be a better resource for clinical applications. In this study, we successfully isolated a rapidly proliferating cell population from limb bud of aborted fetus and termed them “human limb bud–derived mesenchymal stem cells” (hLB-MSCs). Characteristics of their morphology, phenotype, cell cycle, and differentiation properties were analyzed. These adherent cell populations have a typically spindle-shaped morphology. Flow cytometry analysis showed that hLB-MSCs are positive for CD13, CD29, CD90, CD105, and CD106, but negative for CD3, CD4, CD5, CD11b, CD14, CD15, CD34, CD45, CD45RA, and HLA-DR. The detection of cell cycle from different passages indicated that hLB-MSCs have a similar potential for propagation during long culture in vitro. The most novel finding here is that, in addition to their mesodermal differentiation (osteoblasts and adipocytes), hLB-MSCs can also differentiated into extramesenchymal lineages, such as neural (ectoderm) and hepatic (endoderm) progenies. These results indicate that hLB-MSCs have a high level of plasticity and can differentiate into cell lineages from all three embryonic layers in vitro. PMID:22775353

Jiao, Fei; Wang, Juan; Dong, Zhao-lun; Wu, Min-juan; Zhao, Ting-bao; Li, Dan-dan

2012-01-01

31

Influence of flow properties on a structure of a mineral wool primary layer  

Microsoft Academic Search

Mineral wool primary layer formation is influenced by the aerodynamic characteristics of the blow-away airflow and the secondary surrounding airflow. The distribution of mineral wool fibres in the primary layer was determined experimentally using a computer-aided visualization method. The flow properties in the region where the primary layer is formed were analysed. Numerical simulations with experiment-based boundary conditions were performed.

Tom Bajcar; Bogdan Blagojevi?; Brane Širok; Matevž Dular

2007-01-01

32

In vitro Culture of Primary Plasmacytomas Requires Stromal Cell Feeder Layers  

Microsoft Academic Search

Attempts to grow primary murine plasmacytomas in vitro have, to date, been largely unsuccessful. In this study, we demonstrate that long-term in vitro growth of primary plasmacytomas is accomplished by using feeder layers composed of stromal cells from the initial site of plasmacytomagenesis. The early neoplastic lines established in this manner are dependent on physical contact with the stromal layer,

Alberto Degrassi; David M. Hilbert; Stuart Rudikoff; Arthur O. Anderson; Michael Potter; Hayden G. Coon

1993-01-01

33

Origin and Maintenance of the Benthic Nepheloid Layer Primary Investigator: Nathan Hawley -NOAA GLERL  

E-print Network

Origin and Maintenance of the Benthic Nepheloid Layer Primary Investigator: Nathan Hawley - NOAA of chemical substances. In the Great Lakes the benthic nepheloid layer (bnl) may play a significant role transparency in the benthic nepheloid layer. The deployments will be made at a greater depth than the previous

34

Influence of flow properties on a structure of a mineral wool primary layer  

SciTech Connect

Mineral wool primary layer formation is influenced by the aerodynamic characteristics of the blow-away airflow and the secondary surrounding airflow. The distribution of mineral wool fibres in the primary layer was determined experimentally using a computer-aided visualization method. The flow properties in the region where the primary layer is formed were analysed. Numerical simulations with experiment-based boundary conditions were performed. The numerically obtained profile of mineral wool thickness at the collection chamber outlet agreed with the results of the experiment. Presented numerical model confirms that the forming of the primary layer is significantly dependent on local aerodynamic characteristic of the airflow in the collection chamber. Interaction between the local anomalies on the forming layer and the corresponding aerodynamic effects in the surrounding region was also analysed. (author)

Bajcar, Tom; Blagojevic, Bogdan; Sirok, Brane; Dular, Matevz [Faculty of Mechanical Engineering, University of Ljubljana, Askerceva 6, SI - 1000 Ljubljana (Slovenia)

2007-11-15

35

Cancer testis antigen expression in testicular germ cell tumorigenesis.  

PubMed

Cancer testis antigens are encoded by germ line-associated genes that are present in normal germ cells of testis and ovary but not in differentiated tissues. Their expression in various human cancer types has been interpreted as 're-expression' or as intratumoral progenitor cell signature. Cancer testis antigen expression patterns have not yet been studied in germ cell tumorigenesis with specific emphasis on intratubular germ cell neoplasia unclassified as a precursor lesion for testicular germ cell tumors. Immunohistochemistry was used to study MAGEA3, MAGEA4, MAGEC1, GAGE1 and CTAG1B expression in 325 primary testicular germ cell tumors, including 94 mixed germ cell tumors. Seminomatous and non-seminomatous components were separately arranged and evaluated on tissue microarrays. Spermatogonia in the normal testis were positive, whereas intratubular germ cell neoplasia unclassified was negative for all five CT antigens. Cancer testis antigen expression was only found in 3% (CTAG1B), 10% (GAGE1, MAGEA4), 33% (MAGEA3) and 40% (MAGEC1) of classic seminoma but not in non-seminomatous testicular germ cell tumors. In contrast, all spermatocytic seminomas were positive for cancer testis antigens. These data are consistent with a different cell origin in spermatocytic seminoma compared with classic seminoma and support a progression model with loss of cancer testis antigens in early tumorigenesis of testicular germ cell tumors and later re-expression in a subset of seminomas. PMID:24232866

Bode, Peter K; Thielken, Andrea; Brandt, Simone; Barghorn, André; Lohe, Bernd; Knuth, Alexander; Moch, Holger

2014-06-01

36

Apvasa marks germ-cell migration in the parthenogenetic pea aphid Acyrthosiphon pisum (Hemiptera: Aphidoidea).  

PubMed

In the parthenogenetic and viviparous pea aphid Acyrthosiphon pisum, germline specification depends on the germ plasm localized to the posterior region of the egg chamber before the formation of the blastoderm. During blastulation, germline segregation occurs at the egg posterior, and in early gastrulation germ cells are pushed inward by the invaginating germ band. Previous studies suggest that germ cells remain dorsal in the embryo in subsequent developmental stages. In fact, though, it is not known whether germ cells remain in place or migrate dynamically during katatrepsis and germ-band retraction. We cloned Apvasa, a pea aphid homologue of Drosophila vasa, and used it as a germline marker to monitor the migration of germ cells. Apvasa messenger RNA (mRNA) was first restricted to morphologically identifiable germ cells after blastoderm formation but that expression soon faded. Apvasa transcripts were again identified in germ cells from the stage when the endosymbiotic bacteria invaded the embryo, and after that, Apvasa mRNA was present in germ cells throughout all developmental stages. At the beginning of katatrepsis, germ cells were detected at the anteriormost region of the egg chamber as they were migrating into the body cavity. During the early period of germ-band retraction, germ cells were separated into several groups surrounded by a layer of somatic cells devoid of Apvasa staining, suggesting that the coalescence between migrating germ cells and the somatic gonadal mesoderm occurs between late katatrepsis and early germ-band retraction. PMID:17333259

Chang, Chun-Che; Lin, Gee-Way; Cook, Charles E; Horng, Shwu-Bin; Lee, How-Jin; Huang, Ting-Yu

2007-04-01

37

Familial germ cell tumor  

PubMed Central

Familial testicular germ cell tumors are well known in literature. Only few cases are reported where both brother and sister of the same family suffered from germ cell malignancies. We present a family where the proband is a survivor of ovarian dysgerminoma stage IA. Her elder male sibling became acutely ill and was detected to have disseminated testicular malignancy with grossly elevated markers and vegetations in the mitral valve leaflets. Despite all measures he could not be saved. Presence of germ cell malignancies in the siblings of different sex in the same family points toward a genetic susceptibility. Literature review revealed only six similar cases. A discussion regarding the rare occurrence of familial germ cell malignancies with the affected family members may be worthwhile. PMID:22754236

Cyriac, Sanju; Rajendranath, Rejeev; Louis, A Robert; Sagar, T. G.

2012-01-01

38

Ways to Limit Germs  

MedlinePLUS

... who has used the toilet. • After touching an animal or animal waste. Watch the Webcast, "Infection Control & Germs" to ... a timer? Hum the "Happy Birthday" song from beginning to end twice. • Rinse your hands well under ...

39

Monitoring and Control of Quality of the Primary Layer of Mineral Wool on a Disc Spinning Machine  

Microsoft Academic Search

A novel method of measurement and control of the primary layer quality in mineral wool production processes is presented. The measurement method is based on image acquisition and processing of the mineral wool primary layer structure. As a statistical estimator of the primary layer quality, the ratio between the RMS (root mean square) and the average intensity in a selected

B. Blagojevic; B. Sirok; M. Hocevar

2003-01-01

40

Alumina atomic layer deposition nanocoatings on primary diamond particles using a fluidized bed reactor  

E-print Network

Alumina atomic layer deposition nanocoatings on primary diamond particles using a fluidized bed particles in a scalable fluidized bed reactor. The studies of fluidization at reduced pressure show; Atomic layer deposition (ALD); Fluidized bed reactor 1. Introduction Due to its extreme hardness, diamond

George, Steven M.

41

Dppa3 / Pgc7 / stellais a maternal factor and is not required for germ cell specification in mice  

E-print Network

Background: In mice, germ cells are specified through signalling between layers of cells comprising the primitive embryo. The function of Dppa3 (also known as Pgc7 or stella), a gene expressed in primordial germ cells at ...

Bortvin, Alex

42

RNA Granules in Germ Cells  

PubMed Central

Germ granules” are cytoplasmic, nonmembrane-bound organelles unique to germline. Germ granules share components with the P bodies and stress granules of somatic cells, but also contain proteins and RNAs uniquely required for germ cell development. In this review, we focus on recent advances in our understanding of germ granule assembly, dynamics, and function. One hypothesis is that germ granules operate as hubs for the posttranscriptional control of gene expression, a function at the core of the germ cell differentiation program. PMID:21768607

Voronina, Ekaterina; Seydoux, Geraldine; Sassone-Corsi, Paolo; Nagamori, Ippei

2011-01-01

43

Environmentally Induced Transgenerational Epigenetic Reprogramming of Primordial Germ Cells and the Subsequent Germ Line  

PubMed Central

A number of environmental factors (e.g. toxicants) have been shown to promote the epigenetic transgenerational inheritance of disease and phenotypic variation. Transgenerational inheritance requires the germline transmission of altered epigenetic information between generations in the absence of direct environmental exposures. The primary periods for epigenetic programming of the germ line are those associated with primordial germ cell development and subsequent fetal germline development. The current study examined the actions of an agricultural fungicide vinclozolin on gestating female (F0 generation) progeny in regards to the primordial germ cell (PGC) epigenetic reprogramming of the F3 generation (i.e. great-grandchildren). The F3 generation germline transcriptome and epigenome (DNA methylation) were altered transgenerationally. Interestingly, disruptions in DNA methylation patterns and altered transcriptomes were distinct between germ cells at the onset of gonadal sex determination at embryonic day 13 (E13) and after cord formation in the testis at embryonic day 16 (E16). A larger number of DNA methylation abnormalities (epimutations) and transcriptional alterations were observed in the E13 germ cells than in the E16 germ cells. These observations indicate that altered transgenerational epigenetic reprogramming and function of the male germline is a component of vinclozolin induced epigenetic transgenerational inheritance of disease. Insights into the molecular control of germline transmitted epigenetic inheritance are provided. PMID:23869203

Skinner, Michael K.; Haque, Carlos Guerrero-Bosagna M.; Nilsson, Eric; Bhandari, Ramji; McCarrey, John R.

2013-01-01

44

Environmentally induced transgenerational epigenetic reprogramming of primordial germ cells and the subsequent germ line.  

PubMed

A number of environmental factors (e.g. toxicants) have been shown to promote the epigenetic transgenerational inheritance of disease and phenotypic variation. Transgenerational inheritance requires the germline transmission of altered epigenetic information between generations in the absence of direct environmental exposures. The primary periods for epigenetic programming of the germ line are those associated with primordial germ cell development and subsequent fetal germline development. The current study examined the actions of an agricultural fungicide vinclozolin on gestating female (F0 generation) progeny in regards to the primordial germ cell (PGC) epigenetic reprogramming of the F3 generation (i.e. great-grandchildren). The F3 generation germline transcriptome and epigenome (DNA methylation) were altered transgenerationally. Interestingly, disruptions in DNA methylation patterns and altered transcriptomes were distinct between germ cells at the onset of gonadal sex determination at embryonic day 13 (E13) and after cord formation in the testis at embryonic day 16 (E16). A larger number of DNA methylation abnormalities (epimutations) and transcriptional alterations were observed in the E13 germ cells than in the E16 germ cells. These observations indicate that altered transgenerational epigenetic reprogramming and function of the male germline is a component of vinclozolin induced epigenetic transgenerational inheritance of disease. Insights into the molecular control of germline transmitted epigenetic inheritance are provided. PMID:23869203

Skinner, Michael K; Guerrero-Bosagna, Carlos; Haque, M; Nilsson, Eric; Bhandari, Ramji; McCarrey, John R

2013-01-01

45

Genetics of germ cell development  

E-print Network

The germ line represents a continuous cellular link between generations and between species, but the germ cells themselves develop in a specialized, organism-specific context. The model organisms Caenorhabditis elegans, ...

Lesch, Bluma J.

46

Germs and the Body  

NSDL National Science Digital Library

This Science NetLinks lesson explores germs, where they exist, and how they can affect the body. It also addresses a common misconception that students of all ages may have - that factors important to health are beyond their personal control. In studying bacteria, students will also learn preventative measures they can take to stay healthy.

Science Netlinks;

2002-08-01

47

No. 74: : Germs  

NSDL National Science Digital Library

The University of Houston's College of Engineering presents this series about the machines that make our civilization run, and the people whose ingenuity created them. This episode is available in audio format. This page recounts the contributions af various persons to the eventual development of the germ theory of disease.

Lienhard, John H.

1997-01-01

48

Wheat Germ DNA Extraction  

NSDL National Science Digital Library

This laboratory exercise is designed to show learners how DNA can easily be extracted from wheat germ using simple materials. Use this experiment to supplement any unit on genetics and to demonstrate how scientists study DNA. Adult supervision is recommended. This resource guide includes tips and suggestions for instructors as well as other DNA extraction experiments and a chart for learners to answer questions.

Hays, Lana

2009-01-01

49

The effects of temporal variability of mixed layer depth on primary productivity around Bermuda  

NASA Technical Reports Server (NTRS)

Temporal variations in primary production and surface chlorophyll concentrations, as measured by ship and satellite around Bermuda, were simulated with a numerical model. In the upper 450 m of the water column, population dynamics of a size-fractionated phytoplankton community were forced by daily changes of wind, light, grazing stress, and nutrient availability. The temporal variations of production and chlorophyll were driven by changes in nutrient introduction to the euphotic zone due to both high- and low-frequency changes of the mixed layer depth within 32 deg-34 deg N, 62 deg-64 deg W between 1979 and 1984. Results from the model derived from high-frequency (case 1) changes in the mixed layer depth showed variations in primary production and peak chlorophyll concentrations when compared with results from the model derived from low-frequency (case 2) mixed layer depth changes. Incorporation of size-fractionated plankton state variables in the model led to greater seasonal resolution of measured primary production and vertical chlorophyll profiles. The findings of this study highlight the possible inadequacy of estimating primary production in the sea from data of low-frequency temporal resolution and oversimplified biological simulations.

Bissett, W. Paul; Meyers, Mark B.; Walsh, John J.; Mueller-Karger, Frank E.

1994-01-01

50

Less germs, less mucus, less snot: teachers' and health workers' perceptions of the benefits and barriers of ear health programs in lower primary school classes.  

PubMed

This study explored health and education professionals' perceptions of the health benefits and barriers of different ear health programs used in lower primary school classes in two district education areas in the Goldfields South East Health Region, Western Australia. Health and education staff providing services to children in kindergarten to year three primary school classes were sent a questionnaire about ear health programs provided in their school. Sixty-one questionnaires were returned from 43 teachers, 14 community health nurses, three Aboriginal health workers and one teacher's assistant. Some schools implemented all the ear health programs examined at all year levels while others implemented only one of the programs. Teachers, community health nurses and Aboriginal health workers identified that all ear health programs were beneficial to students. Reported physical health benefits included reduced ear infections, early detection of ear infections and improved hearing. Behavioural benefits included improved concentration, alertness and attention in the classroom. Barriers to implementing the programs were obtaining consent from parents/carers, student transience and attendance, time to implement and conduct the programs and human and physical resources. Evaluation methods used varied from no evaluation for the Breathe Blow Cough and tissue spearing programs to limited data collection for audiometry, otoscopy and ear toilet programs. Respondents perceived that ear health programs were effective in improving health and behavioural outcomes for children. A formal pre-post evaluation to provide objective data to confirm this is needed to inform policy around this important health issue. PMID:21138704

Doyle, June; Ristevski, Eli

2010-01-01

51

Analyses of primary side oxide layers on steam generator tubes from PWRs and radiochemical issues on the contamination of primary circuits  

NASA Astrophysics Data System (ADS)

Auger electron spectroscopy, X-ray photoelectron spectroscopy and ?-spectroscopy have been used to investigate primary-side oxide layers on steam generator tubes from three PWRs. The distribution of iron, chromium, nickel and oxygen in the depth of the oxide layer as well as the valency states of these elements show FeCr 2O 4 to be the main chemical compound forming the oxide layer. Nickel occurs in the entire oxide layer in the elementary state. Only a top few nanometer of the oxide layer contain some NiO besides elementary Ni. 60Co is homogeneously distributed in the entire oxide layer. Considering other radiochemical measurements performed in these three plants, it can be stated that only the ionic fraction of the 60Co in the coolant is able to explain the build-in distribution of this radionuclide in the oxide layer and is thus responsible for the primary circuit contamination.

Schuster, E.; Neeb, K. H.; Ahlfänger, W.; Henkelmann, R.; Järnström, R. T.

1988-03-01

52

Specification of the germ line  

Microsoft Academic Search

In C. elegans, the germ line is set apart from the soma early in embryogenesis. Several important themes have emerged in specifying and guiding the development of the nascent germ line. At early stages, the germline blastomeres are maintained in a transcriptionally silent state by the transcriptional repressor PIE-1. When this silencing is lifted, it is postulated that correct patterns

Susan Strome

2005-01-01

53

Germ-like cell differentiation from induced pluripotent stem cells (iPSCs).  

PubMed

Historically, our understanding of molecular genetic aspects of germ cell development has been limited. Recently, results demonstrated that the derivation of pluripotent stem cells may provide the necessary genetic system to study germ cell development. Here, we characterized an induced pluripotent stem cell (iPSC) line, which can spontaneously differentiate into embryonic bodies (EBs) after 3 days of suspension culture, expressing specific markers of three germ layers. Then, we induced the iPSCs to differentiate into germ cells by culturing adherent EBs in retinoic acid (RA) and porcine follicular fluid (PFF) differentiation medium or seminiferous tubule transplantation. Our results indicated that RA and PFF were beneficial for the derivation of germ cells and oocyte-like cells from iPSCs, and iPSCs transplantation could make a contribution to repairing the testis of infertile mice. Our study offers an approach for further study on the development and the differentiation of germ cells derived from iPSCs. PMID:23086862

Niu, Zhiwei; Hu, Yue; Chu, Zhili; Yu, Meng; Bai, Yaofu; Wang, Long; Hua, Jinlian

2013-01-01

54

Correlation between macular changes and the peripapillary nerve fiber layer in primary open angle glaucoma  

PubMed Central

Glaucoma is a leading cause of blindness and the early diagnosis is crucial for treatment and follow-up in the progression of the disease. Objective: To evaluate the changes in mean macular thickness and volume and compare them with the mean thickness of the peripapillary nerve fiber layer in primary open angle glaucoma, using Time Domain (TD) optical coherence tomography ( OCT). Method: The examinations were conducted on 275 eyes of 138 patients, as it follows: 203 eyes of 102 patients diagnosed with primary open angle glaucoma in various stages of evolution, representing the study group, and 72 normal eyes from 36 patients, representing the control group. The study was conducted from March 2010 to December 2012. All the patients gave their consent, in accordance with the Helsinki Declaration. The study group showed a decrease in mean macular thickness and volume, as well as mean thickness of the peripapillary nerve fiber layer (RNFL) compared to the control group. According to the OCT measurements, the results of the study have shown that the decrease of the mean thickness of the RNFL is a better differentiator between glaucomatous and normal eyes compared to the decrease of the mean macular thickness and volume. PMID:24653759

Manasia, D; Voinea, L; Vasinca, ID; Alexandrescu, C

2014-01-01

55

Pineal germ cell tumors.  

PubMed

Intracranial germ cell tumors (GCTs), especially pineal tumors have attracted the special attention of neuropathologists and neurosurgeons because of their unique growth sites, characteristic subtypes with different histology, and high incidence in Japan and other Asian countries. This chapter describes the general clinical features of pineal GCTs and current treatment of intracranial GCTs. Despite excellent long-term results for patients with germinoma treated with radiation therapy, the potential for late effects makes the treatment controversial. Most patients with nongerminomatous tumors treated by conventional treatment with surgery and radiation therapy failed to survive longer than 3 years. After combination chemotherapy with cisplatin was confirmed to be effective in gonadal GCTs, GCTs of the brain became candidates for chemotherapy. For germinoma, a trial with chemotherapy alone failed with a high rate of recurrence, but Japanese and European trials with chemotherapy and reduced dose and volume of radiation therapy demonstrate good event-free survival rates. Ongoing phase II studies with combined chemotherapy and radiation therapy for nongerminomatous tumors will result in a 5-year survival rate of >50%, which is better than that by radiation therapy alone. PMID:19329862

Matsutani, Masao

2009-01-01

56

Palifosfamide in Treating Patients With Recurrent Germ Cell Tumors  

ClinicalTrials.gov

Adult Central Nervous System Germ Cell Tumor; Adult Teratoma; Malignant Extragonadal Germ Cell Tumor; Malignant Extragonadal Non-Seminomatous Germ Cell Tumor; Extragonadal Seminoma; Recurrent Malignant Testicular Germ Cell Tumor; Recurrent Ovarian Germ Cell Tumor; Stage IV Extragonadal Non-Seminomatous Germ Cell Tumor; Stage IV Extragonadal Seminoma; Stage IV Ovarian Germ Cell Tumor

2014-07-16

57

Superficial layer pyramidal cells communicate heterogeneously between multiple functional domains of cat primary visual cortex.  

PubMed

The axons of pyramidal neurons in the superficial layers of the neocortex of higher mammals form lateral networks of discrete clusters of synaptic boutons. In primary visual cortex the clusters are reported to link domains that share the same orientation preferences, but how individual neurons contribute to this network is unknown. Here we performed optical imaging to record the intrinsic signal, which is an indirect measure of neuronal firing, and determined the global map of orientation preferences in the cat primary visual system. In the same experiment, single cells were recorded and labelled intracellularly. We found that individual axons arborise within the retinotopic representation of the classical receptive field, but their bouton clusters were not aligned along their preferred axis of orientation along the retinotopic map. Axon clusters formed in a variety of different orientation domains, not just the like-orientation domains. This topography and heterogeneity of single-cell connectivity provides circuits for normalization and context-dependent feature processing of visual scenes. PMID:25341917

Martin, Kevan A C; Roth, Stephan; Rusch, Elisha S

2014-01-01

58

Germ cell tumour as a diagnostic pitfall of metastatic carcinoma.  

PubMed Central

AIM: Testicular germ cell tumours may present as metastases in cervical lymph nodes, yet the primary tumours remain clinically occult. The aim of the study is to alert pathologists and clinicians to this uncommon but important presentation and highlight the clues and the diagnostic adjuncts to its correct diagnosis. METHODS: The clinical, cytological, histological, and immunohistochemical features of two patients with germ cell tumour initially presenting as cervical lymphadenopathy were described and analysed. RESULTS: Both patients were young adult males, who were found to have metastatic undifferentiated carcinoma on fine needle aspiration of the enlarged cervical lymph nodes. The tumour cells in both cases were positive for placental alkaline phosphatase (PLAP) and negative for epithelial membrane antigen (EMA). CONCLUSIONS: Clinicians and pathologists should be aware of the possibility of germ cell tumour when encountering a young adult male with metastatic poorly differentiated carcinoma. Positivity for PLAP and negativity for EMA are helpful adjuncts in arriving at the correct diagnosis. Images PMID:8675733

Shek, T W; Yuen, S T; Luk, I S; Wong, M P

1996-01-01

59

Dazl regulates mouse embryonic germ cell development  

E-print Network

In the mouse, germ cells can undergo differentiation to become either oocytes or spermatozoa in response to sex of their gonadal environment. The nature of the germ cell-intrinsic aspects of this signaling have not been ...

Gill, Mark E

2010-01-01

60

HISTORY OF GERM CELL MUTAGENESIS  

EPA Science Inventory

Much of the early work on germ cell mutation analysis was conducted with nonmammalian species, but this historical overview will begin with the rodent studies that provided quantitative data on induced mutations. The initial studies of mutation induction utilized the newly develo...

61

PKA, Germ Cells, and Fertility  

NSDL National Science Digital Library

Temporal and spatial regulation of PKA activity are essential for vigorous sperm motility and for the resumption of meiosis in oocytes, two events required for successful fertilization. Genetic mutations in mice that affect PKA signaling in germ cells lead to infertility and illustrate the importance of this pathway in mammalian reproduction.

2007-02-01

62

Survival of patients with nonseminomatous germ cell cancer: a review of the IGCC classification by Cox regression and recursive partitioning  

Microsoft Academic Search

The International Germ Cell Consensus (IGCC) classification identifies good, intermediate and poor prognosis groups among patients with metastatic nonseminomatous germ cell tumours (NSGCT). It uses the risk factors primary site, presence of nonpulmonary visceral metastases and tumour markers alpha-fetoprotein (AFP), human chorionic gonadotrophin (HCG) and lactic dehydrogenase (LDH). The IGCC classification is easy to use and remember, but lacks flexibility.

M R van Dijk; E W Steyerberg; S P Stenning; E Dusseldorp; J D F Habbema; van Dijk

2004-01-01

63

Primary tethered cord syndrome: a new hypothesis of its origin.  

PubMed

Primary tethered cord syndrome is defined as low placement of the spinal cord and thickened filum terminale with associated anomalies. This definition excludes anomalies concomitant with overt myelomeningocele and spinal cord tethering secondary to myelomeningocele repair. Embryologically, the primary tethered cord syndrome is an entirely different entity from overt myelomeningocele and associated Arnold-Chiari type II malformation, but its origins have not been satisfactorily explained. The authors postulate that primary tethered cord syndrome is a manifestation of local dysmorphogenesis of all three germ layers at the lumbosacral area, possibly triggered by a hemorrhagic, inflammatory, or some other local lesion occurring in embryogenesis. PMID:6426276

Sarwar, M; Virapongse, C; Bhimani, S

1984-01-01

64

Aerosol Measurements in the Atmospheric Surface Layer at L'Aquila, Italy: Focus on Biogenic Primary Particles  

NASA Astrophysics Data System (ADS)

Two year measurements of aerosol concentration and size distribution (0.25 ?m < d < 30 ?m) in the atmospheric surface layer, collected in L'Aquila (Italy) with an optical particle counter, are reported and analysed for the different modes of the particle size distribution. A different seasonal behaviour is shown for fine mode aerosols (largely produced by anthropogenic combustion), coarse mode and large-sized aerosols, whose abundance is regulated not only by anthropogenic local production, but also by remote natural sources (via large scale atmospheric transport) and by local sources of primary biogenic aerosols. The observed total abundance of large particles with diameter larger than 10 ?m is compared with a statistical counting of primary biogenic particles, made with an independent technique. Results of these two observational approaches are analysed and compared to each other, with the help of a box model driven by observed meteorological parameters and validated with measurements of fine and coarse mode aerosols and of an atmospheric primary pollutant of anthropogenic origin (NOx). Except in winter months, primary biogenic particles in the L'Aquila measurement site are shown to dominate the atmospheric boundary layer population of large aerosol particles with diameter larger than 10 ?m (about 80 % of the total during summer months), with a pronounced seasonal cycle, contrary to fine mode aerosols of anthropogenic origin. In order to explain these findings, the main mechanisms controlling the abundance and variability of particulate matter tracers in the atmospheric surface layer are analysed with the numerical box-model.

Pitari, Giovanni; Coppari, Eleonora; De Luca, Natalia; Di Carlo, Piero; Pace, Loretta

2014-09-01

65

Aerosol Measurements in the Atmospheric Surface Layer at L'Aquila, Italy: Focus on Biogenic Primary Particles  

NASA Astrophysics Data System (ADS)

Two year measurements of aerosol concentration and size distribution (0.25 ?m < d < 30 ?m) in the atmospheric surface layer, collected in L'Aquila (Italy) with an optical particle counter, are reported and analysed for the different modes of the particle size distribution. A different seasonal behaviour is shown for fine mode aerosols (largely produced by anthropogenic combustion), coarse mode and large-sized aerosols, whose abundance is regulated not only by anthropogenic local production, but also by remote natural sources (via large scale atmospheric transport) and by local sources of primary biogenic aerosols. The observed total abundance of large particles with diameter larger than 10 ?m is compared with a statistical counting of primary biogenic particles, made with an independent technique. Results of these two observational approaches are analysed and compared to each other, with the help of a box model driven by observed meteorological parameters and validated with measurements of fine and coarse mode aerosols and of an atmospheric primary pollutant of anthropogenic origin (NOx). Except in winter months, primary biogenic particles in the L'Aquila measurement site are shown to dominate the atmospheric boundary layer population of large aerosol particles with diameter larger than 10 ?m (about 80 % of the total during summer months), with a pronounced seasonal cycle, contrary to fine mode aerosols of anthropogenic origin. In order to explain these findings, the main mechanisms controlling the abundance and variability of particulate matter tracers in the atmospheric surface layer are analysed with the numerical box-model.

Pitari, Giovanni; Coppari, Eleonora; De Luca, Natalia; Di Carlo, Piero; Pace, Loretta

2014-03-01

66

Retroperitoneal germ cell tumor diagnosed by endoscopic ultrasound-guided fine needle aspiration  

PubMed Central

Isolated extragonadal germ cell tumors can be primary in nature or metastatic from a burned out testicular cancer. Accurate diagnosis is critical as appropriate therapy can be highly curative. We present the case of an isolated extragonadal germ cell tumor in the retroperitoneum diagnosed by endoscopic ultrasound-guided fine needle aspiration. This case underscores the importance of considering germ cell tumors in the differential diagnosis of an unexplained retroperitoneal mass, particularly since immunophenotypic staining may be necessary to establish the diagnosis. PMID:21191538

Womeldorph, Craig M; Zalupski, Mark M; Knoepp, Stewart M; Soltani, Mohammad; Elmunzer, B Joseph

2010-01-01

67

Laminin in the male germ cells of Drosophila  

PubMed Central

To study genes that may be crucial for the male germ cell development of Drosophila we screened a cDNA expression library with a polyclonal antiserum against testis proteins of Drosophila hydei. We identified a cDNA fragment that exhibited a complete sequence similarity with the cDNA of the laminin B2 chain, an important component of the extracellular matrix. Transcripts of laminin B2 were detected in the RNA of male germ cells with the polymerase chain reaction and by in situ hybridization. We studied the reaction of different polyclonal antibodies including those against a Drosophila laminin B2-lac fusion protein, the entire Drosophila laminin complex, or against the mouse laminin complex and against laminin A and B1 chains with specific structures in developing male germ cells of Drosophila. Antigenic sites against laminin B2 were found in the lampbrush loops in primary spermatocyte nuclei, in nuclei of spermatids, and in heads of spermatozoa. The axonemes of elongating spermatids react with antibodies against the Drosophila laminin B1, B2 and laminin A chains. The possible biological functions of the laminin in the male germ cells of Drosophila are discussed. PMID:1429843

1992-01-01

68

Terminal morphology and distribution of corticothalamic fibers originating from layers 5 and 6 of cat primary auditory cortex.  

PubMed

Two types of terminations were observed on corticothalamic fibers arising from cells in different layers of cat auditory cortex. Injections of the anterograde tracers Phaseolus vulgaris leucoagglutinin (PHA-L) or biocytin were made into single cortical loci that included both superficial layer 5 (5a) and layer 6 in the primary auditory cortex (AI). These resulted in labeling of terminal fibers with small (approximately 1 micron) and large (approximately 2 microns) boutons in the medial geniculate complex (MG) and the lateral nucleus of the posterior complex. Large boutons were found in the deep and superficial dorsal nuclei, in the ventrolateral nucleus, and, less frequently, in the medial nucleus of the MG. They usually ended in grape-like clusters of boutons. By contrast, small boutons were found densely in the pars lateralis and pars ovoidea of the ventral nucleus, and to a lesser extent in the medial nucleus of MG. In the anterior third of the ventral nucleus, where the highest density of labeled fibers was observed, the small bouton terminations formed a plate-like plexus. In the inferior colliculus (IC), most terminal boutons on labeled corticotectal fibers were of large size. To reveal the cells of origin of the axons ending in the two different types of corticothalamic terminations, biocytin injections were localized in either layer 5 or layer 6 of AI or PHA-L injections were made into middle layers, including layer 5a but excluding layer 6. Virtually all labeled terminals found in the MG after layer 5 injections were of large size, while those found after layer 6 injections were of small size. The distribution of terminals of single-labeled axons was extensive and variable. For example, an axon recovered after a layer 5 injection of biocytin ended in at least seven patches of clusters of large boutons along much of the anteroposterior axis of MG. Our previous findings showed two neuronal populations situated in superficial layer 5 and in layer 6 of AI and projecting to the thalamus. The axons of these cells had different patterns of collateral distributions in the cortex. The present study shows that the extrinsically projecting axons of these two populations also have different terminal morphologies and distribution patterns in the MG. The findings suggest that the corticothalamic pathway in the cat auditory system consists of at least two feedback projections originating from different cortical layers that exert different influences on distinct thalamic neuronal populations. PMID:7703690

Ojima, H

1994-01-01

69

The importance of the apposition of the submucosal intestinal layers for primary wound healing of intestinal anastomosis.  

PubMed

This study was undertaken to examine the importance of the apposition of the submucosal layers in healing of the intestinal anastomosis. On 18 mongrel dogs, weighing between 8 and 15 kilograms, four anastomoses were performed on the small intestine. Two with a conventional anastomosis and two with rings of polyester-polyethyleneterephtalate, containing small Ticonal magnets. The force between the rings with the magnets varied from 0-3 newton between, respectively, 15 millimeters and zero millimeter distance. After three to four days, the rings cut through and disappeared from the anastomosis. Morphologic and microangiographic studies, undertaken at ten days, revealed that, in instances of good submucosal apposition, direct bridging of the defect in the submucosal layer was seen with rapid restoration of the villous epithelium and an undisturbed vascular pattern in the anastomotic area. This we called primary intestinal healing. In instances of bad submucosal apposition, we saw indirect bridging of the submucosal layer defect by smaller and longer strands of newly synthesized collagen tissue in the outer intestinal layers with a collateral circulation from the submucosal plexus to the arterial plexuses in these layers. In all instances, an epithelial defect still persisted at ten days. This type of wound healing we called secondary intestinal healing. The results showed that, with the magnetic rings, a significantly better apposition of the intestinal layers was achieved. PMID:7455891

Jansen, A; Becker, A E; Brummelkamp, W H; Keeman, J N; Klopper, P J

1981-01-01

70

Transport of germ plasm on astral microtubules directs germ cell development in Drosophila  

PubMed Central

Summary Background In many organisms, germ cells are segregated from the soma through the inheritance of the specialized germ plasm, which contains mRNAs and proteins that specify germ cell fate and promote germline development. Whereas germ plasm assembly has been well characterized, mechanisms mediating germ plasm inheritance are poorly understood. In the Drosophila embryo, germ plasm is anchored to the posterior cortex and nuclei that migrate into this region give rise to the germ cell progenitors, or pole cells. How the germ plasm interacts with these nuclei for pole cell induction and is selectively incorporated into the forming pole cells is not known. Results Live imaging of two conserved germ plasm components, nanos mRNA and Vasa protein, revealed that germ plasm segregation is a dynamic process involving active transport of germ plasm RNA-protein complexes coordinated with nuclear migration. We show that centrosomes accompanying posterior nuclei induce release of germ plasm from the cortex and recruit these components by dynein-dependent transport on centrosome-nucleated microtubules. As nuclei divide, continued transport on astral microtubules partitions germ plasm to daughter nuclei, leading to its segregation into pole cells. Disruption of these transport events prevents incorporation of germ plasm into pole cells and impairs germ cell development. Conclusions Our results indicate that active transport of germ plasm is essential for its inheritance and ensures the production of a discrete population of germ cell progenitors endowed with requisite factors for germline development. Transport on astral microtubules may provide a general mechanism for the effective segregation of cell fate determinants. PMID:21376599

Lerit, Dorothy A.; Gavis, Elizabeth R.

2011-01-01

71

Primary, secondary instabilities and control of the rotating-disk boundary layer  

E-print Network

-disk flow turbulent r´egime laminar flow (Kohama 1984) transition at r 500 · no intrinsic geometrical-similar laminar basic flow no characteristic length scale U(r, z) = rU(z) rV (z) W (z) constant boundary layer and control Leicester, 8 May 2009 11 / 38 Natural flow Linear stability analysis Temporal growth rate

72

UNSW Embryology: movies of germ cell migration  

NSDL National Science Digital Library

Timelapse movies showing GFP labeled primordial germ cells during migration in the mouse from Mark Hill''s site courtesy of Molyneaux KA (Molyneaux KA, Stallock J, Schaible K, Wylie C. [See Related Articles] Time-lapse analysis of living mouse germ cell migration. Dev Biol. 2001 Dec 15;240(2):488-98).

Dr. Mark Hill (University of New South Wales Anatomy)

2007-12-31

73

Thermal stability of the surface layer and its relation to the dispersion of primary pollutants in St. Louis  

NASA Technical Reports Server (NTRS)

The present investigation is concerned with the applicability of the vertical temperature gradient, DT, as a dispersion parameter for urban area sources. Data on DT were tabulated from temperature measurements at 5 m and 30 m obtained on 30 m towers at 12 stations. DT was obtained by subtracting the value at 5 m from that at 30 m. Positive DT values represent an inversion. Accuracy of the DT data is 0.1 K. Hourly measurements of DT along with concentrations of the primary pollutants, CO, NO, and total hydrocarbons (THC), are available from the 1976 RAPS data base for St. Louis. Linear correlations between a given pollutant species concentration and DT are developed from that data set. It could be confirmed that a strong positive correlation exists at night between the thermal stability of the lowest part of the boundary layer and the urban concentration of the primary pollutants CO, NO, and hydrocarbons.

Remsberg, E. E.; Woodbury, G. E.

1982-01-01

74

[Genetics of testicular germ cell tumors].  

PubMed

Testicular cancer is by far the most common neoplasm among young males between the ages of 20 and 40 years and with an increasing incidence rate worldwide. Congenital malformations of the male genitals, such as cryptorchidism or inguinal hernia are established risk factors. Men with a family history of testicular cancer are also associated with an increased risk of the disease. In the testes more than 90?% of tumors develop from germ cells (progenitor cells) and represent a histologically heterogeneous group. Germ cell tumors in extragonadal localizations are rare. Isochromosome i(12p), the typical marker chromosome in testicular germ cell tumors, occurs as an early event in tumorigenesis. Spermatocytic seminoma is a rare variant of germ cell tumors and according to the current classification is a distinct entity with different morphological, clinical and also cytogenetical features compared with other germ cell tumors. PMID:24819977

Verdorfer, I

2014-05-01

75

Expression of Axolotl DAZL RNA, a Marker of Germ Plasm: Widespread Maternal RNA and Onset of Expression in Germ Cells Approaching the Gonad  

Microsoft Academic Search

How germ cell specification occurs remains a fundamental question in embryogenesis. The embryos of several model organisms contain germ cell determinants (germ plasm) that segregate to germ cell precursors. In other animals, including mice, germ cells form in response to regulative mechanisms during development. To investigate germ cell determination in urodeles, where germ plasm has never been conclusively identified, we

Andrew D. Johnson; Rosemary F. Bachvarova; Matthew Drum; Thomas Masi

2001-01-01

76

The pathology of late recurrence of testicular germ cell tumors.  

PubMed

A total of 91 men had histologically documented late recurrences of testicular germ cell tumors characterized by a complete response to treatment with a subsequent disease-free interval of at least 2 years and no evidence of a second primary lesion. Ninety percent of the patients for whom information was available received chemotherapy shortly after their initial diagnosis of testicular germ cell tumors; most of the other patients were known to have stage I disease initially. Overall, 60% of patients had teratoma in their late recurrences, including 20 patients (22%) in whom teratoma was the only element. Thus, teratoma was the most common type of neoplasm in late recurrences. Excluding teratoma coexisting with other types of neoplasms, yolk sac tumor was the most frequent type of tumor in patients with late recurrence. It occurred in 47% of patients, either alone or with teratoma, another nonteratomatous germ cell tumor type, or a "nongerm cell malignant tumor." Unusual types of yolk sac tumor, including glandular, parietal, clear cell, and pleomorphic patterns, were seen frequently in late recurrences and often raised differential diagnostic problems with "nongerm cell" carcinomas. A smaller number of late recurrences consisted of other types of neoplasms. Twenty percent of patients with late recurrence had a nonteratomatous germ cell tumor other than yolk sac tumor, either alone, with yolk sac tumor, or with a "nongerm cell malignant tumor." Most of these nonteratomatous germ cell tumors other than yolk sac tumor were embryonal carcinoma, although rarely seminoma and choriocarcinoma were encountered. "Nongerm cell malignant tumors," including both sarcomas and carcinomas of various types, occurred in 23% of late-recurrence patients, either alone or with a nonteratomatous germ cell tumor. Late recurrences were seen in many different sites in these patients, including the retroperitoneum, abdomen, pelvis, liver, mediastinum, lung, bone (femur, vertebra, and rib), lymph nodes outside the retroperitoneum and mediastinum (supraclavicular, neck, and axillary regions), scrotum and inguinal regions, adrenal gland, chest wall, and buttocks. Follow-up data were available for 79 of the 91 patients studied. Duration of follow-up ranged from 2 months to 13 years after the patient's first late recurrences; the mean length of follow-up was 4.8 years. Patients whose late recurrences consisted of teratoma only had the most favorable outcomes, with 79% having no evidence of disease at last follow-up. Patients whose late recurrences consisted of pure "nongerm cell malignant tumor" or pure germ cell tumor (yolk sac tumor or other types) had a much worse prognosis: Only 36% to 37% were alive with no evidence of disease. Patients with two different types of nonteratomatous malignancies in their late recurrences had a dismal clinical course: Only 17% with both yolk sac tumor and other nonteratomatous germ cell tumor had no evidence of disease, whereas no patient with both nonteratomatous germ cell tumor and "nongerm cell malignant tumor" was disease free. Late recurrences consisting of teratoma alone often have a favorable outcome, but the prognosis in all other patients is poor. Furthermore, late recurrence is not likely to respond to chemotherapy and is best treated by surgical excision when possible. PMID:10680894

Michael, H; Lucia, J; Foster, R S; Ulbright, T M

2000-02-01

77

["Burned out" testicular tumor: a rare form of germ cell neoplasias].  

PubMed

Burned-out tumour of the testis is a rare form of a germ-cell malignancy of testicular localisation which can regress or disappear. This is a rare form of germ-cell neoplasm. We report on 2 patients with such a tumour. The histological findings, on clinical manifestations, on difficult differential diagnosis from primary retroperitoneal germ-cell tumour, therapy, and outcome of this malignancy are discussed. In the absence of palpable testicular tumour the symptomatology is due to metastasis. Burned-out tumour of the testis must be considered in a patient with retroperitoneal lymph node involvement and histology of "germ-cell tumour". In these patients sonography of scrotal contents may be useful to identify intratesticular abnormalities. These are often the site of the primary tumour. If burned-out tumour of the testis is suspected, the indication for surgery is given. If the frozen section is not "normal testicular tissue", orchiectomy should be performed. The metastasis is treated according to the histology and clinical stage of the tumour. It is important to distinguish burned-out tumour of the testis from true extragonadal germ-cell tumours. Primary removal of the testicular tumour is necessary because of the high rate of persistent testicular malignancy, which may be as much as 50% despite systemic chemotherapy. PMID:10093882

Casella, R; Rochlitz, C; Sauter, G; Gasser, T C

1999-02-13

78

Stochastic specification of primordial germ cells from mesoderm precursors in axolotl embryos  

PubMed Central

A common feature of development in most vertebrate models is the early segregation of the germ line from the soma. For example, in Xenopus and zebrafish embryos primordial germ cells (PGCs) are specified by germ plasm that is inherited from the egg; in mice, Blimp1 expression in the epiblast mediates the commitment of cells to the germ line. How these disparate mechanisms of PGC specification evolved is unknown. Here, in order to identify the ancestral mechanism of PGC specification in vertebrates, we studied PGC specification in embryos from the axolotl (Mexican salamander), a model for the tetrapod ancestor. In the axolotl, PGCs develop within mesoderm, and classic studies have reported their induction from primitive ectoderm (animal cap). We used an axolotl animal cap system to demonstrate that signalling through FGF and BMP4 induces PGCs. The role of FGF was then confirmed in vivo. We also showed PGC induction by Brachyury, in the presence of BMP4. These conditions induced pluripotent mesodermal precursors that give rise to a variety of somatic cell types, in addition to PGCs. Irreversible restriction of the germ line did not occur until the mid-tailbud stage, days after the somatic germ layers are established. Before this, germline potential was maintained by MAP kinase signalling. We propose that this stochastic mechanism of PGC specification, from mesodermal precursors, is conserved in vertebrates. PMID:24917499

Chatfield, Jodie; O'Reilly, Marie-Anne; Bachvarova, Rosemary F.; Ferjentsik, Zoltan; Redwood, Catherine; Walmsley, Maggie; Patient, Roger; Loose, Mathew; Johnson, Andrew D.

2014-01-01

79

Stochastic specification of primordial germ cells from mesoderm precursors in axolotl embryos.  

PubMed

A common feature of development in most vertebrate models is the early segregation of the germ line from the soma. For example, in Xenopus and zebrafish embryos primordial germ cells (PGCs) are specified by germ plasm that is inherited from the egg; in mice, Blimp1 expression in the epiblast mediates the commitment of cells to the germ line. How these disparate mechanisms of PGC specification evolved is unknown. Here, in order to identify the ancestral mechanism of PGC specification in vertebrates, we studied PGC specification in embryos from the axolotl (Mexican salamander), a model for the tetrapod ancestor. In the axolotl, PGCs develop within mesoderm, and classic studies have reported their induction from primitive ectoderm (animal cap). We used an axolotl animal cap system to demonstrate that signalling through FGF and BMP4 induces PGCs. The role of FGF was then confirmed in vivo. We also showed PGC induction by Brachyury, in the presence of BMP4. These conditions induced pluripotent mesodermal precursors that give rise to a variety of somatic cell types, in addition to PGCs. Irreversible restriction of the germ line did not occur until the mid-tailbud stage, days after the somatic germ layers are established. Before this, germline potential was maintained by MAP kinase signalling. We propose that this stochastic mechanism of PGC specification, from mesodermal precursors, is conserved in vertebrates. PMID:24917499

Chatfield, Jodie; O'Reilly, Marie-Anne; Bachvarova, Rosemary F; Ferjentsik, Zoltan; Redwood, Catherine; Walmsley, Maggie; Patient, Roger; Loose, Mathew; Johnson, Andrew D

2014-06-01

80

Specification of germ cell fate in mice.  

PubMed Central

An early fundamental event during development is the segregation of germ cells from somatic cells. In many organisms, this is accomplished by the inheritance of preformed germ plasm, which apparently imposes transcriptional repression to prevent somatic cell fate. However, in mammals, pluripotent epiblast cells acquire germ cell fate in response to signalling molecules. We have used single cell analysis to study how epiblast cells acquire germ cell competence and undergo specification. Germ cell competent cells express Fragilis and initially progress towards a somatic mesodermal fate. However, a subset of these cells, the future primordial germ cells (PGCs), then shows rapid upregulation of Fragilis with concomitant transcriptional repression of a number of genes, including Hox and Smad genes. This repression may be a key event associated with germ cell specification. Furthermore, PGCs express Stella and other genes, such as Oct-4 that are associated with pluripotency. While these molecules are also detected in mature oocytes as maternally inherited factors, their early role is to regulate development and maintain pluripotency, and they do not serve the role of classical germline determinants. PMID:14511483

Saitou, Mitinori; Payer, Bernhard; Lange, Ulrike C; Erhardt, Sylvia; Barton, Sheila C; Surani, M Azim

2003-01-01

81

Cell-type-specific sub- and suprathreshold receptive fields of layer 4 and layer 2/3 pyramids in rat primary visual cortex.  

PubMed

Connectivity of cortical pyramidal neurons is layer-specific in the primary visual cortex (V1) and this is thought to be reflected in different receptive field (RF) properties of layer 4 and layer 2/3 pyramidal neurons (L4Ps and L2/3Ps, respectively). However, it remains unclear how the two cell populations convert incoming visually driven synaptic inputs into action potential (AP) outputs. Here I compared postsynaptic potentials (PSPs) and AP responses of L4Ps and L2/3Ps in the binocular portion of rat V1 by intrinsic optical imaging (IOI)-targeted whole-cell recordings followed by anatomical identification and dendritic reconstructions. L2/3Ps had about 2-fold longer dendritic branches and a higher number of branch points and endings in their apical portions. Functionally, L2/3Ps had more hyperpolarized resting potentials and lower rates of spontaneous APs (medians: 0.07 vs. 0.60 AP/s). PSP responses to optimally oriented moving bars were comparable in terms of amplitude (16.0±0.9 vs. 17.3±1.1 mV for L2/3Ps and L4Ps, respectively), reliability and size of the RF. The modulated component of subthreshold responses of L4Ps to optimal sinusoidal drifting gratings was larger and their PSP onset latency in response to bars flashed in the cell's RF center were shorter (60 vs. 86 ms). In contrast to the similarities of PSP responses to moving bars, AP responses of L2/3Ps were more sparse (medians: 0.7 vs. 2.9 APs/stimulus passage), less reliable, but sharper in terms of angular size. Based on the differences of subthreshold inputs, I conclude that L4Ps may receive mostly thalamic inputs, whereas L2/3Ps may receive both thalamic and cortical inputs from layer 4. The comparable subthreshold responses to moving bars are converted by L2/3Ps into sparser but sharper AP outputs possibly by cell-type-specific AP-generating mechanisms or differences in visually driven inhibitory inputs. PMID:21704132

Medini, P

2011-09-01

82

Development of a tooth germ within an autogenous clavicular graft.  

PubMed

The left side of the mandible distal to the second primary molar of a 3 years old Southern Chinese boy was resected as a result of osteomyelitis. A diaphyseal clavicular graft pedicled on the sternomastoid muscle was selected for the reconstruction of the mandible. By the age of 6 years, the mandible although stunted in size did exhibit appropriate remodelling. In addition a tooth germ in the region of the second permanent molar was found developing in the autogenous bone graft of the mandible. PMID:3279069

King, N M; Chik, F F; Ma, G

1988-02-01

83

Derivation of Pluripotent Stem Cells from Cultured Human Primordial Germ Cells  

Microsoft Academic Search

Human pluripotent stem cells would be invaluable for in vitro studies of aspects of human embryogenesis. With the goal of establishing pluripotent stem cell lines, gonadal ridges and mesenteries containing primordial germ cells (PGCs, 5-9 weeks postfertilization) were cultured on mouse STO fibroblast feeder layers in the presence of human recombinant leukemia inhibitory factor, human recombinant basic fibroblast growth factor,

Michael J. Shamblott; Joyce Axelman; Shunping Wang; Elizabeth M. Bugg; John W. Littlefield; Peter J. Donovan; Paul D. Blumenthal; George R. Huggins; John D. Gearhart

1998-01-01

84

Primary hydatid cyst of the supraspinatus muscle: complete removal of the germinal layer and cytodiagnosis by fine-needle aspiration.  

PubMed

Primary hydatid disease of the skeletal muscle without systemic involvement is rare. The purpose of this report is to document the novel clinical presentation and the interesting facets of fine-needle aspiration in a case of hydatid disease. It was a case of primary hydatid cyst of the left supraspinatus muscle in an Indian woman living in Kuwait, which was clinically diagnosed as a lipoma. Fine-needle aspiration (FNA) yielded 2 ml of clear fluid with white particulate material. The cytocentrifuged smears prepared from the aspirated fluid showed many scolices, occasional laminated cyst wall fragments and numerous hooklets. The laminated cyst wall and scolices were PAS positive. Trichrome staining imparted a demon-head-like appearance to the scolices. The cytodiagnosis of hydatid cyst was corroborated by histopathological examination of an excised whitish membrane and an irregular cystic fragment, which showed parallel laminations without germinal layer, and skeletal muscle with granulomas and a dense eosinophilic infiltration, respectively. Quantitative serological (indirect hemagglutination) test on blood sample collected 9 days after the excision of the cyst showed insignificant antibody titer to Echinococcus sp. and after 6 weeks the antibodies were completely absent. CT scan of the chest and abdomen performed 7 weeks after removal of cyst showed no evidence of visceral hydatid cyst. PMID:23008130

Das, Dilip K; El-Sharawy, Maha; Ayyash, Emad H; Al-Enezi, Nadia A; Iqbal, Jamshed R; Madda, John P

2014-03-01

85

Corticothalamic cells in layers 5 and 6 of primary and secondary sensory cortex express GAP-43 mRNA in the adult rat.  

PubMed

The expression of a presynaptic phosphoprotein, growth-associated protein (GAP)-43, is associated with synaptogenesis during development and synaptic remodeling in the adult. This study examined GAP-43 mRNA expression and distribution in primary and secondary areas of visual, auditory, and somatosensory cortex of the adult rat, by in situ hybridization with a digoxigenin-coupled mRNA probe, focusing particularly on the corticothalamic cells in layers 5 and 6. In the six cortical areas studied, GAP-43 mRNA was expressed predominantly in layers 5 and 6 and was greater in secondary than primary areas. There were densely labeled cells in layers 5 and 6 of all areas, which showed a restricted sublaminar distribution in primary areas and more even distribution in secondary areas. Combining retrograde transport of rhodamine beads with in situ hybridization in visual and auditory cortex showed that corticothalamic cells in layers 5 and 6 express GAP-43 mRNA. There are more of these GAP-43 mRNA positive corticothalamic cells in layer 5 of secondary areas than in primary areas. The evidence suggests that in the adult rat, plasticity related to GAP-43 is present in primary and secondary sensory cortex and more so in secondary areas. PMID:14648693

Feig, Sherry L

2004-01-01

86

Germ cell development in the descended and cryptorchid testis and the effects of hormonal manipulation  

Microsoft Academic Search

Germ cell development is an active process in normal testes during the first 4 years after birth, with transformation of the neonatal gonocytes into adult dark spermatogonia and then primary spermatocytes. The hormonal regulation of these changes is not fully understood, with evidence both for and against a role for gonadotrophins and androgens. Early surgical intervention in infancy aims to prevent

C. Ong; S. Hasthorpe; J. M. Hutson

2005-01-01

87

Surgery and Combination Chemotherapy in Treating Children With Extracranial Germ Cell Tumors  

ClinicalTrials.gov

Childhood Embryonal Tumor; Childhood Extracranial Germ Cell Tumor; Childhood Extragonadal Germ Cell Tumor; Childhood Malignant Ovarian Germ Cell Tumor; Childhood Malignant Testicular Germ Cell Tumor; Childhood Teratoma; Ovarian Embryonal Carcinoma; Ovarian Yolk Sac Tumor; Stage II Malignant Testicular Germ Cell Tumor; Stage IIA Ovarian Germ Cell Tumor; Stage IIB Ovarian Germ Cell Tumor; Stage IIC Ovarian Germ Cell Tumor; Stage III Malignant Testicular Germ Cell Tumor; Stage IIIA Ovarian Germ Cell Tumor; Stage IIIB Ovarian Germ Cell Tumor; Stage IIIC Ovarian Germ Cell Tumor; Testicular Choriocarcinoma and Yolk Sac Tumor; Testicular Embryonal Carcinoma

2014-02-28

88

Patterns of supradiaphragmatic metastases in testicular germ cell tumours.  

PubMed

The imaging and clinical findings of 31 patients with supradiaphragmatic nodal metastases from primary testicular germ cell cancers were reviewed. In 11 patients the primary testicular tumor was a seminoma, and in 20 a non-seminomatous germ cell tumour (NSGCT). The patterns of spread of these tumour types were compared. All patients had chest radiographs (CXR): 27 had chest computed tomography (CT). One patient with seminoma and eight with NSGCT (40%) had lung metastases. Mediastinal lymphadenopathy was seen on CT in seven patients with seminoma (64%) and in nine patients with NSGCT (45%). Neck lymphadenopathy was present in 10 of 11 (91%) patients with seminoma, and 13 of 20 (65%) patients with NSGCT. Neck disease co-existed with mediastinal disease in six of 11 (55%) patients with seminoma, but in only two of 20 (10%) patients with NSGCT (P=0.012). This study gives further supporting evidence for the relative importance of haematogenous spread in teratoma, and lymphatic spread in seminoma. The contiguous nature of disease spread from abdomen to chest and neck in seminoma is confirmed. In NSGCT, supradiaphragmatic spread is more random but tends to occur in the paraoesophageal and subcarinal groups. PMID:8617040

Wood, A; Robson, N; Tung, K; Mead, G

1996-04-01

89

Postchemotherapy surgery for germ cell tumors--what have we learned in 35 years?  

PubMed

Postchemotherapy surgery for advanced testicular cancer has evolved over the last couple of decades. Patients with nonseminomatous germ cell tumors and residual retroperitoneal mass ?1 cm should undergo postchemotherapy retroperitoneal lymph node dissection (RPLND). For seminoma, RPLND is considered in those patients with masses ?3 cm that are also positron emission tomography positive. Masses that occur outside of the retroperitoneum should be completely resected with the possible exception of bilateral lung masses when resection of the first mass shows necrosis. The role of surgery in patients with extragonadal germ cell tumors is most vital in those with primary mediastinal nonseminomatous germ cell tumors. Importantly, patient selection, surgical planning, and consideration of referral to centers with this expertise are important to optimize success. PMID:24718515

Riggs, Stephen B; Burgess, Earl F; Gaston, Kris E; Merwarth, Caroline A; Raghavan, Derek

2014-05-01

90

Layer 4 in Primary Visual Cortex of the Awake Rabbit: Contrasting Properties of Simple Cells and Putative Feedforward Inhibitory Interneurons  

PubMed Central

Extracellular recordings were obtained from two cell classes in layer 4 of the awake rabbit primary visual cortex (V1): putative inhibitory interneurons [suspected inhibitory interneurons (SINs)] and putative excitatory cells with simple receptive fields. SINs were identified solely by their characteristic response to electrical stimulation of the lateral geniculate nucleus (LGN, 3+ spikes at >600 Hz), and simple cells were identified solely by receptive field structure, requiring spatially separate ON and/or OFF subfields. Notably, no cells met both criteria, and we studied 62 simple cells and 33 SINs. Fourteen cells met neither criterion. These layer 4 populations were markedly distinct. Thus, SINs were far less linear (F1/F0 < 1), more broadly tuned to stimulus orientation, direction, spatial and temporal frequency, more sensitive to contrast, had much higher spontaneous and stimulus-driven activity, and always had spatially overlapping ON/OFF receptive subfields. SINs responded to drifting gratings with increased firing rates (F0) for all orientations and directions. However, some SINs showed a weaker modulated (F1) response sharply tuned to orientation and/or direction. SINs responded at shorter latencies than simple cells to stationary stimuli, and the responses of both populations could be sustained or transient. Transient simple cells were more sensitive to contrast than sustained simple cells and their visual responses were more frequently suppressed by high contrasts. Finally, cross-correlation between LGN and SIN spike trains confirmed a fast and precisely timed monosynaptic connectivity, supporting the notion that SINs are well suited to provide a fast feedforward inhibition onto targeted cortical populations. PMID:23843510

Zhuang, Jun; Stoelzel, Carl R.; Bereshpolova, Yulia; Huff, Joseph M.; Hei, Xiaojuan; Alonso, Jose-Manuel

2013-01-01

91

Cadmium Increases Human Fetal Germ Cell Apoptosis  

PubMed Central

Background Cadmium (Cd) is a common environmental pollutant and a major constituent of tobacco smoke. Adverse effects of this heavy metal on reproductive function have been identified in adults; however, no studies have examined its effects on human reproductive organs during development. Objectives Using our previously developed organ culture system, we investigated the effects of cadmium chloride on human gonads at the beginning of fetal life, a critical stage in the development of reproductive function. Methods Human fetal gonads were recovered during the first trimester (7–11 weeks postconception) and cultured with or without Cd. We used different concentrations of Cd and compared results with those obtained with mouse fetal gonads at similar stages. Results Cd, at concentrations as low as 1 ?M, significantly decreased the germ cell density in human fetal ovaries. This correlated with an increase in germ cell apoptosis, but there was no effect on proliferation. Similarly, in the human fetal testis, Cd (1 ?M) reduced germ cell number without affecting testosterone secretion. In mouse fetal gonads, Cd increased only female germ cell apoptosis. Conclusions This is the first experimental demonstration that Cd, at low concentrations, alters the survival of male and female germ cells in humans. Considering data demonstrating extensive human exposure, we believe that current environmental levels of Cd could be deleterious to early gametogenesis. PMID:20064782

Angenard, Gaelle; Muczynski, Vincent; Coffigny, Herve; Pairault, Catherine; Duquenne, Clotilde; Frydman, Rene; Habert, Rene; Rouiller-Fabre, Virginie; Livera, Gabriel

2010-01-01

92

Histologically confirmed intracranial germ cell tumors; an analysis of 62 patients in a single institute  

Microsoft Academic Search

This study was undertaken to document the clinicopathologic characteristics of histologically verified, primary intracranial\\u000a germ cell tumors (GCTs), determine treatment outcomes, and to identify prognostic factors. The records of 62 patients (45\\u000a males and 17 females) with a primary intracranial GCT were retrospectively analyzed. Mean patient age was 18 years, and median\\u000a follow-up was 41 months. The most common histological subtypes were

Dakeun Lee; Yeon-Lim Suh

2010-01-01

93

Correlation between peripapillary retinal nerve fiber layer thickness and fundus autofluorescence in primary open-angle glaucoma  

PubMed Central

Purpose To investigate the relationship between retinal nerve fiber layer (RNFL) thickness and retinal pigment epithelium alterations in patients with advanced glaucomatous visual field defects. Methods A consecutive, prospective series of 82 study eyes with primary open-angle glaucoma and advanced glaucomatous visual field defects were included in this study. All study participants underwent a full ophthalmic examination followed by visual field testing with standard automated perimetry as well as spectral-domain optical coherence tomography (SD-OCT) for peripapillary RNFL thickness and Optos wide-field fundus autofluorescence (FAF) images. A pattern grid with corresponding locations between functional visual field sectors and structural peripapillary RNFL thickness was aligned to the FAF images at corresponding location. Mean FAF intensity (range: 0 = black and 255 = white) of each evaluated sector (superotemporal, temporal, inferotemporal, inferonasal, nasal, superonasal) was correlated with the corresponding peripapillary RNFL thickness obtained with SD-OCT. Results Correlation analyses between sectoral RNFL thickness and standardized FAF intensity in the corresponding topographic retina segments revealed partly significant correlations with correlation coefficients ranging between 0.004 and 0.376 and were statistically significant in the temporal inferior central field (r = 0.324, P = 0.036) and the nasal field (r = 0.376, P = 0.014). Conclusion Retinal pigment epithelium abnormalities correlate with corresponding peripapillary RNFL damage, especially in the temporal inferior sector of patients with advanced glaucomatous visual field defects. A further evaluation of FAF as a potential predictive parameter for glaucomatous damage is necessary. PMID:24092967

Reznicek, Lukas; Seidensticker, Florian; Mann, Thomas; Hubert, Irene; Buerger, Alexandra; Haritoglou, Christos; Neubauer, Aljoscha S; Kampik, Anselm; Hirneiss, Christoph; Kernt, Marcus

2013-01-01

94

"Life in a Germ-Free World":  

PubMed Central

Summary: This article examines a specific technology, the germ-free "isolator," tracing its development across three sites: (1) the laboratory for the production of standard laboratory animals, (2) agriculture for the efficient production of farm animals, and (3) the hospital for the control and prevention of cross-infection and the protection of individuals from infection. Germ-free technology traveled across the laboratory sciences, clinical and veterinary medicine, and industry, yet failed to become institutionalized outside the laboratory. That germ-free technology worked was not at issue. Working, however, was not enough. Examining the history of a technology that failed to find widespread application reveals the labor involved in aligning cultural, societal, and material factors necessary for successful medical innovation. PMID:23000838

Kirk, Robert G. W.

2012-01-01

95

Germ-cell tumors of the mediastinum.  

PubMed

Mediastinal germ-cell tumors (GCTs) usually occur within the anterior mediastinum, accounting for about 15% of all mediastinal cysts and tumors. They are associated with the thymus, presumably arising from extragonadal germ cells or thymic cells with germ-cell potential. Mediastinal seminoma develops primarily in young males with rare cases reported in females; likewise, embryonal carcinoma, endodermal sinus tumor or yolk-sac tumor, choriocarcinoma, and malignant mixed or combined GCTs also overwhelmingly affect males. Mature cystic teratoma affects males and females equally. The prognosis for mediastinal mature cystic teratoma and seminoma is very good. Nonseminomatous malignant GCTs of the mediastinum often present with advanced disease and do not respond as well to chemotherapy as their gonadal counterparts. Nonetheless, it is important to separate mediastinal GCTs from other undifferentiated malignant tumors, especially thymic carcinoma, which has a poor prognosis. Clearly, some patients with mediastinal GCTs respond very well to modern therapies. PMID:10355653

Weidner, N

1999-02-01

96

Intracardiac metastasis from germ cell testicular tumor.  

PubMed

Intracardiac metastases of germ cell testicular tumors are not commonly seen in clinical practice. The clinical presentation of right-sided heart metastases ranges widely. Depending upon its size and intracardiac location, it could be highly symptomatic, leading to a congestive heart failure, pulmonary embolism, and death, or completely asymptomatic. Improved imaging techniques and treatment strategies demonstrate that right-sided heart metastasis should be considered a potentially dangerous but treatable disease. Presented is the case of a 24-year-old man with a testicular nonseminomatous germ cell tumor, which after metastasizing in the right atrium differentiated into a teratoma and resulted in an inflow obstruction of the right ventricle. PMID:22361719

Jonjev, Z S; Raji?, J; Majin, M; Donat, D

2012-09-01

97

Seasonal variability of primary production and phytoplankton biomass in the western Pacific subarctic gyre: Control by light availability within the mixed layer  

NASA Astrophysics Data System (ADS)

distinct seasonal variation of primary production was revealed from shipboard observations conducted from 2005 to 2013 at time series station K2 in the western Pacific subarctic gyre (WSG). The mean depth-integrated primary production was highest (569 ± 162 mg C m-2 d-1) in summer and lowest (101 ± 16 mg C m-2 d-1) in winter. Strong winter mixing enriched the mixed layer (ML) with nutrients that were not fully consumed during the remainder of the year, the result being that the WSG was a high-nutrient, low-chlorophyll (HNLC) region. The deep ML reduced primary production by reducing light availability in winter, whereas primary production was enhanced by strong light availability in the shallower ML as summer progressed. However, primary production was often attenuated by a reduction of light availability attributable to dense sea fog in summer. We found a significant relationship between primary production and light availability in this HNLC region. However, chlorophyll a was less variable seasonally than primary production. The highest depth-integrated chlorophyll a was observed in summer (54.6 ± 13.4 mg m-2), but chlorophyll a remained high in winter (45.3 ± 7.7 mg m-2). Reduced light availability depressed primary production, but a reduction of the chlorophyll a concentration was prevented by a relaxation of grazing in the deep ML during winter. We found that light availability exerted an important control on the seasonal variability of primary production and phytoplankton biomass in the WSG.

Matsumoto, Kazuhiko; Honda, Makio C.; Sasaoka, Kosei; Wakita, Masahide; Kawakami, Hajime; Watanabe, Shuichi

2014-09-01

98

Germ cell nuclear factor is not required for the down-regulation of pluripotency markers in fetal ovarian germ cells  

E-print Network

In mouse, germ cells retain expression of the pluripotency markers Oct4 and Nanog longer than any other cells in the body. While somatic cells repress these markers during gastrulation, female germ cells continue to express ...

Okumura, Leah M

2012-01-01

99

Changes in retinal nerve fibre layer, optic nerve head morphology, and visual field after acute primary angle closure  

PubMed Central

Aims/Purpose To determine and correlate the long-term changes in retinal nerve fibre layer (RNFL) thickness, optic nerve head (ONH) morphology, and visual fields after a single episode of acute primary angle closure (APAC). Methods This was a cross-sectional comparative study of patients at National University Hospital (Singapore) from 2000 to 2006 after an episode of unilateral APAC. The peripapillary and macular RNFL were measured using Stratus optical coherence tomography (OCT) and ONH configuration was assessed using Heidelberg Retina Tomography (HRT)-III. Humphrey perimetry was also performed, and the presence of disc pallor was noted. APAC eyes were compared with fellow eyes as matched controls. Results Twenty-five patients were assessed at a median of 33 months (range, 11–85 months) after APAC. OCT showed that there was a reduction in the peripapillary and outer macular RNFL thickness in APAC eyes compared with controls. Humphrey perimetry revealed significantly reduced mean deviation (P=0.006) and increased pattern standard deviation (P=0.045) in APAC eyes compared with controls. HRT-III showed no difference in mean rim area, rim volume, or cup–disc ratio between APAC eyes and controls. Disc pallor was present in nine APAC eyes (36%) but was absent in fellow eyes (P=0.002), and was associated with peripapillary RNFL thinning, visual field loss, and an increased interval between the onset of symptoms and normalization of intraocular pressure (P=0.023). Conclusion APAC results in peripapillary and outer macular RNFL loss, visual field defects, and optic disc pallor, even in cases in which the ONH configuration remains unchanged. PMID:21436844

Sng, C C A; See, J S L; Ngo, C S; Singh, M; Chan, Y-H; Aquino, M C; Tan, A M; Shabana, N; Chew, P T K

2011-01-01

100

Memory in the Germ-plasm  

Microsoft Academic Search

IF ``a lamb's tail is shortened'' and the germ-cell ``records'' the event, surely there is more to be ``remembered'' by it than a ``momentary cut'', viz. a permanent change of shape? Setting aside mutilations, there remain use-acquirements. From infancy forwards a man develops physically and mentally, principally under the stimulus of use. For instance, the muscles of an infant's limbs

G. Archdall Reid

1908-01-01

101

Food applications of corn germ protein products  

Microsoft Academic Search

Many convenience foods such as meat analogs, breakfast foods, and baked goods use ingredients prepared from cereal grains\\u000a and their processed products. Among the most important new cereal protein products, corn germ protein products appear to have\\u000a the greatest potential food markets.

G. E. Inglett; C. W. Blessin

1979-01-01

102

GermOnline, a cross-species community knowledgebase on germ cell differentiation  

PubMed Central

GermOnline provides information and microarray expression data for genes involved in mitosis and meiosis, gamete formation and germ line development across species. The database has been developed, and is being curated and updated, by life scientists in cooperation with bioinformaticists. Information is contributed through an online form using free text, images and the controlled vocabulary developed by the GeneOntology Consortium. Authors provide up to three references in support of their contribution. The database is governed by an international board of scientists to ensure a standardized data format and the highest quality of GermOnline’s information content. Release 2.0 provides exclusive access to microarray expression data from Saccharomyces cerevisiae and Rattus norvegicus, as well as curated information on ?700 genes from various organisms. The locus report pages include links to external databases that contain relevant annotation, microarray expression and proteome data. Conversely, the Saccharomyces Genome Database (SGD), S.cerevisiae GeneDB and Swiss-Prot link to the budding yeast section of GermOnline from their respective locus pages. GermOnline, a fully operational prototype subject-oriented knowledgebase designed for community annotation and array data visualization, is accessible at http://www.germonline.org. The target audience includes researchers who work on mitotic cell division, meiosis, gametogenesis, germ line development, human reproductive health and comparative genomics. PMID:14681481

Wiederkehr, C.; Basavaraj, R.; Sarrauste de Menthiere, C.; Hermida, L.; Koch, R.; Schlecht, U.; Amon, A.; Brachat, S.; Breitenbach, M.; Briza, P.; Caburet, S.; Cherry, M.; Davis, R.; Deutschbauer, A.; Dickinson, H. G.; Dumitrescu, T.; Fellous, M.; Goldman, A.; Grootegoed, J. A.; Hawley, R.; Ishii, R.; Jegou, B.; Kaufman, R. J.; Klein, F.; Lamb, N.; Maro, B.; Nasmyth, K.; Nicolas, A.; Orr-Weaver, T.; Philippsen, P.; Pineau, C.; Rabitsch, K. P.; Reinke, V.; Roest, H.; Saunders, W.; Schroder, M.; Schedl, T.; Siep, M.; Villeneuve, A.; Wolgemuth, D. J.; Yamamoto, M.; Zickler, D.; Esposito, R. E.; Primig, M.

2004-01-01

103

GermOnline, a cross-species community knowledgebase on germ cell differentiation.  

PubMed

GermOnline provides information and microarray expression data for genes involved in mitosis and meiosis, gamete formation and germ line development across species. The database has been developed, and is being curated and updated, by life scientists in cooperation with bioinformaticists. Information is contributed through an online form using free text, images and the controlled vocabulary developed by the GeneOntology Consortium. Authors provide up to three references in support of their contribution. The database is governed by an international board of scientists to ensure a standardized data format and the highest quality of GermOnline's information content. Release 2.0 provides exclusive access to microarray expression data from Saccharomyces cerevisiae and Rattus norvegicus, as well as curated information on approximately 700 genes from various organisms. The locus report pages include links to external databases that contain relevant annotation, microarray expression and proteome data. Conversely, the Saccharomyces Genome Database (SGD), S.cerevisiae GeneDB and Swiss-Prot link to the budding yeast section of GermOnline from their respective locus pages. GermOnline, a fully operational prototype subject-oriented knowledgebase designed for community annotation and array data visualization, is accessible at http://www.germonline.org. The target audience includes researchers who work on mitotic cell division, meiosis, gametogenesis, germ line development, human reproductive health and comparative genomics. PMID:14681481

Wiederkehr, C; Basavaraj, R; Sarrauste de Menthière, C; Hermida, L; Koch, R; Schlecht, U; Amon, A; Brachat, S; Breitenbach, M; Briza, P; Caburet, S; Cherry, M; Davis, R; Deutschbauer, A; Dickinson, H G; Dumitrescu, T; Fellous, M; Goldman, A; Grootegoed, J A; Hawley, R; Ishii, R; Jégou, B; Kaufman, R J; Klein, F; Lamb, N; Maro, B; Nasmyth, K; Nicolas, A; Orr-Weaver, T; Philippsen, P; Pineau, C; Rabitsch, K P; Reinke, V; Roest, H; Saunders, W; Schröder, M; Schedl, T; Siep, M; Villeneuve, A; Wolgemuth, D J; Yamamoto, M; Zickler, D; Esposito, R E; Primig, M

2004-01-01

104

Optimization of primary drying condition for pharmaceutical lyophilization using a novel simulation program with a predictive model for dry layer resistance.  

PubMed

The purpose of this study was to develop a novel simulation program to accurately predict the maximum product temperature and the primary drying time in lyophilization using the predictive model for dry layer resistance, which is the resistance of dried cake against water vapor flow. Ten percent sucrose aqueous solution was selected as a model formulation. It was demonstrated that the deviations between the predicted and measured maximum product temperature were attributed to the error of dry layer resistance at a given drying condition, which was different from the measured dry layer resistance in a preliminary lyophilization run for the simulation program. However, when the predictive model of dry layer resistance was used for the simulation program, the model remarkably enhanced the accuracy of the simulation program to predict the maximum product temperature and primary drying time under various operating conditions. Furthermore, the primary drying condition required for minimized drying at a close collapse temperature was successfully discovered through one preliminary run. Therefore, it is expected that the developed simulation program is useful for designing the lyophilization cycle without a trial and error approach. PMID:24492585

Kodama, Tatsuhiro; Sawada, Hiroyuki; Hosomi, Hiroshi; Takeuchi, Masahito; Wakiyama, Naoki; Yonemochi, Etsuo; Terada, Katsuhide

2014-01-01

105

The biology of the germ line in echinoderms.  

PubMed

The formation of the germ line in an embryo marks a fresh round of reproductive potential. The developmental stage and location within the embryo where the primordial germ cells (PGCs) form, however, differs markedly among species. In many animals, the germ line is formed by an inherited mechanism, in which molecules made and selectively partitioned within the oocyte drive the early development of cells that acquire this material to a germ-line fate. In contrast, the germ line of other animals is fated by an inductive mechanism that involves signaling between cells that directs this specialized fate. In this review, we explore the mechanisms of germ-line determination in echinoderms, an early-branching sister group to the chordates. One member of the phylum, sea urchins, appears to use an inherited mechanism of germ-line formation, whereas their relatives, the sea stars, appear to use an inductive mechanism. We first integrate the experimental results currently available for germ-line determination in the sea urchin, for which considerable new information is available, and then broaden the investigation to the lesser-known mechanisms in sea stars and other echinoderms. Even with this limited insight, it appears that sea stars, and perhaps the majority of the echinoderm taxon, rely on inductive mechanisms for germ-line fate determination. This enables a strongly contrasted picture for germ-line determination in this phylum, but one for which transitions between different modes of germ-line determination might now be experimentally addressed. PMID:23900765

Wessel, Gary M; Brayboy, Lynae; Fresques, Tara; Gustafson, Eric A; Oulhen, Nathalie; Ramos, Isabela; Reich, Adrian; Swartz, S Zachary; Yajima, Mamiko; Zazueta, Vanessa

2014-08-01

106

A mediastinal germ cell tumor mimicking an ectopic pregnancy  

PubMed Central

The objective is to report the case of a 36 year-old female with a primary mediastinal germ cell tumor mimicking an ectopic pregnancy. The patient under birth control pill presented, at seven weeks of amenorrhea, a ?-human chorionic gonadotropin (?-hCG) level of 850 UI and uterine vacuity with left lateral uterine heterogeneous mass but no bleeding and no pain. She received left adnexectomy, uterine curettage and further treatment by methotrexate because of persistent high ?-hCG markers. Computed tomography scan finally permitted to discover a voluminous anterior mediastinal tumor. We may recommend investigating patients with a simple chest X-ray that present with persistent increased ?-hCG despite efficient ectopic pregnancy treatment. PMID:22247806

Poingt, Marion; Vandenbossche, Francois; Jougon, Jacques

2011-01-01

107

[Studies on primary aromatic amines (PAAs) migration from multi-layer plastic food packaging by HPLC method].  

PubMed

The aim of this study was to identify of primary aromatic amines (PAAs) and to determine their migration from plastic food packaging. The magnitude of the migration of these substances from plastic food packaging consists a base for the evaluation of their compliance with the requirements of EU legislation and hazard for human health taking into account their migration into food. The unprinted and printed multi-layer plastic packaging (laminates), domestic and imported, were examined in these studies. PAAs migration tests from the laminates into food simulant (3% acetic acid) was performed according to the appropriate procedures recommended in the EU for testing migration from food contact articles under standard conditions reflecting the real use of laminates (10 days, 40 degrees C) and under ,, worst case scenario" conditions (2 h, 70 degrees C). PAAs present in migration solutions were concentrated on SPE columns and then seven PAAs (aniline, 1,3-phenylenediamine, 2, 6-toluenediamine, 2,4-toluenediamine, 4,4'-oxydianiline, 4,4'-methylenedianiline and 3,3 '-dimethylbenzidyne) were identified and determined by previously validated HPLC-DAD method. Depending on the migration conditions the PAAs content was different. When the "worst case scenario" conditions were applied the migration of 4,4 '-methylenedianiline (4,4 '-MDA) ranged from below detection limit (LOD = 0.51 microg/kg) up to 9.86 microg/kg, and aniline was released in the range from below detection limit (LOD = 0,98 microg/kg) up to 7.04 microg/kg. In two laminate samples of eight examined, the sum of PAAs (aniline and 4,4'-MDA) was 13.32 microg/kg and 14.72 microg/kg showing that the permitted limit (10 microg/kg) was exceeded. In the standard conditions, the migration of aniline and 4,4'-MDA was significantly lower Regarding the carcinogenic potential of PAAs, the laminates causing the amines migration above the permitted limit should not be used as food packaging. PMID:22435290

Cwiek-Ludwicka, Kazimiera; Pawlicka, Marzena; Starski, Andrzej; Pó?torak, Hanna; Kar?owski, Kazimierz

2011-01-01

108

Primary yolk sac tumor of the cerebellar vermis: a case report.  

PubMed

Extragonadal germ cell tumors are rare and comprise 2-5% of all germ cell tumors. Seminoma/dysgerminoma, teratoma, yolk sac tumor (YST) and mixed germ cell tumors are few of the extragonadal germ cell tumors arising within the brain. Of these, primary pure YSTs arising in the brain are extremely rare and arise in the pineal (62%) and suprasellar (31%) regions. Primary YST occurring in the cerebellum is exceedingly rare, associated with a very poor prognosis and has been reported in less than 10 cases in literature. We herein report a case of primary pure yolk sac tumor in the cerebellar vermis in a 2-year-old child. PMID:24943765

Shenoy, Asha S; Desai, Heena M; Tyagi, Devendra K; Savant, Hemant V; Kavishwar, Vikas S; Balasubramaniam, Meenakshi

2014-01-01

109

Germ Cell Development in the Scleractinian Coral Euphyllia ancora (Cnidaria, Anthozoa)  

PubMed Central

Sexual reproduction of scleractinian coral is among the most important means of establishing coral populations. However, thus far, little is known about the mechanisms underlying coral gametogenesis. To better understand coral germ cell development, we performed a histological analysis of gametogenesis in Euphyllia ancora and characterized the coral homolog of the Drosophila germline marker gene vasa. The histological analysis revealed that E. ancora gametogenesis occurs in the mesenterial mesoglea between the mesenterial filaments and the retractor muscle bands. The development of germ cells takes approximately one year in females and half a year in males. Staining of tissue sections with an antibody against E. ancora Vasa (Eavas) revealed anti-Eavas immunoreactivity in the oogonia, early oocyte, and developing oocyte, but only faint or undetectable reactivity in developing oocytes that were >150 µm in diameters. In males, Eavas could be detected in the spermatogonia and primary spermatocytes but was only faintly detectable in the secondary spermatocytes, spermatids, and sperms. Furthermore, a reverse transcription-polymerase chain reaction analysis and Western blotting analysis of unfertilized mature eggs proved the presence of Eavas transcripts and proteins, suggesting that Eavas may be a maternal factor. Vasa may represent a germ cell marker for corals, and would allow us to distinguish germ cells from somatic cells in coral bodies that have no distinct organs. PMID:22848529

Shikina, Shinya; Chen, Chieh-Jhen; Liou, Jhe-Yu; Shao, Zi-Fan; Chung, Yi-Jou; Lee, Yan-Horn; Chang, Ching-Fong

2012-01-01

110

Combination Chemotherapy in Treating Young Patients With Recurrent or Resistant Malignant Germ Cell Tumors  

ClinicalTrials.gov

Childhood Extracranial Germ Cell Tumor; Childhood Extragonadal Germ Cell Tumor; Childhood Malignant Ovarian Germ Cell Tumor; Childhood Malignant Testicular Germ Cell Tumor; Ovarian Choriocarcinoma; Ovarian Embryonal Carcinoma; Ovarian Yolk Sac Tumor; Recurrent Childhood Malignant Germ Cell Tumor; Recurrent Malignant Testicular Germ Cell Tumor; Recurrent Ovarian Germ Cell Tumor; Testicular Choriocarcinoma; Testicular Choriocarcinoma and Embryonal Carcinoma; Testicular Choriocarcinoma and Yolk Sac Tumor; Testicular Embryonal Carcinoma; Testicular Embryonal Carcinoma and Yolk Sac Tumor; Testicular Yolk Sac Tumor

2014-03-18

111

Metformin Hydrochloride, Carboplatin, and Paclitaxel in Treating Patients With Recurrent Ovarian, Fallopian Tube, or Primary Peritoneal Cancer  

ClinicalTrials.gov

Ovarian Papillary Serous Carcinoma; Ovarian Serous Cystadenocarcinoma; Recurrent Fallopian Tube Cancer; Recurrent Ovarian Epithelial Cancer; Recurrent Ovarian Germ Cell Tumor; Recurrent Primary Peritoneal Cavity Cancer

2014-01-28

112

Alvocidib and Oxaliplatin With or Without Fluorouracil and Leucovorin Calcium in Treating Patients With Relapsed or Refractory Germ Cell Tumors  

ClinicalTrials.gov

Recurrent Extragonadal Germ Cell Tumor; Recurrent Extragonadal Non-seminomatous Germ Cell Tumor; Recurrent Extragonadal Seminoma; Recurrent Malignant Testicular Germ Cell Tumor; Recurrent Ovarian Germ Cell Tumor; Stage III Malignant Testicular Germ Cell Tumor; Stage IV Extragonadal Non-seminomatous Germ Cell Tumor; Stage IV Extragonadal Seminoma; Stage IV Ovarian Germ Cell Tumor

2014-10-09

113

A feedforward inhibitory circuit mediates lateral refinement of sensory representation in upper layer 2/3 of mouse primary auditory cortex.  

PubMed

Sensory information undergoes ordered and coordinated processing across cortical layers. Whereas cortical layer (L) 4 faithfully acquires thalamic information, the superficial layers appear well staged for more refined processing of L4-relayed signals to generate corticocortical outputs. However, the specific role of superficial layer processing and how it is specified by local synaptic circuits remains not well understood. Here, in the mouse primary auditory cortex, we showed that upper L2/3 circuits play a crucial role in refining functional selectivity of excitatory neurons by sharpening auditory tonal receptive fields and enhancing contrast of frequency representation. This refinement is mediated by synaptic inhibition being more broadly recruited than excitation, with the inhibition predominantly originating from interneurons in the same cortical layer. By comparing the onsets of synaptic inputs as well as of spiking responses of different types of neuron, we found that the broadly tuned, fast responding inhibition observed in excitatory cells can be primarily attributed to feedforward inhibition originating from parvalbumin (PV)-positive neurons, whereas somatostatin (SOM)-positive interneurons respond much later compared with the onset of inhibitory inputs to excitatory neurons. We propose that the feedforward circuit-mediated inhibition from PV neurons, which has an analogous function to lateral inhibition, enables upper L2/3 excitatory neurons to rapidly refine auditory representation. PMID:25297094

Li, Ling-Yun; Ji, Xu-Ying; Liang, Feixue; Li, Ya-Tang; Xiao, Zhongju; Tao, Huizhong W; Zhang, Li I

2014-10-01

114

Lin28a regulates germ cell pool size and fertility  

PubMed Central

Overexpression of LIN28A is associated with human germ cell tumors and promotes primordial germ cell (PGC) development from embryonic stem cells in vitro and in chimeric mice. Knockdown of Lin28a inhibits PGC development in vitro, but how constitutional Lin28a deficiency affects the mammalian reproductive system in vivo remains unknown. Here, we generated Lin28a knockout (KO) mice and found that Lin28a deficiency compromises the size of the germ cell pool in both males and females by affecting PGC proliferation during embryogenesis. Interestingly however, in Lin28a KO males the germ cell pool partially recovers during postnatal expansion, while fertility remains impaired in both males and females mated to wild type mice. Embryonic overexpression of let-7, a microRNA negatively regulated by Lin28a, reduces the germ cell pool, corroborating the role of the Lin28a/let-7 axis in regulating the germ lineage. PMID:23378032

Shinoda, Gen; de Soysa, T. Yvanka; Seligson, Marc T.; Yabuuchi, Akiko; Fujiwara, Yuko; Huang, Pei Yi; Hagan, John P.; Gregory, Richard I.; Moss, Eric G.; Daley, George Q.

2013-01-01

115

Embryonic stem cells can form germ cells in vitro  

Microsoft Academic Search

Knock-in embryonic stem (ES) cells, in which GFP or lacZ was expressed from the endogenous mouse vasa homolog (Mvh), which is specifically expressed in differentiating germ cells, were used to visualize germ cell production during in vitro differentiation. The appearance of MVH-positive germ cells depended on embryoid body formation and was greatly enhanced by the inductive effects of bone morphogenic

Yayoi Toyooka; Naoki Tsunekawa; Ryuko Akasu; Toshiaki Noce

2003-01-01

116

Overview of the Graphical User Interface for the GERM Code (GCR Event-Based Risk Model  

NASA Technical Reports Server (NTRS)

The descriptions of biophysical events from heavy ions are of interest in radiobiology, cancer therapy, and space exploration. The biophysical description of the passage of heavy ions in tissue and shielding materials is best described by a stochastic approach that includes both ion track structure and nuclear interactions. A new computer model called the GCR Event-based Risk Model (GERM) code was developed for the description of biophysical events from heavy ion beams at the NASA Space Radiation Laboratory (NSRL). The GERM code calculates basic physical and biophysical quantities of high-energy protons and heavy ions that have been studied at NSRL for the purpose of simulating space radiobiological effects. For mono-energetic beams, the code evaluates the linear-energy transfer (LET), range (R), and absorption in tissue equivalent material for a given Charge (Z), Mass Number (A) and kinetic energy (E) of an ion. In addition, a set of biophysical properties are evaluated such as the Poisson distribution of ion or delta-ray hits for a specified cellular area, cell survival curves, and mutation and tumor probabilities. The GERM code also calculates the radiation transport of the beam line for either a fixed number of user-specified depths or at multiple positions along the Bragg curve of the particle. The contributions from primary ion and nuclear secondaries are evaluated. The GERM code accounts for the major nuclear interaction processes of importance for describing heavy ion beams, including nuclear fragmentation, elastic scattering, and knockout-cascade processes by using the quantum multiple scattering fragmentation (QMSFRG) model. The QMSFRG model has been shown to be in excellent agreement with available experimental data for nuclear fragmentation cross sections, and has been used by the GERM code for application to thick target experiments. The GERM code provides scientists participating in NSRL experiments with the data needed for the interpretation of their experiments, including the ability to model the beam line, the shielding of samples and sample holders, and the estimates of basic physical and biological outputs of the designed experiments. We present an overview of the GERM code GUI, as well as providing training applications.

Kim, Myung-Hee; Cucinotta, Francis A.

2010-01-01

117

Germ tube-specific antigens of Candida albicans cell walls  

SciTech Connect

Studies were performed to characterize the surface differences between blastospores and germ tubes of the pathogenic, dimorphic yeast, Candida albicans, and to identify components of yeast cells responsible for these differences. Investigation of surfaces differences of the two growth forms was facilitated by the production of rabbit antiserum prepared against Formalin-treated yeast possessing germ tubes. To prepare antiserum specific for germ tubes, this serum was adsorbed with stationary phase blastospores. Whereas the unadsorbed antiserum reacted with both blastospore and germ tube forms by immunofluorescence and Enzyme-Linked Immunosorbent Assay, the adsorbed antiserum did not react with blastospores but detected germ tube-specific antigens in hyphal forms. The differences between blastospores and germ tubes of Candida albicans, were further studied by comparing enzymatic digests of cell walls of both growth forms in radiolabeled organisms. Organisms were labeled either on the surface with /sup 125/I, or metabolically with (/sup 35/S) methionine or (/sup 3/H) mannose. Three-surface-located components (as shown by antibody adsorption and elution experiments) were precipitated from Zymolase digests. All three components were mannoproteins as shown by their ability to bind Concanavalin A, and to be labeled in protein labeling procedures, and two of these (200,000 and 155,000 molecular weight) were germ tube specific, as shown by their ability to be precipitated by germ tube-specific antiserum. Monoclonal antibodies were prepared to C. albicans, using blastospores bearing germ tubes as immunogen.

Sundstrom, P.R.

1986-01-01

118

Topology of the germ plasm and development of primordial germ cells in inverted amphibian eggs  

NASA Technical Reports Server (NTRS)

Inverted Xenopus eggs have reduced numbers of primordial germ cells (PGCs). The extent of the reduction varies from spawning to spawning. Histologic examination revealed that PGC counts were lowest in inverted eggs which displayed the greatest amount of shift in the vegetal mass of large yolk platelets, although the germ plasm itself always remained localized in the egg's original vegetal hemisphere. Even at blastulation the germ plasm continued to be localized in the egg's original vegetal hemisphere. In many cases, however, it was confined to the periphery of the embryo, which probably accounts for the reduced PGC number in some tadpoles. In other cases it may have been dispersed and therefore not detectable in histologic analyses. Although the altered site of involution in inverted embryos did not influence PGC development, subsequent cell movement patterns apparently did. Those embryos which displayed the largest degree of pattern reversal at the tail-bud stage also exhibited the most extreme reduction in PGC numbers. A brief cold shock (4 degrees C, 10 min) prior to first cleavage leads to a further reduction in PGC numbers in inverted embryos, probably as a result of the displacement of the germ plasm away from its original vegetal pole location.

Wakahara, M.; Neff, A. W.; Malacinski, G. M.

1984-01-01

119

Gene manipulation: churches against germ changes.  

PubMed

An immediate ban on human genetic engineering that alters germ cells is called for in a resolution, written by activist Jeremy Rifkin, that was released last week over the signatures of 21 Catholic bishops, a broad spectrum of Protestant and Jewish religious leaders, and three scientists. The resolution takes a much harder line than was espoused by religious leaders in a letter to the now-defunct President's Commission for the Study of Ethical Problems in Medicine and Biomedical and Behavioral Research. Several of the signers indicated that they did not fully agree with the resolution, but saw it as a good vehicle to encourage public discussion. PMID:6574323

Budiansky, S

120

Mixed germ cell tumor of ovary and clitoromegaly in Swyer's syndrome: a case report.  

PubMed

Swyer syndrome is a type of pure gonadal dysgenesis correlating with 46 XY karyotype, primary amenorrhea, and female internal and external genitalia. It reveals a testicular differentiation abnormality.A 16-year old girl admitted to our center with primary amenorrhea and abdominal mass. In spite of the absence of normal testis, clitoromegaly was noticed. Peripheral blood karyotype analysis showed 46 XY. Histopathology of the excised gonads determined mixed germ cell tumor in right ovary and streak left gonad without gonadoblastoma in left side. In patients suffering from Swyer syndrome, high risk of gonadal neoplasia dictates early prophylactic gonadal excision to lengthen survival. PMID:22773216

Aminimoghaddam, S; Mokri, B; Mahmoodzadeh, F

2012-07-01

121

The epigenetic regulator PLZF represses L1 retrotransposition in germ and progenitor cells  

PubMed Central

Germ cells and adult stem cells maintain tissue homeostasis through a finely tuned program of responses to both physiological and stress-related signals. PLZF (Promyelocytic Leukemia Zinc Finger protein), a member of the POK family of transcription factors, acts as an epigenetic regulator of stem cell maintenance in germ cells and haematopoietic stem cells. We identified L1 retrotransposons as the primary targets of PLZF. PLZF-mediated DNA methylation induces silencing of the full-length L1 gene and inhibits L1 retrotransposition. Furthermore, PLZF causes the formation of barrier-type boundaries by acting on inserted truncated L1 sequences in protein coding genes. Cell stress releases PLZF-mediated repression, resulting in L1 activation/retrotransposition and impaired spermatogenesis and myelopoiesis. These results reveal a novel mechanism of action by which, PLZF represses retrotransposons, safeguarding normal progenitor homeostasis. PMID:23727884

Puszyk, William; Down, Thomas; Grimwade, David; Chomienne, Christine; Oakey, Rebecca J; Solomon, Ellen; Guidez, Fabien

2013-01-01

122

Molecular genetics of testicular germ cell tumors  

PubMed Central

Testicular germ cell tumors (TGCT) are the most common malignancy in young men. While most TGCT are potentially curable, approximately 5% of patients with TGCT may develop chemoresistance and die from the disease. This review article summarizes current knowledge in genetics underlying the development, progression and chemoresistance of TGCT. Most post-pubertal TGCT originate from intratubular germ cell neoplasia unclassified (IGCNU), which are transformed fetal gonocytes. Development of IGCNU may involve aberrantly activated KITLG/KIT pathway and overexpression of embryonic transcription factors such as NANOG and POU5F1, which leads to suppression of apoptosis, increased proliferation, and accumulation of mutations in gonocytes. Invasive TGCT consistently show gain of chromosome 12p, typically isochromosome 12p. Single gene mutations are uncommon in TGCT. KIT, TP53, KRAS/NRAS, and BRAF are genes most commonly mutated in TGCT and implicated in their pathogenesis. Different histologic subtypes of TGCT possess different gene expression profiles that reflect different directions of differentiation. Their distinct gene expression profiles are likely caused by epigenetic regulation, in particular DNA methylation, but not by gene copy number alterations. Resistance of TGCT to chemotherapy has been linked to karyotypic aberrations, single-gene mutations, and epigenetic regulation of gene expression in small-scale studies. The study of TGCT genetics could ultimately translate into development of new molecular diagnostic and therapeutic modalities for these tumors and improve the care of patients with these malignancies. PMID:22432056

Sheikine, Yuri; Genega, Elizabeth; Melamed, Jonathan; Lee, Peng; Reuter, Victor E.; Ye, Huihui

2012-01-01

123

Primary intratesticular rhabdomyosarcoma in pediatrics.  

PubMed

Testicular sarcomas constitute only 1-2% of all testicular tumors and are mostly associated with germ cell tumor. Primary intratesticular rhabdomyosarcoma is rare and only 14 cases have been reported in the literature till date. It should be differentiated from germ cell tumor with sarcomatous component, other intratesticular spindle-cell sarcomas and paratesticular rhabdomyosarcoma. Accurate diagnosis and early treatment is essential as it is an aggressive tumor with high metastatic potential and poor prognosis. Orchidectomy is the treatment of choice. Chemo-radiotherapy is recommended in case of recurrence and metastasis. PMID:23671375

Nasit, Jitendra G; Parikh, Biren; Trivedi, Priti; Shah, Manoj

2013-01-01

124

Avemar (Wheat Germ Extract) in Cancer Prevention and Treatment  

Microsoft Academic Search

Many healthy foods are derived from wheat germ. The molecular composition of these products, however, greatly differs as shown by normal-phase HPLC-mass spectrometry analysis; thus, experimental data obtained by one of them is not necessarily true for the other. Avemar is a nontoxic wheat germ extract registered as a special nutriment for cancer patients in Hungary. It shows potent anticancer

András Telekes; Márta Heged?s; Chang-Hoon Chae; Károly Vékey

2009-01-01

125

Hand WashingHand Washing Germ Fighting 101  

E-print Network

Hand WashingHand Washing Germ Fighting 101 Hand washing may be a simple task, but it is extremely important in preventing the spread of contagious illnesses in child-care settings. Wash your hands often to remove disease-causing germs. Wash your hands upon arrival to the child-care setting in addition to: Wet

126

Hand WashingHand Washing Germ Fighting 101  

E-print Network

Hand WashingHand Washing Germ Fighting 101 Hand washing may be a simple task, but it is extremely important in preventing the spread of contagious illnesses. Wash your hands often to remove disease-causing germs. Wash your hands: Wet hands with warm water. When warm water isn't available, wash for a longer

127

Gonadal germ cell tumors in children and adolescents  

PubMed Central

Pediatric germ cell tumors (GCT) are rare tumors: 80% are benign, 20% malignant (2-3% of all malignant pediatric tumors). The gonadal sites (ovary and testis) account for 40% of cases. Ovarian GCTs: Represent 30% of GCTs and 70% of neoplastic ovarian masses, being the most common ovarian neoplasms in children and teenagers. Benign and immature forms (teratomas) constitute about 80% of all ovarian GCTs, malignant forms represent 20% increasing during adolescence. The most common malignant entity in children is the yolk sac tumors (YST); dysgerminoma is frequent during adolescence and being bilateral in 10% of cases. Presentation is similar in malignant and benign lesions; abdominal pain (70-80%) and lower abdominal mass are common symptoms. Evaluation of alpha-fetoprotein (?FP) or beta subunit of human chorionic gonadotropin (?HCG) is essential to address the nature of the tumors: Their elevation means presence of malignancy. Surgery includes intraoperative staging procedures and requires ovariectomy or ovarosalpingectomy for malignant lesions, but may be conservative in selected benign tumors. Since malignant GCTs are very chemosensitive, primary chemotherapy is recommended in metastatic or locally advanced tumors. Testicular GCT: Represent 10% of pediatric GCT, and about 30% of malignant GCT with two age peaks: Children <3 years may experience mature teratoma and malignant GCTs, represented almost exclusively by YST, while adolescents may also show seminomas or other mixed tumors. The main clinical feature is a painless scrotal mass. Surgery represents the cornerstone of the management of testicular GCTs, with an inguinal approach and a primary high orchidectomy for malignant tumors, while a testis-sparing surgery can be considered for benign lesions. A retroperitoneal lymph node (LN) biopsy may be necessary to define the staging when the involvement of retroperitoneal LN is uncertain at imaging investigations. Conclusion: Patients with gonadal malignant GCTs fare better than those with extragonadal mediastinal germ cell tumors (MGCTs) and survival rate exceeds 90% in localized forms. Chemotherapy has significantly improved the outcome of malignant forms since the introduction of platinum based regimens. The surgical procedure has to be performed in agreement with the ongoing protocols. PMID:25336799

Cecchetto, Giovanni

2014-01-01

128

[Mediastinal germ cell tumors: anatomopathology, classification, teratomas and malignant tumors].  

PubMed

Mediastinal germ cell tumors are rare tumors. It is classic to divide those tumors into two categories, seminomas and nonseminomatous germ cell tumors: teratomas (mature or immature), embryonal carcinomas, yolk sac tumors, and choriocarcinomas. Each histological sub-type can be associated to another sub-type that realise a so-called mixed germ cell tumor. Diagnosis strategy is currently well codified for malignant mediastinal germ cell tumors. It greatly benefits from tumoral markers (alpha-fetoprotein and beta human chorionic gonadotrophin). For instance, the treatment strategy still raises some specific problems to each histological type. The treatment of seminomatous tumors is standardised--chemotherapy/surgery on residual tumor greater than 3 cm/radiotherapy on viable persistent residual tumors--and provides very satisfying results. As for the nonseminomatous germ cell tumors, the situation is dramatically different. The treatment strategy is less standardised--association of chemotherapy and surgery--and the prognosis is very severe. PMID:20207298

Chetaille, B; Massard, G; Falcoz, P-E

2010-02-01

129

Origin and development of the germ line in sea stars.  

PubMed

This review summarizes and integrates our current understanding of how sea stars make gametes. Although little is known of the mechanism of germ line formation in these animals, recent results point to specific cells and to cohorts of molecules in the embryos and larvae that may lay the ground work for future research efforts. A coelomic outpocketing forms in the posterior of the gut in larvae, referred to as the posterior enterocoel (PE), that when removed, significantly reduces the number of germ cell later in larval growth. This same PE structure also selectively accumulates several germ-line associated factors-vasa, nanos, piwi-and excludes factors involved in somatic cell fate. Since its formation is relatively late in development, these germ cells may form by inductive mechanisms. When integrated into the morphological observations of germ cells and gonad development in larvae, juveniles, and adults, the field of germ line determination appears to have a good model system to study inductive germ line determination to complement the recent work on the molecular mechanisms in mice. We hope this review will also guide investigators interested in germ line determination and regulation of the germ line into how these animals can help in this research field. The review is not intended to be comprehensive-sea star reproduction has been studied for over 100 years and many reviews are comprehensive in their coverage of, for example, seasonal growth of the gonads in response to light, nutrient, and temperature. Rather the intent of this review is to help the reader focus on new experimental results attached to the historical underpinnings of how the germ cell functions in sea stars with particular emphasis to clarify the important areas of priority for future research. PMID:24648114

Wessel, Gary M; Fresques, Tara; Kiyomoto, Masato; Yajima, Mamiko; Zazueta, Vanesa

2014-05-01

130

Origin and development of the germ line in sea stars  

PubMed Central

This review summarizes and integrates our current understanding of how sea stars make gametes. Although little is known of the mechanism of germ line formation in these animals, recent results point to specific cells and to cohorts of molecules in the embryos and larvae that may lay the ground work for future research efforts. A coelomic outpocketing forms in the posterior of the gut in larvae, referred to as the posterior enterocoel (PE), that when removed, significantly reduces the number of germ cell later in larval growth. This same PE structure also selectively accumulates several germ-line associated factors – vasa, nanos, piwi – and excludes factors involved in somatic cell fate. Since its formation is relatively late in development, these germ cells may form by inductive mechanisms. When integrated into the morphological observations of germ cells and gonad development in larvae, juveniles, and adults, the field of germ line determination appears to have a good model system to study inductive germ line determination to complement the recent work on the molecular mechanisms in mice. We hope this review will also guide investigators interested in germ line determination and regulation of the germ line in how these animals can help in this research field. The review is not intended to be comprehensive – sea star reproduction has been studied over 100 years and many reviews are comprehensive in their coverage of, for example, seasonal growth of the gonads in response to light, nutrient, and temperature. Rather the intent of this review is to help the reader focus on new experimental results attached to the historical underpinnings of how the germ cell functions in sea stars with particular emphasis to clarify the important areas of priority for future research. PMID:24648114

Wessel, Gary M.; Fresques, Tara; Kiyomoto, Masato; Yajima, Mamiko; Zazueta, Vanesa

2014-01-01

131

The sensitivity of primary productivity to intra-seasonal mixed layer variability in the sub-Antarctic Zone of the Atlantic Ocean  

NASA Astrophysics Data System (ADS)

The seasonal cycle of primary productivity is impacted by seasonal and intra-seasonal dynamics of the mixed layer through the changing balance between mixing and buoyancy forcing, which regulates nutrient supply and light availability. Of particular recent interest is the role of synoptic scale events in supplying nutrients, particularly iron, to the euphotic zone in the Sub Antarctic Zone (SAZ), where phytoplankton blooms occur throughout summer. In this study, we present high resolution measurements of net community production (NCP) constrained by ?O2/Ar ratios, and mixed layer depth (MLD) in the Atlantic SAZ. We found a non-linear relationship between NCP and MLD, with the highest and most variable NCP observed in shallow MLDs (< 45 m). We propose that NCP variability in the SAZ may be driven by alternating states of synoptic-scale deepening of the mixed layer, leading to the entrainment of iron (dFe), followed by restratification, allowing rapid growth in an iron replete, high light environment. Synoptic iron fluxes into the euphotic zone based on water column dFe profiles and high resolution glider MLD data, reveal a potentially significant contribution of "new iron" which could sustain NCP throughout summer. Future process studies will help elaborate these findings further.

Joubert, W. R.; Swart, S.; Tagliabue, A.; Thomalla, S. J.; Monteiro, P. M. S.

2014-03-01

132

Resection of thoracic and abdominal teratoma in patients after cisplatin-based chemotherapy for germ cell tumor. Late results.  

PubMed

Fifty-one patients with primary testicular (N = 46) or mediastinal germ cell cancer (N = 5) were treated from April, 1975, through May, 1981, and had teratoma resected from residual disease after cisplatin-based combination chemotherapy. All patients had normal serum markers before resection of pulmonary (N = 12), mediastinal (N = 5), thoracoabdominal (N = 8), supraclavicular (N = 1) or abdominal disease (N = 25). Teratoma was classified as mature teratoma (N = 29), immature teratoma (N = 15), or immature teratoma with non-germ cell elements (N = 7). Thirty of 51 (60%) patients remain free of recurrent disease, whereas 20 patients have either recurrent carcinoma (N = 10) or teratoma (N = 10). One patient has a presumed second malignancy. After additional chemotherapy, four patients with recurrent carcinoma are alive and disease free and six have died. After an additional operation, eight of 10 patients with recurrent teratoma are long-term survivors. In four patients the initial relapse of carcinoma developed more than 2 years after therapy; in an additional patient carcinoma recurred after a 32 month disease-free survival period. Univariate factors predicting for relapse include tumor burden, immature teratoma with non-germ cell elements, and site (mediastinum), whereas only immature teratoma with non-germ cell elements and site predicted for survival. Immature teratoma and mature teratoma had similar relapse-free intervals and overall survival intervals. According to a multivariate analysis, primary tumor site at the mediastinum is the most significant adverse factor predictive for both relapse and survival (two of five patients survived). This study appears to support the various preclinical models that demonstrate multipotential capabilities of teratoma. Complete surgical excision of teratoma remains the most effective treatment with continued close follow-up recommended for high-risk patients (immature teratoma with non-germ cell elements, large tumor burden, or primary mediastinal tumors. PMID:3020319

Loehrer, P J; Mandelbaum, I; Hui, S; Clark, S; Einhorn, L H; Williams, S D; Donohue, J P

1986-10-01

133

Germ cells and transgenesis in chickens.  

PubMed

Chickens have proven to be useful organisms for transgenic research. This work provides enormous benefits in advancing animal biotechnology and aids in the development of unique technologies for bioreactor production and experimental model development. The various advantages of chicken transgenesis are derived from the genetic and physiological characteristics of this organism, although several physiological properties have impeded the development of an efficient transgenic system. We have developed embryo-mediated and testis-mediated transgenic systems using chicken primordial germ cells (PGCs) from embryos and testicular cells from adult males. These methods are efficient and involve minimal technical effort. Here, we review previous transgenic research using PGCs and testicular cells from chickens. Furthermore, we have summarized the development of the chicken model system in biomedical science and biotechnology and our recent achievements in this field. PMID:18249442

Han, Jae Yong

2009-03-01

134

Should extragonadal germ cell tumors be included in studies of families with testicular germ cell tumors?  

PubMed Central

Background Family history is among the few established risk factors for testicular germ cell tumor (TGCT). Approximately 1.4% of newly diagnosed TGCT patients report a positive family history of TGCT. Sons and siblings of TGCT patients have four- to six fold and eight- to tenfold increase in TGCT risk, respectively. In twins of men with TGCT the relative risk of testicular cancer is 37.5 (12.3-115.6). Nevertheless, information about the occurrence of TGCT in relatives of patients with extragonadal germ cell tumor is limited. Case report A 24 year-old male patient was diagnosed with a mediastinum tumor and was submitted to image-guided biopsy, which revealed a seminoma. Two months later, his non-identical asymptomatic twin brother was submitted to an elective ultrasound of the testes, which showed a left testicular mass of 4.2 cm. This patient underwent orchiectomy revealing a seminoma of the left testis. There are no other cases of seminoma or other types of cancers reported in first-degree relatives in this family. Conclusions Although familial aggregations of TGCT have been well described, to the best of our knowledge, no data concerning the association of gonadal and extragonadal germ cell tumor in relatives has been previously reported. Further investigation on this association is warranted and may help in improving our knowledge of familial pattern inheritance. PMID:23510634

2013-01-01

135

Regulation of CCN2 gene expression and possible roles in developing tooth germs.  

PubMed

CCN proteins are extracellular and cell-associated molecules involved in several developmental processes, but their expression patterns and regulation in tooth development remain unclear. Here we first determined the expression patterns of CCN genes in mouse tooth germs. We found that at early stages CCN2 was detected in dental lamina, dental mesenchyme, and primary enamel knot, while other CCN family members were expressed broadly. By the bell stage, all members were expressed in differentiating odontoblasts and ameloblasts, but CCN1 and CCN2 transcripts were conspicuous in differentiating osteoblasts in dental follicle. Next, we asked what signalling molecules regulate CCN2 expression and what roles CCN2 may have. We found that upon surgical removal of dental epithelium CCN2 was not longer expressed in dental mesenchyme in cultured bud stage germs. Implantation of beads pre-coated with BMPs and FGFs onto E12-13 mandibular explants induced CCN2 expression in dental mesenchyme. There was a dose-dependent effect of BMP-4 on CCN2 induction; a concentration of 100 ng/?l was able to induce strong CCN2 expression while a minimum concentration of 25 ng/?l was needed to elicit appreciable expression. Importantly, Noggin treatment inhibited endogenous and BMP-induced CCN2 expression, verifying that CCN2 expression in developing tooth germs requires BMP signalling. Lastly, we found that rCCN2 stimulated proliferation in dental mesenchyme in a dose-dependent manner. Together, the data indicate that expression of CCN genes is spatio-temporally regulated in developing tooth germs. CCN2 expression appears to depend on epithelial and mesenchymal-derived signalling factors, and CCN2 can elicit strong proliferation in dental mesenchyme. PMID:24112732

Kanyama, Manabu; Shimo, Tsuyoshi; Sugito, Hiroki; Nagayama, Motohiko; Kuboki, Takuo; Pacifici, Maurizio; Koyama, Eiki

2013-11-01

136

Metformin Hydrochloride and Combination Chemotherapy in Treating Patients With Stage III-IV Ovarian, Fallopian Tube, or Primary Peritoneal Cancer  

ClinicalTrials.gov

Brenner Tumor; Malignant Ascites; Malignant Pleural Effusion; Ovarian Clear Cell Cystadenocarcinoma; Ovarian Endometrioid Adenocarcinoma; Ovarian Mixed Epithelial Carcinoma; Ovarian Serous Cystadenocarcinoma; Ovarian Undifferentiated Adenocarcinoma; Recurrent Fallopian Tube Cancer; Recurrent Ovarian Epithelial Cancer; Recurrent Ovarian Germ Cell Tumor; Recurrent Primary Peritoneal Cavity Cancer; Stage IIIA Fallopian Tube Cancer; Stage IIIA Ovarian Epithelial Cancer; Stage IIIA Ovarian Germ Cell Tumor; Stage IIIA Primary Peritoneal Cavity Cancer; Stage IIIB Fallopian Tube Cancer; Stage IIIB Ovarian Epithelial Cancer; Stage IIIB Ovarian Germ Cell Tumor; Stage IIIB Primary Peritoneal Cavity Cancer; Stage IIIC Fallopian Tube Cancer; Stage IIIC Ovarian Epithelial Cancer; Stage IIIC Ovarian Germ Cell Tumor; Stage IIIC Primary Peritoneal Cavity Cancer; Stage IV Fallopian Tube Cancer; Stage IV Ovarian Epithelial Cancer; Stage IV Ovarian Germ Cell Tumor; Stage IV Primary Peritoneal Cavity Cancer

2014-04-23

137

SALL4 expression in germ cell and non-germ cell tumors: a systematic immunohistochemical study of 3215 cases.  

PubMed

The SALL4 transcription factor is associated with embryonic cell pluripotency and has been shown as a useful immunohistochemical marker for germ cell tumors. However, information of SALL4 distribution in normal human tissues and non-germ cell tumors is limited. In this study we examined normal human tissues and 3215 tumors for SALL4 expression using a monoclonal antibody 6E3 and automated immunohistochemistry. In a 10-week embryo, SALL4 was expressed in ovocytes, intestine, kidney, and some hepatocytes. In adult tissues, it was only detected in germ cells. SALL4 was consistently expressed in all germ cell tumors except some trophoblastic tumors and mature components of teratomas, in which it was selectively expressed in intestinal-like and some squamous epithelia. In non-germ cell carcinomas, SALL4 was detected in 20% of cases or more of serous carcinoma of the ovary, urothelial high-grade carcinoma, and gastric adenocarcinoma (especially the intestinal type). SALL4 was only rarely (? 5%) expressed in mammary, colorectal, prostatic, and squamous cell carcinomas. Many SALL4-positive carcinomas showed poorly differentiated patterns, and some showed positivity in most tumor cells mimicking the expression in germ cell tumors. SALL4 was commonly expressed in rhabdoid tumors of the kidney and extrarenal sites and in the Wilms tumor. Expression of SALL4 was rare in other mesenchymal and neuroendocrine tumors but was occasionally detected in melanoma, desmoplastic small round cell tumor, epithelioid sarcoma, and rhabdomyosarcoma. All hematopoietic tumors were negative. SALL4 is an excellent marker of nonteratomatous germ cell tumors, but it is also expressed in other tumors, sometimes extensively. Such expression may reflect stem cell-like differentiation and must be considered when using SALL4 as a marker for germ cell tumors. Observed lack of other pluripotency factors, OCT4 and NANOG, in SALL4-positive non-germ cell tumors can also be diagnostically helpful. PMID:24525512

Miettinen, Markku; Wang, Zengfeng; McCue, Peter A; Sarlomo-Rikala, Maarit; Rys, Janusz; Biernat, Wojciech; Lasota, Jerzy; Lee, Yi-Shan

2014-03-01

138

Lack of Bcl10 mutations in testicular germ cell tumours and derived cell lines  

PubMed Central

Aberrations within Bcl10, a gene involved in execution of apoptosis, has most recently been found in a variety of cancers, including cell lines of testicular germ cell tumours of adolescents and adults (TGCTs). To study this in more detail, we screened exons 2 and 3 of this gene for mutations in a larger series of cell lines as well as primary TGCTs by single-strand conformation polymorphism and endonuclease restriction analysis. Because no aberrations were detected, we conclude that inactivation of Bcl10 by mutation is at least far less important in the development of TGCTs than proposed. © 1999 Cancer Research Campaign PMID:10408400

Schothorst, E M van; Mohkamsing, S; Gurp, R J H L M van; Oosterhuis, J W; Saag, P T van der; Looijenga, L H J

1999-01-01

139

Surface characteristics and primary bone marrow stromal cell response of a nanostructured strontium-containing oxide layer produced on a microrough titanium surface.  

PubMed

Strontium (Sr) has been successfully used for the treatment of osteoporotic bone, increasing new bone formation while reducing bone resorption by stimulating proliferation and differentiation of osteoblastic cells and inhibiting osteoclast function. In this study, Sr-incorporated Ti oxide layer was produced on clinically relevant osteoconductive implant surface, that is, a grit-blasted microrough Ti surface, by a simple hydrothermal treatment with the expectation of utilizing the osteoblast response enhancement effect of Sr for the future applications as a more osteoconductive surface of the permanent load-bearing endosseous implants, without altering the original microrough surface features of grit-blasted Ti at the micron-scale. This surface exhibits a hierarchical structure (i.e., a nanoscale surface architecture of the Sr-incorporated Ti oxide layer (SrTiO(3)) imposed on micron-scale rough Ti structure) and Sr ion release into physiological solution. In vitro experiments using primary mouse bone marrow stromal cells (BMSCs) revealed that the hydrothermally produced SrTiO(3) coating promotes both the early and late cell response of BMSCs grown on a microrough Ti surface, with notably enhanced attachment, spreading, focal adhesion, alkaline phosphatase activity, and expression of critical integrins and osteoblastic phenotype genes. These results indicate that a hydrothermally produced SrTiO(3) coating improves the osteoconductivity of the microrough Ti surface by enhancing both the early and late cell response of BMSCs. PMID:22396121

Park, Jin-Woo; Kim, Youn-Jeong; Jang, Je-Hee; Suh, Jo-Young

2012-06-01

140

Tritium effects on germ cells and fertility  

SciTech Connect

Primordial oocytes in juvenile mice show acute gamma-ray LD/sub 50/ as low as 6 rad. This provides opportunities for determining dose-response relations at low doses and chronic exposure in the intact animal - conditions of particular interest for hazard evaluation. Examined in this way, /sup 3/HOH in body water is found to kill murine oocytes exponentially with dose, the LD/sub 50/ level for chronic exposure being only 2..mu..Ci/ml (delivering 0.4 rad/day). At very low doses and dose rates, where comparisons between tritium and other radiations are of special significance for radiological protection, the RBE of tritium compared with /sup 60/Co gamma radiation reaches approximately 3. Effects on murine fertility from tritium-induced oocyte loss have been quantified by reproductive capacity measurements. Chronic low-level exposure has been examined also in three primate species - squirrel, rhesus, and bonnet monkeys. In squirrel monkeys the ovarian germ-cell supply is 99% destroyed by the time of birth from prenatal exposure to body-water levels of /sup 3/HOH (administered in maternal drinking water) of only 3 ..mu..Ci/ml, the LD/sub 50/ level being 0.5 ..mu..Ci/ml (giving 0.1 rad/day), one fourth that in mice. Though not completely ruled out, similar high sensitivity of female germ cells has not been found in macaques; and it probably does not occur in man. The exquisite radiosensitivity of primordial oocytes in mice is apparently due to vulnerability of the plasma membrane (or something of similar geometry and location), not DNA. Evidence for this comes from tritium data as well as neutron studies. Tritium administered as /sup 3/HOH, and therefore generally distributed, is much more effective in killing murine oocytes than is tritium administered as /sup 3/H-TdR, localized in the nucleus. This situation in the mouse may have implications for estimating radiation genetic risk in the human female.

Dobson, R.L.; Kwan, T.C.; Straume, T.

1982-11-19

141

General Information About Childhood Central Nervous System Germ Cell Tumors  

MedlinePLUS

... not started treatment. Children with childhood central nervous system germ cell tumors should have their treatment planned by a team of health care providers who are experts in treating cancer in children. Treatment will be ...

142

Developmental transitions of germ cell lineage of the mouse  

E-print Network

Mammalian germ cells arise during early embryogenesis and migrate to the developing gonad where, under the direction of the somatic environment, they initiate distinct sex-specific developmental programs resulting in the ...

Baltus, Andrew Edmund

2006-01-01

143

Hospitals' High Antibiotic Use May Boost Germs' Resistance  

MedlinePLUS

... sharing features on this page, please enable JavaScript. Hospitals' High Antibiotic Use May Boost Germs' Resistance: Study ... 2014 (HealthDay News) -- About half of all U.S. hospital patients receive antibiotics, and these drugs are commonly ...

144

Germ Cell Transplantation and Testis Tissue Xenografting in Mice  

PubMed Central

Germ cell transplantation was developed by Dr. Ralph Brinster and colleagues at the University of Pennsylvania in 19941,2. These ground-breaking studies showed that microinjection of germ cells from fertile donor mice into the seminiferous tubules of infertile recipient mice results in donor-derived spermatogenesis and sperm production by the recipient animal2. The use of donor males carrying the bacterial ?-galactosidase gene allowed identification of donor-derived spermatogenesis and transmission of the donor haplotype to the offspring by recipient animals1. Surprisingly, after transplantation into the lumen of the seminiferous tubules, transplanted germ cells were able to move from the luminal compartment to the basement membrane where spermatogonia are located3. It is generally accepted that only SSCs are able to colonize the niche and re-establish spermatogenesis in the recipient testis. Therefore, germ cell transplantation provides a functional approach to study the stem cell niche in the testis and to characterize putative spermatogonial stem cells. To date, germ cell transplantation is used to elucidate basic stem cell biology, to produce transgenic animals through genetic manipulation of germ cells prior to transplantation4,5, to study Sertoli cell-germ cell interaction6,7, SSC homing and colonization3,8, as well as SSC self-renewal and differentiation9,10. Germ cell transplantation is also feasible in large species11. In these, the main applications are preservation of fertility, dissemination of elite genetics in animal populations, and generation of transgenic animals as the study of spermatogenesis and SSC biology with this technique is logistically more difficult and expensive than in rodents. Transplantation of germ cells from large species into the seminiferous tubules of mice results in colonization of donor cells and spermatogonial expansion, but not in their full differentiation presumably due to incompatibility of the recipient somatic cell compartment with the germ cells from phylogenetically distant species12. An alternative approach is transplantation of germ cells from large species together with their surrounding somatic compartment. We first reported in 2002, that small fragments of testis tissue from immature males transplanted under the dorsal skin of immunodeficient mice are able to survive and undergo full development with the production of fertilization competent sperm13. Since then testis tissue xenografting has been shown to be successful in many species and emerged as a valuable alternative to study testis development and spermatogenesis of large animals in mice14. PMID:22330955

Dobrinski, Ina

2012-01-01

145

Characterization of a Breast Cancer Cell Line Derived from a Germ-Line BRCA1 Mutation Carrier1  

Microsoft Academic Search

A tumor cell line, HCC1937, was established from a primary breast carcinoma from a 24-year-old patient with a germ-line \\/\\/AT t \\/ mutation. A corresponding B-lymphoblastoid cell line was established from the patient's peripheral blood lymphocytes. BRCA1 analysis revealed that the tumor cell line is homozygous for the BRCA1 5382insC mutation, whereas the patient's lymphocyte DNA is heterozygous for the

Gail E. Tomlinson; Victor A. Stastny; Arvind K. Virmani; Monique A. Spillman; Vijay Tonk; Joanne L. Blum; Nancy R. Schneider; Ignacio I. Wistuba; Jerry W. Shay; John D. Minna; Adi F. Gazdar

146

Changes in Brain Function in Patients With Stage I, Stage II, Stage III, or Stage IV Ovarian, Primary Peritoneal, or Fallopian Tube Cancer Who Are Receiving Chemotherapy  

ClinicalTrials.gov

Brenner Tumor; Cognitive/Functional Effects; Ovarian Carcinosarcoma; Ovarian Choriocarcinoma; Ovarian Clear Cell Cystadenocarcinoma; Ovarian Dysgerminoma; Ovarian Embryonal Carcinoma; Ovarian Endometrioid Adenocarcinoma; Ovarian Mixed Epithelial Carcinoma; Ovarian Mixed Germ Cell Tumor; Ovarian Mucinous Cystadenocarcinoma; Ovarian Polyembryoma; Ovarian Sarcoma; Ovarian Serous Cystadenocarcinoma; Ovarian Stromal Cancer; Ovarian Teratoma; Ovarian Undifferentiated Adenocarcinoma; Ovarian Yolk Sac Tumor; Stage IA Fallopian Tube Cancer; Stage IA Ovarian Epithelial Cancer; Stage IA Ovarian Germ Cell Tumor; Stage IA Primary Peritoneal Cavity Cancer; Stage IB Fallopian Tube Cancer; Stage IB Ovarian Epithelial Cancer; Stage IB Ovarian Germ Cell Tumor; Stage IB Primary Peritoneal Cavity Cancer; Stage IC Fallopian Tube Cancer; Stage IC Ovarian Epithelial Cancer; Stage IC Ovarian Germ Cell Tumor; Stage IC Primary Peritoneal Cavity Cancer; Stage IIA Fallopian Tube Cancer; Stage IIA Ovarian Epithelial Cancer; Stage IIA Ovarian Germ Cell Tumor; Stage IIA Primary Peritoneal Cavity Cancer; Stage IIB Fallopian Tube Cancer; Stage IIB Ovarian Epithelial Cancer; Stage IIB Ovarian Germ Cell Tumor; Stage IIB Primary Peritoneal Cavity Cancer; Stage IIC Fallopian Tube Cancer; Stage IIC Ovarian Epithelial Cancer; Stage IIC Ovarian Germ Cell Tumor; Stage IIC Primary Peritoneal Cavity Cancer; Stage IIIA Fallopian Tube Cancer; Stage IIIA Ovarian Epithelial Cancer; Stage IIIA Ovarian Germ Cell Tumor; Stage IIIA Primary Peritoneal Cavity Cancer; Stage IIIB Fallopian Tube Cancer; Stage IIIB Ovarian Epithelial Cancer; Stage IIIB Ovarian Germ Cell Tumor; Stage IIIB Primary Peritoneal Cavity Cancer; Stage IIIC Fallopian Tube Cancer; Stage IIIC Ovarian Epithelial Cancer; Stage IIIC Ovarian Germ Cell Tumor; Stage IIIC Primary Peritoneal Cavity Cancer; Stage IV Fallopian Tube Cancer; Stage IV Ovarian Epithelial Cancer; Stage IV Ovarian Germ Cell Tumor; Stage IV Primary Peritoneal Cavity Cancer

2014-08-08

147

Adeno-associated virus (AAV)-mediated transduction of male germ line stem cells results in transgene transmission after germ cell transplantation  

Microsoft Academic Search

We explored whether exposure of mam- malian germ line stem cells to adeno-associated virus (AAV), a gene therapy vector, would lead to stable transduction and transgene transmission. Mouse germ cells harvested from experimentally induced crypt- orchid donor testes were exposed in vitro to AAV vectors carrying a GFP transgene and transplanted to germ cell-depleted syngeneic recipient testes, resulting in colonization

Ali Honaramooz; Susan Megee; Wenxian Zeng; Margret M. Destrempes; Susan A. Overton; Jinping Luo; Hannah Galantino-Homer; Mark Modelski; Fangping Chen; Stephen Blash; David T. Melican; William G. Gavin; Sandra Ayres; Fang Yang; P. Jeremy Wang; Yann Echelard; Ina Dobrinski

2007-01-01

148

Expression of BLIMP1\\/PRMT5 and concurrent histone H2A\\/H4 arginine 3 dimethylation in fetal germ cells, CIS\\/IGCNU and germ cell tumors  

Microsoft Academic Search

BACKGROUND: Most testicular germ cell tumors arise from intratubular germ cell neoplasia unclassified (IGCNU, also referred to as carcinoma in situ), which is thought to originate from a transformed primordial germ cell (PGC)\\/gonocyte, the fetal germ cell. Analyses of the molecular profile of IGCNU and seminoma show similarities to the expression profile of fetal germ cells\\/gonocytes. In murine PGCs, expression

Dawid Eckert; Katharina Biermann; Daniel Nettersheim; Ad JM Gillis; Klaus Steger; Hans-Martin Jäck; Annette M Müller; Leendert HJ Looijenga; Hubert Schorle

2008-01-01

149

A Specialized Outer Layer of the Primary Cell Wall Joins Elongating Cotton Fibers into Tissue-Like Bundles1[W][OA  

PubMed Central

Cotton (Gossypium hirsutum) provides the world's dominant renewable textile fiber, and cotton fiber is valued as a research model because of its extensive elongation and secondary wall thickening. Previously, it was assumed that fibers elongated as individual cells. In contrast, observation by cryo-field emission-scanning electron microscopy of cotton fibers developing in situ within the boll demonstrated that fibers elongate within tissue-like bundles. These bundles were entrained by twisting fiber tips and consolidated by adhesion of a cotton fiber middle lamella (CFML). The fiber bundles consolidated via the CFML ultimately formed a packet of fiber around each seed, which helps explain how thousands of cotton fibers achieve their great length within a confined space. The cell wall nature of the CFML was characterized using transmission electron microscopy, including polymer epitope labeling. Toward the end of elongation, up-regulation occurred in gene expression and enzyme activities related to cell wall hydrolysis, and targeted breakdown of the CFML restored fiber individuality. At the same time, losses occurred in certain cell wall polymer epitopes (as revealed by comprehensive microarray polymer profiling) and sugars within noncellulosic matrix components (as revealed by gas chromatography-mass spectrometry analysis of derivatized neutral and acidic glycosyl residues). Broadly, these data show that adhesion modulated by an outer layer of the primary wall can coordinate the extensive growth of a large group of cells and illustrate dynamic changes in primary wall structure and composition occurring during the differentiation of one cell type that spends only part of its life as a tissue. PMID:19369592

Singh, Bir; Avci, Utku; Eichler Inwood, Sarah E.; Grimson, Mark J.; Landgraf, Jeff; Mohnen, Debra; S?rensen, Iben; Wilkerson, Curtis G.; Willats, William G.T.; Haigler, Candace H.

2009-01-01

150

The chemosensitivity of testicular germ cell tumors.  

PubMed

Although rare cancers overall, testicular germ cell tumors (TGCTs) are the most common type of cancer in young males below 40 years of age. Both subtypes of TGCTs, i.e., seminomas and non-seminomas, are highly curable and the majority of even metastatic patients may expect to be cured. These high cure rates are not due to the indolent nature of these cancers, but rather to their sensitivity to chemotherapy (and for seminomas to radiotherapy). The delineation of the cause of chemosensitivity at the molecular level is of paramount importance, because it may provide insights into the minority of TGCTs that are chemo-resistant and, thereby, provide opportunities for specific therapeutic interventions aimed at reverting them to chemosensitivity. In addition, delineation of the molecular basis of TGCT chemo-sensitivity may be informative for the cause of chemo-resistance of other more common types of cancer and, thus, may create new therapeutic leads. p53, a frequently mutated tumor suppressor in cancers in general, is not mutated in TGCTs, a fact that has implications for their chemo-sensitivity. Oct4, an embryonic transcription factor, is uniformly expressed in the seminoma and embryonic carcinoma components of non-seminomas, and its interplay with p53 may be important in the chemotherapy response of these tumors. This interplay, together with other features of TGCTs such as the gain of genetic material from the short arm of chromosome 12 and the association with disorders of testicular development, will be discussed in this paper and integrated in a unifying hypothesis that may explain their chemo-sensitivity. PMID:24692098

Voutsadakis, Ioannis A

2014-04-01

151

Congenital malformations and testicular germ cell tumors  

PubMed Central

Cryptorchidism is one of the few known risk factors for testicular germ cell tumors (TGCT). It has been postulated that other congenital malformations, in particular hypospadias, are also associated with increased risk; however, associations with birth defects have not been extensively studied. Using Swedish population-based registries we evaluated the relationship between birth defects and risk of TGCT. TGCT cases (n=6,593) diagnosed between 15 and 65 years of age were identified from the Swedish Cancer Registry between 1964 and 2008. Five controls per case were randomly selected from the population register and matched on birth year and birth county. Congenital malformations were identified via linkage with the Hospital Discharge Register. Odds ratios (OR) and 95% confidence intervals (CI) for the association between each group of malformations and TGCT were estimated using conditional logistic regression. In addition to the expected association between cryptorchidism and TGCT risk [OR (95% CI): 3.18 (2.50 to 4.04)], hypospadias [2.41 (1.27 to 4.57)], inguinal hernia [1.37 (1.11–1.68)] and other genital malformations [2.19 (1.17 to 4.10)] were associated with an increased risk of TGCT. Mutual adjustment for cryptorchidism, hypospadias, inguinal hernia, and other genital malformations did not appreciably change the associations (ORs: 3.16; 2.25; 1.30; 1.90, respectively). The other (non-genital) malformations evaluated were not associated with TGCT. These data suggest that developmental urogenital abnormalities, specifically cryptorchidism, hypospadias, and inguinal hernia, are associated with an increased risk of TGCT; further supporting the hypothesis that prenatal exposure(s) related to proper genital development are related to this tumor. PMID:23580254

Trabert, Britton; Zugna, Daniela; Richiardi, Lorenzo; McGlynn, Katherine A; Akre, Olof

2014-01-01

152

Visual Tuning Properties of Genetically Identified Layer 2/3 Neuronal Types in the Primary Visual Cortex of Cre-Transgenic Mice  

PubMed Central

The putative excitatory and inhibitory cell classes within the mouse primary visual cortex V1 have different functional properties as studied using recording microelectrode. Excitatory neurons show high selectivity for the orientation angle of moving gratings while the putative inhibitory neurons show poor selectivity. However, the study of selectivity of the genetically identified interneurons and their subtypes remain controversial. Here we use novel Cre-driver and reporter mice to identify genetic subpopulations in vivo for two-photon calcium dye imaging: Wfs1(+)/Gad1(?) mice that labels layer 2/3 excitatory cell population and Pvalb(+)/Gad1(+) mice that labels a genetic subpopulation of inhibitory neurons. The cells in both mice were identically labeled with a tdTomato protein, visible in vivo, using a Cre-reporter line. We found that the Wfs1(+) cells exhibited visual tuning properties comparable to the excitatory population, i.e., high selectivity and tuning to the angle, direction, and spatial frequency of oriented moving gratings. The functional tuning of Pvalb(+) neurons was consistent with previously reported narrow-spiking interneurons in microelectrode studies, exhibiting poorer selectivity than the excitatory neurons. This study demonstrates the utility of Cre-transgenic mouse technology in selective targeting of subpopulations of neurons and makes them amenable to structural, functional, and connectivity studies. PMID:21283555

Zariwala, Hatim A.; Madisen, Linda; Ahrens, Kurt F.; Bernard, Amy; Lein, Edward S.; Jones, Allan R.; Zeng, Hongkui

2011-01-01

153

Trials of new germ cell immunohistochemical stains in 93 extragonadal and metastatic germ cell tumors.  

PubMed

Organic cation transporter 3/4 (OCT3/4) is a transcription factor of embryonic stem cells; c-kit (CD117) is a tyrosine kinase receptor implicated in seminoma carcinogenesis. Their reactivity is well characterized in testicular, but not extragonadal and metastatic, germ cell tumors. A total of 93 germ cell tumors (41 seminoma, 22 embryonal carcinoma, 18 teratoma, and 12 yolk sac tumor) were obtained from the central nervous system (30), mediastinum (23), retroperitoneum/abdomen (31), and other locations (9). Immunohistochemical staining for c-kit, placental-like alkaline phosphatase (PLAP), OCT3/4, and new markers D2-40 and AP-2gamma was performed on seminomas; CD30 and epithelial membrane antigen were added for nonseminomas. In embryonal carcinoma, c-kit reacted in 17 of 22 cases, OCT3/4 in 18 of 22, and PLAP in 13 of 22. OCT3/4 was superior to PLAP in intensity and percent cells staining. In seminoma, OCT3/4 and D2-40 were superior to PLAP in intensity and percent cells; c-kit and AP-2gamma were superior in percent cells. D2-40 stained 23 of 24 seminomas strongly but had only weak focal reactivity in 6 of 17 embryonal carcinomas. Sensitivity and specificity were high for OCT3/4 discriminating seminoma and embryonal carcinoma, and c-kit discriminating seminoma, from other germ cell tumors. For embryonal carcinoma, OCT3/4 had higher specificity (0.94) than CD30 (0.786) owing to CD30 reactivity in 3 of 10 teratomas. Epithelial membrane antigen discriminated teratoma from other nonseminomas with a sensitivity of 1 but reacted occasionally in embryonal carcinoma (3/15) and yolk sac tumor (2/7). In conclusion, for extragonadal seminoma, OCT3/4, AP-2gamma, D2-40, and c-kit were equivalently superior to PLAP. For embryonal carcinoma, OCT3/4 was superior to PLAP and more specific than CD30. D2-40 is recommended to discriminate between seminoma and embryonal carcinoma. PMID:18045648

Iczkowski, Kenneth A; Butler, Samantha L; Shanks, Jonathan H; Hossain, Deloar; Schall, Albrecht; Meiers, Isabelle; Zhou, Ming; Torkko, Kathleen C; Kim, Stacy J; MacLennan, Gregory T

2008-02-01

154

Reproduction of wild birds via interspecies germ cell transplantation.  

PubMed

The present study was conducted to apply an interspecies germ cell transfer technique to wild bird reproduction. Pheasant (Phasianus colchicus) primordial germ cells (PGCs) retrieved from the gonads of 7-day-old embryos were transferred to the bloodstream of 2.5-day-old chicken (Gallus gallus) embryos. Pheasant-to-chicken germline chimeras hatched from the recipient embryos, and 10 pheasants were derived from testcross reproduction of the male chimeras with female pheasants. Gonadal migration of the transferred PGCs, their involvement in spermatogenesis, and production of chimeric semen were confirmed. The phenotype of pheasant progenies derived from the interspecies transfer was identical to that of wild pheasants. The average efficiency of reproduction estimated from the percentage of pheasants to total progenies was 17.5%. In conclusion, interspecies germ cell transfer into a developing embryo can be used for wild bird reproduction, and this reproductive technology may be applicable in conserving endangered bird species. PMID:18685127

Kang, Seok Jin; Choi, Jin Won; Kim, Sun Young; Park, Kyung Je; Kim, Tae Min; Lee, Young Mok; Kim, Heebal; Lim, Jeong Mook; Han, Jae Yong

2008-11-01

155

Germ cell tumors with sarcomatous components: a clinicopathologic and immunohistochemical study of 46 cases.  

PubMed

The clinicopathologic features of 46 patients with germ cell tumors with sarcomatous components (GCTSC) involving either the primary site or their metastases were studied. There were 43 men and 3 women aged 17 to 74 years. Twenty-three tumors arose in the mediastinum, 2 in the retroperitoneum, and 21 in the gonads. The germ cell component consisted of pure mature or immature teratoma (23 cases), teratoma mixed with other seminomatous or nonseminomatous components (17), pure seminoma (2), intratubular germ cell neoplasia (1), and yolk sac tumor (1). The SC included embryonal rhabdomyosarcoma (29), angiosarcoma (6), leiomyosarcoma (4), undifferentiated sarcoma (3), myxoid liposarcoma (1), malignant peripheral nerve sheath tumor (1), malignant "triton" tumor (1), and epithelioid hemangioendothelioma (1). Immunohistochemical studies were carried out in 34 cases with appropriate results supporting the diagnoses. Metastases containing both GCT and SC were observed in 6 cases, metastases of SC alone in 4, and metastases containing only GCT elements in 3. All patients were treated by cisplatinum-based chemotherapy plus other agents followed by surgery. Clinical follow-up was available in 40 patients (1 to 96 mo; mean=24 mo). Thirty-two of 40 patients either died of tumor (25/40; 62.5%) or were alive with advanced, progressive disease (7/40; 17.5%), and only 8/40 (20%) were alive and free of disease between 5 to 40 months (mean=18 mo). Comparison of these patients with an age-matched and stage-matched control group of patients with GCT without SC showed statistically significant differences in survival between the 2 cohorts (P

Malagón, Hugo Domínguez; Valdez, Ana María Cano; Moran, Cesar A; Suster, Saul

2007-09-01

156

[Optimizing treatment of advanced testicular germ cell tumors].  

PubMed

Testicular germ cell cancer represents the most frequent solid neoplasm in young men aged 20-40 years. Depending on the prognosis according to the IGCCCG classification, the treatment of choice for advanced germ cell tumors consists in three to four cycles of bleomycin, etoposide, and cisplatin (BEP) in accordance with the current European Consensus Guidelines. Although residual tumor resection (RTR) adheres to guidelines as the treatment for residual metastatic lesions, numerous questions remain unresolved, which we intend to systematically answer within the scope of our research group by conducting prospective/retrospective and clinical/molecular investigations in cooperation with national and international project groups. PMID:20717647

Pfister, D; Brehmer, B; Thüer, D; Heidenreich, A

2010-09-01

157

The role of retinoic acid in germ cell development in embryonic mouse gonads  

E-print Network

Germ cells are the only cell type to undergo meiosis, a specialized cell division process necessary for the formation of haploid gametes. Timing of this process is sex-specific. Ovarian germ cells initiate meiosis during ...

Koubová, Jana C

2007-01-01

158

Sex determination of the Drosophila germ line:tra anddsx control somatic inductive signals  

Microsoft Academic Search

Abstract In Drosophila, the sex of germ cells is determined by cell-autonomous and inductive signals. XY germ cells autonomously enter spermatogenesis when developing in a female host. In contrast, XX germ cells non-autonomouslybecome,spermatogenic,when developing in a male host. In first instar larvae with two X chromosomes, XX germ cells enter the female or the male pathway depending on the presence

M Steinmann-Zwicky

1994-01-01

159

Evidence against a germ plasm in the milkweed bug Oncopeltus fasciatus, a hemimetabolous insect  

PubMed Central

Summary Primordial germ cell (PGC) formation in holometabolous insects like Drosophila melanogaster relies on maternally synthesised germ cell determinants that are asymmetrically localised to the oocyte posterior cortex. Embryonic nuclei that inherit this “germ plasm” acquire PGC fate. In contrast, historical studies of basally branching insects (Hemimetabola) suggest that a maternal requirement for germ line genes in PGC specification may be a derived character confined principally to Holometabola. However, there have been remarkably few investigations of germ line gene expression and function in hemimetabolous insects. Here we characterise PGC formation in the milkweed bug Oncopeltus fasciatus, a member of the sister group to Holometabola, thus providing an important evolutionary comparison to members of this clade. We examine the transcript distribution of orthologues of 19 Drosophila germ cell and/or germ plasm marker genes, and show that none of them localise asymmetrically within Oncopeltus oocytes or early embryos. Using multiple molecular and cytological criteria, we provide evidence that PGCs form after cellularisation at the site of gastrulation. Functional studies of vasa and tudor reveal that these genes are not required for germ cell formation, but that vasa is required in adult males for spermatogenesis. Taken together, our results provide evidence that Oncopeltus germ cells may form in the absence of germ plasm, consistent with the hypothesis that germ plasm is a derived strategy of germ cell specification in insects. PMID:23789106

Ewen-Campen, Ben; Jones, Tamsin E. M.; Extavour, Cassandra G.

2013-01-01

160

Evolution of predetermined germ cells in vertebrate embryos: implications for macroevolution  

Microsoft Academic Search

SUMMARY The germ line is established in animal embryos with the formation of primordial germ cells (PGCs), which give rise to gametes. Therefore, the need to form PGCs can act as a developmental constraint by inhibiting the evolution of embryonic patterning mechanisms that compromise their development. Conversely, events that stabilize the PGCs may liberate these constraints. Two modes of germ

Andrew D. Johnson; Matthew Drum; Rosemary F. Bachvarova; Thomas Masi; Mary E. White; Brian I. Crotherd

2003-01-01

161

DNA Analysis in Samples From Younger Patients With Germ Cell Tumors and Their Parents or Siblings  

ClinicalTrials.gov

Childhood Malignant Ovarian Germ Cell Tumor; Childhood Malignant Testicular Germ Cell Tumor; Ovarian Choriocarcinoma; Ovarian Embryonal Carcinoma; Ovarian Mixed Germ Cell Tumor; Ovarian Teratoma; Ovarian Yolk Sac Tumor; Testicular Choriocarcinoma; Testicular Embryonal Carcinoma; Testicular Seminoma; Testicular Teratoma; Testicular Yolk Sac Tumor

2014-02-17

162

Avoiding bad genes: oxidatively damaged DNA in germ line and mate choice  

Microsoft Academic Search

Summary August Weismann proposed that genetic changes in somatic cells cannot pass to germ cells and hence to next generations. Nevertheless, evidence is accumulat- ing that some environmental effects can promote herit- able changes in the DNA of germ cells, which implies that some somatic influence on germ line is possible. This influence is mostly detrimental and related to the

Alberto Velando; Roxana Torres; Carlos Alonso-Alvarez

2008-01-01

163

Mediastinal Germ Cell Tumors with an Angiosarcomatous Component: A Report of 12 Cases  

PubMed Central

The development of an angiosarcomatous component in germ cell tumors (GCTs) is rare. Here we studied 12 cases of mediastinal GCTs with an angiosarcomatous component. All patients were men with a mean age of 34 years (range, 24 to 49 years). No patient had a documented testicular GCT. The mean size of mediastinal tumors was 12.9 cm (range, 5.5 to 16.0 cm). Grossly, the tumors were cystic with variegated hemorrhagic, mucinous and fleshy solid areas. Microscopically, all tumors were composed of GCT. The most common GCT component was teratoma (n=10), and other GCT components included seminoma (n=3), yolk sac tumor (n=3), embryonal carcinoma (n=2) and choriocarcinoma (n=1). The angiosarcomatous component was present in primary mediastinal tumors (n=6), metastasis (n=3), or both primary mediastinal tumor and metastasis (n=3). The angiosarcomatous component accounted for an average of 30% (range, 5% to 95%) of the primary mediastinal tumor. In addition, other non–germ cell components, including rhabdomyosarcoma (n = 3), leiomyosarcoma (n = 1), and poorly differentiated carcinoma (n = 1), were also present in the tumors. Of the 10 patients with follow-up available, all patients developed metastasis (n=8) or local recurrence (n=2); seven died of disease at a mean of 33 months (range, 21 to 75 months), and three patients were alive at a mean of 75 months (range, 5 to 120 months). Our findings suggest that the presence of an angiosarcomatous component in mediastinal GCT, even in a small amount, is associated with a poor clinical outcome. PMID:20153508

Contreras, Alejandro Luina; Punar, Metin; Tamboli, Pheroze; Tu, Shi-Ming; Pisters, Louis; Moran, Cesar; Czerniak, Bogdan A.; Guo, Charles C.

2014-01-01

164

Contact Sports Boost Spread of 'Superbug' Germs, Study Says  

MedlinePLUS

... FAQs Contact Us Search MedlinePlus Health Topics Drugs & Supplements Videos & Cool Tools ESPAÑOL To use the sharing features on this page, please enable JavaScript. Contact Sports Boost Spread of 'Superbug' Germs, Study Says College athletes advised to practice good hygiene, and to stop ...

165

Fermented Wheat Germ Extract (Avemar) Inhibits Adjuvant Arthritis  

Microsoft Academic Search

Anti-inflammatory efficacy of the fermented wheat germ extract (FWGE, Avemar) in the rat adjuvant arthritis (AA) model was examined. To Wistar rats with AA, different doses of FWGE and anti- inflammatory drugs (indomethacin, dexamethasone) as monotherapies were administered and FWGE and either diclofenac or dexamethasone were also given in combination. Besides plethysmographies of the paws, histological investigations of synovial tissues

ANDRAS TELEKES; AKOS RESETAR; GEZA BALINT; GABOR BLAZSO; GYORGY FALKAY; KAROLY LAPIS; ERZSEBET RASO; BELA SZENDE; MICHAEL EHRENFELD; Y. Shoenfeld; MATE HIDVEGI

2007-01-01

166

Tropics, Germs, and Crops: How Endowments Influence Economic Development  

Microsoft Academic Search

Does economic development depend on geographic endowments like temperate instead of tropical location, the ecological conditions shaping diseases, or an environment good for grains or certain cash crops? Or do these endowments of tropics, germs, and crops affect economic development only through institutions or policies? We test the endowment, institution, and policy views against each other using cross country evidence.

William Easterly; Ross E. Levine

2002-01-01

167

Tropics, germs, and crops: how endowments influence economic development  

Microsoft Academic Search

Does economic development depend on geographic endowments like temperate instead of tropical location, the ecological conditions shaping diseases, or an environment good for grains or certain cash crops? Or do these endowments of tropics, germs, and crops affect economic development only through institutions or policies? We test the endowment, institution, and policy views against each other using cross country evidence.

William Easterly; Ross Levine

2003-01-01

168

Fetal age estimation using MSCT scans of deciduous tooth germs.  

PubMed

Evaluation of fetal age is an essential element in many fields such as anthropology, odontology, paleopathology, and forensic sciences. This study examines the correlation between fetal age, femoral diaphyseal length (considered as the gold standard), and deciduous tooth germs of fetuses aged 22 to 40 weeks amenorrhea (WA) based on computed tomography (MSCT) reconstructions. Qualitative and quantitative studies of femoral and deciduous tooth germ lengths were performed on 81 fetuses (39 females and 42 males). R software was used for statistical analyses. Intra-observer and inter-observer variabilities and the interclass correlation coefficient (ICC) were calculated. Correlation coefficients (R (2)) and linear regression equations were calculated. Intra- and inter-observer variabilities were very satisfactory (intra-observer ICC???0.96, inter-observer ICC???0.95). Femoral length was significantly correlated with age (R (2)?=?0.9). The correlation coefficient between age and height, width, and dental volume was R (2)???0.73. Tooth germs were good indicators of fetal age. Our method appears to be reliable and reproducible, and the results of this study agreed with those of the literature. The dental formula provided a precise estimation of fetal age between 25 and 32 WA. Tooth germs were reliable indicators of fetal age, and multislice computed tomography was shown to be an innovative and reliable technology for this purpose. PMID:23828625

Minier, Marie; Maret, Delphine; Dedouit, Fabrice; Vergnault, Marion; Mokrane, Fathima-Zohra; Rousseau, Hervé; Adalian, Pascal; Telmon, Norbert; Rougé, Daniel

2014-01-01

169

Functional fixation of autotransplanted tooth germs by using bioresorbable membranes  

Microsoft Academic Search

Objective. The purpose of this study was to evaluate the contribution of a bioresorbable membrane placement to the healing of immature teeth after autotransplantation of tooth buds. Study Design. Six cases were selected: 2 transplantations of wisdom teeth, 2 for premolar agenesis, 1 for ectopia, and 1 premolar in an incisor position. The crown of each tooth germ and the

Eric Gérard; Hervé Membre; Jean-François Gaudy; Patrick Mahler; Pierre Bravetti

2002-01-01

170

GERM-LINE SPECIFIC FACTORS IN CHEMICAL MUTAGENESIS  

EPA Science Inventory

Chemical mutagenesis test results ave not revealed evidence of germ-line specific mutagens. owever, conventional assays have indicated that there are male-female differences in mutagenic response, as well as quantitative/qualitative differences in induced mutations which depend u...

171

Evaluation of soybean RFLP marker diversity in adapted germ plasm  

Microsoft Academic Search

Soybean RFLP markers have been primarily developed and genetically mapped using wide crosses between exotic and adapted genotypes. We have screened 38 soybean lines at 128 RFLP marker loci primarily to characterize germ plasm structure but also to evaluate the utility of RFLP markers identified in unadapted populations. Of these DNA probes 70% detected RFLPs in this set of soybean

P. Keim; W. Beavis; J. Schupp; R. Freestone

1992-01-01

172

Everyday Preventive Actions That Can Help Fight Germs, Like Flu  

E-print Network

Everyday Preventive Actions That Can Help Fight Germs, Like Flu CDC recommends a three-step approach to fighting the flu. CDC recommends a three-step approach to fighting influenza (flu). The first and most important step is to get a flu vaccination each year. But if you get the flu

Tipple, Brett

173

Germ-line induction of the Caenorhabditis elegans vulva  

E-print Network

generates the LIN-3 EGF ligand to induce vulval fates in the underlying hypo- dermis, whereas FBF, FOG-1, and FOG-3 control germ-line devel- opment. Here we report that FBF functions redundantly with FOG-1 and FOG-3 to control vulval induction: animals lacking FBF and either FOG-1 or FOG-3 have multiple vulvae

Kimble, Judith

174

Early orchiopexy: prepubertal intratubular germ cell neoplasia and fertility outcome  

Microsoft Academic Search

Objectives. To investigate the prepubertal prevalence of intratubular germ cell neoplasia of the unclassified type (ITGCNU) and its significance as a predictor of testicular cancer and to evaluate the effect of early orchiopexy (at younger than 2 years of age) on subsequent fertility of patients with bilateral cryptorchidism.Methods. Testicular biopsies (n = 660) from 440 prepubertal patients with cryptorchidism who

Daniel S Engeler; Paul O Hösli; Hubert John; Fridolin Bannwart; Tullio Sulser; Mahul B Amin; Philipp U Heitz; Seife Hailemariam

2000-01-01

175

Retroperitoneal teratoma with somatic malignant transformation: A papillary renal cell carcinoma in a testicular germ cell tumour metastasis following platinum-based chemotherapy  

PubMed Central

Background Malignant transformation describes the phenomenon in which a somatic component of a germ cell teratoma undergoes malignant differentiation. A variety of different types of sarcoma and carcinoma, all non-germ cell, have been described as a result of malignant transformation. Case presentation A 33-year-old man presented with a left testicular mass and elevated tumour markers. Staging investigations revealed retroperitoneal lymphadenopathy with obstruction of the left ureter and distant metastases. Histopathology from the left radical orchiectomy showed a mixed germ cell tumour (Stage III, poor prognosis). The ureter was stented and four cycles of cisplatin, etoposide and bleomycin chemotherapy administered. After initial remission, the patient recurred four years later with a large retroperitoneal mass involving the renal vessels and the left ureter. Left retroperitoneal lymph node dissection with en-bloc resection of the left kidney was performed. Histopathology revealed a germ cell tumour metastasis consisting mainly of mature teratoma. Additionally, within the teratoma a papillary renal cell carcinoma was found. The diagnosis was supported by immunohistochemistry showing positivity for AMACR, CD10 and focal expression of RCC and CK7. There was no radiological or histo-pathological evidence of a primary renal cell cancer. Conclusions To the best of our knowledge, malignant transformation into a papillary renal cell carcinoma has not been reported in a testicular germ cell tumour metastasis following platinum-based chemotherapy. This histological diagnosis might have implications for potential future therapies. In the case of disease recurrence, renal cell cancer as origin of the recurrent tumour has to be excluded because renal cell carcinoma metastases would not respond well to the classical germ cell tumour chemotherapy regimens. PMID:23402579

2013-01-01

176

Leukemia inhibitory factor (LIF) enhances germ cell differentiation from primate embryonic stem cells.  

PubMed

Recently, several research groups have shown that germ cells can be produced in vitro from pluripotent embryonic stem cells (ESCs). In the mouse, live births of offspring using germ cells induced from ESCs in vitro have been reported. Furthermore, some efficient methods for inducing the useful number of germ cells from ESCs have also been developed. On the other hand, in primates, despite the appearances of germ cell-like cells including meiotic cells were observed by spontaneous differentiation or introducing transgenes, it has not been determined whether fully functional germ cells can be derived from ESCs. To elucidate the property for the germ cells induced from primate ESCs, specification of the promoting factors for the germ cell development and improving the efficiency of germ cell derivation are essential. Leukemia inhibitory factor (LIF) has been reported as one of the important factors for mouse primordial germ cell (PGC) survival in vitro. However, the effects of LIF on germ cell formation from pluripotent cells of primates have not been examined. The aim of this study is to determine whether LIF addition can improve in vitro germ cell production from cynomolgus monkey ESCs (cyESCs). After 8 days of differentiation, LIF added culture induced dome-shaped germ cell colonies as indicated by the intense expression of alkaline phosphatase activity (ALP). These cells also demonstrate high-level expression of the germ cell-marker VASA, OCT-4, and BLIMP-1, and show SSEA-1 expression that supports their early stage germ cell identity. Finally, we observed that adding LIF to differentiating cultures inhibited meiotic gene expressions and increased the percentage of ALP-positive cells, and demonstrate that the addition of LIF to differentiation media increases differentiation of early germ cells from the cyESCs. PMID:20698776

Fukunaga, Naoto; Teramura, Takeshi; Onodera, Yuta; Takehara, Toshiyuki; Fukuda, Kanji; Hosoi, Yoshihiko

2010-08-01

177

Coexistence of intracranial germ cell tumor and craniopharyngioma in an adolescent: case report and review of the literature  

PubMed Central

Purpose: We present the case of a patient treated for intracranial germ cell tumor in which elements of craniopharyngioma were found in the residual tumor mass. Findings: A 17 year old patient presented with a history of secondary amenorrhea. She deteriorated with headache and left eyelid drop, paresis of the abducent nerve and convergent strabismus (Parinaud syndrome). ?-HCG was 722mIU/ml and pregnancy was excluded. AFP was 6322 ng/ml. Brain CT scan showed a large endosellar tumor to the hypersellar region. There was left papillary atrophy. MRI confirmed a tumor to dorsum sellae. Primary germ cell intracranial tumor was diagnosed. Severe clinically evident pituitary failure developed with signs of increased intracranial pressure and brain edema as well as diabetes insipidus, while AFP increased to 15786,3ng/ml. Urgent treatment with combination chemotherapy including cisplatin etoposide and bleomycin (?EB) was administered for 4 courses. As a result her clinical condition improved and tumor markers dropped but nevertheless did not become normal. In addition CT scans revealed a remaining endocranial mass and therefore the patient was subjected to high-dose chemotherapy followed by autologous stemcell rescue which resulted in complete clinical and biochemical remission. Due to the persisting mass in the area, it was delivered radiotherapy. Conclusions: The above case is extremely rare in worldwide literature. Dysgerminoma may coexist with craniopharyngioma which in fact may be part of a germ cell tumor in the context of dysembryogenesis and benign “teratoma”. PMID:23573353

Tsoukalas, Nikolaos; Tolia, Maria; Kostakis, Ioannis D; Pistamaltzian, Nikolaos; Tryfonopoulos, Dimitrios; Lypas, Georgios; Koumakis, Georgios; Barbounis, Vasileios; Goutas, Nikolaos; Efremidis, Anna

2013-01-01

178

GAGE Cancer-Germline Antigens Are Recruited to the Nuclear Envelope by Germ Cell-Less (GCL)  

PubMed Central

GAGE proteins are highly similar, primate-specific molecules with unique primary structure and undefined cellular roles. They are restricted to cells of the germ line in adult healthy individuals, but are broadly expressed in a wide range of cancers. In a yeast two-hybrid screen we identified the metazoan transcriptional regulator, Germ cell-less (GCL), as an interaction partner of GAGE12I. GCL directly binds LEM-domain proteins (LAP2?, emerin, MAN1) at the nuclear envelope, and we found that GAGE proteins were recruited to the nuclear envelope inner membrane by GCL. Based on yeast two-hybrid analysis and pull-down experiments of GCL polypeptides, GCL residues 209–320 (which includes the BACK domain) were deduced sufficient for association with GAGE proteins. GAGE mRNAs and GCL mRNA were demonstrated in human testis and most types of cancers, and at the protein level GAGE members and GCL were co-expressed in cancer cell lines. Structural studies of GAGE proteins revealed no distinct secondary or tertiary structure, suggesting they are intrinsically disordered. Interestingly GAGE proteins formed stable complexes with dsDNA in vitro at physiological concentrations, and GAGE12I bound several different dsDNA fragments, suggesting sequence-nonspecific binding. Dual association of GAGE family members with GCL at the nuclear envelope inner membrane in cells, and with dsDNA in vitro, implicate GAGE proteins in chromatin regulation in germ cells and cancer cells. PMID:23029259

Gjerstorff, Morten F.; Rosner, Heike I.; Pedersen, Christina B.; Greve, Katrine B. V.; Schmidt, Steffen; Wilson, Katherine L.; Mollenhauer, Jan; Besir, Huseyin; M?llegaard, Niels Erik; Ditzel, Henrik J.

2012-01-01

179

Gradual recruitment and selective clearing generate germ plasm aggregates in the zebrafish embryo.  

PubMed

Determination of primordial germ cells (PGCs) is one of the earliest decisions in animal embryogenesis. In many species, PGCs are determined through maternally-inherited germ plasm ribonucleoparticles (RNPs). In zebrafish, these are transmitted during oogenesis as dispersed RNPs, which after fertilization multimerize and become recruited as large aggregates at furrows for the first and second cell cycles. Here, we show that the number of recruited germ plasm RNPs is halved every cell cycle. We also show that germ plasm RNPs are recruited during the third cell cycle, but only transiently. Our data support a mechanism in which systematic local gathering of germ plasm RNPs during cytokinesis and threshold-dependent clearing contribute to forming germ plasm aggregates with the highest RNP number and germ cell-inducing potential. PMID:24721731

Eno, Celeste; Pelegri, Francisco

2013-01-01

180

Wheat germ lectin-Sepharose affinity adsorption assay for the soluble glucagon receptor  

SciTech Connect

An assay was developed based on the observation that many hormone receptors are glycoproteins. To test if the glucagon receptor is a glycoprotein, the receptor was used that had (/sup 125/I-Tyr/sup 10/)monoiodoglucagon covalently attached. The covalently labelled receptor was solubilized and exposed to wheat germ lectin-Sepharose in the presence and absence of various sugars. The sugar specificity for the adsorption of the glucagon receptor indicated that the receptor is a glycoprotein. The primary structure of glucagon is known and has been shown that it has no sugars attached to it. Therefore, the different in covalently attached sugars between the hormone and the receptor was used to develop an assay for the solubilized receptor. The hormone-receptor complex was specifically adsorbed onto the lectin-Sepharose while the free hormone remained in solution.

Iyengar, R.; Herberg, J.T.

1985-01-01

181

CNS germ cell tumors: pattern of failure and effects of radiation volume.  

PubMed

This retrospective study was conducted to evaluate local control and overall survival after radiotherapy for patients with intracranial germ cell tumors and to investigate the influence of irradiated field on treatment outcome. Thirty-two patients with surgically confirmed or suspected primary intracranial germ cell tumors (GCT) treated at the Division of Therapeutic Radiology and Oncology, Chiang Mai University, Chiang Mai, Thailand between January 1988 and December 1999 were reviewed Seven patients were not included in the analysis of treatment outcome and survival due to incompleteness of radiation treatment or death before the end of treatment. The median follow up time of 39.5 months (range from 2.3 months to 136.1 months). Median age at diagnosis was 16.5 years with 23 males and 9 females. Patients were irradiated to the primary tumor with an adequate margin in 7 patients, to the whole brain with a cone down boost in 8 patients. Craniospinal irradiation (CSI) was performed in 10 patients. For the 25 evaluable patients, 5 year overall survival was 86.4%. Five-year disease free survival was 72.9%. Five year overall survival rates were 83.1% and 90.0% for the germinoma and nonbiopsied group. (p-value = 0. 6052). Routine prophylactic CSI was not given with a spinal only failure rate of 33.3%. Five-year overall survival were 85.7%, 87.5%, 85.7% for CSI, whole brain irradiation with boost and local field irradiation (p-value = 0.9037). Five-year disease free survival were 85.7%, 72.9%, 85.7% for CSI, WBRT, and local field (p-value = 0. 6403). This retrospective study suggests that definitive radiation therapy is effective in controlling germinoma, and cure rates are excellent with irradiation alone. Craniospinal irradiation can eliminate the risk of relapse especially in patients who had incomplete diagnostic craniospinal evaluation. PMID:16696383

Chitapanarux, Imjai; Lorvidhaya, Vicham; Kamnerdsupaphon, Pimkhuan; Goss, Bryan; Ford, Judith

2006-04-01

182

Lifetime stress experience: transgenerational epigenetics and germ cell programming  

PubMed Central

The transgenerational epigenetic programming involved in the passage of environmental exposures to stressful periods from one generation to the next has been examined in human populations, and mechanistically in animal models. Epidemiological studies suggest that gestational exposures to environmental factors including stress are strongly associated with an increased risk of neurodevelopmental disorders, including attention deficit-hyperactivity disorder, schizophrenia, and autism spectrum disorders. Both maternal and paternal life experiences with stress can be passed on to offspring directly during pregnancy or through epigenetic marks in the germ cell. Animal models of parental stress have examined relevant offspring phenotypes and transgenerational outcomes, and provided unique insight into the germ cell epigenetic changes associated with disruptions in neurodevelopment. Understanding germline susceptibility to exogenous signals during stress exposure and the identification of the types of epigenetic marks is critical for defining mechanisms underlying disease risk. PMID:25364281

Bale, Tracy L.

2014-01-01

183

Germ cell mutagenesis in Drosophila: multiple endpoint analysis.  

PubMed

Genotoxic carcinogens, able to damage DNA by alkylation reactions, represent a very diverse class of agents which are capable of producing a wide range of DNA modifications. The mechanisms leading to genetic changes as a result of exposure to alkylating agents (AAs) have been studied in male germ cells of Drosophila using a structure-activity relationship approach (SAR). The analytical tools available concern both genetic and molecular assays. The genetic tests enable to quantify excision repair and clastogenic potency of the AA after treatment of post-meiotic male germ cells and to determine the degree of germ-cell specificity, i.e., the mutagenic effectiveness in post- versus premeiotic cell stages. For a selected group of alkylating agents the molecular spectra have been studied in post-meiotic cell stages. On the basis of these descriptors clear SAR's between genotoxic activity in germ cells and physico-chemical parameters (s-values and O6/N7-alkylguanine adducts) and carcinogenic potency in rodents became apparent, resulting in five distinct classes of alkylating agents so far. These classes are: 1) SN2-type monofunctional AAs, 2) SN1-type monofunctional AAs, 3) polyfunctional AAs, 4) agents able to form etheno-DNA adducts, and 5) aflatoxin B1 (AFB1) a bulky-adduct forming agent. The recent finding that the molecular data obtained with Drosophila and data of the specific locus tests in male mice show remarkable similarities for most genotoxic agents supports the view that Drosophila is a useful model system for the study of transgenerational damage. PMID:9821883

Nivard, M J; Wijen, J; Vogel, E W

1998-01-01

184

Safety Studies Regarding a Standardized Extract of Fermented Wheat Germ  

Microsoft Academic Search

“Avemar pulvis” is a powder consisting of an aqueous extract of fermented wheat germ, with the drying aids maltodextrin and silicon dioxide, standardized to contain approximately 200 µg\\/g of the natural constituent 2,6-dimethoxy- p -benzoquinone. The results of toxicological and clinical studies of this product demonstrate its safety for its intended use as a dietary supplement ingredient in the United

James T. Heimbach; Gyula Sebestyen; Gabor Semjen; Elke Kennepohl

2007-01-01

185

Pathways to Pluripotency: How Germ Cells Make Stem Cells  

Microsoft Academic Search

\\u000a Recent studies have demonstrated that many types of differentiated cells can be reprogrammed to give rise to pluripotent stem\\u000a cells. Reprogramming of ­differentiated cells is brought about by the forced expression or delivery of defined factors previously\\u000a shown to be associated with pluripotent stem cells. But important questions about the safety, efficiency, and completeness\\u000a of cellular reprogramming remain. Primordial germ

Peter J. Donovan

186

Wheat germ systems for cell-free protein expression.  

PubMed

Cell-free protein expression plays an important role in biochemical research. However, only recent developments led to new methods to rapidly synthesize preparative amounts of protein that make cell-free protein expression an attractive alternative to cell-based methods. In particular the wheat germ system provides the highest translation efficiency among eukaryotic cell-free protein expression approaches and has a very high success rate for the expression of soluble proteins of good quality. As an open in vitro method, the wheat germ system is a preferable choice for many applications in protein research including options for protein labeling and the expression of difficult-to-express proteins like membrane proteins and multiple protein complexes. Here I describe wheat germ cell-free protein expression systems and give examples how they have been used in genome-wide expression studies, preparation of labeled proteins for structural genomics and protein mass spectroscopy, automated protein synthesis, and screening of enzymatic activities. Future directions for the use of cell-free expression methods are discussed. PMID:24931374

Harbers, Matthias

2014-08-25

187

BMP signaling is required for the generation of primordial germ cells in an insect  

PubMed Central

Two modes of germ cell formation are known in animals. Specification through maternally inherited germ plasm occurs in many well-characterized model organisms, but most animals lack germ plasm by morphological and functional criteria. The only known alternative mechanism is induction, experimentally described only in mice, which specify germ cells through bone morphogenetic protein (BMP) signal-mediated induction of a subpopulation of mesodermal cells. Until this report, no experimental evidence of an inductive germ cell signal for specification has been available outside of vertebrates. Here we provide functional genetic experimental evidence consistent with a role for BMP signaling in germ cell formation in a basally branching insect. We show that primordial germ cells of the cricket Gryllus bimaculatus transduce BMP signals and require BMP pathway activity for their formation. Moreover, increased BMP activity leads to ectopic and supernumerary germ cells. Given the commonality of BMP signaling in mouse and cricket germ cell induction, we suggest that BMP-based germ cell formation may be a shared ancestral mechanism in animals. PMID:24591634

Donoughe, Seth; Nakamura, Taro; Ewen-Campen, Ben; Green, Delbert A.; Henderson, Lory; Extavour, Cassandra G.

2014-01-01

188

Germ plasm in Eleutherodactylus coqui, a direct developing frog with large eggs  

PubMed Central

Background RNAs for embryo patterning and for germ cell specification are localized to the vegetal cortex of the oocyte of Xenopus laevis. In oocytes of the direct developing frog Eleutherodactylus coqui, orthologous RNAs for patterning are not localized, raising the question as to whether RNAs and other components of germ plasm are localized in this species. Methods To identify germ plasm, E. coqui embryos were stained with DiOC6(3) or examined by in situ hybridization for dazl and DEADSouth RNAs. The cDNAs for the E. coqui orthologues were cloned by RT-PCR using degenerate primers. To examine activity of the E. coqui orthologues, RNAs, made from constructs of their 3'UTRs with mCherry, were injected into X. laevis embryos. Results Both DiOC6(3) and dazl and DEADSouth in situs identified many small islands at the vegetal surface of cleaving E. coqui embryos, indicative of germ plasm. Dazl was also expressed in primordial germ cells in the genital ridge. The 3'UTRs of E. coqui dazl and DEADSouth directed primordial germ cell specific protein synthesis in X. laevis. Conclusions E. coqui utilizes germ plasm with RNAs localized to the vegetal cortex to specify primordial germ cells. The large number of germ plasm islands suggests that an increase in the amount of germ plasm was important in the evolution of the large E. coqui egg. PMID:21978790

2011-01-01

189

BMP signaling is required for the generation of primordial germ cells in an insect.  

PubMed

Two modes of germ cell formation are known in animals. Specification through maternally inherited germ plasm occurs in many well-characterized model organisms, but most animals lack germ plasm by morphological and functional criteria. The only known alternative mechanism is induction, experimentally described only in mice, which specify germ cells through bone morphogenetic protein (BMP) signal-mediated induction of a subpopulation of mesodermal cells. Until this report, no experimental evidence of an inductive germ cell signal for specification has been available outside of vertebrates. Here we provide functional genetic experimental evidence consistent with a role for BMP signaling in germ cell formation in a basally branching insect. We show that primordial germ cells of the cricket Gryllus bimaculatus transduce BMP signals and require BMP pathway activity for their formation. Moreover, increased BMP activity leads to ectopic and supernumerary germ cells. Given the commonality of BMP signaling in mouse and cricket germ cell induction, we suggest that BMP-based germ cell formation may be a shared ancestral mechanism in animals. PMID:24591634

Donoughe, Seth; Nakamura, Taro; Ewen-Campen, Ben; Green, Delbert A; Henderson, Lory; Extavour, Cassandra G

2014-03-18

190

TECHNICAL ADVANCE The Arabidopsis thaliana MERISTEM LAYER 1 promoter  

E-print Network

is a single layer of cells, whereas L2 and L3 can each comprise more than one cell layer. Restrictions of organs, the L2 gives rise to mesophyll and subepidermal layers of organs as well as to the germ line that the ATML1 transcription unit comprises 11 exons. The 5� region of ATML1 is shown as a diagram in Figure 1

Weigel, Detlef

191

Neocortical layers I and II of the hedgehog ( Erinaceus europaeus )  

Microsoft Academic Search

This study examines the thalamo-cortical projections to the most superficial neocortical layers in the hedgehog (Erinaceus europaeus) after small injections of horseradish peroxidase and horseradish peroxidase conjugated to wheat germ agglutinin in the somato-sensory cortex. The injections were limited to layers I, II and upper parts of layer III\\/IV. Retrogradely labeled cells were plotted in serial sections through the thalamus.

F. Valverde; J. A. Carlos; L. López-Mascaraque; F. Doñate-Oliver

1986-01-01

192

Pineal and CNS germ cell tumors: Royal Marsden Hospital experience 1962-1987.  

PubMed

A retrospective analysis has been made of all patients with pineal and CNS germ cell tumors who were treated at The Royal Marsden Hospital between 1962-1987. A total of 67 new cases were seen: 17 had initial histological verification of tumor type and the remainder were tested for radiosensitivity with a dose of 20 Gy following a shunting procedure. Patients with germ cell or radiosensitive tumors were treated with a uniform policy of whole neuraxis radiotherapy giving 50 Gy to the local tumor and 30 Gy to the remaining brain and spinal cord. Nonresponding lesions continued with local fields to a dose of 50 Gy. Patients were divided into three groups (a) germinoma and radiosensitive tumours, 34 cases; (b) malignant teratoma, 12 cases; (c) non-germ cell, 21 cases. Median follow-up is 83 months (range 2-246 months). Overall and cause specific actuarial 5/10 year survival were for group 1, 81.7%/69.4% and 86.5%;/86.5%; group 2, 18.2%/18.2% and 18.2%/18.2%, and group 3, 64.3%/46.8% and 64.3%/52.6%, respectively. No patient in group 1 treated during the last 12 years has recurred. Univariate analysis of factors at presentation, showed that neurological performance status (p less than .001) as well as tumor type (p less than .001) correlated with outcome. Recurrence was confined to the primary site in only 1 of 4 patients in group 1 compared to 6 of 9 patients in group 2 and 9 of 10 patients in group 3. No isolated spinal recurrence occurred in group 1 patients. A total of eight patients have received platinum containing chemotherapy for recurrence (6 cases) or adjuvant therapy (4 cases). Germinomas appear to respond better than teratomas, all of which have recurred rapidly following initial partial response. Shunting and radiosensitivity testing remains the treatment of choice for tumors compatible with germinoma. Craniospinal irradiation is associated with low morbidity providing spinal growth is complete and is recommended in older patients as salvage following spinal recurrence is unsatisfactory. Aggressive combined modality approaches with surgery, radiotherapy and chemotherapy need to be investigated to improve results in CNS teratoma. PMID:2323968

Dearnaley, D P; A'Hern, R P; Whittaker, S; Bloom, H J

1990-04-01

193

A revised timeline for biological agents: revisiting the early years of the germ theory of disease.  

PubMed

An agreed upon timeline for the initial, scientifically-informed use of biological agents typically begins with the Japanese Army in Manchuria and China prior to the generalized outbreak of World War II (1932 until 1945). The process included human experimentation with multiple biological agents followed by their release in combat (e.g. the plague bacillus) targeting military personnel and civilians. Two postulates are used support these dates. First, allegations of earlier bacteriological weapon experimentation and/or use represented the accidental, small scale, and sporadic dispersion of infectious agents preceding the Germ Theory of Disease. Therefore, attempts prior to the Twentieth Century were uninformed scientifically and are not considered representative. Later, as the Germ Theory was maturing, the hypothetical timeline was derived, in part retrospectively, from reputable historical sources (the Trillat Report and The League of Nations) published immediately upon the conclusion of World War I. These documents explicitly testified to the total absence of bacteriological weapons in any form (experimentation or battlefield application) directed at human subjects-in stark contrast to the utilization of chemical agents-during the course of that war. Therefore the Japanese Army in Manchuria became time zero. Recently, evidence previously hidden from outside study has surfaced demonstrating that a small group of Turkish physicians injected typhus-contaminated serum into Armenian civilians during WWI. Although controversy persists regarding primary intent-immunization, experimentation on human subjects, or the introduction of a crude biological weapon-the discovery might suggest a revision to the accepted timeline. The primitive efforts with contaminated serum that occurred during the First World War may seem trivial, especially when compared to overall fatalities during that conflict, but they did include the informed and fatal application of microbial agents. Furthermore, the actions may have influenced certain behaviors that followed in World War II. PMID:16963192

Rutecki, Gregory W

2007-01-01

194

Testis conserving chemotherapy in germ cell cancer: its potential to increase understanding of the biology and treatment of carcinoma-in-situ.  

PubMed

Prompted by recognition of the potential of chemotherapy to increase the success of testis conserving surgery in patients with germ cell cancer, background and outcome data are reviewed and their contribution to the ongoing debate about how germ cell cancer develops discussed. The review is based on three previous studies of: a) time trends in tumour size in 578 personal series of all stages of testis cancer treated since 1978; b) impact of chemotherapy on actuarial risk of tumours in contralateral testis examined on 1221 patients treated in trials through the Anglian Germ Cell Cancer Consortium; and c) testes conservation attempted using chemotherapy in 78 patients. Since 1978 tumour size has decreased from 4.8 to 3.0 cms while cure has gone from 77 to 97%. There was no overall long term reduction in second cancers beyond 10 years in stage 1 patients after orchidectomy alone compared to stage 1 or metastatic disease patients receiving chemotherapy though the incidence was non significantly lower up to 10 years particularly in those patients receiving etoposide based combination. Testis conservation was initially successful in 28 of 78 (36%). An additional 25 (32%) had no viable cancer in orchidectomy specimen. In the 28 primary tumours cured by chemotherapy there was a 26% late relapse rate between 5 and 10 years (all cured by orchidectomy) compared to less than 5% in those cured with established metastases. In conclusion, testis conservation with chemotherapy is safe and feasible, though relapse is too frequent for routine service use. Confirmation of the high frequency of late relapse by others has raised the question whether these recurrences are due to post pubertal events reinducing CIS in intrauterine oestrogen primed germ cells and highlights the potential of testes conservation studies to better understand germ cell cancer development. PMID:12752243

Oliver, R T D; Ong, J; Berney, D; Nargund, V; Badenoch, D; Shamash, J

2003-01-01

195

From Young Children's Ideas about Germs to Ideas Shaping a Learning Environment  

NASA Astrophysics Data System (ADS)

This paper is concerned with highlighting young children’s ideas about the nature, location and appearance of germs, as well as their reasoning strands about germs’ ontological category and biological functions. Moreover, it is concerned with exploring how all these could be taken into account for shaping a potentially fruitful learning environment. Conducting individual, semi-structured interviews with 35 preschoolers (age 4.5-5.5) of public kindergartens in the broader area of Patras, we attempted to trace their ideas about what germs are, where they may be found, whether they are good or bad and living or non-living and how they might look like in a drawing. Moreover, children were required to attribute a series of biological functions to dogs, chairs and germs, and finally to create a story with germs holding a key-role. The analysis of our qualitative data within the “NVivo” software showed that the informants make a strong association of germs with health and hygiene issues, locate germs mostly in our body and the external environment, are not familiar with the ‘good germs’-idea, and draw germs as ‘human-like’, ‘animal-like’ or ‘abstract’ entities. Moreover, they have significant difficulties not only in employing biological functions as criteria for classifying germs in the category of ‘living’, but also in just attributing such functions to germs using a warrant. Finally, the shift from our findings to a 3-part learning environment aiming at supporting preschoolers in refining their initial conceptualization of germs is thoroughly discussed in the paper.

Ergazaki, Marida; Saltapida, Konstantina; Zogza, Vassiliki

2010-11-01

196

Epigenetic programming of the germ line: effects of endocrine disruptors on the development of transgenerational disease  

Microsoft Academic Search

Epigenetic programming of the germ line occurs during embryonic development in a sex-specific manner. The male germ line becomes imprinted following sex determination. Environmental influences can alter this epigenetic programming and affect not only the developing offspring, but also potentially subsequent generations. Exposure to an endocrine disruptor (i.e. vinclozolin) during embryonic gonadal sex determination can alter the male germ-line epigenetics

Matthew D Anway; Michael K Skinner

2008-01-01

197

Windows for sex-specific methylation marked by DNA methyltransferase expression profiles in mouse germ cells  

Microsoft Academic Search

The acquisition of genomic methylation in the male germ line is initiated prenatally in diploid gonocytes, while DNA methylation in the female germ line is initiated postnatally in growing oocytes. We compared the temporal expression patterns of the DNA methyltransferases, DNMT1, DNMT3a, DNMT3b, and DNMT3l in the male and female germ lines. DNMT1 expression was examined by immunocytochemistry and Northerns

Sophie La Salle; Carmen Mertineit; Teruko Taketo; Peter B Moens; Timothy H Bestor; Jacquetta M Trasler

2004-01-01

198

A FIRE-ACE/SHEBA Case Study of Mixed-Phase Arctic Boundary Layer Clouds: Entrainment Rate Limitations on Rapid Primary Ice Nucleation Processes  

E-print Network

Limitations on Rapid Primary Ice Nucleation Processes ANN M. FRIDLIND,* BASTIAAN VAN DIEDENHOVEN,1 ANDREW S # National Center for Atmospheric Research, Boulder, Colorado @ Rosenstiel School of Marine and Atmospheric distributions and cloud radar reflectivities with rapidly consumed IN in this case, the measured above-cloud NIN

Shupe, Matthew

199

Primary high-grade testicular leiomyosarcoma.  

PubMed

We herein present an extremely rare occurrence of primary intratesticular leiomyosarcoma. A 65-year-old patient presented with painless enlargement of the right testis. A high inguinal orchiectomy was done. Histopathological examination of the excised mass was consistent with high-grade leiomyosarcoma. Pertinent literature is reviewed and the importance of excluding the germ cell tumor and the paratesticular neoplasm is emphasized. PMID:19136794

Kumar, Mohan; Patne, Shashikant C U; Kumar, Sandip; Shukla, V K

2009-01-01

200

A zebrafish homologue of the chemokine receptor Cxcr4 is a germ-cell guidance receptor  

NASA Astrophysics Data System (ADS)

Germ cells preserve an individual's genetic information and transmit it to the next generation. Early in development germ cells are set aside and undergo a specialized developmental programme, a hallmark of which is the migration from their site of origin to the future gonad. In Drosophila, several factors have been identified that control germ-cell migration to their target tissues; however, the germ-cell chemoattractant or its receptor have remained unknown. Here we apply genetics and in vivo imaging to show that odysseus, a zebrafish homologue of the G-protein-coupled chemokine receptor Cxcr4, is required specifically in germ cells for their chemotaxis. odysseus mutant germ cells are able to activate the migratory programme, but fail to undergo directed migration towards their target tissue, resulting in randomly dispersed germ cells. SDF-1, the presumptive cognate ligand for Cxcr4, shows a similar loss-of-function phenotype and can recruit germ cells to ectopic sites in the embryo, thus identifying a vertebrate ligand-receptor pair guiding migratory germ cells at all stages of migration towards their target.

Knaut, Holger; Werz, Christian; Geisler, Robert; Tübingen 2000 Screen Consortium; Nüsslein-Volhard, Christiane

2003-01-01

201

Epigenetic programming of the germ line: effects of endocrine disruptors on the development of transgenerational disease.  

PubMed

Epigenetic programming of the germ line occurs during embryonic development in a sex-specific manner. The male germ line becomes imprinted following sex determination. Environmental influences can alter this epigenetic programming and affect not only the developing offspring, but also potentially subsequent generations. Exposure to an endocrine disruptor (i.e. vinclozolin) during embryonic gonadal sex determination can alter the male germ-line epigenetics (e.g. DNA methylation). The epigenetic mechanism involves the alteration of DNA methylation in the germ line that appears to transmit transgenerational adult onset disease, including spermatogenic defects, prostate disease, kidney disease and cancer. PMID:18252044

Anway, Matthew D; Skinner, Michael K

2008-01-01

202

Cancers by Body Location/System: Unknown Primary  

Cancer.gov

Cancers by Body Location/System: Unknown Primary To find a cancer: select a body location or system — AIDS-RelatedBreastDigestive/GastrointestinalEndocrine and NeuroendocrineEye GenitourinaryGerm CellGynecologicHead and NeckHematologic/Blood MusculoskeletalNeurologicRespiratory/ThoracicSkinUnknown

203

Spinel inclusions in olivine and plagioclase crystals in a layered gabbro: a marker and a tracer for primary phenocrysts in a differentiating magma reservoir  

NASA Astrophysics Data System (ADS)

The problem of whether cumulate rocks were formed by crystal settling or by in situ crystallization after magma emplacement is an important issue concerning the mechanisms of magmatic differentiation. However, it is hard to distinguish these two processes for plutonic rocks because the primary texture and chemical composition have generally been modified by postcumulus processes. To contribute this problem, we studied the distribution and compositions of Cr-spinel inclusions hosted in olivine and plagioclase in the Murotomisaki Gabbroic Intrusion (MGI), SW Japan. It is shown that the olivine-hosted inclusions are restricted to specific horizons where accumulation of olivine phenocrysts is thought to have occurred and that the compositional variations of the Cr-spinel are explained by a secondary compositional modification that probably took place after the magma emplacement. It is also shown that the Cr-spinel inclusions in a chilled margin have suffered the least compositional modification and nearly retains the primary composition. Those in the interior of the intrusion, on the contrary, have been significantly modified by re-equilibration with residual melt driven by cation diffusions through the host phases. Those in plagioclase have been less modified. It is shown that all the spinel inclusions had primarily the same and common composition at the time of magma emplacement. This implies that all the inclusion-bearing crystals, olivine and plagioclase, represent primary phenocrysts that had already existed in the emplaced magma. In this way, spinel inclusion in the MGI may be regarded to be a useful petrographic "marker" for identifying intratelluric phenocrysts and also as a "tracer" to trace the motion of the primary phenocrysts after the magma emplacement.

Hoshide, Takashi; Obata, Masaaki

2014-08-01

204

Retinoic acid induces mouse bone marrow-derived CD15?, Oct4? and CXCR4? stem cells into male germ-like cells in a two-dimensional cell culture system.  

PubMed

We have examined the effect of retinoic acid (RA) on differentiation of bone marrow-derived CD15(+) , Oct4(+) and CXCR4(+) cells into male germ cells. Bone marrow stem cells (BMSCs) were isolated from the femur of 3-4-week-old male C57BL/6 mice. Magnetic-activated cell sorting (MACS) system was used to sort CD15(+) , Oct4(+) and CXCR4(+) cells. RT-PCR was used to follow the expression of pluripotency markers. Sorted CD15(+) , Oct4(+) and CXCR4(+) cells were cultured in an undifferentiated condition on a feeder layer of mitomycin C-inactivated C2C12. The embryoid-like bodies were differentiated into male germ cells by retinoic acid. To identify the expression of male germ specific markers, differentiated cells were analysed by means of reverse transcriptase polymerase chain reaction (RT-PCR) and immunofluorescence staining. RT-PCR and immunofluorescence show that bone marrow-derived CD15(+) , Oct4(+) and CXCR4(+) cells express pluripotency markers, Oct4, Nanog, Rex-1, SOX-2 and AP. The purified CD15(+) , Oct4(+) and CXCR4(+) formed structures like embryoid bodies when plated over a feeder layer; these bodies were alkaline phosphatase positive. When cells were induced by RA, bone marrow-derived CD15(+) , Oct4(+) and CXCR4(+) were positive for Mvh, Dazl, Piwil2, Dppa3 and Stra8, that known molecular markers of male germ cells. Thus RA can induce differentiation of mouse bone marrow-derived CD15(+) , Oct4(+) and CXCR4(+) cells into male germ cells in vitro. Negative results for the gene expression analysis of female germ cells markers, GDF9 and ZP3, confirmed this conclusion. PMID:24677291

Kashani, Iraj Ragerdi; Zarnani, Amir Hassan; Soleimani, Masoud; Abdolvahabi, Mir Abbas; Nayernia, Karim; Shirazi, Reza

2014-06-01

205

Hematogenous extraneural metastasis of the germinomatous component of a pineal mixed germ cell tumor.  

PubMed

A 23-year-old man presented with a mass in the pineal region and obstructive hydrocephalus. A neuroendoscopicbiopsy for the lesion, ventriculoperitoneal (VP)shunting, and focal irradiation were conducted as initial treatment. Histological diagnosis of the biopsy specimen was germinoma. He underwent further irradiation and two tumor resections. Histological diagnosis was mature teratoma without a germinomatous component. After serial treatments, the intracranial lesion was controlled. However,14 months after presentation, extraneural lesions were confirmed in the posterior mediastinum and retroperitoneal space. The biopsy specimen of the retroperitoneal space lesion was histologically diagnosed as germinoma. Although chemotherapy with cisplatin and etoposide was undertaken,extraneural lesions ware uncontrollable and he died. At autopsy, extraneural lesions were confirmed in the posterior mediastinum, retroperitoneal space, and right lung. Histological diagnosis of extraneural lesions was germinoma.This case was considered to be a pineal mixed germ cell tumor mainly consisting of germinoma and mature teratoma,which caused hematogenous metastasis of the germinoma component. Systemic chemotherapy and irradiation for primary lesions as an initial treatment is important to cure the primary lesion and prevent extraneural metastasis. PMID:22286191

Asanuma, Megumi; Aoyama, Tatsuro; Sakai, Keiichi; Asano, Koji; Uehara, Tsuyoshi; Hongo, Kazuhiro

2012-10-01

206

Fine-needle aspiration biopsy of nonteratomatous germ cell tumors of the mediastinum.  

PubMed

We assessed the usefulness of fine-needle aspiration biopsy (FNAB) in the diagnosis of mediastinal germ cell tumors (GCTs). In the archives of 3 pathology departments, we found records of 7 patients with mediastinal GCTs who underwent mediastinal FNAB as part of the diagnostic workup. The FNAB smears, results of the immunocytochemical analysis, the corresponding histologic findings, and the clinical charts were reviewed. All patients were men (age range, 24-44 years; mean, 32 years). One patient had a history of testicular mixed GCT 10 years earlier. The 6 primary mediastinal GCTs consisted of 3 seminomas and 3 yolk sac tumors. Based on the cytologic features and immunocytochemicalfindings, a cytologic diagnosis of GCT was made in 5 cases, including the case of metastatic GCT In 2 cases, the differential diagnosis was between poorly differentiated carcinoma and GCT Results of ancillary studies were noncontributory in 1 case, and the aspirate of the second case demonstrated extensive necrosis. Our findings demonstrate that a diagnosis of mediastinal GCT, primary or secondary, can be established with a high degree of accuracy on the basis of FNAB. Immunocytochemical analysis helps confirm the diagnosis. PMID:12219784

Chhieng, David C; Lin, Oscar; Moran, Cesar A; Eltoum, Isam A; Jhala, Nirag C; Jhala, Darshana N; Simsir, Aylin

2002-09-01

207

Survival outcomes for men with mediastinal germ-cell tumors: The University of Texas M. D. Anderson Cancer Center experience?  

PubMed Central

Objective Primary mediastinal germ-cell tumors are rare, and the effect of newer drugs and treatment strategies in this disease on overall survival is not known. We retrospectively assessed treatment outcomes at a single institution. Materials and methods We identified men seen at our institution from 1998 through 2005 for mediastinal germ-cell tumors. Medical records were reviewed for patient characteristics, histology, tumor markers, treatment, and survival outcome. Results Thirty-four patients met study criteria, of whom 27 had nonseminomatous germ-cell tumor (NSGCT) and 7 had pure seminoma. Eleven patients (41%) with NSGCT were alive at last contact with a median overall survival time of 33.5 months. Among 13 patients with NSGCT referred to us at initial diagnosis, 7 (54%) were alive and recurrence-free at a median follow-up of 56.5 months. Progression-free survival was associated with absence of risk factors (any histology other than endodermal sinus tumor, ?-hCG > 1000 mIU/mL, or disease outside the mediastinum). For the patients whose disease progressed (n = 5) or who had been referred to us for salvage treatment (n = 14), the 3-year overall survival from the date of first progression was 23%. Conversely, patients with seminoma did uniformly well with platinum-based chemotherapy; most did not undergo radiation or surgery. Conclusion Chemotherapy given to maximum effect followed by surgical consolidation resulted in long-term progression-free survival for 54% of patients with mediastinal NSGCT. The number of risk factors present at diagnosis may be associated with survival outcome and should be studied in a larger test group. PMID:20933444

Rodney, Alan J.; Tannir, Nizar M.; Siefker-Radtke, Arlene O.; Liu, Ping; Walsh, Garrett L.; Millikan, Randall E.; Swisher, Stephen G.; Tu, Shi-Ming; Pagliaro, Lance C.

2014-01-01

208

Avemar (wheat germ extract) in cancer prevention and treatment.  

PubMed

Many healthy foods are derived from wheat germ. The molecular composition of these products, however, greatly differs as shown by normal-phase HPLC-mass spectrometry analysis; thus, experimental data obtained by one of them is not necessarily true for the other. Avemar is a nontoxic wheat germ extract registered as a special nutriment for cancer patients in Hungary. It shows potent anticancer activity on cell lines by deeply interfering with glucose metabolism and affecting expressions of several kinases. In in vivo experimental models, Avemar is also effective by enhancing the activity of the immune system such as stimulating NK cell activity (by reducing MHC I molecule expression), enhancing TNF secretion of the macrophages, increasing ICAM 1 molecule expression on the vascular endothelial cells. All of these lead to apoptosis of tumor cells. The wide range of biological activity of Avemar probably cannot be explained by only one active ingredient. Since there are numerous experimental data and the clinical benefit repeatedly confirmed Avemar can be one of the most potent and best researched food supplements available for cancer patients. PMID:20155632

Telekes, András; Hegedus, Márta; Chae, Chang-Hoon; Vékey, Károly

2009-01-01

209

Germ-Line Regulation of the Caenorhabditis elegans Sex-Determining Gene tra-2  

E-print Network

sex-determining gene tra-2 promotes female development of the XX hermaphrodite soma and germ line. We. First, we characterize a 1.8-kb tra-2 mRNA, which is hermaphrodite-specific and germ transform hermaphrodites to females by eliminating hermaphrodite spermatogenesis. Each of the tra-2(mx

Kimble, Judith

210

The role of the sex chromosomes in mammalian germ cell differentiation  

E-print Network

The role of the sex chromosomes in mammalian germ cell differentiation P. S. BURGOYNE Department and their sex-chromosomal make-up. It is concluded that germ cells in an ovary require two functional X chromosomes for optimal development. The effects of X-dosage deficiency are most severe in species where

Paris-Sud XI, Université de

211

Sex chromosome inactivation in germ cells: emerging roles of DNA damage response pathways  

E-print Network

REVIEW Sex chromosome inactivation in germ cells: emerging roles of DNA damage response pathways chromosome inactivation in male germ cells is a paradigm of epigenetic programming during sexual reproduction. Recent progress has revealed the underlying mechanisms of sex chromosome inactivation in male meiosis

Dean, Matthew D.

212

From Young Children's Ideas about Germs to Ideas Shaping a Learning Environment  

ERIC Educational Resources Information Center

This paper is concerned with highlighting young children's ideas about the nature, location and appearance of germs, as well as their reasoning strands about germs' ontological category and biological functions. Moreover, it is concerned with exploring how all these could be taken into account for shaping a potentially fruitful learning…

Ergazaki, Marida; Saltapida, Konstantina; Zogza, Vassiliki

2010-01-01

213

The moduli space of germs of generic families of analytic diffeomorphisms unfolding a parabolic fixed  

Microsoft Academic Search

In this paper we describe the moduli space of germs of generic families of analytic diffeomorphisms which unfold a parabolic fixed point of codimension 1. In (11) (and also (15)), it was shown that the Ecalle-Voroninmodulus can be unfolded to give a complete modulus for such germs. The modulus is defined on a ramified sector in the canonical perturbation parameter

C. Christopher; C. Rousseau

214

Practical issues on the application of the GHS classification criteria for germ cell mutagens  

Microsoft Academic Search

The Globally Harmonized System of Classification and Labeling of Chemicals (GHS) requires classification of chemicals on germ cell mutagenicity. The Japanese government has conducted GHS classification on about 1400 chemicals in a 2-year project (J-GHS) for implementing GHS domestically. Prior to the classification work, the technical guidance for classification of germ cell mutagens was prepared. This guidance introduces the concept

Takeshi Morita; Makoto Hayashi; Madoka Nakajima; Noriho Tanaka; David J. Tweats; Kaoru Morikawa; Toshio Sofuni

2009-01-01

215

Blimp1 is a critical determinant of the germ cell lineage in mice  

Microsoft Academic Search

Germ cell fate in mice is induced in pluripotent epiblast cells in response to signals from extraembryonic tissues. The specification of approximately 40 founder primordial germ cells and their segregation from somatic neighbours are important events in early development. We have proposed that a critical event during this specification includes repression of a somatic programme that is adopted by neighbouring

Yasuhide Ohinata; Bernhard Payer; Dónal O'Carroll; Katia Ancelin; Yukiko Ono; Mitsue Sano; Sheila C. Barton; Tetyana Obukhanych; Michel Nussenzweig; Alexander Tarakhovsky; Mitinori Saitou; M. Azim Surani

2005-01-01

216

Pattern formation in fragmented eggs of the short germ insect Schistocerca gregaria  

Microsoft Academic Search

The effect of transverse fragmentation on the segment pattern of the short germ embryo of the locust Schistocerca gregaria has been investigated at two stages subsequent to the formation of the germ anlage. Following fragmentation both anterior and posterior partial embryos were observed, although rarely in a single egg. Anterior partial patterns usually terminated with a segment visible at the

Jane E. Mee

1986-01-01

217

Derivation of embryonic germ cells and male gametes from embryonic stem cells  

Microsoft Academic Search

Egg and sperm cells (gametes) of the mouse are derived from a founder population of primordial germ cells that are set aside early in embryogenesis. Primordial germ cells arise from the proximal epiblast, a region of the early mouse embryo that also contributes to the first blood lineages of the embryonic yolk sac. Embryonic stem cells differentiate in vitro into

Niels Geijsen; Melissa Horoschak; Kitai Kim; Joost Gribnau; Kevin Eggan; George Q. Daley

2004-01-01

218

Intratubular germ cell neoplasia of the human testis: heterogeneous protein expression and relation to invasive potential.  

PubMed

Testicular germ cell cancer develops from premalignant intratubular germ cell neoplasia, unclassified cells that are believed to arise from failure of normal maturation of fetal germ cells from gonocytes (OCT4(+)/MAGEA4(-)) into pre-spermatogonia (OCT4(-)/MAGEA4(+)). Intratubular germ cell neoplasia cell subpopulations based on stage of germ cell differentiation have been described, however the importance of these subpopulations in terms of invasive potential has not been reported. We hypothesized that cells expressing an immature (OCT4(+)/MAGEA4(-)) germ cell profile would exhibit an increased proliferation rate compared with those with a mature profile (OCT4(+)/MAGEA4(+)). Therefore, we performed triple immunofluorescence and stereology to quantify the different intratubular germ cell neoplasia cell subpopulations, based on expression of germ cell (OCT4, PLAP, AP2?, MAGEA4, VASA) and proliferation (Ki67) markers, in testis sections from patients with preinvasive disease, seminoma, and non-seminoma. We compared these subpopulations with normal human fetal testis and with seminoma cells. Heterogeneity of protein expression was demonstrated in intratubular germ cell neoplasia cells with respect to gonocyte and spermatogonial markers. It included an embryonic/fetal germ cell subpopulation lacking expression of the definitive intratubular germ cell neoplasia marker OCT4, that did not correspond to a physiological (fetal) germ cell subpopulation. OCT4(+)/MAGEA4(-) cells showed a significantly increased rate of proliferation compared with the OCT4(+)/MAGEA4(+) population (12.8 versus 3.4%, P<0.0001) irrespective of histological tumor type, reflected in the predominance of OCT4(+)/MAGEA4(-) cells in the invasive tumor component. Surprisingly, OCT4(+)/MAGEA4(-) cells in patients with preinvasive disease showed significantly higher proliferation compared to those with seminoma or non-seminoma (18.1 versus 10.2 versus 7.2%, P<0.05, respectively). In conclusion, this study has demonstrated that OCT4(+)/MAGEA4(-) cells are the most frequent and most proliferative cell population in tubules containing intratubular germ cell neoplasia, which appears to be an important factor in determining invasive potential of intratubular germ cell neoplasia to seminomas. PMID:24457464

Mitchell, Rod T; E Camacho-Moll, Maria; Macdonald, Joni; Anderson, Richard A; Kelnar, Christopher J H; O'Donnell, Marie; Sharpe, Richard M; Smith, Lee B; Grigor, Ken M; Wallace, W Hamish B; Stoop, Hans; Wolffenbuttel, Katja P; Donat, Roland; Saunders, Philippa Tk; Looijenga, Leendert Hj

2014-09-01

219

The role of BLIMP1 and its putative downstream target TFAP2C in germ cell development and germ cell tumours.  

PubMed

During the past years, much information has been gathered regarding the genetic and epigenetic programmes leading to the specification and maintenance of primordial germ cells. Expression of the transcriptional regulator BLIMP1 (PRDM1) is regarded as the main event in germ cell specification. BLIMP1 induces a set of target genes, one of them being transcription factor TFAP2C (AP-2?, Tcfap2c). In murine loss of function models Blimp1 and Tcfap2c share an identical phenotype, strengthening the assumption that they act in the same pathway. One major role of this pathway is the inhibition of somatic differentiation in germ cells. BLIMP1 and TFAP2C are also expressed in carcinoma in situ (CIS, IGCNU, TIN) and in seminoma. As pointed out herein, the presence of both proteins helps to explain the undifferentiated nature of these germ cell tumours. In addition, we performed a meta-analysis of high-throughput datasets searching for TFAP2C/Tcfap2c target genes. This analysis leads us to suggest Nanos3, Dmrt1 and Dnmt3b as potential TFAP2C/Tcfap2c target genes with relevance to germ cell development and germ cell tumours. PMID:21564135

Schäfer, S; Anschlag, J; Nettersheim, D; Haas, N; Pawig, L; Schorle, H

2011-08-01

220

The Ter Mutation In The Dead End Gene Causes Germ Cell Loss And Testicular Germ Cell Tumours  

SciTech Connect

In mice, the Ter mutation causes primordial germ cell (PGC) loss in all genetic backgrounds1. Ter is also a potent modifier of spontaneous testicular germ cell tumour (TGCT) susceptibility in the 129 family of inbred strains, and markedly increases TGCT incidence in 129-Ter/Ter males2 4. In 129-Ter/Ter mice, some of the remaining PGCs transform into undifferentiated pluripotent embryonal carcinoma cells2 6, and after birth differentiate into various cells and tissues that compose TGCTs. Here, we report the positional cloning of Ter, revealing a point mutation that introduces a termination codon in the mouse orthologue (Dnd1) of the zebrafish dead end (dnd) gene. PGC deficiency is corrected both with bacterial artificial chromosomes that contain Dnd1 and with a Dnd1-encoding transgene. Dnd1 is expressed in fetal gonads during the critical period when TGCTs originate. DND1 has an RNA recognition motif and is most similar to the apobec complementation factor, a component of the cytidine t o uridine RNA-editing complex. These results suggest that Ter may adversely affect essential aspects of RNA biology during PGC development. DND1 is the first protein known to have an RNA recognition motif directly implicated as a heritable cause of spontaneous tumorigenesis. TGCT development in the 129-Ter mouse strain models paediatric TGCT in humans. This work will have important implications for our understanding of the genetic control of TGCT pathogenesis and PGC biology.

Youngren, Kirsten K.; Coveney, Douglas; Peng, Xiaoning; Bhattacharya, Chitralekha; Schmidt, Laura S.; Nickerson, Michael L.; Lamb, Bruce T.; Deng Jian Min; Behringer, Richard R.; Capel, Blanche; Rubin, Edward M.; Nadeau, Joseph H.; Matin, Angabin

2005-01-01

221

Primary cilia in the developing pig testis.  

PubMed

In vertebrates, a variety of cell types generate a primary cilium. Cilia are implicated in determination and differentiation of a wide variety of organs and during embryonic development. However, there is little information on the presence or function of primary cilia in the mammalian testis. Therefore, the objective of this study was to characterize expression of primary cilia in the developing pig testis. Testicular tissue from pigs at 2-10 weeks of age was analyzed for primary cilia by immunocytochemistry. Expression of primary cilia was also analyzed in testicular tissue formed de novo from a single cell suspension ectopically grafted into a mouse host. Functionality of primary cilia was monitored based on cilia elongation after exposure to lithium. Analysis showed that the primary cilium is present in testis cords as well as in the interstitium of the developing pig testis. Germ cells did not express primary cilia. However, we identified Sertoli cells as one of the somatic cell types that produce a primary cilium within the developing testis. Primary cilium expression was reduced from the second to the third week of pig testis development in situ and during de novo morphogenesis of testis tissue from a single cell suspension after xenotransplantation. In vitro, primary cilia were elongated in response to lithium treatment. These results indicate that primary cilia on Sertoli cells may function during testicular development. De novo morphogenesis of testis tissue from single cell suspensions may provide an accessible platform to study and manipulate expression and function of primary cilia. PMID:25107611

Ou, Young; Dores, Camila; Rodriguez-Sosa, Jose-Rafael; van der Hoorn, Frans A; Dobrinski, Ina

2014-11-01

222

The story of a largely unknown evolution - Germ theory hoax.  

PubMed

The Piltdown Man debacle provides us with the most infamous forgery in science. However, another equally intriguing story exists concerning a document by a Bostonian called George Sleeper, which purported to be a pre-Darwin-Wallace anticipation of evolution and an equally convincing account of the germ theory published before Louis Pasteur's famous studies on this subject. The story involves two giants in the world of evolutionary theory, Alfred Russel Wallace and E.B. Poulton. While Wallace was convinced that the Sleeper document was genuine, Poulton's detailed investigations showed that it was a fake and a hoax. Despite this conclusion, doubts still exist about the authenticity of the Sleeper document. PMID:23961141

Wainwright, Milton; Alharbi, Sulaiman Ali

2011-10-01

223

The story of a largely unknown evolution - Germ theory hoax  

PubMed Central

The Piltdown Man debacle provides us with the most infamous forgery in science. However, another equally intriguing story exists concerning a document by a Bostonian called George Sleeper, which purported to be a pre-Darwin–Wallace anticipation of evolution and an equally convincing account of the germ theory published before Louis Pasteur’s famous studies on this subject. The story involves two giants in the world of evolutionary theory, Alfred Russel Wallace and E.B. Poulton. While Wallace was convinced that the Sleeper document was genuine, Poulton’s detailed investigations showed that it was a fake and a hoax. Despite this conclusion, doubts still exist about the authenticity of the Sleeper document. PMID:23961141

Wainwright, Milton; Alharbi, Sulaiman Ali

2011-01-01

224

Intra- and Interindividual Epigenetic Variation in Human Germ Cells  

PubMed Central

Epigenetics represents a secondary inheritance system that has been poorly investigated in human biology. The objective of this study was to perform a comprehensive analysis of DNA methylation variation between and within the germlines of normal males. First, methylated cytosines were mapped using bisulphite modification–based sequencing in the promoter regions of the following disease genes: presenilins (PSEN1 and PSEN2), breast cancer (BRCA1 and BRCA2), myotonic dystrophy (DM1), and Huntington disease (HD). Major epigenetic variation was detected within samples, since the majority of sperm cells of the same individual exhibited unique DNA methylation profiles. In the interindividual analysis, 41 of 61 pairwise comparisons revealed distinct DNA methylation profiles (P=.036 to 6.8 × 10?14). Second, a microarray-based epigenetic profiling of the same sperm samples was performed using a 12,198-feature CpG island microarray. The microarray analysis has identified numerous DNA methylation–variable positions in the germ cell genome. The largest degree of variation was detected within the promoter CpG islands and pericentromeric satellites among the single-copy DNA fragments and repetitive elements, respectively. A number of genes, such as EED, CTNNA2, CALM1, CDH13, and STMN2, exhibited age-related DNA methylation changes. Finally, allele-specific methylation patterns in CDH13 were detected. This study provides evidence for significant epigenetic variability in human germ cells, which warrants further research to determine whether such epigenetic patterns can be efficiently transmitted across generations and what impact inherited epigenetic individuality may have on phenotypic outcomes in health and disease. PMID:16773567

Flanagan, James M.; Popendikyte, Violeta; Pozdniakovaite, Natalija; Sobolev, Martha; Assadzadeh, Abbas; Schumacher, Axel; Zangeneh, Masood; Lau, Lynette; Virtanen, Carl; Wang, Sun-Chong; Petronis, Arturas

2006-01-01

225

Differentiation of Human Embryonic Stem Cells into Embryoid Bodies Comprising the Three Embryonic Germ Layers  

Microsoft Academic Search

Background: Embryonic stem (ES) cells are lines of cells that are isolated from blastocysts. The murine ES cells were demonstrated to be true pluripotent cells as they differentiate into all embry- onic lineages. Yet, in vitro differentiation of rhesus ES cells was somewhat inconsistent and disorga- nized. The recent isolation of human ES cells calls for exploring their pluripotential nature.

Joseph Itskovitz-Eldor

2000-01-01

226

TAp73 is essential for germ cell adhesion and maturation in testis  

PubMed Central

A core evolutionary function of the p53 family is to protect the genomic integrity of gametes. However, the role of p73 in the male germ line is unknown. Here, we reveal that TAp73 unexpectedly functions as an adhesion and maturation factor of the seminiferous epithelium orchestrating spermiogenesis. TAp73 knockout (TAp73KO) and p73KO mice, but not ?Np73KO mice, display a “near-empty seminiferous tubule” phenotype due to massive premature loss of immature germ cells. The cellular basis of this phenotype is defective cell–cell adhesions of developing germ cells to Sertoli nurse cells, with likely secondary degeneration of Sertoli cells, including the blood–testis barrier, which leads to disruption of the adhesive integrity and maturation of the germ epithelium. At the molecular level, TAp73, which is produced in germ cells, controls a coordinated transcriptional program of adhesion- and migration-related proteins including peptidase inhibitors, proteases, receptors, and integrins required for germ–Sertoli cell adhesion and dynamic junctional restructuring. Thus, we propose the testis as a unique organ with strict division of labor among all family members: p63 and p53 safeguard germ line fidelity, whereas TAp73 ensures fertility by enabling sperm maturation. PMID:24662569

Holembowski, Lena; Kramer, Daniela; Riedel, Dietmar; Sordella, Raffaella; Nemajerova, Alice; Dobbelstein, Matthias

2014-01-01

227

PGL proteins self associate and bind RNPs to mediate germ granule assembly in C. elegans  

PubMed Central

Germ granules are germ lineage–specific ribonucleoprotein (RNP) complexes, but how they are assembled and specifically segregated to germ lineage cells remains unclear. Here, we show that the PGL proteins PGL-1 and PGL-3 serve as the scaffold for germ granule formation in Caenorhabditis elegans. Using cultured mammalian cells, we found that PGL proteins have the ability to self-associate and recruit RNPs. Depletion of PGL proteins from early C. elegans embryos caused dispersal of other germ granule components in the cytoplasm, suggesting that PGL proteins are essential for the architecture of germ granules. Using a structure–function analysis in vivo, we found that two functional domains of PGL proteins contribute to germ granule assembly: an RGG box for recruiting RNA and RNA-binding proteins and a self-association domain for formation of globular granules. We propose that self-association of scaffold proteins that can bind to RNPs is a general mechanism by which large RNP granules are formed. PMID:21402787

Hanazawa, Momoyo; Yonetani, Masafumi

2011-01-01

228

Radiation-induced bystander signaling from somatic cells to germ cells in Caenorhabditis elegans.  

PubMed

Recently, radiation-induced bystander effects (RIBE) have been studied in mouse models in vivo, which clearly demonstrated bystander effects among somatic cells. However, there is currently no evidence for RIBE between somatic cells and germ cells in animal models in vivo. In the current study, the model animal Caenorhabditis elegans was used to investigate the bystander signaling from somatic cells to germ cells, as well as underlying mechanisms. C. elegans body size allows for precise microbeam irradiation and the abundant mutant strains for genetic dissection relative to currently adopted mouse models make it ideal for such analysis. Our results showed that irradiation of posterior pharynx bulbs and tails of C. elegans enhanced the level of germ cell apoptosis in bystander gonads. The irradiation of posterior pharynx bulbs also increased the level of DNA damage in bystander germ cells and genomic instability in the F1 progeny of irradiated worms, suggesting a potential carcinogenic risk in progeny even only somatic cells of parents are exposed to ionizing radiation (IR). It was also shown that DNA damage-induced germ cell death machinery and MAPK signaling pathways were both involved in the induction of germ cell apoptosis by microbeam induced bystander signaling, indicating a complex cooperation among multiple signaling pathways for bystander effects from somatic cells to germ cells. PMID:23931723

Guo, Xiaoying; Sun, Jie; Bian, Po; Chen, Lianyun; Zhan, Furu; Wang, Jun; Xu, An; Wang, Yugang; Hei, Tom K; Wu, Lijun

2013-09-01

229

The fog-3 gene and regulation of cell fate in the germ line of Caenorhabditis elegans  

SciTech Connect

In the nematode Caenorhabditis elegans, germ cells normally adopt one of three fates: mitosis, spermatogenesis or oogenesis. We have identified and characterized the gene fog-3, which is required for germ cells to differentiate as sperm rather than as oocytes. Analysis of double mutants suggests that fog-3 is absolutely required for spermatogenesis and acts at the end of the regulatory hierarchy controlling sex determination for the germ line. By contrast, mutations in fog-3 do not alter the sexual identity of other tissues. We also have characterized the null phenotype of fog-1, another gene required for spermatogenesis; we demonstrate that it too controls the sexual identity of germ cells but not of other tissues. Finally, we have studied the same interaction of these two fog genes with gld-1, a gene required for germ cells to undergo oogenesis rather than mitosis. On the basis of these results, we propose that germ-cell fate might be controlled by a set of inhibitory interactions among genes that specify one of three fates: mitosis, spermatogenesis or oogenesis. Such a regulatory network would link the adoption of one germ-cell fate to the suppression of the other two. 68 refs., 7 figs., 6 tabs.

Ellis, R.; Kimble, J. [Univ. of Wisconsin, Madison, WI (United States)

1995-02-01

230

DDX3X, the X homologue of AZFa gene DDX3Y, expresses a complex pattern of transcript variants only in the male germ line.  

PubMed

DDX3X, the functional X homologue of the major AZFa gene, DDX3Y, belongs to the highly conserved PL10-subfamily of DEAD-box RNA helicase genes which are functionally conserved from yeast to man. They are mainly involved in cell cycle control and translation initiation control of gene transcripts with long 5'UTR extensions containing complex secondary structures. Interestingly, in humans both gene copies were found to be expressed at different phases of human spermatogenesis. Whereas DDX3Y transcripts are translated only in premeiotic male germ cells, the DDX3X protein is expressed only in postmeiotic spermatids. In this study, we found that the major class of DDX3X transcripts in human testis become activated first after meiosis and at a specific core promoter not active in somatic tissues and not present upstream of the DDX3Y homologue. Two alternative 5'UTR transcript lengths are subsequently produced by an additional testis-specific 5'UTR splicing event. Both transcripts are mainly processed for polyadenylation in their proximal 3'UTR. A minor transcript class starting at the same male germ line-specific core promoter produces primary transcripts with an extremely long 3'UTR (?17 kb), which is subsequently spliced at distinct sites resulting in six short 3'UTR splice variants (I-VI). Comparative analyses of the DDX3X transcripts in mouse and primates revealed that this complex pattern of male germ line-specific transcript variants first evolved in primates. Our data thus suggest complex translational control mechanism(s) for the human DDX3X gene locus functioning only in the male germ line and resulting in expression of its protein only in the postmeiotic spermatids. PMID:25208899

Rauschendorf, Marc-Alexander; Zimmer, Jutta; Ohnmacht, Caroline; Vogt, Peter H

2014-12-01

231

Human germ cell differentiation from pluripotent embryonic stem cells and induced pluripotent stem cells.  

PubMed

Although 10-15 % of couples are infertile, little is known of the diverse, underlying pathologies in men and women with poor germ cell production; furthermore, for those with few or no high-quality germ cells, there are few options available for treatment. Thus, over the last decade, concerted efforts have been aimed at developing a biological system to probe the fundamentals of human egg and sperm production via pluripotent stem cell cells with the hopes of informing clinical decisions and ultimately providing alternative methods for therapy which may include developing a source of germ cells ultimately for reproductive purposes. PMID:24782029

Medrano, Jose V; Simon, Carlos; Pera, Renee Reijo

2014-01-01

232

Germ-line DICER1 mutations do not make a major contribution to the etiology of familial testicular germ cell tumours  

PubMed Central

Background The RNase III enzyme DICER1 plays a central role in maturation of microRNAs. Identification of neoplasia-associated germ-line and somatic mutations in DICER1 indicates that mis-expression of miRNAs in cancer may result from defects in their processing. As part of a recent study of DICER1 RNase III domains in 96 testicular germ cell tumors, a single RNase IIIb domain mutation was identified in a seminoma. To further explore the importance of DICER1 mutations in the etiology of testicular germ cell tumors (TGCT), we studied germ-line DNA samples from 43 probands diagnosed with familial TGCT. Findings We carried out High Resolution Melting Curve Analysis of DICER1 exons 2–12, 14–19, 21 and 24–27. All questionable melt curves were subjected to confirmatory Sanger sequencing. Sanger sequencing was used for exons 13, 20, 22 and 23. Intron-exon boundaries were included in all analyses. We identified 12 previously reported single nucleotide polymorphisms and two novel single nucleotide variants. No likely deleterious variants were identified; notably no mutations that were predicted to truncate the protein were identified. Conclusions Taken together with previous studies, the findings reported here suggest a very limited role for either germ-line or somatic DICER1 mutations in the etiology of TGCT. PMID:23547758

2013-01-01

233

Extragonadal mixed germ cell tumor of the right arm: description of the first case in the literature  

PubMed Central

Background Extragonadal localization of germ cell tumors (GCTs) is rare; to the best of our knowledge, a location in the soft tissue of the arm has never been previously reported in the literature. Case presentation We report the case of a 37-year-old man who presented with a primary malignant mixed non-seminomatous GCT (teratocarcinoma variety) in the right arm, treated by a combination of cisplatin-based chemotherapy and surgery. After 18 months of close follow-up, no locoregional recurrence or distant metastases have been detected. Conclusions A combination of chemotherapy and surgery is the most appropriate treatment strategy for extragonadal GCTs, to ensure both local and systemic control. PMID:22540884

2012-01-01

234

[Two cases of relapse or refractory germ cell tumor who had been treated with combination chemotherapy of cisplatin and carboplatin].  

PubMed

We tried a combination chemotherapy with cisplatin (CDDP) and carboplatin (CBDCA) (CDDP/CBDCA regimen) as salvage therapy for 2 cases with recurrent or refractory Germ Cell Tumor (GCT). Case 1 was a 29-year-old man with 2nd relapsed embryonal carcinoma and seminoma originating from testis. Case 2 was a 23-year-old man with primary refractory embryonal carcinoma and yolk sac tumor originating from mediastinum. CDDP and CBDCA were administered at the dose of 120 mg/m2 and 350 mg/m2 on day 1, and vinblastin was administered at the dose of 10 mg/body on day 2. In one of two cases, a complete response was obtained. Non-hematologic toxicity of CDDP/CBDCA regimen was tolerable. It is suggested that this combination chemotherapy is useful for GCT recurrence. PMID:8978809

Kiyama, Y; Suzuki, G; Masauzi, N; Ohizumi, H; Kobayashi, N; Ogasawara, M; Naohara, T; Saito, M; Higa, T; Kasai, M

1996-12-01

235

Germ Tube Mediated Invasion of Batrachochytrium dendrobatidis in Amphibian Skin Is Host Dependent  

PubMed Central

Batrachochytrium dendrobatidis (Bd) is the causative agent of chytridiomycosis, a fungal skin disease in amphibians and driver of worldwide amphibian declines. We focussed on the early stages of infection by Bd in 3 amphibian species with a differential susceptibility to chytridiomycosis. Skin explants of Alytes muletensis, Litoria caerulea and Xenopus leavis were exposed to Bd in an Ussing chamber for 3 to 5 days. Early interactions of Bd with amphibian skin were observed using light microscopy and transmission electron microscopy. To validate the observations in vitro, comparison was made with skin from experimentally infected frogs. Additional in vitro experiments were performed to elucidate the process of intracellular colonization in L. caerulea. Early interactions of Bd with amphibian skin are: attachment of zoospores to host skin, zoospore germination, germ tube development, penetration into skin cells, invasive growth in the host skin, resulting in the loss of host cell cytoplasm. Inoculation of A. muletensis and L. caerulea skin was followed within 24 h by endobiotic development, with sporangia located intracellularly in the skin. Evidence is provided of how intracellular colonization is established and how colonization by Bd proceeds to deeper skin layers. Older thalli develop rhizoid-like structures that spread to deeper skin layers, form a swelling inside the host cell to finally give rise to a new thallus. In X. laevis, interaction of Bd with skin was limited to an epibiotic state, with sporangia developing upon the skin. Only the superficial epidermis was affected. Epidermal cells seemed to be used as a nutrient source without development of intracellular thalli. The in vitro data agreed with the results obtained after experimental infection of the studied frog species. These data suggest that the colonization strategy of B. dendrobatidis is host dependent, with the extent of colonization most likely determined by inherent characteristics of the host epidermis. PMID:22911798

Van Rooij, Pascale; Martel, An; D'Herde, Katharina; Brutyn, Melanie; Croubels, Siska; Ducatelle, Richard; Haesebrouck, Freddy; Pasmans, Frank

2012-01-01

236

Testicular germ cell sensitivity to TRAIL-induced apoptosis is dependent upon p53 expression and is synergistically enhanced by DR5 agonistic antibody treatment  

Microsoft Academic Search

The ability of the TRAIL\\/DR5 signaling pathway to induce apoptosis has generally been limited to tumor cells. Here we report\\u000a that in primary testis explants, addition of TRAIL (0.5 ?g\\/ml) caused a three-fold increase in germ cell apoptosis. Furthermore,\\u000a exposure of C57BL\\/6 mice to the testicular toxicant, mono-(2-ethylhexyl) phthalate (MEHP), caused an increased p53 stability\\u000a and elevated DR5 mRNA levels coincident

Chad M. McKee; Yang Ye; John H. Richburg

2006-01-01

237

The effects of growth factors on testicular germ cell apoptosis in the stallion  

E-print Network

recombinant growth factors, stem cell factor (SCF), leukemia inhibiting factor (LIF), granulocyte macrophage-colony stimulating factor (GM-CSF), and one hormone, estradiol (E?), alone or in combination, to prevent apoptosis of germ cells in short-term equine...

Donnelly, Casey Leanne

2012-06-07

238

Analytic continuation of holonomy germs of Riccati foliations along brownian paths  

E-print Network

Analytic continuation of holonomy germs of Riccati foliations along brownian paths Nicolas Hussenot of the dynamic of complex algebraic foliations. In particular, it is proved that for a Riccati foliation of P1

Paris-Sud XI, Université de

239

Spermatogenesis in testes of Dazl null mice after transplantation of wild-type germ cells.  

PubMed

Dazl knockout male mice are infertile because their germ cells are unable to complete the first meiotic prophase in the first wave of spermatogenesis and thereafter decrease in number due to a block at the A-aligned to A1 transition. The ability of the surviving somatic components of the testes to retain their function in the absence of mature germ cells was tested by injecting marked wild-type germ cell suspensions containing spermatogonial stem cells. Comparison of the frequency and extent of colonization of Dazl knockout testes with that of testes chemically depleted of germ cells showed little if any difference. It was concluded that Dazlko testes seem unimpaired in their ability to support spermatogenesis. Therefore, Dazlko testes provide a useful and reliable recipient in which to evaluate spermatogonial stem cells. The results furthermore demonstrate that the somatic compartment of the testis of these animals retains functionality. PMID:14611632

Rilianawati; Speed, R; Taggart, M; Cooke, H J

2003-11-01

240

Moral obligation and the human germ-line gene therapy debate  

E-print Network

genetic engineering, there are few arguments made for a positive moral obligation to genetic intervention. This is especially so with respect to human germ-line gene therapy. Burke. K. Zimmerman makes one of the few arguments that society...

Clark, Alan B

2012-06-07

241

Identification of Germ Plasm-Associated Transcripts by Microarray Analysis of Xenopus Vegetal Cortex RNA  

PubMed Central

RNA localization is a common mechanism for regulating cell structure and function. Localized RNAs in Xenopus oocytes are critical for early development, including germline specification by the germ plasm. Despite the importance of these localized RNAs, only approximately 25 have been identified and fewer are functionally characterized. Using microarrays, we identified a large set of localized RNAs from the vegetal cortex. Overall, our results indicate a minimum of 275 localized RNAs in oocytes, or 2–3% of maternal transcripts, which are in general agreement with previous findings. We further validated vegetal localization for 24 candidates and further characterized three genes expressed in the germ plasm. We identified novel germ plasm expression for reticulon 3.1, exd2 (a novel exonuclease-domain encoding gene), and a putative noncoding RNA. Further analysis of these and other localized RNAs will likely identify new functions of germ plasm and facilitate the identification of cis-acting RNA localization elements. PMID:20503379

Cuykendall, Tawny N.; Houston, Douglas W.

2011-01-01

242

Examination of plants in lunar (germ free) soil in Plant Laboratory  

NASA Technical Reports Server (NTRS)

Dr. Charles Walkenshaw, Manned Spacecraft Center botanist, examines sorghum and tobacco plants in lunar (germ free) soil in the Plant Laboratory of the Lunar Receiving Laboratory. The soil was brought back from the Moon by the Apollo 11 astronauts.

1969-01-01

243

Conservation of Migration and Differentiation Circuits in Primordial Germ Cells Between Avian Species  

PubMed Central

Abstract Germ cell differentiation in reverse-sexed reproductive organs and interspecies germ line chimeras provides insight into the mechanism of germ cell development and represents a useful tool for conservation of endangered birds. We investigated the migration and survival capacity of male chicken primordial germ cells (PGCs) in female chicken embryos and in quail and Korean ring-necked pheasant embryos of both sexes. Interestingly, the PGCs were successfully reintroduced in all cases. Furthermore, the cells survived in the recipient gonads until hatching regardless of sex and species of the recipient. In the case of male recipient chickens, PGC-derived offspring were produced. However, the reverse-sexed female chickens, quails and pheasants of both sexes did not generate any male donor PGC-derived progeny. These results suggest that migration and survival circuits in chicken PGCs are conserved in both sexes and between avian species during embryonic development. PMID:23386102

PARK, Tae Sub; HAN, Jae Yong

2013-01-01

244

Conservation of migration and differentiation circuits in primordial germ cells between avian species.  

PubMed

Germ cell differentiation in reverse-sexed reproductive organs and interspecies germ line chimeras provides insight into the mechanism of germ cell development and represents a useful tool for conservation of endangered birds. We investigated the migration and survival capacity of male chicken primordial germ cells (PGCs) in female chicken embryos and in quail and Korean ring-necked pheasant embryos of both sexes. Interestingly, the PGCs were successfully reintroduced in all cases. Furthermore, the cells survived in the recipient gonads until hatching regardless of sex and species of the recipient. In the case of male recipient chickens, PGC-derived offspring were produced. However, the reverse-sexed female chickens, quails and pheasants of both sexes did not generate any male donor PGC-derived progeny. These results suggest that migration and survival circuits in chicken PGCs are conserved in both sexes and between avian species during embryonic development. PMID:23386102

Park, Tae Sub; Han, Jae Yong

2013-01-01

245

Restroom Hand Dryers Spread More Germs Than Paper Towels, Study Finds  

MedlinePLUS

... JavaScript. Restroom Hand Dryers Spread More Germs Than Paper Towels, Study Finds Bacteria counts in the air around the machines far exceeded those around paper dispensers (*this news item will not be available ...

246

Syphilis - primary  

MedlinePLUS

Primary syphilis; Secondary syphilis; Late syphilis; Tertiary syphilis ... their newborn (congenital syphilis). Syphilis has three stages: Primary syphilis Secondary syphilis Tertiary syphilis (the late phase ...

247

An integrative omics strategy to assess the germ cell secretome and to decipher sertoli-germ cell crosstalk in the Mammalian testis.  

PubMed

Mammalian spermatogenesis, which takes place in complex testicular structures called seminiferous tubules, is a highly specialized process controlled by the integration of juxtacrine, paracrine and endocrine information. Within the seminiferous tubules, the germ cells and Sertoli cells are surrounded by testicular fluid (TF), which probably contains most of the secreted proteins involved in crosstalk between these cells. It has already been established that germ cells can modulate somatic Sertoli cell function through the secretion of diffusible factors. We studied the germ cell secretome, which was previously considered inaccessible, by analyzing the TF collected by microsurgery in an "integrative omics" strategy combining proteomics, transcriptomics, genomics and interactomics data. This approach identified a set of proteins preferentially secreted by Sertoli cells or germ cells. An interaction network analysis revealed complex, interlaced cell-cell dialog between the secretome and membranome of seminiferous cells, mediated via the TF. We then focused on germ cell-secreted candidate proteins, and we identified several potential interacting partners located on the surface of Sertoli cells. Two interactions, APOH/CDC42 and APP/NGFR, were validated in situ, in a proximity ligation assay (PLA). Our results provide new insight into the crosstalk between germ cells and Sertoli cells occurring during spermatogenesis. Our findings also demonstrate that this "integrative omics" strategy is powerful enough for data mining and highlighting meaningful cell-cell communication events between different types of cells in a complex tissue, via a biological fluid. This integrative strategy could be applied more widely, to gain access to secretomes that have proved difficult to study whilst avoiding the limitations of in vitro culture. PMID:25111155

Chalmel, Frédéric; Com, Emmanuelle; Lavigne, Régis; Hernio, Nolwen; Teixeira-Gomes, Ana-Paula; Dacheux, Jean-Louis; Pineau, Charles

2014-01-01

248

Modeling cell elongation during germ band retraction: cell autonomy versus applied anisotropic stress  

PubMed Central

The morphogenetic process of germ band retraction in Drosophila embryos involves coordinated movements of two epithelial tissues – germ band and amnioserosa. The germ band shortens along its rostral-caudal or head-to-tail axis, widens along its perpendicular dorsal-ventral axis, and uncurls from an initial ‘U’ shape. The amnioserosa mechanically assists this process by pulling on the crook of the U-shaped germ band. The amnioserosa may also provide biochemical signals that drive germ band cells to change shape in a mechanically autonomous fashion. Here, we use a finite-element model to investigate how these two contributions reshape the germ band. We do so by modeling the response to laser-induced wounds in each of the germ band’s spatially distinct segments (T1-T3, A1-A9) during the middle of retraction when segments T1-A3 form the ventral arm of the ‘U’, A4-A7 form its crook, and A8-A9 complete the dorsal arm. We explore these responses under a range of externally applied stresses and internal anisotropy of cell edge tensions – akin to a planar cell polarity that can drive elongation of cells in a direction parallel to the minimum edge tension – and identify regions of parameter space (edge-tension anisotropy versus stress anisotropy) that best match previous experiments for each germ band segment. All but three germ band segments are best fit when the applied stress anisotropy and the edge-tension anisotropy work against one another – i.e., when the isolated effects would elongate cells in perpendicular directions. Segments in the crook of the germ band (A4-A7) have cells that elongate in the direction of maximum external stress, i.e., external stress anisotropy is dominant. In most other segments, the dominant factor is internal edge-tension anisotropy. These results are consistent with models in which the amnioserosa pulls on the crook of the germ band to mechanically assist retraction. In addition, they suggest a mechanical cue for edge-tension anisotropy whereby cells do not globally orient their internal elongation axis towards the amnioserosa, but instead orient this axis perpendicular to the local principal stress direction. PMID:24839394

Lynch, Holley E.; Veldhuis, Jim; Brodland, G. Wayne; Hutson, M. Shane

2014-01-01

249

Multidimensional representations: The knowledge domain of germs held by students, teachers and medical professionals  

NASA Astrophysics Data System (ADS)

The present study examined the understandings held by 5th, 8th, and 11th-grade students, their teachers and medical professionals about germs. Specifically, this study describes the content and structure of students' and adults' conceptions in the areas of germ contraction, transmission, and treatment of infectious and non-infectious diseases caused by microorganisms. Naturalistic and empirical research methods were used to investigate participants' conceptions. Between and within group similarities were found using data from concept maps on the topic "flu," drawings of germs, a 20 word card sort related to germs and illness, and a semi-structured interview. Concept maps were coded according to techniques by Novak and Gowan (1984). Drawings of germs were coded into four main categories (bacteria, viruses, animal cell, other) and five subcategories (disease, caricature, insect, protozoa, unclassified). Cluster patterns for the card sorts of each group were found using multidimensional scaling techniques. Six coding categories emerged from the interview transcripts: (a) transmission, (b) treatment, (c) effect of weather on illness, (d) immune response, (e) location of germs, and (f) similarities and differences between bacteria and viruses. The findings showed students, teachers and medical professionals have different understandings about bacteria and viruses and the structures of those understandings vary. Gaps or holes in the participants knowledge were found in areas such as: (a) how germs are transmitted, (b) where germs are found, (c) how the body transports and uses medicine, (d) how the immune system functions, (e) the difference between vaccines and non-prescription medicines, (f) differences that exist between bacteria and viruses, and (g) bacterial resistance to medication. The youngest students relied heavily upon personal experiences with germs rather than formal instruction when explaining their conceptions. As a result, the influence of media was evident in the students' understandings and images of microbes. Students also viewed germs as a human problem rather than seeing microorganisms as an independent member of the ecosystem. Teachers' explanations about germs varied in explicitness based on the grade level they taught while medical professionals based their understandings on formal knowledge and tended to use explicit technical language in their explanations of the phenomena.

Rua, Melissa Jo

250

Stimulation of rat Sertoli cell secretory activity in vitro by germ cells and residual bodies  

Microsoft Academic Search

Summary. The direct influence of germ cells and residual bodies on Sertoli cell basal and FSH-stimulated secretion of androgen-binding protein (ABP) was studied using Sertoli cells, recovered from 20-day-old rats, cultured alone or cocultured with a crude germ cell preparation from adult rats or with pachytene spermatocytes, round sperma- tids or populations of residual bodies enriched by centrifugal elutriation. The

B. Le Magueresse; F. Le Gac; M. Loir; B. Jegou

1986-01-01

251

Immunohistochemical study of nuclear changes associated with male germ cell death and spermiogenesis  

Microsoft Academic Search

In a previous study on the effects of gestational and lactational exposure of para-nonylphenol on male rats, we noted in both\\u000a induced and uninduced rats, that variations in cleaved caspase-3 immunostaining patterns were associated with distinct nuclear\\u000a alterations in mainly basally located germ cells (spermatogonia and preleptotene spermatocytes). These were re-analysed and\\u000a compared with cleaved caspase-3-labeled germ cells in the

Leon M. McCluskySean; Sean Patrick; Irene E. J. Barnhoorn; Jacobus C. van Dyk; Christiaan de Jager; Maria S. Bornman

2009-01-01

252

Patterns of codon recognition by isoacceptor aminoacyl-tRNAs from wheat germ.  

PubMed Central

Isoacceptors of Ala-, Arg-, Glu-, Gln-, Ile-, Leu-, Lys-, Ser-, Thr- and Val-tRNAs from wheat germ have been resolved by reverse phast chromatography. Codon recognition properties have been determined on isolated fractions of each of these aa-tRNAs and codon assignments have been made to a number of isoacceptors. Evolutionary changes which have occurred in patterns of codon recognition by isoacceptor aa-tRNAs in wheat germ and other organisms are discussed. PMID:251931

Hatfield, D; Rice, M

1978-01-01

253

Apoptosis mediated by phosphatidylserine externalization in the elimination of aneuploid germ cells during human spermatogenesis.  

PubMed

It has been described that aneuploidies trigger cell cycle checkpoints leading to apoptosis. The aim of this study was to assess the relationship between the presence of chromosomal abnormalities and apoptosis in germ cells and in Sertoli cells. Fourteen diagnostic testicular biopsies from infertile patients were processed following a sequential methodology, which included enzymatic disaggregation, apoptotic staining, cell sorting, cell fixation, and fluorescent in situ hybridization analysis. The chromosome constitution of germ cells (interphase pre-meiotic germ cells, meiotic figures, post-reductional germ cells, and spermatozoa) and Sertoli cells was evaluated in non-sorted and flow-sorted cell populations (apoptotic and viable). The mean percentage of aneuploidy was compared between the three fractions in each cell type using a Kruskal-Wallis test. If significant results were obtained, a two-by-two Chi-squared test was performed. There were significant differences between the apoptotic fraction and the viable and non-sorted fractions in the pre-meiotic germ cells (p < 0.01). In the remaining cell types, no association between the presence of aneuploidy and apoptotic processes was observed, even in the case of post-reductional germ cells in which we detected the highest rates of aneuploidy regardless of the fraction analyzed. From our data, it can be inferred that most of the aneuploid post-reductional germ cells are efficiently removed from the testicular epithelium without differentiating into spermatozoa. Our results suggest that the elimination of aneuploid testicular epithelial cells is triggered by different mechanisms. Accordingly, the cellular elimination of aneuploid germ cells beyond the blood-testis barrier does not involve phosphatidylserine externalization. PMID:25213174

Garcia-Quevedo, L; Blanco, J; Sarrate, Z; Vidal, F

2014-11-01

254

Bioinformatic analysis of P granule-related proteins: insights into germ granule evolution in nematodes  

Microsoft Academic Search

Germ cells in many animals possess a specialized cytoplasm in the form of granules that contain RNA and protein complexes\\u000a essential for the function and preservation of the germline. The mechanism for the formation of these granules is still poorly\\u000a understood; however, the lack of conservation in their components across different species suggests evolutionary convergence\\u000a in the assembly process. Germ

Luis A. Bezares-Calderón; Arturo Becerra; Laura S. Salinas; Ernesto Maldonado; Rosa E. Navarro

2010-01-01

255

In?vivo RNA interference in oyster - vasa silencing inhibits germ cell development  

Microsoft Academic Search

This study investigated the potential of RNA interference, which is technically challenging in bivalve mollusc species, to assess gene function in the oyster Crassostrea gigas. We designed dsRNA targeting the oyster vasa-like gene (Oyvlg), specifically expressed in oyster germ cells. In vivo injection of oyvl-dsRNA into the gonad provokes a knockdown phenotype corresponding to germ cell underproliferation and prematurely arrested

Caroline Fabioux; Charlotte Corporeau; Virgile Quillien; Pascal Favrel; Arnaud Huvet

2009-01-01

256

Good-risk-advanced germ cell tumors: historical perspective and current standards of care  

Microsoft Academic Search

Outcomes for patients with metastatic germ cell tumors have improved dramatically over the last 30 years with today’s cure\\u000a rates approaching 80%. A critical contribution to the treatment of metastatic disease was the development of the universally\\u000a accepted international germ cell cancer collaborative group (IGCCCG) outcome prediction model. With this system, patients\\u000a are classified into good, intermediate, and poor-risk groups, each

Darren R. Feldman; Robert J. Motzer

2009-01-01

257

Molecular analysis for p53 and mdm2 in intracranial germ cell tumors  

Microsoft Academic Search

Intracranial germ cell tumors (ICGTs) are uncommon neoplasms. The histological appearance of ICGTs is indistinguishable from\\u000a that of the usual testicular germ cell tumors (TGTs). Recently, several reports have associated molecular abnormalities of\\u000a p53 and mdm2 in TGTs with their malignancies. However, whether ICGTs are associated with molecular abnormalities is still\\u000a unknown. We analyzed a series of 16 ICGTs for

M. Iwato; O. Tachibana; Y. Tohma; H. Nitta; Y. Hayashi; J. Yamashita

2000-01-01

258

Reversine promotes porcine muscle derived stem cells (PMDSCs) differentiation into female germ-like cells.  

PubMed

A small molecular chemical-Reversine has been shown to promote cell reprogramming and induce dedifferentiation of multiple terminally differentiated mesodermal origin cells, and then differentiate into other cell types within mesodermal lineages as well as neuroectodermal. However, the possibilities of these cells to give rise to germ cell lineages have not been examined. The objective of the current study was to detect the effect of Reversine on PMDSCs differentiation into germ cells. PMDSCs from fetal porcine skeletal muscle and their potential of differentiation into germ cells in vitro were investigated. The phenotype, proliferation potential, characteristic markers of the first adhesion cells (pp1), and the purified 2 times cells (pp3) were analyzed by growth curve, FACS, and RT-PCR, respectively. Then, the purified cells were induced with 10% or 20% bovine follicular fluid (FF), the results showed that some of the induced pp3 cells were similar as porcine oocyte, and expressed germ cell and oocyte markers analyzed by semi-quantitative RT-PCR and immunofluorescent staining. Reversine clearly increased the potentiality of PMDSCs differentiation into large round germ-like cells in FF induction medium analyzed by morpholgogy, QRT-PCR and immunofluoresce. The BrdU labeled PMDSCs might differentiate into female germ-like cells in recipient's kidney capsule, which were positive for germ cell and meiotic markers (Dazl, Vasa, Figla, Stra8, Scp3) and oocyte markers (Zp2, Zp3). These findings provided an efficient model to study the mechanism of cell proliferation and germ cell differentiation in livestock promoted by Reversine. PMID:22821411

Lv, Xiao; Zhu, Haijing; Bai, Yaofu; Chu, Zhili; Hu, Yue; Cao, Hui; Liu, Chao; He, Xin; Peng, Sha; Gao, Zhimin; Yang, Chunrong; Hua, Jinlian

2012-12-01

259

Localisation of RNAs into the Germ Plasm of Vitellogenic Xenopus Oocytes  

PubMed Central

We have studied the localisation of mRNAs in full-grown Xenopus laevis oocytes by injecting fluorescent RNAs, followed by confocal microscopy of the oocyte cortex. Concentrating on RNA encoding the Xenopus Nanos homologue, nanos1 (formerly Xcat2), we find that it consistently localised into aggregated germ plasm ribonucleoprotein (RNP) particles, independently of cytoskeletal integrity. This implies that a diffusion/entrapment-mediated mechanism is active, as previously reported for previtellogenic oocytes. Sometimes this was accompanied by localisation into scattered particles of the “late”, Vg1/VegT pathway; occasionally only late pathway localisation was seen. The Xpat RNA behaved in an identical fashion and for neither RNA was the localisation changed by any culture conditions tested. The identity of the labelled RNP aggregates as definitive germ plasm was confirmed by their inclusion of abundant mitochondria and co-localisation with the germ plasm protein Hermes. Further, the nanos1/Hermes RNP particles are interspersed with those containing the germ plasm protein Xpat. These aggregates may be followed into the germ plasm of unfertilized eggs, but with a notable reduction in its quantity, both in terms of injected molecules and endogenous structures. Our results conflict with previous reports that there is no RNA localisation in large oocytes, and that during mid-oogenesis even germ plasm RNAs localise exclusively by the late pathway. We find that in mid oogenesis nanos1 RNA also localises to germ plasm but also by the late pathway. Late pathway RNAs, Vg1 and VegT, also may localise into germ plasm. Our results support the view that mechanistically the two modes of localisation are extremely similar, and that in an injection experiment RNAs might utilise either pathway, the distinction in fates being very subtle and subject to variation. We discuss these results in relation to their biological significance and the results of others. PMID:23626739

Nijjar, Sarbjit; Woodland, Hugh R.

2013-01-01

260

Minireview Schistosoma mansoni: Germ-line transformation approaches and actin-promoter analysis  

Microsoft Academic Search

Towards germ-line transformation miracidia were biolistically transformed with GFP reporter gene constructs and successfully rein- troduced into the schistosome cycle. By PCR and confocal microscopy the presence and the expression of GFP were confirmed in cerca- riae or adults of the F0 and F1 generations. This indicated the presence of the constructs in the germ-line, although no evidence for genome

Svenja Beckmann; Volker Wippersteg; Akram El-Bahay; Guilherme Oliveira; Christoph G. Grevelding

261

Schistosoma mansoni: Germ-line transformation approaches and actin-promoter analysis  

Microsoft Academic Search

Towards germ-line transformation miracidia were biolistically transformed with GFP reporter gene constructs and successfully reintroduced into the schistosome cycle. By PCR and confocal microscopy the presence and the expression of GFP were confirmed in cercariae or adults of the F0 and F1 generations. This indicated the presence of the constructs in the germ-line, although no evidence for genome integration was

Svenja Beckmann; Volker Wippersteg; Akram El-Bahay; Jörg Hirzmann; Guilherme Oliveira; Christoph G. Grevelding

2007-01-01

262

Early segregation of germ and somatic lineages during gonadal regeneration in the annelid Enchytraeus japonensis.  

PubMed

Although regeneration studies are useful for understanding how organs renew, little information is available about regeneration of reproductive organs and germ cells. We here describe the behavior of germ-cell precursors during regeneration of the oligochaete annelid worm Enchytraeus japonensis, which has the remarkable feature of undergoing asexual (by fission) and sexual reproduction . We first found that the gonad can regenerate from any body fragment yielded by fission during asexual reproduction. We then examined behavior of germ-cell lineage during this regenerative process, by using a homolog of the Piwi gene (Ej-piwi) as a marker. We found that in asexually growing animals, specialized cells expressing Ej-piwi are distributed widely in the body as single cells. These cells seem to serve as a reservoir of germ-cell precursors because during asexual propagation these cells migrate into the regenerating tissue, where they ultimately settle in the prospective gonads, and give rise to germ cells upon sexualization. These cells are distinct from the neoblasts, thought to be stem cells in other animals. This is the first report to directly show that the germ and somatic lineages are segregated in asexually growing animals and behave differently during regeneration. PMID:16713959

Tadokoro, Ryosuke; Sugio, Mutsumi; Kutsuna, Junko; Tochinai, Shin; Takahashi, Yoshiko

2006-05-23

263

Influence of Exposure to Benzo[a]pyrene on Mice Testicular Germ Cells during Spermatogenesis  

PubMed Central

The objective of this study was to assess the toxicological effect of exposure to benzo(a)pyrene, B[a]P, on germ cells during spermatogenesis. Mice were exposed to B[a]P at 1, 10, 50, and 100?mg/kg/day for 30 days via oral ingestion. Germ cells, including spermatogonia, spermatocytes, pachytene spermatocytes, and round spermatids, were recovered from testes of mice exposed to B[a]P, while mature spermatozoa were isolated from vas deferens. Reproductive organs were collected and weighed. Apoptotic response of germ cells and mature spermatozoa were qualified using the terminal deoxynucleotidyl transferase mediated deoxy-UTP nick end labeling (TUNEL) assay. B[a]P exposure at ?10?mg/kg/day for 30 days did not significantly alter concentrations of germ cells and mature spermatozoa and apoptotic response in germ cells and mature spermatozoa. Exposure to B[a]P at 50 and 100?mg/kg/day induced testicular atrophy and yielded a significant reduction in the concentrations of spermatogonia, spermatocytes, pachytene spermatocytes, and round spermatid cells as compared with the control. Also, mature spermatozoa experienced decreased concentrations and viability. B[a]P-exposed mice experienced a significant increase in apoptotic germ cells as compared to the control mice. However, the mice dose concentrations were not relevant for comparison to human exposure. PMID:24454362

Jeng, Hueiwang Anna; Bocca, Silvina M.

2013-01-01

264

Morphometric Approach to Pulp Fibroblast Development in Tooth Germ  

PubMed Central

This paper builds a morphometric framework for the analysis of dental pulp fibroblast evolution during tooth development. We investigated 15 tooth germs (cases) organized, by histological criteria, in three groups corresponding to cap, early bell, and late bell stages, respectively. Each group comprised five cases. The morphometric description used the following parameters: area (A), perimeter (P)—automatically extracted by a color segmentation technique, and form factor (FF)—calculated as 4?A/P2. The designed framework operated at inter- and intragroup levels. The intergroup analysis quantified the differences between groups, in the sense of a relative distance (RD) adequately defined by mean-value scaling. We showed that the stage of early bell is approximately 5 times closer to late bell than to cap. The quantification procedure required concomitant information about A, P parameters (as P versus A dependences, or FF values), whereas the procedure failed for A or P separately used. The intragroup analysis quantified the similarity of the cases belonging to the same stage. We proved that, unlike the intergroup tests, the individual exploitation of all three descriptors A, P, and FF is effective, yielding highly compatible results. Within any group, most cases presented RDs less than 10% from the group mean value, regardless of the descriptor type. PMID:25057501

Caruntu, Irina-Draga; Savinescu, Sergiu Daniel; Amalinei, Cornelia

2014-01-01

265

Safety studies regarding a standardized extract of fermented wheat germ.  

PubMed

"Avemar pulvis" is a powder consisting of an aqueous extract of fermented wheat germ, with the drying aids maltodextrin and silicon dioxide, standardized to contain approximately 200 microg/g of the natural constituent 2,6-dimethoxy-p-benzoquinone. The results of toxicological and clinical studies of this product demonstrate its safety for its intended use as a dietary supplement ingredient in the United States. Avemar pulvis has been used in Hungary since 1998 and is approved in that country, as well as in the Czech Republic, Bulgaria, and Romania, as a "medical nutriment for cancer patients." Acute and subacute toxicity studies using rodents orally administered Avemar pulvis showed that dose levels (2000 to 3000 mg/kg body weight [bw]/day) exceeding the normal recommended oral dosage (8.5 g/day or 121 mg/kg bw/day for a 70-kg individual) by up to approximately 25-fold caused no adverse effects. The test substance showed no evidence of mutagenicity or genotoxicity in vitro or in vivo. Clinical studies using Avemar pulvis as a supplement to drug therapy in cancer patients at doses of 8.5 g/day not only showed no evidence of toxicity, but also showed a reduction in the side effects of chemotherapy. Overall, it was concluded that Avemar pulvis would not be expected to cause adverse effects under the conditions of its intended use as an ingredient in dietary supplements. PMID:17564907

Heimbach, James T; Sebestyen, Gyula; Semjen, Gabor; Kennepohl, Elke

2007-01-01

266

Fermented wheat germ extract - nutritional supplement or anticancer drug?  

PubMed Central

Background Fermented wheat germ extract (FWGE) is a multisubstance composition and, besides others, contains 2-methoxy benzoquinone and 2, 6-dimethoxy benzoquinone which are likely to exert some of its biological effects. FWGE interferes with anaerobic glycolysis, pentose cycle and ribonucleotide reductase. It has significant antiproliferative effects and kills tumor cells by the induction of apoptosis via the caspase-poly [ADP-ribose] polymerase-pathway. FWGE interacts synergistically with a variety of different anticancer drugs and exerted antimetastatic properties in mouse models. In addition, FWGE modulates immune response by downregulation of MHC-I complex and the induction of TNF-? and various interleukins. Data in the F-344 rat model provide evidence for a colon cancer preventing effect of FWGE. Clinical data from a randomized phase II trial in melanoma patients indicate a significant benefit for patients treated with dacarbazine in combination with FWGE in terms of progression free survival (PFS) and overall survival (OS). Similarly, data from studies in colorectal cancer suggested a benefit of FWGE treatment. Besides extension of OS and PFS, FWGE improved the quality of life in several studies. Conclusion In conclusion, available data so far, justify the use of FWGE as a non-prescription medical nutriment for cancer patients. Further randomized, controlled and large scale clinical studies are mandatory, to further clarify the value of FWGE as a drug component of future chemotherapy regimens. PMID:21892933

2011-01-01

267

Fermented wheat germ extract (avemar) inhibits adjuvant arthritis.  

PubMed

Anti-inflammatory efficacy of the fermented wheat germ extract (FWGE, Avemar) in the rat adjuvant arthritis (AA) model was examined. To Wistar rats with AA, different doses of FWGE and anti-inflammatory drugs (indomethacin, dexamethasone) as monotherapies were administered and FWGE and either diclofenac or dexamethasone were also given in combination. Besides plethysmographies of the paws, histological investigations of synovial tissues were also performed along with detection of CD4+ and CD8+ T lymphocytes. Gene expressions of COX-1 and 2 were determined by real-time polymerase chain reaction (PCR). FWGE monotherapy significantly inhibited the development of the secondary (immune-mediated) response in AA, and dexamethasone and indomethacin exerted inhibitory effects in a degree comparable to that of FWGE. Histological analysis of the affected joints confirmed the results. FWGE inhibited COX-1 and -2, while indomethacin enhanced COX-2 gene expressions. FWGE had an additive interaction with diclofenac. It is concluded that FWGE has significant anti-inflammatory efficacy confirmed by plethysmography, histology, and real-time PCR. PMID:17911450

Telekes, Andras; Resetar, Akos; Balint, Geza; Blazso, Gabor; Falkay, Gyorgy; Lapis, Karoly; Raso, Erzsebet; Szende, Bela; Ehrenfeld, Michael; Shoenfeld, Yehuda; Hidvegi, Mate

2007-09-01

268

[A mixed germ cell tumor that underwent dramatic size changes].  

PubMed

This report describes a mixed germ cell tumor that underwent dramatic size changes. A 12-year-old boy presented to our hospital with a headache that had persisted for two months. Initial magnetic resonance imaging (MRI) revealed a pineal tumor and hydrocephalus. The patient required external ventricular drainage and underwent two endoscopic biopsies. His evaluation involved a total of nine computed tomography (CT) scans prior to the second biopsy;the tumor size had decreased before the second endoscopic biopsy. The tumor consisted of both a germinoma and a teratoma component. The patient was treated with three courses of carboplatin-etoposide (CBDCA-VP) chemotherapy and whole-ventricle radiotherapy (32.1 Gy). However, during the adjuvant therapy, the tumor size increased, necessitating total tumor resection. We speculate that the tumor's initial size reduction was caused by leakage of the cyst component and exposure to the brain CT irradiation. The tumor's subsequent increase in size was due to the recollection of the cystic components and intracranial growing teratoma syndrome (iGTS). Therefore, frequent brain CTs and angiography should be avoided before definitive pathological diagnosis is achieved. Further, the tumor size should be considered, with surgical resection being performed at the optimal time. PMID:25179200

Kuwayama, Kazuyuki; Takai, Hiroki; Nishiyama, Akira; Hirai, Satoshi; Yokosuka, Kimihiko; Toi, Hiroyuki; Hirano, Kazuhiro; Matsubara, Shunji; Uno, Masaaki; Nishimura, Hirotake

2014-09-01

269

Bmi1 expression in long-term germ stem cells.  

PubMed

Asingle cells in undifferentiated spermatogonia are considered to be the most primitive forms of germ stem cells (GSCs). Although GFR?1 is thought to be a marker of Asingle cells, we found that Bmi1(High) is more specific than GFR?1 for Asingle cells. Bmi1(High) expression in Asingle cells is correlated with seminiferous stages, and its expression was followed by the proliferative stage of Asingle GSCs. In contrast, GFR?1 expression was seminiferous stage-independent. Fate analyses of EdU-positive Bmi1(High)-positive cell-derived Asingle cells revealed that these cells self-renewed or generated transient amplifying Apaired cells. Bmi1(High)-positive cells were resistant to irradiation-induced injury, after which they regenerated. Elimination of Bmi1(High)-positive cells from seminiferous tubules resulted in the appearance of tubules with seminiferous stage mismatches. Thus, in this study, we found that Bmi1(High) is a seminiferous stage-dependent marker for long-term GSCs and that Bmi1(High)-positive cells play important roles in maintaining GSCs and in regenerating spermatogenic progenitors after injury. PMID:25146451

Komai, Yoshihiro; Tanaka, Toshihiro; Tokuyama, Yoko; Yanai, Hirotsugu; Ohe, Shuichi; Omachi, Taichi; Atsumi, Naho; Yoshida, Naoko; Kumano, Keiki; Hisha, Hiroko; Matsuda, Tadashi; Ueno, Hiroo

2014-01-01

270

PHYSICAL ACTIVITY IN ADOLESCENCE AND TESTICULAR GERM CELL CANCER RISK  

PubMed Central

Objective Several, but not all, studies have observed increased risks of testicular germ cell cancer (TGCC) associated with bicycling and other recreational activities. To further examine whether physical activity (PA) in adolescence is associated with TGCC risk, the authors conducted a case-control study in western Washington State. Methods Cases (n=391) were men diagnosed with TGCC who were identified through a population-based cancer registry. Controls (n=1023) were men identified from the general population in western Washington State by using random digit telephone dialing. Participants were queried about various specific PA in grades 7–12 including bicycling, horseback riding, competitive sports, physical education class, as well as moderate, vigorous, and sedentary activities in general. Results In multivariate analyses, bicycling, vigorous-intensity activities, and sedentary activities were not associated with TGCC risk, while horseback riding and wrestling were associated with decreased risks, and moderate-intensity activities, soccer, basketball and intermediate duration of competitive activities were associated with increased risks. Conclusions The lack of internal consistency of the findings within the current study and of findings among prior studies, suggests that PA contributes little, if any, to the risk of TGCC. PMID:19399630

Littman, Alyson J; Doody, David R; Biggs, Mary L; Weiss, Noel S; Starr, Jacqueline R; Schwartz, Stephen M

2010-01-01

271

Repression of kit Expression by Plzf in Germ Cells?  

PubMed Central

Male mice lacking expression of Plzf, a DNA sequence-specific transcriptional repressor, show progressive germ cell depletion due to exhaustion of the spermatogonial stem cell population. This is likely due to the deregulated expression of genes controlling the switch between spermatogonial self-renewal and differentiation. Here we show that Plzf directly represses the transcription of kit, a hallmark of spermatogonial differentiation. Plzf represses both endogenous kit expression and expression of a reporter gene under the control of the kit promoter region. A discrete sequence of the kit promoter, required for Plzf-mediated kit transcriptional repression, is bound by Plzf both in vivo and in vitro. A 3-bp mutation in this Plzf binding site abolishes the responsiveness of the kit promoter to Plzf repression. A significant increase in kit expression is also found in the undifferentiated spermatogonia isolated from Plzf?/? mice. Thus, we suggest that one mechanism by which Plzf maintains the pool of spermatogonial stem cells is through a direct repression of kit expression. PMID:17664282

Filipponi, Doria; Hobbs, Robin M.; Ottolenghi, Sergio; Rossi, Pellegrino; Jannini, Emmanuele A.; Pandolfi, Pier Paolo; Dolci, Susanna

2007-01-01

272

The Origin And Migration Of Primordial Germ Cells In Sturgeons  

PubMed Central

Primordial germ cells (PGCs) arise elsewhere in the embryo and migrate into developing gonadal ridges during embryonic development. In several model animals, formation and migration patterns of PGCs have been studied, and it is known that these patterns vary. Sturgeons (genus Acipenser) have great potential for comparative and evolutionary studies of development. Sturgeons belong to the super class Actinoptergii, and their developmental pattern is similar to that of amphibians, although their phylogenetic position is an out-group to teleost fishes. Here, we reveal an injection technique for sturgeon eggs allowing visualization of germplasm and PGCs. Using this technique, we demonstrate that the PGCs are generated at the vegetal pole of the egg and they migrate on the yolky cell mass toward the gonadal ridge. We also provide evidence showing that PGCs are specified by inheritance of maternally supplied germplasm. Furthermore, we demonstrate that the migratory mechanism is well-conserved between sturgeon and other remotely related teleosts, such as goldfish, by a single PGCs transplantation (SPT) assay. The mode of PGCs specification in sturgeon is similar to that of anurans, but the migration pattern resembles that of teleosts. PMID:24505272

Saito, Taiju; Psenicka, Martin; Goto, Rie; Adachi, Shinji; Inoue, Kunio; Arai, Katsutoshi; Yamaha, Etsuro

2014-01-01

273

Germ-line DICER1 mutations do not make a major contribution to the etiology of familial testicular germ cell tumours  

E-print Network

Abstract Background The RNase III enzyme DICER1 plays a central role in maturation of microRNAs. Identification of neoplasia-associated germ-line and somatic mutations in DICER1 indicates that mis-expression of miRNAs in cancer may result from...

Sabbaghian, Nelly; Bahubeshi, Amin; Shuen, Andrew Y; Kanetsky, Peter A; Tischkowitz, Marc D; Nathanson, Katherine L; Foulkes, William D

2013-04-01

274

Early transcriptional response in the jejunum of germ-free piglets after oral infection with virulent rotavirus  

PubMed Central

Germ-free piglets were orally infected with virulent rotavirus to collect jejunal mucosal scrapings at 12 and 18 hours post infection (two piglets per time point). IFN-gamma mRNA expression was stimulated in the mucosa of all four infected piglets, indicating that they all responded to the rotavirus infection. RNA pools prepared from two infected piglets were used to compare whole mucosal gene expression at 12 and 18 hpi to expression in uninfected germ-free piglets (n = 3) using a porcine intestinal cDNA microarray. Microarray analysis identified 13 down-regulated and 17 up-regulated genes. Northern blot analysis of a selected group of genes confirmed the data of the microarray. Genes were functionally clustered in interferon-regulated genes, proliferation/differentiation genes, apoptosis genes, cytoskeleton genes, signal transduction genes, and enterocyte digestive, absorptive, and transport genes. Down-regulation of the transport gene cluster reflected in part the loss of rotavirus-infected enterocytes from the villous tips. Data mining suggested that several genes were regulated in lower- or mid-villus immature enterocytes and goblet cells, probably to support repair of the damaged epithelial cell layer at the villous tips. Furthermore, up-regulation was observed for IFN-? induced guanylate binding protein 2, a protein that effectively inhibited VSV and EMCV replication in vitro (Arch Virol 150:1213–1220, 2005). This protein may play a role in the small intestine’s innate defense against enteric viruses like rotavirus. Electronic supplementary material The online version of this article (doi:10.1007/s00705-008-0118-6) contains supplementary material, which is available to authorized users. PMID:18523839

Kerstens, Hinri; de Wit, Agnes; Smits, Mari; van der Meulen, Jan; Niewold, Theo

2008-01-01

275

Survival of patients with nonseminomatous germ cell cancer: a review of the IGCC classification by Cox regression and recursive partitioning.  

PubMed

The International Germ Cell Consensus (IGCC) classification identifies good, intermediate and poor prognosis groups among patients with metastatic nonseminomatous germ cell tumours (NSGCT). It uses the risk factors primary site, presence of nonpulmonary visceral metastases and tumour markers alpha-fetoprotein (AFP), human chorionic gonadotrophin (HCG) and lactic dehydrogenase (LDH). The IGCC classification is easy to use and remember, but lacks flexibility. We aimed to examine the extent of any loss in discrimination within the IGCC classification in comparison with alternative modelling by formal weighing of the risk factors. We analysed survival of 3048 NSGCT patients with Cox regression and recursive partitioning for alternative classifications. Good, intermediate and poor prognosis groups were based on predicted 5-year survival. Classifications were further refined by subgrouping within the poor prognosis group. Performance was measured primarily by a bootstrap corrected c-statistic to indicate discriminative ability for future patients. The weights of the risk factors in the alternative classifications differed slightly from the implicit weights in the IGCC classification. Discriminative ability, however, did not increase clearly (IGCC classification, c=0.732; Cox classification, c=0.730; Recursive partitioning classification, c=0.709). Three subgroups could be identified within the poor prognosis groups, resulting in classifications with five prognostic groups and slightly better discriminative ability (c=0.740). In conclusion, the IGCC classification in three prognostic groups is largely supported by Cox regression and recursive partitioning. Cox regression was the most promising tool to define a more refined classification. British Journal of Cancer (2004) 90, 1176-1183. doi:10.1038/sj.bjc.6601665 www.bjcancer.com Published online 24 February 2004 PMID:15026798

van Dijk, M R; Steyerberg, E W; Stenning, S P; Dusseldorp, E; Habbema, J D F

2004-03-22

276

Environmental Tobacco Smoke Exposure during Intrauterine Period, Promotes Caspase Dependent and Independent DNA Fragmentation in Sertoli-Germ Cells  

PubMed Central

Objectives. To investigate the effect of cigarette smoke exposure during intrauterine period on neonatal rat testis. Methods. Twenty-five rats were randomized to be exposed to cigarette smoke with the Walton Smoking Machine or to room air during their pregnancies. The newborn male rats (n = 21) were grouped as group 1 (n = 15) which were exposed to cigarette smoke during intrauterine life and group 2 (n = 6) which were exposed to room air during intrauterine life. The orchiectomy materials were analyzed with TUNEL immunofluorescent staining for detection of DNA damage. To detect apoptosis, immunohistochemical analyses with caspase-3 were performed. Primary outcomes were apoptotic index and immunohistochemical scores (HSCORES); secondary outcomes were Sertoli-cell count and birth-weight of rats. Results. Sertoli cell apoptosis was increased in group 1 (HSCORE = 210.6 ± 41.9) when compared to group 2 (HSCORE = 100.0 ± 17.8) (P = 0.001). Sertoli cell count was decreased in group 1 (P = 0.043). The HSCORE for the germ cells was calculated as 214.0 ± 46.2 in group 1 and 93.3 ± 10.3 in group 2 (P = 0.001) referring to an increased germ cell apoptosis in group 1. The apoptotic indexes for group 1 were 49.6 ± 9.57 and 29.98 ± 2.34 for group 2 (P = 0.001). The immunofluorescent technique demonstrated increased DNA damage in seminiferous epithelium in group 1. Conclusions. Intrauterine exposure to cigarette smoke adversely affects neonatal testicular structuring and diminishes testicular reserve. PMID:25045542

Yuksel, Beril; Kilic, Sevtap; Lortlar, Nese; Tasdemir, Nicel; Sertyel, Semra; Bardakci, Yesim; Aksu, Tarik; Batioglu, Sertac

2014-01-01

277

Transgene-mediated cosuppression and RNA interference enhance germ-line apoptosis in Caenorhabditis elegans.  

PubMed

Introduction of multiple copies of a germ-line-expressed gene elicits silencing of the corresponding endogenous gene during Caenorhabditis elegans oogenesis; this process is referred to as germ-line cosuppression. Transformed plasmids assemble into extrachromosomal arrays resembling extra minichromosomes with repetitive structures. Loss of the transgene extrachromosomal array leads to reversion of the silencing phenomenon. Cosuppression and RNAi depend upon some of the same genes. In the C. elegans germ line, about half the cells undergo a physiological programmed cell death that shares most genetic requirements with somatic apoptosis. In addition, apoptosis is stimulated by DNA damage and synaptic failure mediated through different apoptotic checkpoints. We found that both germ-line cosuppression and RNAi of germ-line-expressed genes enhance apoptosis during C. elegans oogenesis. In contrast, apoptosis is not enhanced by extrachromosomal arrays carrying genes not driven by germ-line-specific promoters that thus do not elicit transgene-mediated cosuppression/silencing. Similarly, introduction of doubled-stranded RNA that shares no homology with endogenous genes has no effect on apoptosis. "Silencing-induced apoptosis" is dependent upon sir-2.1 and cep-1 (the worm p53 ortholog), and is accompanied by a rise in RAD-51 foci, a marker for ongoing DNA repair, indicating induction of DNA double-strand breaks. This finding suggests that the DNA damage-response pathway is involved. RNAi and cosuppression have been postulated as defense mechanisms against genomic intruders. We speculate that the mechanism here described may trigger the elimination of germ cells that have undergone viral infection or transposon activation. PMID:22331911

Adamo, Adele; Woglar, Alexander; Silva, Nicola; Penkner, Alexandra; Jantsch, Verena; La Volpe, Adriana

2012-02-28

278

Lactate Regulates Rat Male Germ Cell Function through Reactive Oxygen Species  

PubMed Central

Besides giving structural support, Sertoli cells regulate the fate of germ cells by supplying a variety of factors. These factors include hormones, several pro- and anti-apoptotic agents and also energetic substrates. Lactate is one of the compounds produced by Sertoli cells, which is utilized as an energetic substrate by germ cells, particularly spermatocytes and spermatids. Beyond its function as an energy source, some studies have proposed a role of lactate in the regulation of gene expression not strictly related to the energetic state of the cells. The general hypothesis that motivated this investigation was that lactate affects male germ cell function, far beyond its well-known role as energetic substrate. To evaluate this hypothesis we investigated: 1) if lactate was able to regulate germ cell gene expression and if reactive oxygen species (ROS) participated in this regulation, 2) if different signal transduction pathways were modified by the production of ROS in response to lactate and 3) possible mechanisms that may be involved in lactate stimulation of ROS production. In order to achieve these goals, cultures of germ cells obtained from male 30-day old rats were exposed to 10 or 20 mM lactate. Increases in lactate dehydrogenase (LDH) C and monocarboxylate transporter (MCT)2 expression, in Akt and p38-MAPK phosphorylation levels and in ROS production were observed. These effects were impaired in the presence of a ROS scavenger. Lactate stimulated ROS production was also inhibited by a LDH inhibitor or a NAD(P)H oxidase (NOX) inhibitor. NOX4 expression was identified in male germ cells. The results obtained herein are consistent with a scenario where lactate, taken up by germ cells, becomes oxidized to pyruvate with the resultant increase in NADH, which is a substrate for NOX4. ROS, products of NOX4 activity, may act as second messengers regulating signal transduction pathways and gene expression. PMID:24498241

Galardo, Maria Noel; Regueira, Mariana; Riera, Maria Fernanda; Pellizzari, Eliana Herminia; Cigorraga, Selva Beatriz; Meroni, Silvina Beatriz

2014-01-01

279

Novel somatic and germline mutations in intracranial germ cell tumours.  

PubMed

Intracranial germ cell tumours (IGCTs) are a group of rare heterogeneous brain tumours that are clinically and histologically similar to the more common gonadal GCTs. IGCTs show great variation in their geographical and gender distribution, histological composition and treatment outcomes. The incidence of IGCTs is historically five- to eightfold greater in Japan and other East Asian countries than in Western countries, with peak incidence near the time of puberty. About half of the tumours are located in the pineal region. The male-to-female incidence ratio is approximately 3-4:1 overall, but is even higher for tumours located in the pineal region. Owing to the scarcity of tumour specimens available for research, little is currently known about this rare disease. Here we report the analysis of 62 cases by next-generation sequencing, single nucleotide polymorphism array and expression array. We find the KIT/RAS signalling pathway frequently mutated in more than 50% of IGCTs, including novel recurrent somatic mutations in KIT, its downstream mediators KRAS and NRAS, and its negative regulator CBL. Novel somatic alterations in the AKT/mTOR pathway included copy number gains of the AKT1 locus at 14q32.33 in 19% of patients, with corresponding upregulation of AKT1 expression. We identified loss-of-function mutations in BCORL1, a transcriptional co-repressor and tumour suppressor. We report significant enrichment of novel and rare germline variants in JMJD1C, which codes for a histone demethylase and is a coactivator of the androgen receptor, among Japanese IGCT patients. This study establishes a molecular foundation for understanding the biology of IGCTs and suggests potentially promising therapeutic strategies focusing on the inhibition of KIT/RAS activation and the AKT1/mTOR pathway. PMID:24896186

Wang, Linghua; Yamaguchi, Shigeru; Burstein, Matthew D; Terashima, Keita; Chang, Kyle; Ng, Ho-Keung; Nakamura, Hideo; He, Zongxiao; Doddapaneni, Harshavardhan; Lewis, Lora; Wang, Mark; Suzuki, Tomonari; Nishikawa, Ryo; Natsume, Atsushi; Terasaka, Shunsuke; Dauser, Robert; Whitehead, William; Adekunle, Adesina; Sun, Jiayi; Qiao, Yi; Marth, Gábor; Muzny, Donna M; Gibbs, Richard A; Leal, Suzanne M; Wheeler, David A; Lau, Ching C

2014-07-10

280

Endogenous DNA Damage and Risk of Testicular Germ Cell Tumors  

SciTech Connect

Testicular germ cell tumors (TGCT) are comprised of two histologic groups, seminomas and nonseminomas. We postulated that the possible divergent pathogeneses of these histologies may be partially explained by variable endogenous DNA damage. To assess our hypothesis, we conducted a case-case analysis of seminomas and nonseminomas using the alkaline comet assay to quantify single-strand DNA breaks and alkali-labile sites. The Familial Testicular Cancer study and the U.S. Radiologic Technologists cohort provided 112 TGCT cases (51 seminomas & 61 nonseminomas). A lymphoblastoid cell line was cultured for each patient and the alkaline comet assay was used to determine four parameters: tail DNA, tail length, comet distributed moment (CDM) and Olive tail moment (OTM). Odds ratios (OR) and 95% confidence intervals (95%CI) were estimated using logistic regression. Values for tail length, tail DNA, CDM and OTM were modeled as categorical variables using the 50th and 75th percentiles of the seminoma group. Tail DNA was significantly associated with nonseminoma compared to seminoma (OR{sub 50th percentile} = 3.31, 95%CI: 1.00, 10.98; OR{sub 75th percentile} = 3.71, 95%CI: 1.04, 13.20; p for trend=0.039). OTM exhibited similar, albeit statistically non-significant, risk estimates (OR{sub 50th percentile} = 2.27, 95%CI: 0.75, 6.87; OR{sub 75th percentile} = 2.40, 95%CI: 0.75, 7.71; p for trend=0.12) whereas tail length and CDM showed no association. In conclusion, the results for tail DNA and OTM indicate that endogenous DNA damage levels are higher in patients who develop nonseminoma compared with seminoma. This may partly explain the more aggressive biology and younger age-of-onset of this histologic subgroup compared with the relatively less aggressive, later-onset seminoma.

Cook, M B; Sigurdson, A J; Jones, I M; Thomas, C B; Graubard, B I; Korde, L; Greene, M H; McGlynn, K A

2008-01-18

281

Spermatogenesis and chromatin condensation in male germ cells of sea cucumber Holothuria leucospilota (Clark, 1920).  

PubMed

Male germ cells in the testis of Holothuria leucospilota can be divided into 12 stages based on ultrastructure and patterns of chromatin condensation. The spermatogonium (Sg) is a spherical-shaped cell with a diameter of about 6.5-7microm. Its nucleus mostly contains euchromatin and small blocks of heterochromatin scattered throughout the nucleus. The nucleolus is prominent. Primary spermatocytes are divided into six stages, i.e., leptotene (LSc), zygotene (ZSc), pachytene (PSc), diplotene (DSc), diakinesis (DiSc) and metaphase (MSc). The early cells are round while in DiSc and in MSc cells are oval in shape. From LSc to MSc, the sizes of cells range from 3.5 to 4microm. LSc contains large blocks of heterochromatin as a result of increasingly condensed 17nm fibers. In ZSc, the nucleus contains prominent synaptonemal complexes but a nucleolus is absent. In PSc, heterochromatin blocks are tightly packed together by 26nm fibers and appeared as large patches in DSc. Heterochromatin patches were enlarged to form chromosomes in DiSc and MSc and then the chromosome are moved to be aligned along equatorial region. The secondary spermatocyte (SSc) is an oval cell about 4.5-5.5microm. Their nuclei contain large clumps of heterochromatin along the nuclear envelope and in the center nuclear region. Spermatids are divided into two stages, i.e., early spermatid (ESt) and late spermatid (LSt). The nuclei decrease in size by a half and become spherical; thus the chromatin fibers condensed into 20nm and are closely packed together leaving only small spaces in LSt. The spermatozoa (Sz), with chromatin tightly packed in the spherical nucleus with a diameter of 2microm and a small acrosome situated at the anterior of the nucleus. The tail consists of a pair of centrioles lying perpendicular to each other and surrounded by a mitochondrial ring, and an axonemal complex, surrounded by a plasma membrane. PMID:18336850

Thongkukiatkul, A; Jungudomjaroen, S; Ratanapahira, C

2008-06-01

282

Reprogramming of primordial germ cells begins before migration into the genital ridge, making these cells inadequate donors for reproductive cloning  

Microsoft Academic Search

Germ cells undergo epigenetic modifications as they develop, which suggests that they may be ideal donors for nuclear transfer (cloning). In this study, nuclei from confirmed embryonic germ cells were used as donors to determine whether they are competent for cloning and at which stage they are most competent. Embryos cloned from migrating 10.5-days-postcoitum (dpc) primordial germ cells (PGCs) showed

Yukiko Yamazaki; Mellissa R. W. Mann; Susan S. Lee; Joel Marh; John R. McCarrey; Ryuzo Yanagimachi; Marisa S. Bartolomei

2003-01-01

283

Fas or FasL-deficient mice display an increased sensitivity to nitrobenzene-induced testicular germ cell apoptosis  

Microsoft Academic Search

We have previously reported that the Fas\\/Apo-1\\/CD95-mediated apoptosis-inducing signaling system participates in the initiation of toxicant-induced testicular germ cell apoptosis. The contribution of Fas-mediated signaling is especially evident in the initiation of germ cell apoptosis after mono-(2-ethylhexyl)phthalate (MEHP)-induced Sertoli cell injury. In previous work, we demonstrated that the incidence of germ cell apoptosis after MEHP exposure is significantly reduced in

John H Richburg; Adrian Nañez

2003-01-01

284

fog-2, a Germ-Line-Specific Sex Determination Gene Required for Hermaphrodite Spermatogenesis in Caenorhabditis elegans  

Microsoft Academic Search

This paper describes the isolation and characterization of 16 mutations in the germ-line sex determination gene fog-2 (fog for feminization of the germ line). In the nematode Caenorhabditis elegans there are normally two sexes, self-fertilizing hermaphrodites (XX) and males (XO). Wild- type XX animals are hermaphrodite in the germ line (spermatogenesis followed by oogenesis), and female in the soma. fog-2

Tim Schedl; Judith Kimble

285

Primary thrombocythemia  

MedlinePLUS

Primary thrombocythemia is when the bone marrow is making too many platelets without a known cause. Platelets ... Primary thrombocythemia is caused by too much growth of a type of cell that is used to ...

286

[Fermented wheat germ extract in the supportive therapy of colorectal cancer].  

PubMed

The role of the product in the treatment of colorectal cancer is reviewed in the light of experimental and clinical results to date. The fermented wheat germ extract (code name: MSC, trade name: Avemar) registered as a dietary food for special medical purposes for cancer patients to complement the active oncotherapy, exerted a growth inhibitory effect in HCR-25 human colon carcinoma xenograft, and had a synergistic effect with 5-FU in mouse C-38 colorectal carcinoma. The product is capable of chemoprevention of colon carcinoma in F-344 rats. One of the most significant underlying mechanism is a highly cancer cell specific induction of caspase-3 mediated cleavage of PARP. In the frame of supportive therapy, fermented wheat germ extract proved to be efficient in the treatment of colorectal cancer in humans. 30 patients following radical operation were treated with standard postoperative therapy, 12 of them were given fermented wheat germ extract as additive treatment: following a 9 month long administration, no new distant metastases were detected, in contrast to 4 out 18 treated with standard therapy alone. Out of 34 patients following radical surgery and treated with chemotherapy, 17 who were given fermented wheat germ extract, achieved an improved survival rate. In the frame of a controlled multicenter open label cohort study, 170 colorectal cancer patients received anticancer therapies (chemo/radiotherapy) completed with fermented wheat germ extract in 66 of them. Results (fermented wheat germ extract vs. control): new recurrences: 3.0% vs. 17.3% (p < 0.01); new metastases: 7.6% vs. 23.1% (p < 0.01); deaths: 12.1% vs. 31.7% (p < 0.01), progression-related events in total: 16.7% vs. 42.3% (p < 0.001). Survival analysis showed significant improvements in the fermented wheat germ extract group, regarding progression-free (p = 0.0184) and overall survival probabilities (p = 0.0278). Strong predictors of survival determined by Cox's proportional hazards were UICC stage and fermented wheat germ extract treatment. Mild gastrointestinal side effects were observed in 9 cases. Supportive application of fermented wheat germ extract in colorectal cancer is highly recommended. PMID:16255377

Farkas, Elek

2005-09-11

287

Gender differences in the induction of chromosomal aberrations and gene mutations in rodent germ cells  

SciTech Connect

Germ cell mutagenicity testing provides experimental data to quantify genetic risk for exposed human populations. The majority of tests are performed with exposure of males, and female data are relatively rare. The reason for this paucity lies in the differences between male and female germ cell biology. Male germ cells are produced throughout reproductive life and all developmental stages can be ascertained by appropriate breeding schemes. In contrast, the female germ cell pool is limited, meiosis begins during embryogenesis and oocytes are arrested over long periods of time until maturation processes start for small numbers of oocytes during the oestrus cycle in mature females. The literature data are reviewed to point out possible gender differences of germ cells to exogenous agents such as chemicals or ionizing radiation. From the limited information, it can be concluded that male germ cells are more sensitive than female germ cells to the induction of chromosomal aberrations and gene mutations. However, exceptions are described which shed doubt on the extrapolation of experimental data from male rodents to the genetic risk of the human population. Furthermore, the female genome may be more sensitive to mutation induction during peri-conceptional stages compared to the male genome of the zygote. With few exceptions, germ cell experiments have been carried out under high acute exposure to optimize the effects and to compensate for the limited sample size in animal experiments. Human exposure to environmental agents, on the other hand, is usually chronic and involves low doses. Under these conditions, gender differences may become apparent that have not been studied so far. Additionally, data are reviewed that suggest a false impression of safety when responses are negative under high acute exposure of male rodents while a mutational response is induced by low chronic exposure. The classical (morphological) germ cell mutation tests are not performed anymore because they are animal and time consuming. Nevertheless, information is needed to place genetic risk extrapolations on more solid grounds and thereby to prevent an increased genetic burden to future generations. It is pointed out that modern molecular methodologies are available now to experimentally address the open questions.

Adler, Ilse-Dore [GSF-Institute of Experimental Genetics, Neuherberg D-85758 (Germany); Carere, Angelo [Istituto Superiore di Sanita, Viale Regina Elena 299, Rome 00161 (Italy); Eichenlaub-Ritter, Ursula [Institute of Genetechnology/Microbiology, University of Bielefeld, Bielefeld D-33501 (Germany)]. E-mail: EiRi@uni-bielefeld.de; Pacchierotti, Francesca [Section of Toxicology and Biomedical Sciences, ENEA, CR Casaccia, Via Anguillarese 301, Rome 00060 (Italy)

2007-05-15

288

Human germ cell formation in xenotransplants of induced pluripotent stem cells carrying X chromosome aneuploidies.  

PubMed

Turner syndrome is caused by complete or partial loss of the second sex chromosome and is characterized by spontaneous fetal loss in >90% of conceptions. Survivors possess an array of somatic and germline clinical characteristics. Induced pluripotent stem cells (iPSCs) offer an opportunity for insight into genetic requirements of the X chromosome linked to Turner syndrome. We derived iPSCs from Turner syndrome and control individuals and examined germ cell development as a function of X chromosome composition. We demonstrate that two X chromosomes are not necessary for reprogramming or maintenance of pluripotency and that there are minimal differences in gene expression, at the single cell level, linked to X chromosome aneuploidies. Formation of germ cells, as assessed in vivo through a murine xenotransplantation model, indicated that undifferentiated iPSCs, independent of X chromosome composition, are capable of forming germ-cell-like cells (GCLCs) in vivo. In combination with clinical data regarding infertility in women with X chromosome aneuploidies, results suggest that two intact X chromosomes are not required for human germ cell formation, qualitatively or quantitatively, but rather are likely to be required for maintenance of human germ cells to adulthood. PMID:25242416

Dominguez, Antonia A; Chiang, H Rosaria; Sukhwani, Meena; Orwig, Kyle E; Reijo Pera, Renee A

2014-01-01

289

Autonomy in specification of primordial germ cells and their passive translocation in the sea urchin  

PubMed Central

The process of germ line determination involves many conserved genes, yet is highly variable. Echinoderms are positioned at the base of Deuterostomia and are crucial to understanding these evolutionary transitions, yet the mechanism of germ line specification is not known in any member of the phyla. Here we demonstrate that small micromeres (SMics), which are formed at the fifth cell division of the sea urchin embryo, illustrate many typical features of primordial germ cell (PGC) specification. SMics autonomously express germ line genes in isolated culture, including selective Vasa protein accumulation and transcriptional activation of nanos; their descendants are passively displaced towards the animal pole by secondary mesenchyme cells and the elongating archenteron during gastrulation; Cadherin (G form) has an important role in their development and clustering phenotype; and a left/right integration into the future adult anlagen appears to be controlled by a late developmental mechanism. These results suggest that sea urchin SMics share many more characteristics typical of PGCs than previously thought, and imply a more widely conserved system of germ line development among metazoans. PMID:22991443

Yajima, Mamiko; Wessel, Gary M.

2012-01-01

290

TOPAZ1, a Novel Germ Cell-Specific Expressed Gene Conserved during Evolution across Vertebrates  

PubMed Central

Background We had previously reported that the Suppression Subtractive Hybridization (SSH) approach was relevant for the isolation of new mammalian genes involved in oogenesis and early follicle development. Some of these transcripts might be potential new oocyte and granulosa cell markers. We have now characterized one of them, named TOPAZ1 for the Testis and Ovary-specific PAZ domain gene. Principal Findings Sheep and mouse TOPAZ1 mRNA have 4,803 bp and 4,962 bp open reading frames (20 exons), respectively, and encode putative TOPAZ1 proteins containing 1,600 and 1653 amino acids. They possess PAZ and CCCH domains. In sheep, TOPAZ1 mRNA is preferentially expressed in females during fetal life with a peak during prophase I of meiosis, and in males during adulthood. In the mouse, Topaz1 is a germ cell-specific gene. TOPAZ1 protein is highly conserved in vertebrates and specifically expressed in mouse and sheep gonads. It is localized in the cytoplasm of germ cells from the sheep fetal ovary and mouse adult testis. Conclusions We have identified a novel PAZ-domain protein that is abundantly expressed in the gonads during germ cell meiosis. The expression pattern of TOPAZ1, and its high degree of conservation, suggests that it may play an important role in germ cell development. Further characterization of TOPAZ1 may elucidate the mechanisms involved in gametogenesis, and particularly in the RNA silencing process in the germ line. PMID:22069478

Baillet, Adrienne; Le Bouffant, Ronan; Volff, Jean Nicolas; Luangpraseuth, Alix; Poumerol, Elodie; Thepot, Dominique; Pailhoux, Eric; Livera, Gabriel; Cotinot, Corinne; Mandon-Pepin, Beatrice

2011-01-01

291

Heterozygosity for a Bub1 mutation causes female-specific germ cell aneuploidy in mice  

SciTech Connect

Aneuploidy, the most common chromosomal abnormality at birth and the main ascertained cause of pregnancy loss in humans, originates primarily from chromosome segregation errors during oogenesis. Here we report that heterozygosity for a mutation in the mitotic checkpoint kinase gene, Bub1, induces aneuploidy in female germ cells of mice, and that the effect increases with advancing maternal age. Analysis of Bub1 heterozygous oocytes showed that aneuploidy occurred primarily during the first meiotic division and involved premature sister chromatid separation. Furthermore, aneuploidy was inherited in zygotes and resulted in the loss of embryos after implantation. The incidence of aneuploidy in zygotes was sufficient to explain the reduced litter size in matings with Bub1 heterozygous females. No effects were seen in germ cells from heterozygous males. These findings show that Bub1 dysfunction is linked to inherited aneuploidy in female germ cells and may contribute to the maternal age-related increase in aneuploidy and pregnancy loss.

Leland, Shawn; Nagarajan, Prabakaran; Polyzos, Aris; Thomas, Sharon; Samaan, George; Donnell, Robert; Marchetti, Francesco; Venkatachalam, Sundaresan

2009-06-24

292

Is the Blood-Brain Barrier Relevant in Metastatic Germ Cell Tumor?  

SciTech Connect

Purpose: Germ cell tumors are uniquely chemosensitive and curable, even with advanced metastatic disease. Central nervous system recurrence can terminate a complete remission in other chemosensitive tumors, such as small cell lung cancer, because of the blood-brain barrier (BBB). We propose to document that the BBB is also relevant in germ cell tumors despite their dramatic chemosensitivity. Methods and Materials: We present five cases illustrating the concept of the BBB in patients with metastatic testicular cancer treated with chemotherapy. Results: In our large series of patients with metastatic testicular cancer treated with chemotherapy, we identified 5 unique patients. These patients were rendered free of disease only to experience relapse in the brain alone. This included 1 patient who initially had good-risk metastatic disease by means of the International Germ Cell Collaborative Group staging system at the onset of chemotherapy. Conclusions: The BBB is relevant in patients with metastatic testicular cancer.

Azar, Jose M. [Department of Medicine, Division of Hematology and Oncology, Indiana University, Indianapolis, IN (United States); Walther Cancer Institute, Indianapolis, IN (United States)], E-mail: jazar@iupui.edu; Schneider, Bryan P.; Einhorn, Lawrence H. [Department of Medicine, Division of Hematology and Oncology, Indiana University, Indianapolis, IN (United States); Walther Cancer Institute, Indianapolis, IN (United States)

2007-09-01

293

Human germ-line therapy: the case for its development and use.  

PubMed

The rationale for pursuing the development and use of germ-line selection and modification techniques is examined in this essay. The argument is put forth that it is the moral obligation of the medical profession to make available to the public any technology that can cure or prevent pathology leading to death and disability, in both the present and future generations. Society should pursue the development of strategies for preventing or correcting, at the germ-line level, genetic features that will lead to, or enhance, pathological conditions. Because prenatal screening and even early embryo screening and selection can prevent only a subset of known genetic disorders, direct genetic intervention is the only way in which certain couples can exercise their rights to reproductive health. Finally, the arguments most often raised against the pursuit of and use of methods for germ-line intervention shall be discussed. PMID:1787389

Zimmerman, B K

1991-12-01

294

Metastable primordial germ cell-like state induced from mouse embryonic stem cells by Akt activation  

SciTech Connect

Specification to primordial germ cells (PGCs) is mediated by mesoderm-induction signals during gastrulation. We found that Akt activation during in vitro mesodermal differentiation of embryonic stem cells (ESCs) generated self-renewing spheres with differentiation states between those of ESCs and PGCs. Essential regulators for PGC specification and their downstream germ cell-specific genes were expressed in the spheres, indicating that the sphere cells had commenced differentiation to the germ lineage. However, the spheres did not proceed to spermatogenesis after transplantation into testes. Sphere cell transfer to the original feeder-free ESC cultures resulted in chaotic differentiation. In contrast, when the spheres were cultured on mouse embryonic fibroblasts or in the presence of ERK-cascade and GSK3 inhibitors, reversion to the ESC-like state was observed. These results indicate that Akt signaling promotes a novel metastable and pluripotent state that is intermediate to those of ESCs and PGCs.

Yamano, Noriko [Graduate School of Frontier Biosciences, Osaka University, 2-2 Yamada-oka, Suita, Osaka 565-0871 (Japan)] [Graduate School of Frontier Biosciences, Osaka University, 2-2 Yamada-oka, Suita, Osaka 565-0871 (Japan); Kimura, Tohru, E-mail: tkimura@patho.med.osaka-u.ac.jp [Department of Pathology, Medical School, Osaka University, 2-2 Yamada-oka, Suita, Osaka 565-0871 (Japan)] [Department of Pathology, Medical School, Osaka University, 2-2 Yamada-oka, Suita, Osaka 565-0871 (Japan); Watanabe-Kushima, Shoko [Graduate School of Frontier Biosciences, Osaka University, 2-2 Yamada-oka, Suita, Osaka 565-0871 (Japan)] [Graduate School of Frontier Biosciences, Osaka University, 2-2 Yamada-oka, Suita, Osaka 565-0871 (Japan); Shinohara, Takashi [Department of Molecular Genetics, Graduate School of Medicine, Kyoto University, Kyoto 606-8501 (Japan)] [Department of Molecular Genetics, Graduate School of Medicine, Kyoto University, Kyoto 606-8501 (Japan); Nakano, Toru, E-mail: tnakano@patho.med.osaka-u.ac.jp [Graduate School of Frontier Biosciences, Osaka University, 2-2 Yamada-oka, Suita, Osaka 565-0871 (Japan) [Graduate School of Frontier Biosciences, Osaka University, 2-2 Yamada-oka, Suita, Osaka 565-0871 (Japan); Department of Pathology, Medical School, Osaka University, 2-2 Yamada-oka, Suita, Osaka 565-0871 (Japan)

2010-02-12

295

[Multidrug-resistant Germs in Neurological Early Rehabilitation (2004-2013)].  

PubMed

Multidrug-resistant germs are an increasing problem in neurological and neurosurgical early rehabilitation but reliable data is missing. The present study examined the prevalence of methicillin-resistant Staphylococcus aureus (MRSA), vancomycin-resistant enterococci (VRE), and multidrug-resistant gram negative germs (MRGN) in a German neurological early rehabilitation facility (BDH Clinic Hessisch Oldendorf). Observation period was 2004-2013 (10 years). MRSA prevalence on admission was 11.4%, MRGN prevalence during rehabilitation 11.8%. A combination of different multidrug-resistant germs (MRSA plus MRGN) was observed in 3.8% of all cases. VRE were first detected in 2009, prevalence was as low as 0.1%. High prevalence of MRSA and MRGN raises major financial, medical, and ethical problems in early rehabilitation facilities. The authors encourage further multi-center studies and suggest a better recompense for this group of patients in the German DRG-system (Diagnosis Related Groups). PMID:25317899

Rollnik, J D; Samady, A-M; Grüter, L

2014-10-01

296

Germ cell development in the postnatal testis: the key to prevent malignancy in cryptorchidism?  

PubMed Central

To permit normal postnatal germ cell development, the mammalian testis undergoes a complex, multi-staged process of descent to the scrotum. Failure of any part of this process leads to congenital cryptorchidism, wherein the malpositioned testis finds itself at the wrong temperature after birth, which leads to secondary germ cell loss and later infertility and risk of cancer. Recent studies suggest that neonatal gonocytes transform into the putative spermatogenic stem cells between 3 and 9 months, and this initial postnatal step is deranged in cryptorchid testes. In addition, it is thought the abnormality high temperature may also impair apoptosis of remaining gonocytes, allowing some to persist to become the possible source of carcinoma in situ and malignancy after puberty. The biology of postnatal germ cell development is of intense interest, as it is likely to be the key to the optimal timing for orchidopexy. PMID:23316184

Hutson, John M.; Li, Ruili; Southwell, Bridget R.; Petersen, Bodil L.; Thorup, Jorgen; Cortes, Dina

2013-01-01

297

Genome analysis of Elysia chlorotica Egg DNA provides no evidence for horizontal gene transfer into the germ line of this Kleptoplastic Mollusc.  

PubMed

The sea slug Elysia chlorotica offers a unique opportunity to study the evolution of a novel function (photosynthesis) in a complex multicellular host. Elysia chlorotica harvests plastids (absent of nuclei) from its heterokont algal prey, Vaucheria litorea. The "stolen" plastids are maintained for several months in cells of the digestive tract and are essential for animal development. The basis of long-term maintenance of photosynthesis in this sea slug was thought to be explained by extensive horizontal gene transfer (HGT) from the nucleus of the alga to the animal nucleus, followed by expression of algal genes in the gut to provide essential plastid-destined proteins. Early studies of target genes and proteins supported the HGT hypothesis, but more recent genome-wide data provide conflicting results. Here, we generated significant genome data from the E. chlorotica germ line (egg DNA) and from V. litorea to test the HGT hypothesis. Our comprehensive analyses fail to provide evidence for alga-derived HGT into the germ line of the sea slug. Polymerase chain reaction analyses of genomic DNA and cDNA from different individual E. chlorotica suggest, however, that algal nuclear genes (or gene fragments) are present in the adult slug. We suggest that these nucleic acids may derive from and/or reside in extrachromosomal DNAs that are made available to the animal through contact with the alga. These data resolve a long-standing issue and suggest that HGT is not the primary reason underlying long-term maintenance of photosynthesis in E. chlorotica. Therefore, sea slug photosynthesis is sustained in as yet unexplained ways that do not appear to endanger the animal germ line through the introduction of dozens of foreign genes. PMID:23645554

Bhattacharya, Debashish; Pelletreau, Karen N; Price, Dana C; Sarver, Kara E; Rumpho, Mary E

2013-08-01

298

Genome Analysis of Elysia chlorotica Egg DNA Provides No Evidence for Horizontal Gene Transfer into the Germ Line of This Kleptoplastic Mollusc  

PubMed Central

The sea slug Elysia chlorotica offers a unique opportunity to study the evolution of a novel function (photosynthesis) in a complex multicellular host. Elysia chlorotica harvests plastids (absent of nuclei) from its heterokont algal prey, Vaucheria litorea. The “stolen” plastids are maintained for several months in cells of the digestive tract and are essential for animal development. The basis of long-term maintenance of photosynthesis in this sea slug was thought to be explained by extensive horizontal gene transfer (HGT) from the nucleus of the alga to the animal nucleus, followed by expression of algal genes in the gut to provide essential plastid-destined proteins. Early studies of target genes and proteins supported the HGT hypothesis, but more recent genome-wide data provide conflicting results. Here, we generated significant genome data from the E. chlorotica germ line (egg DNA) and from V. litorea to test the HGT hypothesis. Our comprehensive analyses fail to provide evidence for alga-derived HGT into the germ line of the sea slug. Polymerase chain reaction analyses of genomic DNA and cDNA from different individual E. chlorotica suggest, however, that algal nuclear genes (or gene fragments) are present in the adult slug. We suggest that these nucleic acids may derive from and/or reside in extrachromosomal DNAs that are made available to the animal through contact with the alga. These data resolve a long-standing issue and suggest that HGT is not the primary reason underlying long-term maintenance of photosynthesis in E. chlorotica. Therefore, sea slug photosynthesis is sustained in as yet unexplained ways that do not appear to endanger the animal germ line through the introduction of dozens of foreign genes. PMID:23645554

Bhattacharya, Debashish; Pelletreau, Karen N.; Price, Dana C.; Sarver, Kara E.; Rumpho, Mary E.

2013-01-01

299

Non-viral transfection of goat germline stem cells by nucleofection results in production of transgenic sperm after germ cell transplantation.  

PubMed

Germline stem cells (GSCs) can be used for large animal transgenesis, in which GSCs that are genetically manipulated in vitro are transplanted into a recipient testis to generate donor-derived transgenic sperm. The objectives of this study were to explore a non-viral approach for transgene delivery into goat GSCs and to investigate the efficiency of nucleofection in producing transgenic sperm. Four recipient goats received fractionated irradiation at 8 weeks of age to deplete endogenous GSCs. Germ cell transplantations were performed 8-9 weeks post-irradiation. Donor cells were collected from testes of 9-week-old goats, enriched for GSCs by Staput velocity sedimentation, and transfected by nucleofection with a transgene construct harboring the human growth hormone gene under the control of the goat beta-casein promoter (GBC) and a chicken beta-globin insulator (CBGI) sequence upstream of the promoter. For each recipient, transfected cells from 10 nucleofection reactions were pooled, mixed with non-transfected cells to a total of 1.5?×?10(8) cells in 3?ml, and transplanted into one testis (n?=?4 recipients) by ultrasound-guided cannulation of the rete testis. The second testis of each recipient was removed. Semen was collected, starting at 9 months after transplantation, for a period of over a year (a total of 62 ejaculates from four recipients). Nested genomic PCR for hGH and CBGI sequences demonstrated that 31.3%?±?12.6% of ejaculates were positive for both hGH and CBGI. This study provides proof-of-concept that non-viral transfection (nucleofection) of primary goat germ cells followed by germ cell transplantation results in transgene transmission to sperm in recipient goats. PMID:22231935

Zeng, W; Tang, L; Bondareva, A; Luo, J; Megee, S O; Modelski, M; Blash, S; Melican, D T; Destrempes, M M; Overton, S A; Gavin, W G; Ayres, S; Echelard, Y; Dobrinski, I

2012-04-01

300

Joint Effects of Germ-Line p53 Mutation, MDM2 SNP309, and Gender on Cancer Risk in Family Studies of Li-Fraumeni Syndrome  

PubMed Central

Li-Fraumeni syndrome (LFS) is a rare familial cancer syndrome characterized by early cancer onset, diverse tumor types, and multiple primary tumors. Germ-line p53 mutations have been identified in most LFS families. A high-frequency genetic variant of single-nucleotide polymorphism (SNP) 309 in the MDM2 gene was recently confirmed to be a modifier of cancer risk in several case-control studies: substantially earlier cancer onset was observed in SNP309 G-allele carriers than in wild-type individuals by 7–16 years. However, risk analyses in family studies that jointly account for measured hereditary p53 mutations and SNP309 have not been evaluated. Here, we extended the statistical method that we recently developed to determine the combined effects of measured p53 mutations, SNP309, and gender and their interactions simultaneously. The method is structured for age-specific risk models based on Cox proportional hazards regression for censored age-of-onset traits. We analyzed the cancer incidence in 19 extended pedigrees with multiple germ-line p53 mutations ascertained through clinical LFS phenotype. The dataset consisted of 463 individuals with 129 p53 mutation carriers. Our analyses showed that the p53 germ-line mutation and its interaction with gender were strongly associated with familial cancer incidence and that the association between SNP309 and increased cancer risk was modest. In contrast with several outcomes in case-control studies, the interaction between SNP309 and p53 mutation was not statistically significant. The causal role of SNP309 in family studies was consistent with a previous finding that SNP309 G-alleles are associated with accelerated tumor formation in patients with sporadic and hereditary cancers. PMID:21305319

Wu, Chih-Chieh; Krahe, Ralf; Lozano, Guillermina; Zhang, Baili; Wilson, Charmaine D; Jo, Eun-Ji; Shete, Sanjay; Amos, Christopher I; Strong, Louise C

2014-01-01

301

Establishment and Characterization of a new Human Extragonadal Germ Cell Line, SEM-1, and its Comparison With TCam-2 and JKT-1  

PubMed Central

OBJECTIVE To describe the establishment and characterization of a human cell line, SEM-1, from a patient diagnosed with a mediastinal seminoma. METHODS A small percentage of germ cell tumors develop as primary lesions in extragonadal sites, and the etiology of these tumors is poorly understood. Currently, only 2 cell lines from seminoma patients have been reported, JKT-1 and TCam-2, both derived from the testis. The cell line was characterized by heterotransplantation in Nude mice, cytogenetic studies, immunohistochemical and flow cytometry staining for germ cell tumor biomarkers, quantitative reverse-transcription polymerase chain reaction for cancer testis antigen expression, and BRAF mutation screening with quantitative polymerase chain reaction. RESULTS Characterization studies confirmed the human extragonadal seminoma origin of SEM-1 and demonstrated that it had more features in common with TCam-2 than JKT-1. Specifically, SEM-1 was positive for Sal-like protein 4 (SALL-4), activator protein-2? (AP-2?), and cytokeratin CAM5.2, and demonstrated heterogeneous expression of stem cell markers octamer-binding transcription factor 3/4, NANOG, c-KIT, SOX17, and SOX2. Cytogenetic analysis revealed a hypotriploid chromosome number, with multiple copies of 12p, but isochromosome 12p and the BRAF mutation V600E were not identified. The cell lines also did not contain the BRD4/NUT gene rearrangement [t(15,19)] seen in midline carcinomas nor did they contain overexpressed nuclear protein in testis (NUT) genes. CONCLUSION SEM-1 is the first cell line derived from an extragonadal germ cell tumor showing intermediate characteristics between seminoma and nonseminoma, and as such, is an important model to study the molecular pathogenesis of this malignancy. PMID:23374840

Russell, Sarah M.; Lechner, Melissa G.; Mokashi, Anusuya; Megiel, Carolina; Jang, Julie K.; Taylor, Clive R.; Looijenga, Leendert H.J.; French, Christopher A.; Epstein, Alan L.

2014-01-01

302

Comparative molecular portraits of human unfertilized oocytes and primordial germ cells at 10 weeks of gestation.  

PubMed

Primordial germ cells (PGCs) are precursors of gametes and share several features in common with pluripotent stem cells, such as alkaline phosphatase activity and the expression of pluripotency-associated genes such as OCT4 and NANOG. PGCs are able to differentiate into oocytes and spermatogonia and establish totipotency after fertilization. However, our knowledge of human germ cell development is still fragmentary. In this study, we have carried out genome-wide comparisons of the transcriptomes and molecular portraits of human male PGCs (mPGCs), female PGCs (fPGCs) and unfertilized oocytes. We detected 9210 genes showing elevated expression in fPGCs, 9184 in mPGCs and 9207 in oocytes, with 6342 of these expressed in common. As well as known germ cell-related genes such as BLIMP1/PRDM1, PIWIL2, VASA/DDX4, DAZL, STELLA/DPPA3 and LIN28, we also identified 465 novel non-annotated genes with orthologs in the mouse. A plethora of olfactory receptor-encoding genes were detected in all samples, which would suggest their involvement not only in sperm chemotaxis, but also in the development of female germ cells and oocytes. We anticipate that our data might increase our meagre knowledge of the genes and associated signaling pathways operative during germ cell development. This in turn might aid in the development of strategies enabling better differentiation and molecular characterisation of germ cells derived from either embryonic or induced pluripotent stem cells. Ultimately, this would have a profound relevance for reproductive as well as regenerative medicine. PMID:23417401

Diedrichs, Ferdinand; Mlody, Barbara; Matz, Peggy; Fuchs, Heiko; Chavez, Lukas; Drews, Katharina; Adjaye, James

2012-01-01

303

The effects of periradicular inflamation and infection on a primary tooth and permanent successor.  

PubMed

Primary teeth and the permanent successors must be understood as interdependent units, where each one of them interacts with and depends on each other. Pulpal inflammation/infection of a primary tooth and the spread of this condition over the periradicular tissues can lead to alterations in the dental germ of the permanent successor and to the surrounding structures if no therapy is done, i.e. endodontics or extraction. This work will present cases of permanent teeth that showed alteration in eruption and / or in development, as a consequence of inflammation / infection of the preceding primary teeth, such as: hypoplasia, morphological alteration on the dental crown or total arrest of. radicular formation. The teeth analysed in this study belong to patients who attended the Universidade Federal de Santa Catarina Children's Dentistry Clinic. The earlier these lesions are diagnosed, the less were the destructive effects and the consequences on the primary tooth/permanent germ unit. PMID:15926433

Cordeiro, Mabel Mariela Rodriguez; Rocha, Maria Jose de Carvalho

2005-01-01

304

Malignant pineal germ-cell tumors: An analysis of cases from three tumor registries  

PubMed Central

The exact incidence of pineal germ-cell tumors is largely unknown. The tumors are rare, and the number of patients with these tumors, as reported in clinical series, has been limited. The goal of this study was to describe pineal germ-cell tumors in a large number of patients, using data from available brain tumor databases. Three different databases were used: Surveillance, Epidemiology, and End Results (SEER) database (1973–2001); Central Brain Tumor Registry of the United States (CBTRUS; 1997–2001); and National Cancer Data Base (NCDB; 1985–2003). Tumors were identified using the International Classification of Diseases for Oncology, third edition (ICD-O-3), site code C75.3, and categorized according to histology codes 9060–9085. Data were analyzed using SAS/STAT release 8.2, SEER*Stat version 5.2, and SPSS version 13.0 software. A total of 1,467 cases of malignant pineal germ-cell tumors were identified: 1,159 from NCDB, 196 from SEER, and 112 from CBTRUS. All three databases showed a male predominance for pineal germ-cell tumors (>90%), and >72% of patients were Caucasian. The peak number of cases occurred in the 10- to 14-year age group in the CBTRUS data and in the 15- to 19-year age group in the SEER and NCDB data, and declined significantly thereafter. The majority of tumors (73%–86%) were germinomas, and patients with germinomas had the highest survival rate (>79% at 5 years). Most patients were treated with surgical resection and radiation therapy or with radiation therapy alone. The number of patients included in this study exceeds that of any study published to date. The proportions of malignant pineal germ-cell tumors and intracranial germ-cell tumors are in range with previous studies. Survival rates for malignant pineal germ-cell tumors are lower than results from recent treatment trials for intracranial germ-cell tumors, and patients that received radiation therapy in the treatment plan either with surgery or alone survived the longest. PMID:18287340

Villano, J. Lee; Propp, Jennifer M.; Porter, Kimberly R.; Stewart, Andrew K.; Valyi-Nagy, Tibor; Li, Xinyu; Engelhard, Herbert H.; McCarthy, Bridget J.

2008-01-01

305

LIN-35/Rb causes starvation-induced germ cell apoptosis via CED-9/Bcl2 downregulation in Caenorhabditis elegans.  

PubMed

Apoptosis is an important mechanism for maintaining germ line health. In Caenorhabditis elegans, germ cell apoptosis occurs under normal conditions to sustain gonad homeostasis and oocyte quality. Under stress, germ cell apoptosis can be triggered via different pathways, including the following: (i) the CEP-1/p53 pathway, which induces germ cell apoptosis when animals are exposed to DNA damage; (ii) the mitogen-activated protein kinase kinase (MAPKK) pathway, which triggers germ cell apoptosis when animals are exposed to heat shock, oxidative stress, or osmotic stress; and (iii) an unknown mechanism that triggers germ cell apoptosis during starvation. Here, we address how starvation induces germ cell apoptosis. Using polysomal profiling, we found that starvation for 6 h reduces the translationally active ribosomes, which differentially affect the mRNAs of the core apoptotic machinery and some of its regulators. During starvation, lin-35/Rb mRNA increases its expression, resulting in the accumulation of this protein. As a consequence, LIN-35 downregulates the expression of the antiapoptotic gene ced-9/Bcl-2. We observed that the reduced translation of ced-9/Bcl-2 mRNA during food deprivation together with its downregulation drastically affects its protein accumulation. We propose that CED-9/Bcl-2 downregulation via LIN-35/Rb triggers germ cell apoptosis in C. elegans in response to starvation. PMID:24752899

Láscarez-Lagunas, L I; Silva-García, C G; Dinkova, T D; Navarro, R E

2014-07-01

306

Cell lineage studies in the crayfish Cherax destructor (Crustacea, Decapoda) : germ band formation, segmentation, and early neurogenesis  

Microsoft Academic Search

The cell division pattern of the germ band of Cherax destructor is described from gastrulation to segmentation, limb bud formation, and early neurogenesis. The naupliar segments are formed almost simultaneously from scattered ectoderm cells arranged in a V-shaped germ disc, anterior to the blastopore. No specific cell division pattern is recognisable. The post-naupliar segments are formed successively from front to

Gerhard Scholtz

1992-01-01

307

Prognostic factors in patients progressing after cisplatin-based chemotherapy for malignant non-seminomatous germ cell tumours  

Microsoft Academic Search

The aim of this study was to define prognostic parameters for survival in patients with malignant germ cell tumours progressing after platinum-based induction chemotherapy with or without surgery. A total of 164 progressing patients (testicular: 83%, extragonadal: 17%) were identified out of 795 patients treated with platinum-based induction chemotherapy for metastatic germ cell malignancy with or without surgery. ‘Progressive disease’

S D Fosså; S P Stenning; A Gerl; A Horwich; P I Clark; P M Wilkinson; W G Jones; M V Williams; R T Oliver; E S Newlands; G M Mead; M H Cullen; S B Kaye; G J S Rustin; P A Cook

1999-01-01

308

Spatio-temporal expression of a DAZ -like gene in the Japanese newt Cynops pyrrhogaster that has no germ plasm  

Microsoft Academic Search

To investigate the germ cell specification in urodeles, we cloned a DAZ-like sequence from the Japanese newt Cynops pyrrhogaster, Cydazl, and raised antibodies specific to Cydazl. Cydazl is a homologue of the human DAZ (deleted in azoospermia), DAZL, and Xenopus dazl genes, which are involved in gametogenesis or germ cell specification. During gametogenesis, expression of Cydazl mRNA and Cydazl protein

Yoichiro Tamori; Toshiharu Iwai; Koichi Mita; Masami Wakahara

2004-01-01

309

A role for Dazl in commitment to gametogenic fate in embryonic germ cells of C57BL/6 mice  

E-print Network

Germ cells can be defined as the cells that undergo the terminal differentiating process of meiosis. In mice, as XX germ cells enter meiosis around Embryonic days 13.5-14.5 (E13.5-E14.5), they form meiotic figures and ...

Lin, Yanfeng, Ph. D. Massachusetts Institute of Technology

2005-01-01

310

Analysis of a novel gene, Sdgc, reveals sex chromosome-dependent differences of medaka germ cells prior to gonad formation.  

PubMed

In vertebrates that have been examined to date, the sexual identity of germ cells is determined by the sex of gonadal somatic cells. In the teleost fish medaka, a sex-determination gene on the Y chromosome, DMY/dmrt1bY, is expressed in gonadal somatic cells and regulates the sexual identity of germ cells. Here, we report a novel mechanism by which sex chromosomes cell-autonomously confer sexually different characters upon germ cells prior to gonad formation in a genetically sex-determined species. We have identified a novel gene, Sdgc (sex chromosome-dependent differential expression in germ cells), whose transcripts are highly enriched in early XY germ cells. Chimeric analysis revealed that sexually different expression of Sdgc is controlled in a germ cell-autonomous manner by the number of Y chromosomes. Unexpectedly, DMY/dmrt1bY was expressed in germ cells prior to gonad formation, but knockdown and overexpression of DMY/dmrt1bY did not affect Sdgc expression. We also found that XX and XY germ cells isolated before the onset of DMY/dmrt1bY expression in gonadal somatic cells behaved differently in vitro and were affected by Sdgc. Sdgc maps close to the sex-determination locus, and recombination around the two loci appears to be repressed. Our results provide important insights into the acquisition and plasticity of sexual differences at the cellular level even prior to the developmental stage of sex determination. PMID:25078651

Nishimura, Toshiya; Herpin, Amaury; Kimura, Tetsuaki; Hara, Ikuyo; Kawasaki, Toshihiro; Nakamura, Shuhei; Yamamoto, Yasuhiro; Saito, Taro L; Yoshimura, Jun; Morishita, Shinichi; Tsukahara, Tatsuya; Kobayashi, Satoru; Naruse, Kiyoshi; Shigenobu, Shuji; Sakai, Noriyoshi; Schartl, Manfred; Tanaka, Minoru

2014-09-01

311

Production of placental alkaline phosphatase (PLAP) and PLAP-like material by epithelial germ cell and non-germ cell tumours in vitro.  

PubMed Central

Placental and placental-like alkaline phosphatase (PLAP) levels in the culture media of 87 cell lines of neoplastic and 'normal' origin were measured by a conventional immunosorbent enzymatic assay (IAEA) and by a new immunoradiometric assay (IRMA). The IRMA detected immunoreactive PLAP in 37 of 80 (46%) human epithelial and germ cell cultures, while the IAEA detected PLAP in only 25 (33%). Of the 52 non-germ cell tumour cultures, the IRMA detected expression in 24 (46%) and the IAEA in only 16 (31%). In 17 cases (21%) the IRMA recorded levels double that of the IAEA, while in five cultures (6%) the reverse was true. The IRMA was much more robust than the IAEA and had considerably lower inter- and intra-assay coefficients of variation (3.75-8.5% vs 5.2-46%). Detection of PLAP(-like) expression by IAEA is dependent on neoplastic expression of enzymatically functional molecules and quantification assumes constant enzyme kinetics. PLAP-like material has a higher catalytic rate constant than PLAP and thus will give higher values on a stoichiometric basis in an IAEA. The higher detection rate and levels of PLAP-like material in neoplastic cultures when measured by the IRMA clearly demonstrate ectopic expression of non-enzymatic PLAP and PLAP-like genes. The incidence of PLAP(-like) expression by non-germ cell and possible germ cell tumours has been underestimated and its utility as a tumour marker should be re-examined using assays which measure antigen mass rather than phosphatase activity. PMID:8297725

Iles, R. K.; Ind, T. E.; Chard, T.

1994-01-01

312

A set of genes critical to development is epigenetically poised in mouse germ cells from fetal stages through completion of meiosis  

E-print Network

In multicellular organisms, germ cells carry the hereditary material from one generation to the next. Developing germ cells are unipotent gamete precursors, and mature gametes are highly differentiated, specialized cells. ...

Lesch, Bluma J.

313

GLD-4-Mediated Translational Activation Regulates the Size of the Proliferative Germ Cell Pool in the Adult C. elegans Germ Line  

PubMed Central

To avoid organ dysfunction as a consequence of tissue diminution or tumorous growth, a tight balance between cell proliferation and differentiation is maintained in metazoans. However, cell-intrinsic gene expression mechanisms controlling adult tissue homeostasis remain poorly understood. By focusing on the adult Caenorhabditis elegans reproductive tissue, we show that translational activation of mRNAs is a fundamental mechanism to maintain tissue homeostasis. Our genetic experiments identified the Trf4/5-type cytoplasmic poly(A) polymerase (cytoPAP) GLD-4 and its enzymatic activator GLS-1 to perform a dual role in regulating the size of the proliferative zone. Consistent with a ubiquitous expression of GLD-4 cytoPAP in proliferative germ cells, its genetic activity is required to maintain a robust proliferative adult germ cell pool, presumably by regulating many mRNA targets encoding proliferation-promoting factors. Based on translational reporters and endogenous protein expression analyses, we found that gld-4 activity promotes GLP-1/Notch receptor expression, an essential factor of continued germ cell proliferation. RNA-protein interaction assays documented also a physical association of the GLD-4/GLS-1 cytoPAP complex with glp-1 mRNA, and ribosomal fractionation studies established that GLD-4 cytoPAP activity facilitates translational efficiency of glp-1 mRNA. Moreover, we found that in proliferative cells the differentiation-promoting factor, GLD-2 cytoPAP, is translationally repressed by the stem cell factor and PUF-type RNA-binding protein, FBF. This suggests that cytoPAP-mediated translational activation of proliferation-promoting factors, paired with PUF-mediated translational repression of differentiation factors, forms a translational control circuit that expands the proliferative germ cell pool. Our additional genetic experiments uncovered that the GLD-4/GLS-1 cytoPAP complex promotes also differentiation, forming a redundant translational circuit with GLD-2 cytoPAP and the translational repressor GLD-1 to restrict proliferation. Together with previous findings, our combined data reveals two interconnected translational activation/repression circuitries of broadly conserved RNA regulators that maintain the balance between adult germ cell proliferation and differentiation. PMID:25254367

Millonigg, Sophia; Eckmann, Christian R.

2014-01-01

314

MEETING REPORT ASSESSING HUMAN GERM-CELL MUTAGENESIS IN THE POST-GENOME ERA: A CELEBRATION OF THE LEGACY OF WILLIAM LAWSON (BILL) RUSSELL  

EPA Science Inventory

Although numerous germ-cell mutagens have been identified in animal model systems, to date, no human germ-cell mutagens have been confirmed. Because the genomic integrity of our germ cells is essential for the continuation of the human species, a resolution of this enduring conu...

315

Copyright 0 1988 by the Genetics Society of America fog-2, a Germ-Line-SpecificSex Determination Gene Required for  

E-print Network

Copyright 0 1988 by the Genetics Society of America fog-2, a Germ-Line-SpecificSex Determination of 16 mutations in the germ-line sex determination gene fog-2 (fog for feminization of the germ line by oogenesis), and female in the soma. fog-2 loss-of-function mutations transform XX animals into females while

Kimble, Judith

316

Functional significance of genotoxicity in fish germ cells Alain Devaux 1  

E-print Network

Functional significance of genotoxicity in fish germ cells Alain Devaux 1 , Christian Gillet2 , Luc receptacle for anthropogenic compounds. Recent works show that about one third of them could have genotoxic of the ecological risks associated with environmental genotoxic exposure is usually based on individual responses

Paris-Sud XI, Université de

317

Fermented Wheat Germ Extract (Avemar) in the Treatment of Cancer and Autoimmune Diseases  

Microsoft Academic Search

Avemar, the product of industrial fermentation of wheat germ, possesses unique cancer-fighting characteristics. Taken orally, Avemar can inhibit metastatic tumor dissemination and proliferation during and after chemotherapy, surgery, or radiation. Benefits of Avemar treatment have been shown in various human cancers, in cultures of in vitro grown cancer cells, in the prevention of chemical carcinogenesis, and also in some autoimmune

LASZLO G. BOROS; MICHELE NICHELATTI; YEHUDA SHOENFELDc

2005-01-01

318

Anti-Mllerian hormone and freemartinism : inhibition of germ cell development and induction of seminiferous cord-  

E-print Network

Anti-Müllerian hormone and freemartinism : inhibition of germ cell development and induction of seminiferous cord- like structures in rat fetal ovaries exposed in vitro to purified bovine AMH (1) B. VIGIER Debrousse, 69005 Lyon, France. Summary. In 13 and 14-day old fetal rat ovaries maintained 3 to 10 days

Boyer, Edmond

319

ANEUPLOIDIES AND MICRONUCLEI IN THE GERM CELLS OF MALE MICE OF ADVANCED AGE  

EPA Science Inventory

The objective of this research was to determine whether the frequencies of chromosomally defective germ cells increased with age in male laboratory mice. wo types of chromosomal abnormalities were characterized: (1) testicular spermatid aneuploidy (TSA) as measured by a new metho...

320

DAZL Limits Pluripotency, Differentiation, and Apoptosis in Developing Primordial Germ Cells  

PubMed Central

Summary The scarcity of primordial germ cells (PGCs) in the developing mammalian embryo hampers robust biochemical analysis of the processes that underlie early germ cell formation. Here, we demonstrate that DAZL, a germ cell-specific RNA binding protein, is a robust PGC marker during in vitro germ cell development. Using Dazl-GFP reporter ESCs, we demonstrate that DAZL plays a central role in a large mRNA/protein interactive network that blocks the translation of core pluripotency factors, including Sox2 and Sall4, as well as of Suz12, a polycomb family member required for differentiation of pluripotent cells. Thus, DAZL limits both pluripotency and somatic differentiation in nascent PGCs. In addition, we observed that DAZL associates with mRNAs of key Caspases and similarly inhibits their translation. This elegant fail-safe mechanism ensures that, whereas loss of DAZL results in prolonged expression of pluripotency factors, teratoma formation is avoided due to the concomitant activation of the apoptotic cascade.

Chen, Hsu-Hsin; Welling, Maaike; Bloch, Donald B.; Muñoz, Javier; Mientjes, Edwin; Chen, Xinjie; Tramp, Cody; Wu, Jie; Yabuuchi, Akiko; Chou, Yu-Fen; Buecker, Christa; Krainer, Adrian; Willemsen, Rob; Heck, Albert J.; Geijsen, Niels

2014-01-01

321

Regulation of sex chromosome constitution of somatic and germ cells in the wood lemming  

E-print Network

Regulation of sex chromosome constitution of somatic and germ cells in the wood lemming A. GROPP K displays certain peculiar features. (a) The sex ratio shows a prevalence of females, and some females produce only female offspring. (b) A conside- rable proportion of the females has XY sex chromosomes

Paris-Sud XI, Université de

322

The emerging role of matrix metalloproteases of the ADAM family in male germ cell apoptosis  

PubMed Central

Constitutive germ cell apoptosis during mammalian spermatogenesis is a key process for controlling sperm output and to eliminate damaged or unwanted cells. An increase or decrease in the apoptosis rate has deleterious consequences and leads to low sperm production. Apoptosis in spermatogenesis has been widely studied, but the mechanism by which it is induced under physiological or pathological conditions has not been clarified. We have recently identified the metalloprotease ADAM17 (TACE) as a putative physiological inducer of germ cell apoptosis. The mechanisms involved in regulating the shedding of the ADAM17 extracellular domain are still far from being understood, although they are important in order to understand cell-cell communications. Here, we review the available data regarding apoptosis during mammalian spermatogenesis and the localization of ADAM proteins in the male reproductive tract. We propose an integrative working model where ADAM17, p38 MAPK, protein kinase C (PKC) and the tyrosine kinase c-Abl participate in the physiological signalling cascade inducing apoptosis in germ cells. In our model, we also propose a role for the Sertoli cell in regulating the Fas/FasL system in order to induce the extrinsic pathway of apoptosis in germ cells. This working model could be applied to further understand constitutive apoptosis in spermatogenesis and in pathological conditions (e.g., varicocele) or following environmental toxicants exposure (e.g., genotoxicity or xenoestrogens). PMID:22319668

Urriola-Munoz, Paulina; Lagos-Cabre, Raul

2011-01-01

323

Wash Hands: Fight Disease-Causing Germs Renee R. Boyer, Extension Specialist, Food Safety, Virginia Tech*  

E-print Network

Wash Hands: Fight Disease-Causing Germs Renee R. Boyer, Extension Specialist, Food Safety, Virginia. publication 348-965 *Originally written by Tim Roberts, Former Extension Specialist, Food Safety, Virginia. Individuals who practice poor personal hygiene while preparing food may spread diseases such as hepatitis A

Liskiewicz, Maciej

324

?-Tubulin function during female germ-cell development and oogenesis in Drosophila  

PubMed Central

A series of unconventional microtubule organizing centers play a fundamental role during egg chamber development in Drosophila. To gain a better understanding of their molecular nature, we have studied the centrosomal component ?-tubulin during Drosophila oogenesis. We find that although single mutations in either of the two ?-tubulin genes identified in Drosophila do not affect oogenesis progression the simultaneous depletion of both protein products has severe consequences. The combination of loss-of-function mutant alleles for the two ?-tubulin genes leads to mitotic defects in female germ cells, resulting in agametic ovaries. A combination of weaker mutant alleles instead allows female germ-cell development to proceed, although the resulting egg chambers display pleiotropic abnormalities, most frequently affecting the number of nurse cells and oocytes per egg chamber. Thus, ?-tubulin is required for several processes at different stages of germ-cell development and oogenesis, including oocyte determination and differentiation. Our data provide a functional link between a component of the peri-centriolar material, such as ?-tubulin, and microtubule organization during Drosophila oogenesis. In addition, our results show that ?-tubulin is required for female germcell proliferation and that the two ?-tubulins present in Drosophila are functionally equivalent during female germ-cell development and oogenesis. PMID:12915734

Tavosanis, Gaia; Gonzalez, Cayetano

2003-01-01

325

of the exposed germ, which may reduce germination and emergence. Yields of current hulless barley lines  

E-print Network

of the exposed germ, which may reduce germination and emergence. Yields of current hulless barley barley until it is nearly mature. The glumes begin to separate from the seed when it is almost mature and become to- tally separated when the grain is combined. The grain of hulless barley looks more like wheat

Liskiewicz, Maciej

326

Digestive enzymes in the germ-free animal T. CORRING, Catherine JUSTE, C. SIMOES-NUNES  

E-print Network

for studying the role of gastrointestinal microflora in the nutrition of its host. The large intestine contains of the germ-free animal has a number of characte- ristics (cecal hypertrophy, slower small intestine cell renewal, slower gastric emptying and intestinal transit) which distinguish it from

Paris-Sud XI, Université de

327

Selfsimilarity properties of natural images Antonio Turiel \\Lambda , Germ' an Mato y , N' estor Parga z  

E-print Network

flows. There is however no model to explain the scaling behaviour that they observed. On the other handSelf­similarity properties of natural images Antonio Turiel \\Lambda , Germ' an Mato y , N' estor be predicted in terms of a multiplicative log­Poisson process. This is the very same model that was used very

Parga, Néstor

328

Epignathus: a germ-cell tumour presenting as neonatal respiratory distress  

Microsoft Academic Search

A full-term neonate developed acute upper airway obstruction immediately after birth secondary to a polypoidal mass in the oropharynx. After the child’s airway had been secured, the mass was excised and found to be a nasopharyngeal teratoma, a rare congenital germ cell tumour which is frequently associated with other congenital malformations. It is sometimes possible to diagnose these tumours in

R. Demajumdar; N. Bhat

1999-01-01

329

Increased mortality rates in young and middle-aged patients with malignant germ cell tumours  

Microsoft Academic Search

Cisplatin-based chemotherapy of malignant germ cell tumours (MGCT) has been reported to increase the risk of cardiovascular morbidity. A high incidence of second nongerm cell malignancies is well documented in MGCT survivors. The death risk due to these conditions is, however, more unknown in MGCT patients. Standard mortality rates (SMRs) were established in 3378 Norwegian MGCT patients treated from 1962

S D Fosså; N Aass; S Harvei; S Tretli

2004-01-01

330

The function of RNA Binding Protein 9 in germ cell differentiation in Drosophila ovary  

E-print Network

. Though Rbp9 is critical for cyst differentiation, over-expression of Rbp9 does not affect germ cell development in germarium region. But Rbp9 over-expression will affect number of cyst division times and mid stage egg chamber development. Moreover, we...

Yao, Min

2013-12-31

331

Recent advances in understanding the etiology and pathogenesis of pediatric germ cell tumors.  

PubMed

Pediatric germ cell tumors (GCTs) are rare neoplasms arising predominantly in the gonads and sacrococcygeal, mediastinal, and intracranial localizations. In this article, we review current knowledge of pathogenesis of pediatric GCTs, which differs from adult/adolescent GCTs. One distinctive feature is the absence of a progenitor stage, such as carcinoma in situ or gonadoblastoma, which are seen in adult/adolescent GCTs, except spermatocytic seminoma. The primordial germ cell (PGC) is the suggested origin of all GCTs, with variations in histology reflecting differentiation stage. Expression of pluripotency transcription factors OCT-3/4, NANOG, and AP-2? in germinomas/seminomas/dysgerminomas is consistent with retaining a germ cell phenotype. Teratomas, in contrast, develop through a pathway of aberrant somatic differentiation of immature germ cells, and the yolk sac tumors and choriocarcinomas result from abnormal extraembryonic differentiation. In pediatric GCTs, origin is suggested at an earlier developmental stage because of predisposing genetic factors, although responsible genes remain largely unknown. Some extragonadal GCTs have been linked to overexpression of the KIT/KITLG system, allowing for survival of aberrantly migrated ectopic PGCs. Infant gonadal/sacrococcygeal GCTs may be caused by apoptosis-related pathways, consistent with an association with polymorphisms in BAK1. Although recent advances have identified candidate pathways, further effort is needed to answer central questions of pathogenesis of these fascinating tumors. PMID:24577549

Mosbech, Christiane H; Rechnitzer, Catherine; Brok, Jesper S; Rajpert-De Meyts, Ewa; Hoei-Hansen, Christina E

2014-05-01

332

Truthful germs are contagious: A local to global characterization of truthfulness  

E-print Network

Truthful germs are contagious: A local to global characterization of truthfulness Aaron Archer AT of outcomes is truthful, i.e. implementable by a truthful mechanism. In particular, if the restriction of f to every "simple" subset of the type space is truthful, does it imply that f is truthful? Saks and Yu

Kleinberg, Robert D.

333

Primary Science Focus: Where's Primary?  

ERIC Educational Resources Information Center

In this article, the author discusses the deliberate policy on the part of Primary Science Committee (PSC) to ensure that not only is primary science embedded in all aspects of the work of ASE but is seen to be there. She also describes the events for the 2010 Annual Conference. Over the coming months, PSC will continue to put much thought into…

Lawrence, Liz

2009-01-01

334

Sensitivity of spore germination and germ tube elongation of Saccharina japonica to metal exposure.  

PubMed

The sensitivity of early life stages of the brown seaweed Saccharina japonica to six metals (Cd, Cu, Hg, Ni, Pb, Zn) and two waste-water samples were investigated and a new toxicity bioassay developed. The two endpoints used were spore germination and germ tube elongation with an exposure time of 24 h. Optimal test conditions determined for photon irradiance, pH, salinity and temperature were darkness, pH 8, 35‰ and 15°C, respectively. The toxicity ranking of five metals was: Hg (EC(50) of 41 and 42 ?g l(-1)) > Cu (120 and 81 ?g l(-1)) > Ni (2,009 and 1,360 ?g l(-1)) > Zn (3,024 and 3,897 ?g l(-1)) > Pb (4,760 and 4,429 ?g l(-1)) > Cd (15,052 and 7,541 ?g l(-1)) for germination and germ tube elongation, respectively. The sensitivities to Cd, Cu and Ni were greater in germ tube elongation than in germination process. When tested against two different waste-water samples (processed animal and printed circuit board waste-water) values of EC(50) were between 21.29 and 32.02% for germination and between 5.33 and 8.98% for germ tube elongation. Despite differences in their chemical composition, the toxic effects of waste-water samples, as indicated by EC(50) values, did not differ significantly for the same endpoints. The CV range for both germination and germ tube elongation was between 4.61 and 37.69%, indicating high levels of precision of the tests. The results compare favourably with those from more established test procedures employing micro- and macroalgae. The advantages and potential limitations of the bioassay for the assessment of anthropogenic impacts on coastal ecosystems and commercial cultivation areas in near-shore environments are discussed. PMID:21833545

Han, Taejun; Kong, Jeong-Ae; Kang, Hee-Gyu; Kim, Seon-Jin; Jin, Gyo-Sun; Choi, Hoon; Brown, Murray T

2011-11-01

335

Effects of Lactobacillus kefiranofaciens M1 Isolated from Kefir Grains on Germ-Free Mice  

PubMed Central

Lactobacillus kefiranofaciens M1 is a novel probiotic strain that was isolated from kefir grains. Previously, we have demonstrated the immunoregulatory, anti-allergic, anti-asthmatic and anti-colitis abilities of L. kefiranofaciens M1 in a number of in-vitro and in-vivo experiments. However, whether the effects of L. kefiranofaciens M1 are elicited directly on the host or act by regulating the host's microbiota remains unknown. A number of studies have used germ-free or gnotobiotic animals to investigate the relationship between probiotics and colitis; therefore the aim of this study was to investigate the effects of L. kefiranofaciens M1 on germ-free mice. Such an approach should help in determining the direct effects of L. kefiranofaciens M1 on the host itself. Four-week-old female germ-free mice were inoculated intragastrically with 2×108 CFU/mouse L. kefiranofaciens M1 once or at 2-day intervals for 14 days. Bacterial colonization, the Th1/Th2 cytokine profile of the mice's splenocytes and the anti-colitis effect of L. kefiranofaciens M1 were investigated. The strongest response in terms of splenic Th1 cytokine IFN-? and IL-12 production upon TLR activation was detected in the continuous treatment group when comparing to the single inoculation group and the germ-free control. In addition, continuous inoculation with L. kefiranofaciens M1 was found to ameliorate the symptoms of DSS-induced colitis in germ-free mice. However, L. kefiranofaciens M1 failed to colonize the host. Thus it would seem that L. kefiranofaciens M1 is likely to act directly on the host and not be involved in microbiota regulation. PMID:24244362

Chen, Yen-Po; Chen, Ming-Ju

2013-01-01

336

Dynamic changes in DNA modification states during late gestation male germ line development in the rat  

PubMed Central

Background Epigenetic reprogramming of fetal germ cells involves the genome-wide erasure and subsequent re-establishment of DNA methylation. Mouse studies indicate that DNA demethylation may be initiated at embryonic day (e) 8 and completed between e11.5 and e12.5. In the male germline, DNA remethylation begins around e15 and continues for the remainder of gestation whilst this process occurs postnatally in female germ cells. Although 5-methylcytosine (5mC) dynamics have been extensively characterised, a role for the more recently described DNA modifications (5-hydroxymethylcytosine (5hmC), 5-formylcytosine (5fC) and 5-carboxylcytosine (5caC)) remains unclear. Moreover, the extent to which the developmental dynamics of 5mC reprogramming is conserved across species remains largely undetermined. Here, we sought to describe this process during late gestation in the male rat. Results Using immunofluorescence, we demonstrate that 5mC is re-established between e18.5 and e21.5 in the rat, subsequent to loss of 5hmC, 5fC and 5caC, which are present in germ cells between e14.5 and e16.5. All of the evaluated DNA methyl forms were expressed in testicular somatic cells throughout late gestation. 5fC and 5caC can potentially be excised through Thymine DNA Glycosylase (TDG) and repaired by the base excision repair (BER) pathway, implicating 5mC oxidation in active DNA demethylation. In support of this potential mechanism, we show that TDG expression is coincident with the presence of 5hmC, 5fC and 5caC in male germ cell development. Conclusion The developmental dependent changes in germ cell DNA methylation patterns suggest that they are linked with key stages of male rat germline progression. PMID:25225576

2014-01-01

337

Germ cell specification and ovary structure in the rotifer Brachionus plicatilis  

PubMed Central

Background The segregation of the germline from somatic tissues is an essential process in the development of all animals. Specification of the primordial germ cells (PGCs) takes place via different strategies across animal phyla; either specified early in embryogenesis by the inheritance of maternal determinants in the cytoplasm of the oocyte ('preformation') or selected later in embryonic development from undifferentiated precursors by a localized inductive signal ('epigenesis'). Here we investigate the specification and development of the germ cells in the rotifer Brachionus plicatilis, a member of the poorly-characterized superphyla Lophotrochozoa, by isolating the Brachionus homologues of the conserved germ cell markers vasa and nanos, and examining their expression using in situ hybridization. Results Bpvasa and Bpnos RNA expression have very similar distributions in the Brachionus ovary, showing ubiquitous expression in the vitellarium, with higher levels in the putative germ cell cluster. Bpvas RNA expression is present in freshly laid eggs, remaining ubiquitous in embryos until at least the 96 cell stage after which expression narrows to a small cluster of cells at the putative posterior of the embryo, consistent with the developing ovary. Bpnos RNA expression is also present in just-laid eggs but expression is much reduced by the four-cell stage and absent by the 16-cell stage. Shortly before hatching of the juvenile rotifer from the egg, Bpnos RNA expression is re-activated, located in a subset of posterior cells similar to those expressing Bpvas at the same stage. Conclusions The observed expression of vasa and nanos in the developing B. plicatilis embryo implies an epigenetic origin of primordial germ cells in Rotifer. PMID:20849649

2010-01-01

338

Expression Patterns and miRNA Regulation of DNA Methyltransferases in Chicken Primordial Germ Cells  

PubMed Central

DNA methylation is widespread in most species, from bacteria to mammals, and is crucial for genomic imprinting, gene expression, and embryogenesis. DNA methylation occurs via two major classes of enzymatic reactions: maintenance-type methylation catalyzed by DNA (cytosine-5-)-methyltransferase (DNMT) 1, and de novo methylation catalyzed by DNMT 3 alpha (DNMT3A) and -beta (DNMT3B). The expression pattern and regulation of DNMT genes in primordial germ cells (PGCs) and germ line cells has not been sufficiently established in birds. Therefore, we employed bioinformatics, RT-PCR, real-time PCR, and in situ hybridization analyses to examine the structural conservation and conserved expression patterns of chicken DNMT family genes. We further examined the regulation of a candidate de novo DNA methyltransferase gene, cDNMT3B by cotransfection of cDNMT3B 3?UTR- and cDNMT3B 3?UTR-specific miRNAs through a dual fluorescence reporter assay. All cDNMT family members were differentially detected during early embryonic development. Of interest, cDNMT3B expression was highly detected in early embryos and in PGCs. During germ line development and sexual maturation, cDNMT3B expression was reestablished in a female germ cell-specific manner. In the dual fluorescence reporter assay, cDNMT3B expression was significantly downregulated by four miRNAs: gga-miR-15c (25.82%), gga-miR-29b (30.01%), gga-miR-383 (30.0%), and gga-miR-222 (31.28%). Our data highlight the structural conservation and conserved expression patterns of chicken DNMTs. The miRNAs investigated in this study may induce downregulation of gene expression in chicken PGCs and germ cells. PMID:21559294

Lee, Sang In; Seo, Hee Won; Han, Jae Yong

2011-01-01

339

DDX4 (VASA) is conserved in germ cell development in marsupials and monotremes.  

PubMed

DDX4 (VASA) is an RNA helicase expressed in the germ cells of all animals. To gain greater insight into the role of this gene in mammalian germ cell development, we characterized DDX4 in both a marsupial (the tammar wallaby) and a monotreme (the platypus). DDX4 is highly conserved between eutherian, marsupial, and monotreme mammals. DDX4 protein is absent from tammar fetal germ cells but is present from Day 1 postpartum in both sexes. The distribution of DDX4 protein during oogenesis and spermatogenesis in the tammar is similar to eutherians. Female tammar germ cells contain DDX4 protein throughout all stages of postnatal oogenesis. In males, DDX4 is in gonocytes, and during spermatogenesis it is present in spermatocytes and round spermatids. A similar distribution of DDX4 occurs in the platypus during spermatogenesis. There are several DDX4 isoforms in the tammar, resulting from both pre- and posttranslational modifications. DDX4 in marsupials and monotremes has multiple splice variants and polyadenylation motifs. Using in silico analyses of genomic databases, we found that these previously unreported splice variants also occur in eutherians. In addition, several elements implicated in the control of Ddx4 expression in the mouse, including RGG (arginine-glycine-glycine) and dimethylation of arginine motifs and CpG islands within the Ddx4 promoter, are also highly conserved. Collectively these data suggest that DDX4 is essential for the regulation of germ cell proliferation and differentiation across all three extant mammalian groups-eutherians, marsupials, and monotremes. PMID:21653890

Hickford, Danielle E; Frankenberg, Stephen; Pask, Andrew J; Shaw, Geoff; Renfree, Marilyn B

2011-10-01

340

The problem of the origin of primordial germ cells (PGCs) in vertebrates: historical review and a possible solution.  

PubMed

A concise review of the articles about the origin of primordial germ cells (PGCs) in vertebrates is provided. Differences among various taxa concerning the origin of PGCs, not easily understandable on the base of traditional knowledge, are pointed out. All those differences can be explained taking into consideration the recent ?theory of the endoderm as secondary layer?. That theory allows us to understand that those differences are only apparent, being related to modifications of stages of the consequent embryogeny, overall, to a different amount of yolk in the egg. Eggs very rich in yolk became meroblastic, and the portion of primordial ectomesenchyme destined to give rise to a part of the mesoderm and the PGCs separates early from the part destined to give rise to the rest of the mesoderm and to the digestive endoderm in order to form the vitelline hypoblast lamina. To this lamina, in contrast to the traditional interpretation, a mesodermal, not endodermal, origin must be attributed. With the misunderstanding regarding the origin of this lamina clarified, all the differences about the origin of PGCs disappears. Furthermore, in taxa where PGCs were considered to be of endodermal origin, they too have a mesodermal origin. Considering that a mesodermal origin of PGCs has been demonstrated in all sponges and cnidarians, as well, a unique, mesodermal origin of germinal cells in all pluricellular animals results. PMID:24623072

Pilato, Giovanni; Pilato, Giovanni; D'Urso, Vera; Viglianisi, Fabio; Sammartano, Francesca; Sabella, Giorgio; Lisi, Oscar

2013-01-01

341

Three-Step Method for Proliferation and Differentiation of Human Embryonic Stem Cell (hESC)-Derived Male Germ Cells  

PubMed Central

The low efficiency of differentiation into male germ cell (GC)-like cells and haploid germ cells from human embryonic stem cells (hESCs) reflects the culture method employed in the two-dimensional (2D)-microenvironment. In this study, we applied a three-step media and calcium alginate-based 3D-culture system for enhancing the differentiation of hESCs into male germ stem cell (GSC)-like cells and haploid germ cells. In the first step, embryoid bodies (EBs) were derived from hESCs cultured in EB medium for 3 days and re-cultured for 4 additional days in EB medium with BMP4 and RA to specify GSC-like cells. In the second step, the resultant cells were cultured in GC-proliferation medium for 7 days. The GSC-like cells were then propagated after selection using GFR-?1 and were further cultured in GC-proliferation medium for 3 weeks. In the final step, a 3D-co-culture system using calcium alginate encapsulation and testicular somatic cells was applied to induce differentiation into haploid germ cells, and a culture containing approximately 3% male haploid germ cells was obtained after 2 weeks of culture. These results demonstrated that this culture system could be used to efficiently induce GSC-like cells in an EB population and to promote the differentiation of ESCs into haploid male germ cells. PMID:24690677

Lim, Jung Jin; Shim, Myung Sun; Lee, Jeoung Eun; Lee, Dong Ryul

2014-01-01

342

Activation of the germ-cell potential of human bone marrow-derived cells by a chemical carcinogen  

PubMed Central

Embryonic/germ cell traits are common in malignant tumors and are thought to be involved in malignant tumor behaviors. The reasons why tumors show strong embryonic/germline traits (displaced germ cells or gametogenic programming reactivation) are controversial. Here, we show that a chemical carcinogen, 3-methyl-cholanthrene (3-MCA), can trigger the germ-cell potential of human bone marrow-derived cells (hBMDCs). 3-MCA promoted the generation of germ cell-like cells from induced hBMDCs that had undergone malignant transformation, whereas similar results were not observed in the parallel hBMDC culture at the same time point. The malignant transformed hBMDCs spontaneously and more efficiently generated into germ cell-like cells even at the single-cell level. The germ cell-like cells from induced hBMDCs were similar to natural germ cells in many aspects, including morphology, gene expression, proliferation, migration, further development, and teratocarcinoma formation. Therefore, our results demonstrate that a chemical carcinogen can reactivate the germline phenotypes of human somatic tissue-derived cells, which might provide a novel idea to tumor biology and therapy. PMID:24998261

Liu, Chunfang; Ma, Zhan; Xu, Songtao; Hou, Jun; Hu, Yao; Yu, Yinglu; Liu, Ruilai; Chen, Zhihong; Lu, Yuan

2014-01-01

343

Ex vivo Culture of Drosophila Pupal Testis and Single Male Germ-line Cysts: Dissection, Imaging, and Pharmacological Treatment.  

PubMed

During spermatogenesis in mammals and in Drosophila melanogaster, male germ cells develop in a series of essential developmental processes. This includes differentiation from a stem cell population, mitotic amplification, and meiosis. In addition, post-meiotic germ cells undergo a dramatic morphological reshaping process as well as a global epigenetic reconfiguration of the germ line chromatin-the histone-to-protamine switch. Studying the role of a protein in post-meiotic spermatogenesis using mutagenesis or other genetic tools is often impeded by essential embryonic, pre-meiotic, or meiotic functions of the protein under investigation. The post-meiotic phenotype of a mutant of such a protein could be obscured through an earlier developmental block, or the interpretation of the phenotype could be complicated. The model organism Drosophila melanogaster offers a bypass to this problem: intact testes and even cysts of germ cells dissected from early pupae are able to develop ex vivo in culture medium. Making use of such cultures allows microscopic imaging of living germ cells in testes and of germ-line cysts. Importantly, the cultivated testes and germ cells also become accessible to pharmacological inhibitors, thereby permitting manipulation of enzymatic functions during spermatogenesis, including post-meiotic stages. The protocol presented describes how to dissect and cultivate pupal testes and germ-line cysts. Information on the development of pupal testes and culture conditions are provided alongside microscope imaging data of live testes and germ-line cysts in culture. We also describe a pharmacological assay to study post-meiotic spermatogenesis, exemplified by an assay targeting the histone-to-protamine switch using the histone acetyltransferase inhibitor anacardic acid. In principle, this cultivation method could be adapted to address many other research questions in pre- and post-meiotic spermatogenesis. PMID:25286189

Gärtner, Stefanie M K; Rathke, Christina; Renkawitz-Pohl, Renate; Awe, Stephan

2014-01-01

344

European consensus on diagnosis and treatment of germ cell cancer: a report of the European Germ Cell Cancer Consensus Group (EGCCCG).  

PubMed

Germ cell tumour is the most frequent malignant tumour type in young men with a 100% rise in the incidence every 20 years. Despite this, the high sensitivity of germ cell tumours to platinum-based chemotherapy, together with radiation and surgical measures, leads to the high cure rate of > or = 99% in early stages and 90%, 75-80% and 50% in advanced disease with 'good', 'intermediate' and 'poor' prognostic criteria (IGCCCG classification), respectively. The high cure rate in patients with limited metastatic disease allows the reduction of overall treatment load, and therefore less acute and long-term toxicity, e.g. organ sparing surgery for specific cases, reduced dose and treatment volume of irradiation or substitution of node dissection by surveillance or adjuvant chemotherapy according to the presence or absence of vascular invasion. Thus, different treatment options according to prognostic factors including histology, stage and patient factors and possibilities of the treating centre as well may be used to define the treatment strategy which is definitively chosen for an individual patient. However, this strategy of reduction of treatment load as well as the treatment itself require very high expertise of the treating physician with careful management and follow-up and thorough cooperation by the patient as well to maintain the high rate for cure. Treatment decisions must be based on the available evidence which has been the basis for this consensus guideline delivering a clear proposal for diagnostic and treatment measures in each stage of gonadal and extragonadal germ cell tumour and individual clinical situations. Since this guideline is based on the highest evidence level available today, a deviation from these proposals should be a rare and justified exception. PMID:15319245

Schmoll, H J; Souchon, R; Krege, S; Albers, P; Beyer, J; Kollmannsberger, C; Fossa, S D; Skakkebaek, N E; de Wit, R; Fizazi, K; Droz, J P; Pizzocaro, G; Daugaard, G; de Mulder, P H M; Horwich, A; Oliver, T; Huddart, R; Rosti, G; Paz Ares, L; Pont, O; Hartmann, J T; Aass, N; Algaba, F; Bamberg, M; Bodrogi, I; Bokemeyer, C; Classen, J; Clemm, S; Culine, S; de Wit, M; Derigs, H G; Dieckmann, K P; Flasshove, M; Garcia del Muro, X; Gerl, A; Germa-Lluch, J R; Hartmann, M; Heidenreich, A; Hoeltl, W; Joffe, J; Jones, W; Kaiser, G; Klepp, O; Kliesch, S; Kisbenedek, L; Koehrmann, K U; Kuczyk, M; Laguna, M P; Leiva, O; Loy, V; Mason, M D; Mead, G M; Mueller, R P; Nicolai, N; Oosterhof, G O N; Pottek, T; Rick, O; Schmidberger, H; Sedlmayer, F; Siegert, W; Studer, U; Tjulandin, S; von der Maase, H; Walz, P; Weinknecht, S; Weissbach, L; Winter, E; Wittekind, C

2004-09-01

345

Fibroblast growth factor signalling controls successive cell behaviours during mesoderm layer formation in Drosophila  

PubMed Central

Fibroblast growth factor (FGF)-dependent epithelial-mesenchymal transitions and cell migration contribute to the establishment of germ layers in vertebrates and other animals, but a comprehensive demonstration of the cellular activities that FGF controls to mediate these events has not been provided for any system. The establishment of the Drosophila mesoderm layer from an epithelial primordium involves a transition to a mesenchymal state and the dispersal of cells away from the site of internalisation in a FGF-dependent fashion. We show here that FGF plays multiple roles at successive stages of mesoderm morphogenesis in Drosophila. It is first required for the mesoderm primordium to lose its epithelial polarity. An intimate, FGF-dependent contact is established and maintained between the germ layers through mesoderm cell protrusions. These protrusions extend deep into the underlying ectoderm epithelium and are associated with high levels of E-cadherin at the germ layer interface. Finally, FGF directs distinct hitherto unrecognised and partially redundant protrusive behaviours during later mesoderm spreading. Cells first move radially towards the ectoderm, and then switch to a dorsally directed movement across its surface. We show that both movements are important for layer formation and present evidence suggesting that they are controlled by genetically distinct mechanisms. PMID:21613323

Clark, Ivan B. N.; Muha, Villo; Klingseisen, Anna; Leptin, Maria; Muller, Hans-Arno J.

2011-01-01

346

Ghrelin modulates testicular germ cells apoptosis and proliferation in adult normal rats.  

PubMed

Under normal condition in the most mammals, spermatogenesis is closely associated with the balance between germ cells proliferation and apoptosis. The present study was designed to determine the effects of ghrelin treatment on in vivo quality and quantity expression of apoptosis and proliferation specific indices in rat testicular germ cells. Twenty eight adult normal rats were subdivided into equal control and treatment groups. Treatment group received 3 nmol of ghrelin as subcutaneous injection for 30 consecutive days or vehicle to the control animals. The rats from each group (n=7) were killed on days 10 and 30 and their testes were taken for immunocytochemical evaluation and caspase-3 assay. Immunohistochemical analysis indicated that the accumulations of Bax and PCNA peptides are generally more prominent in spermatocytes and spermatogonia of both groups. Likewise, the mean percentage of immunoreactive spermatocytes against Bax increased (P<0.01) in the ghrelin-treated group on day 10, while despite of 30% increment in the Bax level of spermatocytes in the treated rats on day 30, however, it was not statistically significant. During the experimental period, only a few spermatogonia represented Bax expression and the changes of Bax immunolabling cells were negligible upon ghrelin treatment. Likewise, there were immunostaining cells against Bcl-2 in each germ cell neither in the control nor in the treated animals. In fact, ghrelin balanced Bax/Bcl-2 ratio toward at increase of Bax level in the spermatocytes and therefore may stimulate apoptosis in these germ cells. In contrast, ghrelin administration significantly suppressed proliferation-associated peptide PCNA in the spermatocytes as well as spermatogonia (P<0.05). Whereas, caspase-3 activity did not show any marked alteration during the experiment in both groups (P>0.05). Upstream of Bax substance parallel to down-regulation of PCNA demonstrate that ghrelin may prevent massive accumulation of germ cells during normal spermatogenesis. These observations also indicate that ghrelin may be considered as a modulator of spermatogenesis in normal adult rats and could be potentially implicated for abnormal spermatogenesis in some testicular germ cell tumors. PMID:22360851

Kheradmand, Arash; Dezfoulian, Omid; Alirezaei, Masoud; Rasoulian, Bahram

2012-03-01

347

STAGE-SPECIFIC DAMAGE TO SYNAPTONEMAL COMPLEXES AND METAPHASE CHROMOSOME INDUCED BY X RAYS IN MALE MOUSE GERM CELLS  

EPA Science Inventory

Synaptonemal complexes (SCs) reveal mutagen-induced effects in germ cell meiotic chromosomes. his study was aimed at characterizing relationships between SC and metaphase I chromosome damage following radiation exposure at various stages of spermatogenesis. Male mice were irradia...

348

Licensing of gametogenesis, dependent on RNA binding protein DAZL, as a gateway to sexual differentiation of fetal germ cells  

E-print Network

Mammalian oocytes and spermatozoa derive from fetal cells shared by the sexes. These primordial germ cells (PGCs) migrate to the developing somatic gonad, giving rise to oocytes or spermatozoa. These opposing sexual fates ...

Gill, Mark E.

349

Identification of a germ-line mutation in the p53 gene in a patient with an intracranial ependymoma  

SciTech Connect

The authors detected a germ-line mutation of the p53 gene in a patient with a malignant ependymoma of the posterior fossa. This mutation, which was found at codon 242, resulted in an amino acid substitution in a highly conserved site of exon 7 of the p53 gene; the same mutation was found in both the germ-line and tumor tissue. This is the most common region of previously described somatic p53 mutations in tumor specimens and of the germ-line p53 mutations in patients with the Li-Fraumeni cancer syndrome. Evaluation of the patient's family revealed several direct maternal and paternal relatives who had died at a young age from different types of cancer. The association of a germ-line p53 mutation with an intracranial malignancy and a strong family history of cancer suggests that p53 gene mutations predispose a person to malignancy and, like retinoblastoma mutations, may be inherited.

Metzger, A.K.; Duyk, G.; Daneshvar, L.; Edwards, M.S.B.; Cogen, P.H. (Univ. of California, San Francisco (United States)); Sheffield, V.C. (Univ. of Iowa, Iowa City (United States))

1991-09-01

350

vasa and nanos expression patterns in a sea anemone and the evolution of bilaterian germ cell specification mechanisms  

E-print Network

vasa and nanos expression patterns in a sea anemone and the evolution of bilaterian germ cell in the sea anemone Nematostella vectensis, we examined the expression of members of the vasa and nanos gene

Extavour, Cassandra

351

The Ligand Binding Domain of GCNF Is Not Required for Repression of Pluripotency Genes in Mouse Fetal Ovarian Germ Cells  

E-print Network

In mice, successful development and reproduction require that all cells, including germ cells, transition from a pluripotent to a differentiated state. This transition is associated with silencing of the pluripotency genes ...

Okumura, Leah M.

352

Increased Risk of Carcinoma In Situ In Patients With Testicular Germ Cell Cancer With Ultrasonic Microlithiasis In the Contralateral Testicle  

Microsoft Academic Search

PurposeWe compared clinical and histological data regarding the contralateral testicle in a population of men diagnosed with testicular germ cell cancer to find features associated with an increased risk of bilateral neoplasia.

METTE HOLM; CHRISTINA E. HOEI-HANSEN; EWA RAJPERT-DE MEYTS; NIELS E. SKAKKEBÆK

2003-01-01

353

Germ cell comparative Drosophila mutagenesis: sensitivity and mutation pattern in chemically treated stem cells  

SciTech Connect

Mutagenesis studies on Drosophila oogonial cells with methylnitrosourea, dimethylnitrosamine, and diethylnitrosamine revealed unexpectedly high rates of sex-linked recessive lethals relative to other male and female germ cell stages. Indeed, the oogonial mutation rates with chemicals are higher than with massive x-ray or neutron exposures of oogonia. Analysis of the distribution of lethals per treated female suggests most of the mutations recovered are of independent origin, with very small levels of clustering of identical mutations. In the male stem cell population (spermatogonia) on the other hand, the distribution of lethals is primarily nonrandom and highly clustered. The nature of the mutational endpoint and the different pattern of germ cell development in the two sexes are the probable causes of this difference. The oogonial sensitivity to chemical mutagens may have important bearing on strategies for assessing human hazard.

Abrahamson, S.; Houtchens, K.; Li Jia, X.; Foureman, P.

1983-01-01

354

Vasa genes: Emerging roles in the germ line and in multipotent cells  

PubMed Central

Sexually reproducing metazoans establish a cell lineage during development that is ultimately dedicated to gamete production. Work in a variety of animals suggests that a group of conserved molecular determinants function in this germ line maintenance and function. The most universal of these genes are vasa and vasa-like DEAD box RNA helicase genes. However, recent evidence indicates that vasa genes also function in other cell types, distinct from the germ line. Here we evaluate our current understanding of vasa function and its regulation during development, addressing vasa’s emerging role in multipotent cells. We also explore the evolutionary diversification of the amino-terminal domain of this gene and how this impacts the association of vasa with nuage-like perinuclear structures. PMID:20586054

Gustafson, Eric A.; Wessel, Gary M.

2011-01-01

355

A spindle-independent cleavage pathway controls germ cell formation in Drosophila  

PubMed Central

The primordial germ cells (PGCs) are the first cells to form during Drosophila melanogaster embryogenesis. While the process of somatic cell formation has been studied in detail, the mechanics of PGC formation are poorly understood. Here, using 4D multi-photon imaging combined with genetic and pharmacological manipulations, we find that PGC formation requires an anaphase spindle-independent cleavage pathway. In addition to utilizing core regulators of cleavage, including the small GTPase RhoA (Drosophila Rho) and the Rho associated kinase, ROCK (Drosophila Rok), we show that this pathway requires Germ cell-less (Gcl), a conserved BTB-domain protein not previously implicated in cleavage mechanics. This alternate form of cell formation suggests that organisms have evolved multiple molecular strategies for regulating the cytoskeleton during cleavage. PMID:23728423

Cinalli, Ryan M.; Lehmann, Ruth

2013-01-01

356

The seeds and the worms: Ludwik Fleck and the early history of germ theories.  

PubMed

The Polish microbiologist and philosopher of science, Ludwik Fleck (1896-1961), was a pioneer in constructivist history and philosophy of science. Based on studies in the history of syphilis, Fleck hypothesized that many established scientific facts are linked, in their development, to pre-scientific "proto-ideas." In 1935, Fleck proposed that the history of germ theories could be approached through his thesis on proto-ideas. His proposal, however, remained little more than a vague suggestion and was never developed in further detail. This paper introduces the concept of proto-ideas and discusses the central epistemological and historiographical implications of Fleck's thesis. The Fleckian approach offers an attractive alternative to positivist reconstructions of the early history of germ theories and provides a useful framework for a deeper understanding of the sociocultural background of the development of modern knowledge of infection. PMID:16489277

Brorson, Stig

2006-01-01

357

Efficient germ-line transmission obtained with transgene-free induced pluripotent stem cells  

PubMed Central

Induced pluripotent stem (iPS) cells hold great promise for regenerative medicine. To overcome potential problems associated with transgene insertions, efforts have been directed over the past several years to generate transgene-free iPS cells by using non-viral-vector approaches. To date, however, cells generated through such procedures have had problems producing reproductively competent animals, suggesting that their quality needed further improvement. Here we report the use of optimized assemblies of reprogramming factors and selection markers incorporated into single plasmids as nonintegrating episomes to generate germ-line–competent iPS cells. In particular, the pMaster12 episome can produce transgene-free iPS cells that, when grown in 2i medium, recapitulate good mouse ES cells, in terms of their competency for generating germ-line chimeras. PMID:25002522

Wu, Sen; Wu, Yuanyuan; Zhang, Xi; Capecchi, Mario R.

2014-01-01

358

Characteristics of long-term cultures of avian primordial germ cells and gonocytes.  

PubMed

Avian cell lines derived from germinal crescent primordial germ cells and gonadal gonocytes with long-term proliferative capacity in vitro and their subsequent rates of colonization and germline transmission are described. In general, male cultures proliferate more rapidly than female cultures although both can be developed into cell lines of >2 × 10(6) cells, at which time, they can be grown indefinitely and a cell bank can be established. All the cell lines injected into embryos transmitted through the germline with the percentage of germline transmission of both male and female cell lines varying from single digits to the high 90s. The derivation of these primordial germ cell and gonadal cell lines and the subsequent robustness of germline transmission validates these cells as suitable for establishment of lines of chickens bearing novel genetic modifications. PMID:24337317

Song, Yonghong; Duraisamy, Sivakumar; Ali, Jahabar; Kizhakkayil, Jaleel; Jacob, Victor Doss; Mohammed, Mohammed Ahmed; Eltigani, Mohammed A; Amisetty, Suresh; Shukla, Manoj Kumar; Etches, Robert J; de Lavoir, Marie-Cecile van

2014-01-01

359

Large mixed germ cell tumor in a young patient presenting as an intrapulmonary mass.  

PubMed

We present the case of a 26-year-old man with a bland medical history, who presented to the general practitioner because of severe cough and dyspnea. The chest X-ray revealed a massive organ-displacing tumor in the right chest not delineable from the mediastinum. The subsequent needle core biopsy was diagnostic for a mixed germ cell tumor comprising immature teratoma and seminoma. After an initially good response to chemotherapy, tumor markers and tumor size were progressive. The right-sided pneumonectomy revealed an intrapulmonary tumor with cystic and solid components, hemorrhage, and necrosis with a tumor diameter of 18cm. Histology confirmed a teratoma with mature and immature components accompanied by residual seminomatous tumor cells. Despite maximal intensive care, the patient died four weeks after surgery from acute respiratory distress syndrome. We describe this exceptional large intrapulmonary germ cell tumor and discuss the spectrum of such rare tumors. PMID:19201104

Fritzsche, Florian R; Kristiansen, Glen; Frauenfelder, Thomas; Opitz, Isabelle; Bode, Peter; Moch, Holger; Montani, Matteo

2009-01-01

360

Assessing Human Germ-Cell Mutagenesis in the Postgenome Era: A Celebration of the Legacy of William Lawson (Bill) Russell  

PubMed Central

Birth defects, de novo genetic diseases, and chromosomal abnormality syndromes occur in ~5% of all live births, and affected children suffer from a broad range of lifelong health consequences. Despite the social and medical impact of these defects, and the 8 decades of research in animal systems that have identified numerous germ-cell mutagens, no human germ-cell mutagen has been confirmed to date. There is now a growing consensus that the inability to detect human germ-cell mutagens is due to technological limitations in the detection of random mutations rather than biological differences between animal and human susceptibility. A multidisciplinary workshop responding to this challenge convened at The Jackson Laboratory in Bar Harbor, Maine. The purpose of the workshop was to assess the applicability of an emerging repertoire of genomic technologies to studies of human germ-cell mutagenesis. Workshop participants recommended large-scale human germ-cell mutation studies be conducted using samples from donors with high-dose exposures, such as cancer survivors. Within this high-risk cohort, parents and children could be evaluated for heritable changes in (a) DNA sequence and chromosomal structure, (b) repeat sequences and minisatellites, and (c) global gene expression profiles and pathways. Participants also advocated the establishment of a bio-bank of human tissue samples from donors with well-characterized exposure, including medical and reproductive histories. This mutational resource could support large-scale, multiple-endpoint studies. Additional studies could involve the examination of transgenerational effects associated with changes in imprinting and methylation patterns, nucleotide repeats, and mitochondrial DNA mutations. The further development of animal models and the integration of these with human studies are necessary to provide molecular insights into the mechanisms of germ-cell mutations and to identify prevention strategies. Furthermore, scientific specialty groups should be convened to review and prioritize the evidence for germ-cell mutagenicity from common environmental, occupational, medical, and lifestyle exposures. Workshop attendees agreed on the need for a full-scale assault to address key fundamental questions in human germ-cell environmental mutagenesis. These include, but are not limited to, the following: Do human germ-cell mutagens exist? What are the risks to future generations? Are some parents at higher risk than others for acquiring and transmitting germ-cell mutations? Obtaining answers to these, and other critical questions, will require strong support from relevant funding agencies, in addition to the engagement of scientists outside the fields of genomics and germ-cell mutagenesis. PMID:17295306

Wyrobek, Andrew J.; Mulvihill, John J.; Wassom, John S.; Malling, Heinrich V.; Shelby, Michael D.; Lewis, Susan E.; Witt, Kristine L.; Preston, R. Julian; Perreault, Sally D.; Allen, James W.; DeMarini, David M.; Woychik, Richard P.; Bishop, Jack B.

2007-01-01

361

Posterior localization of ApVas1 positions the preformed germ plasm in the sexual oviparous pea aphid Acyrthosiphon pisum  

PubMed Central

Background Germline specification in some animals is driven by the maternally inherited germ plasm during early embryogenesis (inheritance mode), whereas in others it is induced by signals from neighboring cells in mid or late development (induction mode). In the Metazoa, the induction mode appears as a more prevalent and ancestral condition; the inheritance mode is therefore derived. However, regarding germline specification in organisms with asexual and sexual reproduction it has not been clear whether both strategies are used, one for each reproductive phase, or if just one strategy is used for both phases. Previously we have demonstrated that specification of germ cells in the asexual viviparous pea aphid depends on a preformed germ plasm. In this study, we extended this work to investigate how germ cells were specified in the sexual oviparous embryos, aiming to understand whether or not developmental plasticity of germline specification exists in the pea aphid. Results We employed Apvas1, a Drosophila vasa ortholog in the pea aphid, as a germline marker to examine whether germ plasm is preformed during oviparous development, as has already been seen in the viviparous embryos. During oogenesis, Apvas1 mRNA and ApVas1 protein were both evenly distributed. After fertilization, uniform expression of Apvas1 remained in the egg but posterior localization of ApVas1 occurred from the fifth nuclear cycle onward. Posterior co-localization of Apvas1/ApVas1 was first identified in the syncytial blastoderm undergoing cellularization, and later we could detect specific expression of Apvas1/ApVas1 in the morphologically identifiable germ cells of mature embryos. This suggests that Apvas1/ApVas1-positive cells are primordial germ cells and posterior localization of ApVas1 prior to cellularization positions the preformed germ plasm. Conclusions We conclude that both asexual and sexual pea aphids rely on the preformed germ plasm to specify germ cells and that developmental plasticity of germline specification, unlike axis patterning, occurs in neither of the two aphid reproductive phases. Consequently, the maternal inheritance mode implicated by a preformed germ plasm in the oviparous pea aphid becomes a non-canonical case in the Hemimetabola, where so far the zygotic induction mode prevails in most other studied insects. PMID:24855557

2014-01-01

362

Single Exposure to Heat Induces Stage-Specific Germ Cell Apoptosis in Rats: Role of Intratesticular Testosterone on Stage Specificity  

Microsoft Academic Search

Short term exposure of the testis to heat causes degeneration of germ cells. However, the mechanisms underlying this process are poorly understood. The major objectives of this study were to deter- mine whether the heat-induced loss of germ cells in the adult rat occurs via apoptosis, to document its stage-specific and cell-specific distribution, and to examine whether intratesticular testosterone (T)

YAH-HE LUE; AMIYA P. SINHA HIKIM; RONALD S. SWERDLOFF; PAUL IM; KHAY SENG TAING; TAN BUI; ANDREW LEUNG; CHRISTINA WANG

1999-01-01

363

Representation of the group of holomorphic symmetries of a real germ in the symmetry group of its model surface  

Microsoft Academic Search

Local polynomial models of real submanifolds of complex spaces were constructed and studied in a series of papers. Among the\\u000a main features of model surfaces, there is the property that the dimension of the local group of holomorphic symmetries of\\u000a a germ does not exceed that of the same group of the tangent model surface of this germ. In the

V. K. Beloshapka

2007-01-01

364

Renal Carcinogenesis, Hepatic Hemangiomatosis, and Embryonic Lethality Caused by a Germ-Line Tsc2 Mutation in Mice1  

Microsoft Academic Search

Germ-line mutations of the human TSC2 tumor suppressor gene cause tuberous sclerosis (TSC), a disease characterized by the development of hamartomas in various organs. In the Eker rat, however, a germ-line Tsc2 mutation gives rise to renal cell carcinomas with a complete penetrance. The molecular mechanism for this phenotypic difference between man and rat is currently unknown, and the physiological

Toshiyuki Kobayashi; Osamu Minowa; Junko Kuno; Hiroaki Mitani; Okio Hino; Tetsuo Noda

1999-01-01

365

On Facts and Conceptual Systems: Young Children’s Integration of Their Understandings of Germs and Contagion  

Microsoft Academic Search

Five studies argue against claims that preschoolers understand a biological germ theory of illness. In Studies 1–3, participants were read stories in which characters develop symptoms (e.g., a bellyache) caused by germs, poisons, or events (e.g., eating too much candy) and were asked whether another character could catch the symptoms from the first. Few children made judgments in terms of

Gregg E. A. Solomon; Nicholas L. Cassimatis

1999-01-01

366

Layered Slopes  

NASA Technical Reports Server (NTRS)

4 June 2004 This Mars Global Surveyor (MGS) Mars Orbiter Camera (MOC) image shows exposures of layered material on slopes in the south polar region near 81.9oS, 72.2oW. Layers record the history of a place, but accessing the information contained in these layers may one day require a visit by a human or robotic explorer. The south polar layers, in general, are believed to be accumulations of dust and ice that were built up in the most recent billion years or so. However, they could just as easily be sedimentary rocks from much earlier in martian history. The picture covers an area about 3 km (1.9 mi) across. The scene is illuminated by sunlight from the upper left.

2004-01-01

367

Tracking cross-contamination transfer dynamics at a mock retail deli market using GloGerm.  

PubMed

Ready-to-eat (RTE) deli meats are considered a food at high risk for causing foodborne illness. Deli meats are listed as the highest risk RTE food vehicle for Listeria monocytogenes. Cross-contamination in the retail deli market may contribute to spread of pathogens to deli meats. Understanding potential cross-contamination pathways is essential for reducing the risk of contaminating various products. The objective of this study was to track cross-contamination pathways through a mock retail deli market using an abiotic surrogate, GloGerm, to visually represent how pathogens may spread through the deli environment via direct contact with food surfaces. Six contamination origination sites (slicer blade, meat chub, floor drain, preparation table, employee's glove, and employee's hands) were evaluated separately. Each site was inoculated with 20 ml of GloGerm, and a series of standard deli operations were completed (approximately 10 min of work). Photographs were then taken under UV illumination to visualize spread of GloGerm throughout the deli. A sensory panel evaluated the levels of contamination on the resulting contaminated surfaces. Five of the six contamination origination sites were associated with transfer of GloGerm to the deli case door handle, slicer blade, meat chub, preparation table, and the employee's gloves. Additional locations became contaminated (i.e., deli case shelf, prep table sink, and glove box), but this contamination was not consistent across all trials. Contamination did not spread from the floor drain to any food contact surfaces. The findings of this study reinforce the need for consistent equipment cleaning and food safety practices among deli workers to minimize cross-contamination. PMID:23433375

Maitland, Jessica; Boyer, Renee; Gallagher, Dan; Duncan, Susan; Bauer, Nate; Kause, Janell; Eifert, Joseph

2013-02-01

368

Smoking cessation in long-term survivors of germ cell tumour  

Microsoft Academic Search

Purpose  Long-term survivors of germ cell tumours (GCT) are at increased risk of cardiovascular morbidity. We investigated the use of tobacco in patients after therapy for GCT.Methods  Four hundred and seventy-four patients treated between 1979 and 2000 at the University of Munich were asked to complete a self-report questionnaire on psychosocial dimensions which included items on tobacco smoking before and after treatment

Marcus Hentrich; Martin J. Fegg; Stephanie Meiler; Christoph Jost; Arthur Gerl

2006-01-01

369

Differentiation and Neuro-Protective Properties of Immortalized Human Tooth Germ Stem Cells  

Microsoft Academic Search

Stem cells are considered to be promising therapeutic options in many neuro-degenerative diseases and injuries to the central\\u000a nervous system, including brain ischemia and spinal cord trauma. Apart from the gold standard embryonic and mesenchymal origin,\\u000a human tooth germ stem cells (hTGSCs) have also been shown to enjoy the characteristics of mesenchymal stem cells (MSCs) and\\u000a the ability to differentiate

Mehmet E. Yalvaç; Aysu Yilmaz; Dilek Mercan; Safa Aydin; Aysegul Dogan; Ahmet Arslan; Zeynel Demir; Ilnur I. Salafutdinov; Aygul K. Shafigullina; Fikrettin Sahin; Albert A. Rizvanov; András Palotás

370

Model of a chronic cholera vibrio carrier state in germ-free rats  

Microsoft Academic Search

Germ-free or monofloral (contaminated with a nonpathogenic spore-bearing bacillus), and ordinary albino rats of the OFA strain were infected withVibriocholerae El-Tor of the “Ogawa” and “Inaba” serotypes (6·109 bacterial cells in 1.5 ml physiological saline per rat). Approximately 1 week after infection the number of vibrios reached hundreds of millions per gram feces, and it remained at this level for

O. V. Baroyan; O. V. Chakhava; I. N. Gailonskaya; N. Yu. Abrikosova; N. I. Blinova; N. M. Shustrova

1976-01-01

371

Primordial germ cell migration in the rat: preliminary evidence for a role of galactosyltransferase.  

PubMed

The precise cellular mechanism of primordial germ cell (PGC) migration remains unknown. Cell surface galactosyltransferase (GalTase) is known to play unique roles in the process of locomotion of many migratory cells. With an objective to seek evidence for possible involvement of GalTase in the migratory process of PGC, we evaluated germ cell migration in the rat following experimental modulation of embryonic GalTase activity. Pregnant rats were laparotomized under anesthesia on Day 10 of pregnancy. While embryos of one uterine horn received lysozyme (100 microg/fetus), those of the other received alpha-lactalbumin (LA; 100 microg/fetus), N-acetylglucosamine (GlcNAc; 250 nmole/fetus), uridine 5'-monophosphate (UMP; 2.5 micromole/fetus), uridine diphosphate-galactose (UDP-gal; 250 nmole/fetus), or a combination of 250 nmole of UDP-gal and 2.5 micromole of UMP/fetus. Between gestation Days 12 and 14, embryos were dissected out and processed for histochemical localization of PGC on the basis of binding of Dolichos biflorus agglutinin on the surface glycoconjugate of the germ cells. The number of PGC in each embryo was counted. There was a daywise increase in the number of PGC in all groups. As compared with lysozyme-exposed controls, the numbers of PGCs at the day-specific sites on all days of examination were significantly lower in the LA- as well as GlcNAc-exposed groups. UMP or UDP-gal individually exerted little or no influence, while the total PGC count rose significantly over the respective control values under simultaneous exposure to UMP and UDP-gal. The present findings suggest a likely catalytic role of GalTase in the process of germ cell migration. PMID:15286041

Bandyopadhyay, Soma; Banerjee, Sutapa; Pal, Alok K; Goswami, Sourendra K; Chakravarty, Baidyanath; Kabir, Syed N

2004-12-01

372

Promising cytotoxic activity profile of fermented wheat germ extract (Avemar ® ) in human cancer cell lines  

Microsoft Academic Search

Fermented wheat germ extract (FWGE) is currently used as nutrition supplement for cancer patients. Limited recent data suggest\\u000a antiproliferative, antimetastatic and immunological effects which were at least in part exerted by two quinones, 2-methoxy\\u000a benzoquinone and 2,6-dimethoxybenzquinone as ingredients of FWGE. These activity data prompted us to further evaluate the\\u000a in vitro antiproliferative activity of FWGE alone or in combination

Thomas Mueller; Karin Jordan; Wieland Voigt

2011-01-01

373

Fermented Wheat Germ Extract (Avemar) in the Treatment of Cardiac Remodeling and Metabolic Symptoms in Rats  

Microsoft Academic Search

Avemar, a product of industrial fermentation of wheat germ with a standardized content of benzoquinone and plant flavonoids, has been tested as an anti-cancer and immunomodulatory dietary supplement. Proposed mechanisms include anti-oxidant and anti-inflammatory actions. This study has determined whether these actions of Avemar may also be useful in the treatment of cardiovascular diseases. Two experimental rat models of cardiovascular

Abishek Iyer; Lindsay Brown

2009-01-01

374

Regulation of Sertoli-Germ Cell Adhesion and Sperm Release by FSH and Nonclassical Testosterone Signaling  

PubMed Central

Testosterone and FSH act in synergy to produce the factors required to maximize the production of spermatozoa and male fertility. However, the molecular mechanisms by which these hormones support spermatogenesis are not well established. Recently, we identified a nonclassical mechanism of testosterone signaling in cultured rat Sertoli cells. We found that testosterone binding to the androgen receptor recruits and activates Src tyrosine kinase. Src then causes the activation of the epidermal growth factor receptor, which results in the phosphorylation and activation of the ERK MAPK and the cAMP response element-binding protein transcription factor. In this report, we find that FSH inhibits testosterone-mediated activation of ERK and the MAPK pathway in Sertoli cells via the protein kinase A-mediated inhibition of Raf kinase. In addition, FSH, as well as inhibitors of Src and ERK kinase activity, reduced germ cell attachment to Sertoli cells in culture. Using pathway-specific androgen receptor mutants we found that the nonclassical pathway is required for testosterone-mediated increases in germ cell attachment to Sertoli cells. Studies of seminiferous tubule explants determined that Src kinase, but not ERK kinase, activity is required for the release of sperm from seminiferous tubule explants. These findings suggest the nonclassical testosterone-signaling pathway acts via Src and ERK kinases to facilitate the adhesion of immature germ cells to Sertoli cells and through Src to permit the release of mature spermatozoa. In contrast, FSH acts to limit testosterone-mediated ERK kinase activity and germ cell attachment. PMID:21177760

Shupe, John; Cheng, Jing; Puri, Pawan; Kostereva, Nataliya

2011-01-01

375

Sex reversal in zebrafish fancl mutants is caused by Tp53-mediated germ cell apoptosis.  

PubMed

The molecular genetic mechanisms of sex determination are not known for most vertebrates, including zebrafish. We identified a mutation in the zebrafish fancl gene that causes homozygous mutants to develop as fertile males due to female-to-male sex reversal. Fancl is a member of the Fanconi Anemia/BRCA DNA repair pathway. Experiments showed that zebrafish fancl was expressed in developing germ cells in bipotential gonads at the critical time of sexual fate determination. Caspase-3 immunoassays revealed increased germ cell apoptosis in fancl mutants that compromised oocyte survival. In the absence of oocytes surviving through meiosis, somatic cells of mutant gonads did not maintain expression of the ovary gene cyp19a1a and did not down-regulate expression of the early testis gene amh; consequently, gonads masculinized and became testes. Remarkably, results showed that the introduction of a tp53 (p53) mutation into fancl mutants rescued the sex-reversal phenotype by reducing germ cell apoptosis and, thus, allowed fancl mutants to become fertile females. Our results show that Fancl function is not essential for spermatogonia and oogonia to become sperm or mature oocytes, but instead suggest that Fancl function is involved in the survival of developing oocytes through meiosis. This work reveals that Tp53-mediated germ cell apoptosis induces sex reversal after the mutation of a DNA-repair pathway gene by compromising the survival of oocytes and suggests the existence of an oocyte-derived signal that biases gonad fate towards the female developmental pathway and thereby controls zebrafish sex determination. PMID:20661450

Rodríguez-Marí, Adriana; Cañestro, Cristian; Bremiller, Ruth A; Nguyen-Johnson, Alexandria; Asakawa, Kazuhide; Kawakami, Koichi; Postlethwait, John H

2010-07-01

376

Semen characteristics and production of germ cells in male sheep-goat chimeras  

Microsoft Academic Search

Semen from 11 male sheep-goat chimeras and one male sheep-goat hybrid-sheep chimera was evaluated on criteria commonly used as in vitro measures of semen quality. In addition, the species origin of germ cells was determined. Five males that were sex chimeras produced spermatozoa only from their XY cells. Three XY\\/XY sheep-goat males were shown by electrophoretic separation of sperm isozymes

G. B Anderson; D. L Anderson; R. H Bondurant; J. M Cash; L. A MacLaren; A. L Moyer; M. C. T Penedo

1995-01-01

377

Retinoic acid improve germ cell differentiation from human embryonic stem cells  

PubMed Central

Background: Creation of artificial gametes may provide a universal solution for these patients with no gametes. Stem cell technology may provide a way to obtain fully functional gametes. Retinoic acid (RA) can initiate meiosis. Several studies have demonstrated that RA can promote sperm cells differentiation from mouse embryonic stem cells (mESCs) and other cells from human embryonic stem cells (hESCs). Objective: We sought to determine whether RA could promote differentiation of germ cells from hESCs. Materials and Methods: hESCs were differentiated as embryoid bodies (EBs) in suspension with all-trans RA (atRA) or without atRA for 0, 1, 3, 5 and 7 days, and then the expression of VASA, SCP3, GDF9 and TEKT1 were compared by real-time PCR. The statistical differences were evaluated by one way ANOVA. Results: The expression of germ cell-specific markers including the gonocyte marker VASA, the meiotic marker SCP3, and post meiotic markers, GDF9 and TEKT1, all increased in the presence and absence of RA as EB differentiation progressed. In addition, the expression of these markers increased an average of 9.3, 6.9, 7.2 and 11.8 fold respectively in the presence of RA, compared to the absence of RA, over 5 days differentiation. Conclusion: Our results indicate that hESCs may have the potential to differentiate to primordial germ cells (PGCs) and early gametes. RA can improve germ cells differentiation from hESCs. PMID:24639715

Xuemei, Liu; Jing, Yue; Bei, Xu; Juan, Hu; Xinling, Ren; Qun, Liu; Guijin, Zhu

2013-01-01

378

Critical Period of Nonpromoter DNA Methylation Acquisition during Prenatal Male Germ Cell Development  

PubMed Central

The prenatal period of germ cell development is a key time of epigenetic programming in the male, a window of development that has been shown to be influenced by maternal factors such as dietary methyl donor supply. DNA methylation occurring outside of promoter regions differs significantly between sperm and somatic tissues and has recently been linked with the regulation of gene expression during development as well as successful germline development. We examined DNA methylation at nonpromoter, intergenic sequences in purified prenatal and postnatal germ cells isolated from wildtype mice and mice deficient in the DNA methyltransferase cofactor DNMT3L. Erasure of the parental DNA methylation pattern occurred by 13.5 days post coitum (dpc) with the exception of approximately 8% of loci demonstrating incomplete erasure. For most loci, DNA methylation acquisition occurred between embryonic day 13.5 to 16.5 indicating that the key phase of epigenetic pattern establishment for intergenic sequences in male germ cells occurs prior to birth. In DNMT3L-deficient germ cells at 16.5 dpc, average DNA methylation levels were low, about 30% of wildtype levels; however, by postnatal day 6, about half of the DNMT3L deficiency-specific hypomethylated loci had acquired normal methylation levels. Those loci normally methylated earliest in the prenatal period were the least affected in the DNMT3L-deficient mice, suggesting that some loci may be more susceptible than others to perturbations occurring prenatally. These results indicate that the critical period of DNA methylation programming of nonpromoter, intergenic sequences occurs in male germline progenitor cells in the prenatal period, a time when external perturbations of epigenetic patterns could result in diminished fertility. PMID:21949694

Niles, Kirsten M.; Chan, Donovan; La Salle, Sophie; Oakes, Christopher C.; Trasler, Jacquetta M.

2011-01-01

379

Apoptosis of male germ-line stem cells after laser ablation of their niche  

Microsoft Academic Search

Male germ-line stem cells (GSCs) and their niche-the apical cells or hub cells-display a unique feature at the apices of insect testicular follicles. In the locust, Locusta migratoria, the niche consists of only one large apical cell surrounded by about 60 GSCs. The apical cell can be readily identified in the intact follicle. Using laser ablation it is feasible to

Johannes Zahn; Philipp Doormann; August Dorn; David C. Dorn

2007-01-01

380

Wheat germ agglutinin-reactive chains of giant hemoglobin from the polychaete Perinereis aibuhitensis  

Microsoft Academic Search

Wheat germ agglutinin-reactive chains of multisubunit extracellular hemoglobin from the polychaete Perinereis aibuhitensis were identified to clarify the carbohydrate gluing which is the carbohydrate-dependent supramolecular architecture of the hemoglobin (Ebina S. et al. (1995) Proc. Natl. Acad. Sci. USA 92, 7367–7371). Electron microscope micrographs of Perinereis hemoglobin showed a characteristic shape of two-tiered hexagonal rings whose diameter and height were

Keiko Matsubara; Mariko Yamaki; Kuniaki Nagayama; Kiyohiro Imai; Hiroyoshi Ishii; Toshio Gotoh; Satoshi Ebina

1996-01-01

381

Involvement of apoptosis in the rat germ cell degeneration induced by nitrobenzene  

Microsoft Academic Search

Nitrobenezene (NB) produces germ cell degeneration, especially of spermatocytes in rats. To examine the possible involvement\\u000a of apoptosis in this process, the extent and nature of nuclear DNA fragmentation after NB dosing were assessed using both\\u000a terminal deoxynucleotidyl transferase-mediated dUTP nick end-labeling (TUNEL) and DNA gel electrophoresis, in addition to\\u000a conventional histological and electron microscopic procedures. Adult Sprague Dawley rats

Kazutoshi Shinoda; Kunitoshi Mitsumori; Kazuo Yasuhara; Chikako Uneyama; Hiroshi Onodera; Kiyoshi Takegawa; Michihito Takahashi; Takashi Umemura

1998-01-01

382

Acute and Late Vascular Complications Following Chemotherapy for Germ Cell Tumors  

Microsoft Academic Search

Summary Side effects of cisplatin-based chemotherapy for germ cell tumors include myelosup-pression, nephro-, neuro- and ototoxicity. These side effects as well as the pulmonary toxicity of bleomycin are dose-dependent. On the contrary, chemotherapy-associated vascular complications are unpredictable. Whereas Raynaud’s phenomenon is observed in a considerable proportion of patients, myocardial infarction, stroke, and pulmonary embolism appear to occur infrequently. The fact

A. G. Gerl; C. Clemm; W. Wilmanns

1993-01-01

383

Detection and characterization of primordial germ cells in pheasant ( Phasianus colchicus) embryos  

Microsoft Academic Search

The developmental similarity between the chicken and pheasant (Phasianus colchicus) allows the novel biotechnologies developed in the chicken to be applied to the production of transgenic pheasants and interspecies germline chimeras. To detect pheasant primordial germ cells (PGCs) efficiently, which is important for inducing germline transmission, the ultrastructure of PGCs and their reactivity to several antibodies (2C9, QB2, anti-SSEA-1, and

Jin Nam Kim; Young Mok Lee; Tae Sub Park; Jin Gyoung Jung; Byeong Wook Cho; Jeong Mook Lim; Jae Yong Han

2005-01-01

384

Mouse Germ Cell-Less as an Essential Component for Nuclear Integrity  

Microsoft Academic Search

A mouse homologue of the Drosophila melanogaster germ cell-less (mgcl-1) gene is expressed ubiquitously, and its gene product is localized to the nuclear envelope based on its binding to LAP2 (lamina-associated polypeptide 2). To elucidate the role of mgcl-1, we analyzed two mutant mouse lines that lacked mgcl-1 gene expression. Abnormal nuclear morphologies that were probably due to impaired nuclear

Tohru Kimura; Chizuru Ito; Shoko Watanabe; Tohru Takahashi; Masahito Ikawa; Kentaro Yomogida; Yukiko Fujita; Megumi Ikeuchi; Noriko Asada; Kiyomi Matsumiya; Akihiko Okuyama; Masaru Okabe; Kiyotaka Toshimori; Toru Nakano

2003-01-01

385

A rare germ-cell tumor site: vaginal endodermal sinus tumor  

Microsoft Academic Search

Malignant germ-cell tumors (MGCT) are rare tumors of childhood accounting for less than 3% of pediatric malignancies. Endodermal sinus tumor (EST) forms the most common histologic subtype of MGCT. The vagina is an extremely rare site for GCTs. A 9-month-old female was admitted with a short history of vaginal bleeding, a mass protruding from the vagina, and difficulty in passing

M. Arora; R. Shrivastav; M. Jaiprakash

2002-01-01

386

Effects of the steel gene product on mouse primordial germ cells in culture  

Microsoft Academic Search

MUTATIONS at the steel (si) and dominant white spotting (W) loci in the mouse affect primordial germ cells (PGC), melanoblasts and haemopoietic stem cells1. The W gene encodes a cell-surface receptor of the tyrosine kinase family2,3, the proto-oncogene c-kit. In situ analysis has shown c-kitmessenger RNA expression in PGC in the early genital ridges4. The SI gene encodes the ligand

I. Godin; R. Deed; J. Cooke; K. Zsebo; M. Dexter; C. C. Wylie

1991-01-01

387

Tbx3 improves the germ-line competency of induced pluripotent stem cells.  

PubMed

Induced pluripotent stem (iPS) cells can be obtained by the introduction of defined factors into somatic cells. The combination of Oct4 (also known as Pou5f1), Sox2 and Klf4 (which we term OSK) constitutes the minimal requirement for generating iPS cells from mouse embryonic fibroblasts. These cells are thought to resemble embryonic stem cells (ESCs) on the basis of global gene expression analyses; however, few studies have tested the ability and efficiency of iPS cells to contribute to chimaerism, colonization of germ tissues, and most importantly, germ-line transmission and live birth from iPS cells produced by tetraploid complementation. Using genomic analyses of ESC genes that have roles in pluripotency and fusion-mediated somatic cell reprogramming, here we show that the transcription factor Tbx3 significantly improves the quality of iPS cells. iPS cells generated with OSK and Tbx3 (OSKT) are superior in both germ-cell contribution to the gonads and germ-line transmission frequency. However, global gene expression profiling could not distinguish between OSK and OSKT iPS cells. Genome-wide chromatin immunoprecipitation sequencing analysis of Tbx3-binding sites in ESCs suggests that Tbx3 regulates pluripotency-associated and reprogramming factors, in addition to sharing many common downstream regulatory targets with Oct4, Sox2, Nanog and Smad1. This study underscores the intrinsic qualitative differences between iPS cells generated by different methods, and highlights the need to rigorously characterize iPS cells beyond in vitro studies. PMID:20139965

Han, Jianyong; Yuan, Ping; Yang, Henry; Zhang, Jinqiu; Soh, Boon Seng; Li, Pin; Lim, Siew Lan; Cao, Suying; Tay, Junliang; Orlov, Yuriy L; Lufkin, Thomas; Ng, Huck-Hui; Tam, Wai-Leong; Lim, Bing

2010-02-25

388

Sex Reversal in Zebrafish fancl Mutants Is Caused by Tp53-Mediated Germ Cell Apoptosis  

PubMed Central

The molecular genetic mechanisms of sex determination are not known for most vertebrates, including zebrafish. We identified a mutation in the zebrafish fancl gene that causes homozygous mutants to develop as fertile males due to female-to-male sex reversal. Fancl is a member of the Fanconi Anemia/BRCA DNA repair pathway. Experiments showed that zebrafish fancl was expressed in developing germ cells in bipotential gonads at the critical time of sexual fate determination. Caspase-3 immunoassays revealed increased germ cell apoptosis in fancl mutants that compromised oocyte survival. In the absence of oocytes surviving through meiosis, somatic cells of mutant gonads did not maintain expression of the ovary gene cyp19a1a and did not down-regulate expression of the early testis gene amh; consequently, gonads masculinized and became testes. Remarkably, results showed that the introduction of a tp53 (p53) mutation into fancl mutants rescued the sex-reversal phenotype by reducing germ cell apoptosis and, thus, allowed fancl mutants to become fertile females. Our results show that Fancl function is not essential for spermatogonia and oogonia to become sperm or mature oocytes, but instead suggest that Fancl function is involved in the survival of developing oocytes through meiosis. This work reveals that Tp53-mediated germ cell apoptosis induces sex reversal after the mutation of a DNA–repair pathway gene by compromising the survival of oocytes and suggests the existence of an oocyte-derived signal that biases gonad fate towards the female developmental pathway and thereby controls zebrafish sex determination. PMID:20661450

Rodriguez-Mari, Adriana; Canestro, Cristian; BreMiller, Ruth A.; Nguyen-Johnson, Alexandria; Asakawa, Kazuhide; Kawakami, Koichi; Postlethwait, John H.

2010-01-01

389

Molecular Characteristics of Malignant Ovarian Germ Cell Tumors and Comparison With Testicular Counterparts: Implications for Pathogenesis  

PubMed Central

This review focuses on the molecular characteristics and development of rare malignant ovarian germ cell tumors (mOGCTs). We provide an overview of the genomic aberrations assessed by ploidy, cytogenetic banding, and comparative genomic hybridization. We summarize and discuss the transcriptome profiles of mRNA and microRNA (miRNA), and biomarkers (DNA methylation, gene mutation, individual protein expression) for each mOGCT histological subtype. Parallels between the origin of mOGCT and their male counterpart testicular GCT (TGCT) are discussed from the perspective of germ cell development, endocrinological influences, and pathogenesis, as is the GCT origin in patients with disorders of sex development. Integrated molecular profiles of the 3 main histological subtypes, dysgerminoma (DG), yolk sac tumor (YST), and immature teratoma (IT), are presented. DGs show genomic aberrations comparable to TGCT. In contrast, the genome profiles of YST and IT are different both from each other and from DG/TGCT. Differences between DG and YST are underlined by their miRNA/mRNA expression patterns, suggesting preferential involvement of the WNT/?-catenin and TGF-?/bone morphogenetic protein signaling pathways among YSTs. Characteristic protein expression patterns are observed in DG, YST and IT. We propose that mOGCT develop through different developmental pathways, including one that is likely shared with TGCT and involves insufficient sexual differentiation of the germ cell niche. The molecular features of the mOGCTs underline their similarity to pluripotent precursor cells (primordial germ cells, PGCs) and other stem cells. This similarity combined with the process of ovary development, explain why mOGCTs present so early in life, and with greater histological complexity, than most somatic solid tumors. PMID:23575763

Kraggerud, Sigrid Marie; Hoei-Hansen, Christina E.; Alagaratnam, Sharmini; Skotheim, Rolf I.; Abeler, Vera M.

2013-01-01

390

Production of human CD59-transgenic pigs by embryonic germ cell nuclear transfer  

SciTech Connect

Research highlights: {yields} Human CD59 (hCD59) gene was introduced into porcine embryonic germ (EG) cells. {yields} hCD59-transgenic EG cells were resistant to hyperacute rejection in cytolytic assay. {yields} hCD59-transgenic pigs were produced by EG cell nuclear transfer. -- Abstract: This study was performed to produce transgenic pigs expressing the human complement regulatory protein CD59 (hCD59) using the nuclear transfer (NT) of embryonic germ (EG) cells, which are undifferentiated stem cells derived from primordial germ cells. Because EG cells can be cultured indefinitely in an undifferentiated state, they may provide an inexhaustible source of nuclear donor cells for NT to produce transgenic pigs. A total of 1980 NT embryos derived from hCD59-transgenic EG cells were transferred to ten recipients, resulting in the birth of fifteen piglets from three pregnancies. Among these offspring, ten were alive without overt health problems. Based on PCR analysis, all fifteen piglets were confirmed as hCD59 transgenic. The expression of the hCD59 transgene in the ten living piglets was verified by RT-PCR. Western analysis showed the expression of the hCD59 protein in four of the ten RT-PCR-positive piglets. These results demonstrate that hCD59-transgenic pigs could effectively be produced by EG cell NT and that such transgenic pigs may be used as organ donors in pig-to-human xenotransplantation.

Ahn, Kwang Sung; Won, Ji Young [Department of Physiology, Dankook University School of Medicine, Cheonan (Korea, Republic of)] [Department of Physiology, Dankook University School of Medicine, Cheonan (Korea, Republic of); Park, Jin-Ki [Animal Biotechnology Division, National Institute of Animal Science, Suwon (Korea, Republic of)] [Animal Biotechnology Division, National Institute of Animal Science, Suwon (Korea, Republic of); Sorrell, Alice M. [Department of Physiology, Dankook University School of Medicine, Cheonan (Korea, Republic of)] [Department of Physiology, Dankook University School of Medicine, Cheonan (Korea, Republic of); Heo, Soon Young; Kang, Jee Hyun [Department of Nanobiomedical Science, Dankook University, Cheonan (Korea, Republic of)] [Department of Nanobiomedical Science, Dankook University, Cheonan (Korea, Republic of); Woo, Jae-Seok [Animal Biotechnology Division, National Institute of Animal Science, Suwon (Korea, Republic of)] [Animal Biotechnology Division, National Institute of Animal Science, Suwon (Korea, Republic of); Choi, Bong-Hwan [Genomics and Bioinformatics Division, National Institute of Animal Science, Suwon (Korea, Republic of)] [Genomics and Bioinformatics Division, National Institute of Animal Science, Suwon (Korea, Republic of); Chang, Won-Kyong [Animal Biotechnology Division, National Institute of Animal Science, Suwon (Korea, Republic of)] [Animal Biotechnology Division, National Institute of Animal Science, Suwon (Korea, Republic of); Shim, Hosup, E-mail: shim@dku.edu [Department of Nanobiomedical Science, Dankook University, Cheonan (Korea, Republic of) [Department of Nanobiomedical Science, Dankook University, Cheonan (Korea, Republic of); Institute of Tissue Regeneration Engineering, Dankook University, Cheonan (Korea, Republic of)

2010-10-01

391

Clinical implementation of germ line cancer pharmacogenetic variants during the next-generation sequencing era.  

PubMed

More than 100 medications approved by the US Food and Drug Administration include pharmacogenetic biomarkers in the drug label, many with cancer indications referencing germ line DNA variations. With the advent of next-generation sequencing (NGS) and its rapidly increasing uptake into cancer research and clinical practice, an enormous amount of data to inform documented gene-drug associations will be collected that must be exploited to optimize patient benefit. This review focuses on the implementation of germ line cancer pharmacogenetics in clinical practice. Specifically, it discusses the importance of germ line variation in cancer and the role of NGS in pharmacogenetic discovery and implementation. In the context of a scenario in which massive amounts of NGS-based genetic information will be increasingly available to health stakeholders, this review explores the ongoing debate regarding the threshold of evidence necessary for implementation, provides an overview of recommendations in cancer by professional organizations and regulatory bodies, and discusses limitations of current guidelines and strategies to improve third-party coverage. PMID:24136381

Gillis, N K; Patel, J N; Innocenti, F

2014-03-01

392

Practical issues on the application of the GHS classification criteria for germ cell mutagens.  

PubMed

The Globally Harmonized System of Classification and Labeling of Chemicals (GHS) requires classification of chemicals on germ cell mutagenicity. The Japanese government has conducted GHS classification on about 1400 chemicals in a 2-year project (J-GHS) for implementing GHS domestically. Prior to the classification work, the technical guidance for classification of germ cell mutagens was prepared. This guidance introduces the concept of heritable mutagenicity, and presents detailed criteria for germ cell mutagens, test data to be used, and a practical decision tree for classification. These practical guidance and supporting explanations are useful for non-expert Classifiers (scientists applying the classification criteria). Several issues, however, were identified during the course of J-GHS and in re-evaluating the classification results. These include: (1) the information sources when available data are limited; (2) lack of understanding GHS classification criteria or insufficient review of the information by Classifiers; (3) varying opinions of experts on data quality and weight of evidence, and; (4) decision tree approaches, e.g., inadequacy for use in overall evaluation in some cases. Ideally, classification should be performed by Classifiers with high expertise using high quality information sources. Genetic toxicologists as experts should consider data quality and reliability, and give a critical review of all available information for support of classification. A weight of evidence approach is also required to assess mutagenic potential of chemicals. Critical points for suitable classification for GHS are discussed. PMID:19505521

Morita, Takeshi; Hayashi, Makoto; Nakajima, Madoka; Tanaka, Noriho; Tweats, David J; Morikawa, Kaoru; Sofuni, Toshio

2009-10-01

393

Induction of mouse germ-cell fate by transcription factors in vitro.  

PubMed

The germ-cell lineage ensures the continuity of life through the generation of male and female gametes, which unite to form a totipotent zygote. We have previously demonstrated that, by using cytokines, embryonic stem cells and induced pluripotent stem cells can be induced into epiblast-like cells (EpiLCs) and then into primordial germ cell (PGC)-like cells with the capacity for both spermatogenesis and oogenesis, creating an opportunity for understanding and regulating mammalian germ-cell development in both sexes in vitro. Here we show that, without cytokines, simultaneous overexpression of three transcription factors, Blimp1 (also known as Prdm1), Prdm14 and Tfap2c (also known as AP2?), directs EpiLCs, but not embryonic stem cells, swiftly and efficiently into a PGC state. Notably, Prdm14 alone, but not Blimp1 or Tfap2c, suffices for the induction of the PGC state in EpiLCs. The transcription-factor-induced PGC state, irrespective of the transcription factors used, reconstitutes key transcriptome and epigenetic reprogramming in PGCs, but bypasses a mesodermal program that accompanies PGC or PGC-like-cell specification by cytokines including bone morphogenetic protein 4. Notably, the transcription-factor-induced PGC-like cells contribute to spermatogenesis and fertile offspring. Our findings provide a new insight into the transcriptional logic for PGC specification, and create a foundation for the transcription-factor-based reconstitution and regulation of mammalian gametogenesis. PMID:23913270

Nakaki, Fumio; Hayashi, Katsuhiko; Ohta, Hiroshi; Kurimoto, Kazuki; Yabuta, Yukihiro; Saitou, Mitinori

2013-09-12

394

Minocycline up-regulates BCL-2 levels in mitochondria and attenuates male germ cell apoptosis.  

PubMed

In this study, we determined the efficacy of minocycline, a second generation tetracycline, in preventing male germ cell apoptosis after withdrawal of gonadotropins and intratesticular testosterone (T). Groups of 5 male rats received one of the following treatments daily for 5 days: (i) daily sc injection of GnRH-A (1.6 mg/kg BW), (ii) oral administration of 30% gum acacia as a vehicle control, and (iii) GnRH-A + oral administration of 50 or 100 mg/kg BW of minocycline. Minocycline at both 50 and 100 mg dose levels significantly (P < 0.05) prevented GnRH-A -induced germ cell apoptosis by 59.4% and 62.2%, respectively, and fully prevented PARP cleavage. Minocycline-mediated protection occurred at the mitochondria, involving the restoration of the BCL-2 levels and, in turn, suppression of cytochrome c and DIABLO release. Minocycline was also effective in preventing human male germ cell apoptosis induced by hormone free culture condition. PMID:16202388

Castanares, Mark; Vera, Yanira; Erkkilä, Krista; Kyttänen, Sauli; Lue, Yanhe; Dunkel, Leo; Wang, Christina; Swerdloff, Ronald S; Hikim, Amiya P Sinha

2005-11-18

395

The majority of early primordial germ cells acquire pluripotency by AKT activation.  

PubMed

Primordial germ cells (PGCs) are undifferentiated germ cells in embryos, the fate of which is to become gametes; however, mouse PGCs can easily be reprogrammed into pluripotent embryonic germ cells (EGCs) in culture in the presence of particular extracellular factors, such as combinations of Steel factor (KITL), LIF and bFGF (FGF2). Early PGCs form EGCs more readily than do later PGCs, and PGCs lose the ability to form EGCs by embryonic day (E) 15.5. Here, we examined the effects of activation of the serine/threonine kinase AKT in PGCs during EGC formation; notably, AKT activation, in combination with LIF and bFGF, enhanced EGC formation and caused ?60% of E10.5 PGCs to become EGCs. The results indicate that the majority of PGCs at E10.5 could acquire pluripotency with an activated AKT signaling pathway. Importantly, AKT activation did not fully substitute for bFGF and LIF, and AKT activation without both LIF and bFGF did not result in EGC formation. These findings indicate that AKT signal enhances and/or collaborates with signaling pathways of bFGF and of LIF in PGCs for the acquisition of pluripotency. PMID:25359722

Matsui, Yasuhisa; Takehara, Asuka; Tokitake, Yuko; Ikeda, Makiko; Obara, Yuka; Morita-Fujimura, Yuiko; Kimura, Tohru; Nakano, Toru

2014-12-01

396

Ribosome Synthesis and MAPK Activity Modulate Ionizing Radiation-Induced Germ Cell Apoptosis in Caenorhabditis elegans  

PubMed Central

Synthesis of ribosomal RNA by RNA polymerase I (RNA pol I) is an elemental biological process and is key for cellular homeostasis. In a forward genetic screen in C. elegans designed to identify DNA damage-response factors, we isolated a point mutation of RNA pol I, rpoa-2(op259), that leads to altered rRNA synthesis and a concomitant resistance to ionizing radiation (IR)-induced germ cell apoptosis. This weak apoptotic IR response could be phenocopied when interfering with other factors of ribosome synthesis. Surprisingly, despite their resistance to DNA damage, rpoa-2(op259) mutants present a normal CEP-1/p53 response to IR and increased basal CEP-1 activity under normal growth conditions. In parallel, rpoa-2(op259) leads to reduced Ras/MAPK pathway activity, which is required for germ cell progression and physiological germ cell death. Ras/MAPK gain-of-function conditions could rescue the IR response defect in rpoa-2(op259), pointing to a function for Ras/MAPK in modulating DNA damage-induced apoptosis downstream of CEP-1. Our data demonstrate that a single point mutation in an RNA pol I subunit can interfere with multiple key signalling pathways. Ribosome synthesis and growth-factor signalling are perturbed in many cancer cells; such an interplay between basic cellular processes and signalling might be critical for how tumours evolve or respond to treatment. PMID:24278030

Eberhard, Ralf; Stergiou, Lilli; Hofmann, E. Randal; Hofmann, Jen; Haenni, Simon; Teo, Youjin; Furger, Andre; Hengartner, Michael O.

2013-01-01

397

It's All in Your Mind: Determining Germ Cell Fate by Neuronal IRE-1 in C. elegans  

PubMed Central

The C. elegans germline is pluripotent and mitotic, similar to self-renewing mammalian tissues. Apoptosis is triggered as part of the normal oogenesis program, and is increased in response to various stresses. Here, we examined the effect of endoplasmic reticulum (ER) stress on apoptosis in the C. elegans germline. We demonstrate that pharmacological or genetic induction of ER stress enhances germline apoptosis. This process is mediated by the ER stress response sensor IRE-1, but is independent of its canonical downstream target XBP-1. We further demonstrate that ire-1-dependent apoptosis in the germline requires both CEP-1/p53 and the same canonical apoptotic genes as DNA damage-induced germline apoptosis. Strikingly, we find that activation of ire-1, specifically in the ASI neurons, but not in germ cells, is sufficient to induce apoptosis in the germline. This implies that ER stress related germline apoptosis can be determined at the organism level, and is a result of active IRE-1 signaling in neurons. Altogether, our findings uncover ire-1 as a novel cell non-autonomous regulator of germ cell apoptosis, linking ER homeostasis in sensory neurons and germ cell fate. PMID:25340700

Levi-Ferber, Mor; Salzberg, Yehuda; Safra, Modi; Haviv-Chesner, Anat; Bulow, Hannes E.; Henis-Korenblit, Sivan

2014-01-01

398

Special Article From Embryonic Stem Cells to Functioning Germ Cells: Science, Clinical and Ethical Perspectives  

E-print Network

Embryonic stem cells have been well recognized as cells having a versatile potential to differentiate into all types of cells in the body including germ cells. There are many research studies focusing on the differentiation processes and protocols to derive various types of somatic cells from embryonic stem cells. However, germ cells have unique differentiation process and developmental pathway compared with somatic cells. Consequently, they will require different differentiation protocols and special culture techniques. More understanding and established in vitro systems for gametogenesis will greatly contribute to further progression of knowledge and technology in germ cell biology, reproductive biology and reproductive medicine. Moreover, if oocytes can be efficiently produced in vitro, this will play an important role on progression in nuclear transfer and nuclear reprogramming technology. The present article will provide concise review on past important discoveries, current ongoing studies and future views of this challenging research area. An ethical perspective has also been proposed to give comprehensive summary and viewpoint for future clinical application.

Sorapop Kiatpongsan Md

399

Slide preparation method to preserve three-dimensional chromatin architecture of testicular germ cells.  

PubMed

During testicular germ cell differentiation, the structure of nuclear chromatin dynamically changes. The following describes a method designed to preserve the three-dimensional chromatin arrangement of testicular germ cells found in mice; this method has been termed as the three-dimensional (3D) slide method. In this method, testicular tubules are directly treated with a permeabilization step that removes cytoplasmic material, followed by a fixation step that fixes nuclear materials. Tubules are then dissociated, the cell suspension is cytospun, and cells adhere to slides. This method improves sensitivity towards detection of subnuclear structures and is applicable for immunofluorescence, DNA, and RNA fluorescence in situ hybridization (FISH) and the combination of these detection methods. As an example of a possible application of the 3D slide method, a Cot-1 RNA FISH is shown to detect nascent RNAs. The 3D slide method will facilitate the detailed examination of spatial relationships between chromatin structure, DNA, and RNA during testicular germ cell differentiation. PMID:24457971

Namekawa, Satoshi H

2014-01-01

400

Growth and Invasiveness of Candida albicans in the Germ-Free and Conventional Mouse After Oral Challenge  

PubMed Central

Candida albicans was established in large numbers throughout the gut after one oral challenge in the germ-free and in the conventional mouse. Of the strains tested, only the germ-free ND 1 mouse appeared to be susceptible to infection, and this was confined to the stomach mucosa; lesions contained large numbers of hyphal and mycelial forms with blastospores. These forms were also seen in the gut of resistant germ-free ND 4 mice after challenge. Only budding yeast forms were seen in the gut contents from conventional animals. The concentration of sulfhydryl-containing compounds was decreased in the stomach contents from germ-free mice. The stomach tissue of conventional animals seemed to be more acidic than that of germ-free animals, and association of C. albicans with conventional mice neutralized some of this acidity. Eh values of contents from the gut of unchallenged mice were usually higher in conventional than in germ-free animals; after challenge, the Eh in both groups decreased. Some reciprocal effects of intestinal microorganisms and host are discussed in relation to intestinal candidiasis. PMID:5970461

Phillips, A. W.; Balish, Edward

1966-01-01

401

Toward a More Precise and Informative Nomenclature Describing Fetal and Neonatal Male Germ Cells in Rodents1  

PubMed Central

ABSTRACT The germ cell lineages are among the best characterized of all cell lineages in mammals. This characterization includes precise nomenclature that distinguishes among numerous, often subtle, changes in function or morphology as development and differentiation of germ cells proceed to form the gametes. In male rodents, there are at least 41 distinct cell types that occur during progression through the male germ cell lineage that gives rise to spermatozoa. However, there is one period during male germ cell development—that which occurs immediately following the primordial germ cell stage and prior to the spermatogonial stage—for which the system of precise and informative cell type terminology is not adequate. Often, male germ cells during this period are referred to simply as “gonocytes.” However, this term is inadequate for multiple reasons, and it is suggested here that nomenclature originally proposed in the 1970s by Hilscher et al., which employs the terms M-, T1-, and T2-prospermatogonia, is preferable. In this Minireview, the history, proper utilization, and advantages of this terminology relative to that of the term gonocytes are described. PMID:23843236

McCarrey, John R.

2013-01-01

402

Cytoplasmic connection of sperm cells to the pollen vegetative cell nucleus: potential roles of the male germ unit revisited.  

PubMed

The male germ cells of angiosperm plants are neither free-living nor flagellated and therefore are dependent on the unique structure of the pollen grain for fertilization. During angiosperm male gametogenesis, an asymmetric mitotic division produces the generative cell, which is completely enclosed within the cytoplasm of the larger pollen grain vegetative cell. Mitotic division of the generative cell generates two sperm cells that remain connected by a common extracellular matrix with potential intercellular connections. In addition, one sperm cell has a cytoplasmic projection in contact with the vegetative cell nucleus. The shared extracellular matrix of the two sperm cells and the physical association of one sperm cell to the vegetative cell nucleus forms a linkage of all the genetic material in the pollen grain, termed the male germ unit. Found in species representing both the monocot and eudicot lineages, the cytoplasmic projection is formed by vesicle formation and microtubule elongation shortly after the formation of the generative cell and tethers the male germ unit until just prior to fertilization. The cytoplasmic projection plays a structural role in linking the male germ unit, but potentially plays other important roles. Recently, it has been speculated that the cytoplasmic projection and the male germ unit may facilitate communication between the somatic vegetative cell nucleus and the germinal sperm cells, via RNA and/or protein transport. This review focuses on the nature of the sperm cell cytoplasmic projection and the potential communicative function of the male germ unit. PMID:21357775

McCue, Andrea D; Cresti, Mauro; Feijó, José A; Slotkin, R Keith

2011-03-01

403

Prostaglandin D2 acts through the Dp2 receptor to influence male germ cell differentiation in the foetal mouse testis.  

PubMed

Through intercellular signalling, the somatic compartment of the foetal testis is able to program primordial germ cells to undergo spermatogenesis. Fibroblast growth factor 9 and several members of the transforming growth factor ? superfamily are involved in this process in the foetal testis, counteracting the induction of meiosis by retinoic acid and activating germinal mitotic arrest. Here, using in vitro and in vivo approaches, we show that prostaglandin D2 (PGD2), which is produced through both L-Pgds and H-Pgds enzymatic activities in the somatic and germ cell compartments of the foetal testis, plays a role in mitotic arrest in male germ cells by activating the expression and nuclear localization of the CDK inhibitor p21(Cip1) and by repressing pluripotency markers. We show that PGD2 acts through its Dp2 receptor, at least in part through direct effects in germ cells, and contributes to the proper differentiation of male germ cells through the upregulation of the master gene Nanos2. Our data identify PGD2 signalling as an early pathway that acts in both paracrine and autocrine manners, and contributes to the differentiation of germ cells in the foetal testis. PMID:25142465

Moniot, Brigitte; Ujjan, Safdar; Champagne, Julien; Hirai, Hiroyuki; Aritake, Kosuke; Nagata, Kinya; Dubois, Emeric; Nidelet, Sabine; Nakamura, Masataka; Urade, Yoshihiro; Poulat, Francis; Boizet-Bonhoure, Brigitte

2014-09-01

404

[Primary immunodeficiency].  

PubMed

Primary (inborn) immunodeficiency is caused by gene defects that impact both the innate and the adaptive immune system. Individuals with an immunedeficiency primarily come to medical attention with recurrent infections. Most diagnoses are first made in childhood and include cellular immunodeficiency, defects of phagocyte function and other primary immunodeficiencies. Antibody deficiencies, particularly common variable immunodeficiency (CVID) and complement defects may, however, not become manifested until adulthood. A pathological susceptibility to infection in adults is defined as more than three infections per year that require treatment with antibiotics and last longer than 4 weeks each. Clinical clues for immunodeficiency are pathological susceptibility to infections and immune dysregulation. The former is characterized by frequent and severe infections with often unusual pathogens, localization, course and/or intensity. Immune dysregulation comprises granulomas, autoimmune diseases, recurrent fever/chronic inflammation, tendency to eczema, lymphoproliferation and chronic enteritis. There are evidence-based guidelines and consensus documents for the diagnosis and treatment of primary immunodeficiencies. Therapeutic approaches depend on the nature of the immune defect and range from immunoglobulin substitution for antibody deficiencies to bone marrow transplantation for severe cellular immune defects. PMID:23989691

Engelhardt, K R; Grimbacher, B; Niehues, T

2013-09-01

405

Lava Layering  

NSDL National Science Digital Library

This is a lesson about geologic history. Learners will work together to create models of volcanic lava flows and analyze the layers that form on a planet's surface. They will sequence lava flows produced by multiple eruptions. Students will be asked to observe where the flows travel, make a model, and interpret the stratigraphy. Students will use their volcanic layering model to demonstrate the relative dating and geologic mapping principles to later be applied to satellite imagery. The lesson models scientific inquiry using the 5E instructional model and includes teacher notes and vocabulary.

406

Germ-line origins of mutation in families with hemophilia B: The sex ratio varies with the type of mutation  

SciTech Connect

Previous epidemiological and biochemical studies have generated conflicting estimates of the sex ratio of mutation. Direct genomic sequencing in combination with haplotype analysis extends previous analyses by allowing the precise mutation to be determined in a given family. From analysis of the factor IX gene of 260 consecutive families with hemophilia B, the authors report the germ-line origin of mutation in 25 families. When combined with 14 origins of mutation reported by others and with 4 origins previously reported by them, a total of 25 occur in the female germ line, and 18 occur in the male germ line. The excess of germ-line origins in females does not imply an overall excess mutation rate per base pair in the female germ line. Bayesian analysis of the data indicates that the sex ratio varies with the type of mutation. The aggregate of single-base substitutions shows a male predominance of germ-line mutations (P < .002). The maximum-likelihood estimate of the male predominance is 3.5-fold. Of the single-base substitutions, deletions display a sex ratio of unity. Analysis of the parental age at transmission of a new mutation suggests that germ-line mutations are associated with a small increase in parental age in females but little, if any, increase in males. Although direct genomic sequencing offers a general method for defining the origin of mutation in specific families, accurate estimates of the sex ratios of different mutational classes require large sample sizes and careful correction for multiple biases of ascertainment. The biases in the present data result in an underestimate of the enhancement of mutation in males. 62 refs., 1 fig., 5 tabs.

Ketterling, R.P.; Vielhaber, E.; Bottema, C.D.K.; Schaid, D.J.; Sommer, S.S. (Mayo Clinic/Foundation, Rochester, MN (United States)); Cohen, M.P. (Vanderbilt Univ., Nashville, TN (United States)); Sexauer, C.L. (Children's Hospital, Oklahoma City, OK (United States))

1993-01-01

407

A Primary Pure Yolk Sac Tumor of the Lung Exhibiting CDX-2 Immunoreactivity and Increased Serum Levels of Alkaline Phosphatase Intestinal Isoenzyme  

Microsoft Academic Search

Malignant extragonadal germ cell tumors primary to the lung are quite uncommon lesions, but pure yolk sac tumor is even more exceptional. This is believed to be the first reported case of yolk sac tumor of the lung in which an intense and diffuse immunoreactivity for CDX2, a marker of intestinal differentiation reportedly expressed also in gonadal yolk sac tumor,

Giuseppe Pelosi; Francesco Petrella; Maria Teresa Sandri; Lorenzo Spaggiari; Domenico Galetta; Giuseppe Viale

2006-01-01

408

Serum Organochlorine Pesticide Residues and Risk of Testicular Germ Cell Carcinoma: A Population-Based Case-Control Study  

PubMed Central

Testicular germ cell carcinoma (TGCC) is the most common malignancy among men aged 20–34. Although the pathogenesis of TGCC is poorly understood, sub-optimal androgen levels or impaired androgen signaling may play a role. Some persistent organochlorine pesticides commonly found in human tissue possess anti-androgenic properties. We examined whether the risk of TGCC is associated with serum levels of 11 organochlorine pesticides, including p,p’-DDE, and whether the p,p-DDE-TGCC association is modified by CAG or GGN repeat polymorphisms in the androgen receptor (AR) gene. We conducted a population-based case-control study among 18–44 year-old male residents of three Washington State counties. Cases (n=246) were diagnosed during 1999–2003 with a first, primary TGCC. Controls (n=630) were men of similar age with no history of TGCC from the same population identified through random-digit telephone dialing. Questionnaires elicited information on demographic, medical, and lifestyle factors. A blood specimen provided serum for gas chromatography-high resolution mass spectrometry analysis of organochlorine pesticide residues, and DNA for genotyping. We observed no clear patterns between TGCC risk and concentrations of any of the organochlorines measured, nor did we observe that the risk associated with p,p’-DDE was modified by AR CAG (<23 vs.23+ repeats) or GGN (<17 vs.17+ repeats) genotype. This study does not provide support for the hypothesis that adult exposure to organochlorine pesticides is associated with risk of TGCC. Due to uncertainty regarding how well organochlorine levels measured in adulthood reflect exposures during early life, further research is needed using exposure measurements collected in utero or during infancy. PMID:18708392

Biggs, Mary L.; Davis, Mark D.; Eaton, David L.; Weiss, Noel S.; Barr, Dana B.; Doody, David R.; Fish, Sherianne; Needham, Larry L.; Chen, Chu; Schwartz, Stephen M.

2008-01-01

409

Treatment Outcomes, Growth Height, and Neuroendocrine Functions in Patients With Intracranial Germ Cell Tumors Treated With Chemoradiation Therapy  

SciTech Connect

Purpose: We carried out a retrospective review of patients receiving chemoradiation therapy (CRT) for intracranial germ cell tumor (GCT) using a lower dose than those previously reported. To identify an optimal GCT treatment strategy, we evaluated treatment outcomes, growth height, and neuroendocrine functions. Methods and Materials: Twenty-two patients with GCT, including 4 patients with nongerminomatous GCT (NGGCT) were treated with CRT. The median age at initial diagnosis was 11.5 years (range, 6-19 years). Seventeen patients initially received whole brain irradiation (median dose, 19.8 Gy), and 5 patients, including 4 with NGGCT, received craniospinal irradiation (median dose, 30.6 Gy). The median radiation doses delivered to the primary site were 36 Gy for pure germinoma and 45 Gy for NGGCT. Seventeen patients had tumors adjacent to the hypothalamic-pituitary axis (HPA), and 5 had tumors away from the HPA. Results: The median follow-up time was 72 months (range, 18-203 months). The rates of both disease-free survival and overall survival were 100%. The standard deviation scores (SDSs) of final heights recorded at the last assessment tended to be lower than those at initial diagnosis. Even in all 5 patients with tumors located away from the HPA, final height SDSs decreased (p = 0.018). In 16 patients with tumors adjacent to the HPA, 8 showed metabolic changes suggestive of hypothalamic obesity and/or growth hormone deficiency, and 13 had other pituitary hormone deficiencies. In contrast, 4 of 5 patients with tumors away from the HPA did not show any neuroendocrine dysfunctions except for a tendency to short stature. Conclusions: CRT for GCT using limited radiation doses resulted in excellent treatment outcomes. Even after limited radiation doses, insufficient growth height was often observed that was independent of tumor location. Our study suggests that close follow-up of neuroendocrine functions, including growth hormone, is essential for all patients with GCT.

Odagiri, Kazumasa, E-mail: t086016a@yokohama-cu.ac.jp [Department of Radiology, Yokohama City University Graduate School of Medicine, Yokohama (Japan) [Department of Radiology, Yokohama City University Graduate School of Medicine, Yokohama (Japan); Department of Radiology, Kanagawa Children's Medical Center, Yokohama (Japan); Omura, Motoko [Department of Radiology, Yokohama City University Graduate School of Medicine, Yokohama (Japan) [Department of Radiology, Yokohama City University Graduate School of Medicine, Yokohama (Japan); Department of Radiology, Kanagawa Children's Medical Center, Yokohama (Japan); Hata, Masaharu [Department of Radiology, Yokohama City University Graduate School of Medicine, Yokohama (Japan)] [Department of Radiology, Yokohama City University Graduate School of Medicine, Yokohama (Japan); Aida, Noriko; Niwa, Tetsu [Department of Radiology, Kanagawa Children's Medical Center, Yokohama (Japan)] [Department of Radiology, Kanagawa Children's Medical Center, Yokohama (Japan); Ogino, Ichiro [Department of Radiology, Yokohama City University Medical Center, Yokohama (Japan)] [Department of Radiology, Yokohama City University Medical Center, Yokohama (Japan); Kigasawa, Hisato [Division of Hemato-oncology/Regeneration Medicine, Kanagawa Children's Medical Center, Yokohama (Japan)] [Division of Hemato-oncology/Regeneration Medicine, Kanagawa Children's Medical Center, Yokohama (Japan); Ito, Susumu [Department of Neurosurgery, Kanagawa Children's Medical Center, Yokohama (Japan)] [Department of Neurosurgery, Kanagawa Children's Medical Center, Yokohama (Japan); Adachi, Masataka [Department of Endocrinology, Kanagawa Children's Medical Center, Yokohama (Japan)] [Department of Endocrinology, Kanagawa Children's Medical Center, Yokohama (Japan); Inoue, Tomio [Department of Radiology, Yokohama City University Graduate School of Medicine, Yokohama (Japan)] [Department of Radiology, Yokohama City University Graduate School of Medicine, Yokohama (Japan)

2012-11-01

410

Vasa and nanos are coexpressed in somatic and germ line tissue from early embryonic cleavage stages through adulthood in the polychaete Capitella sp. I  

Microsoft Academic Search

Members of the vasa and nanos gene families are involved in germ line development in a number of diverse animals. As a polychaete annelid model for studies\\u000a of the germ line, Capitella sp. I has several advantages including the presence of dedicated gonads, individuals that reproduce multiple times, and the\\u000a presence of males, females, and hermaphrodites. Germ line development has

Kariena K. Dill; Elaine C. Seaver

2008-01-01